Suplementos: Desperdício ou Necessidade

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  • 1. SUPLEMENTOS:DESPERDÍCIO OU NECESSIDADE? Pedro Carrera Bastos
  • 2. EUA Carne, Peixe 1,4 Ovos 18,6 15,7 Oleaginosas, Açúcares 3,1 Leguminosas, Óleos 3,3 Fruta Vegetais Cereais Lácteos Hortaliças/17,8 4,8 Tubérculos 0,8 Outros 23,9 10,6 Cordain L et al. Am J Clin Nutr. 2005 Feb;81(2):341-54!
  • 3. GASTO ENERGÉTICO DOS HOMINÍDEOS Taxa Metabólica Basal Gasto Enérgetico Total 60 50Kcal/kg/day 40 30 20 10 0 Homo habilis Homo erectus Homo sapiens Ache CR Homo sapiens 2.2 MYA 1.7 MYA (arcaico) sedentário 0.6 MYA Moderno Moderno Cordain L, et al. Int J Sport Med 1998;19:328-335.
  • 4. HÁBITOS MODERNOS DE SONO
  • 5. Todos osESTILO Humanos nosMODERNO países industrializados é exposto à luz de formaESTILO biologicamenteANTIGO atípica ! ! Disrupção do ritmo circadiano normal! % SIGNIFICATIVA DA POPULAÇÃO OCIDENTAL DORME! < 6 HORAS POR NOITE. !
  • 6. EXPOSIÇÃO SOLAR
  • 7. Liu H, et al. Am J Hum Genet. 2006 Aug;79(2):230-7!
  • 8. TABACO!
  • 9. OVERTRAINING DIETA INADEQUADA SONO fffffff INSUFICIENTE !PERFORMANCE REDUZIDA EXPOSIÇÃO SOLAR STRESS CRÓNICO LIMIAR PARA APARECIMENTO DE SINTOMAS FENÓTIPO “PATOLÓGICO”11
  • 10. SUPLEMENTOS???!
  • 11. Minerais Vitaminas AntioxidantesÁcidos Gordos essenciais
  • 12. ESTAMOS A INGERIR O SUFICIENTE?! INE, Dezembro 2006
  • 13. DEFICIÊNCIAS DE MICRONUTRIENTES 
 (POPULAÇÃO GERAL - EUA) ! Nutriente % norte-americanos que não atinge DDR Vit E 93 Magnésio 56 Vit A 44 Vit C 31 Vit B6 14 Zinco 12 Folato 8 Cobre 5 Ferro 5 Tiamina 5 USDA What we Eat in America (NHANES 2001-2002) Sept. 2005 Disponível em:http://www.ars.usda.gov/SP2UserFiles/Place/12355000/pdf/usualintaketables2001-02.pdf
  • 14. DEFICIÊNCIAS DE MICRONUTRIENTES 
 (POPULAÇÃO GERAL - EUA) !Nutriente %H %H %H %M %M %M 14-18 a 19-30 a 31-50 a 14-18 a 19-30 a 31-50 aVit E 97 89 90 97 97 97Magnésio 78 55 61 91 64 65Vit C 26 37 40 42 40 41Zinco 4 6 4 26 13 11Folato 4 6 <3 19 14 16Ferro <3 <3 <3 16 15 17 USDA What we Eat in America (NHANES 2001-2002) Sept. 2005 Disponível em: http://www.ars.usda.gov/SP2UserFiles/Place/12355000/pdf/usualintaketables2001-02.pdf
  • 15. FONTES DE MAGNÉSIOAlimentos de Qtd de Magnésio Alimentos de Qtd de Magnésioorigem animal mg origem vegetal 100 grsc 100 grs Fígado 21,0 Grão 122,0Carne magra 22,0 Nozes 358,0 Sardinha 25,1 Amêndoas 270 Atum 28 Avelãs 163 Linguado 25,1 Pescada 29,0 Amendoim 166 Mexilhão 23 Pão Trigo 25,1 Gambas 42 Massa Trigo 53,0 Ovo 12,0 Batata 19,9Iogurte natural 14,3 Leite inteiro 11,6 Espinafres 58,0
  • 16. RR comparing the highest quintile to non-supplement users was 0.77 (95% CI 0.56 –1.06, p for Conclusions: These results suggest that intake of magnesium may have a modest inverse as Magnesium and Risk of Coronary Heart Disea risk of CHD among men. INTRODUCTION cohort no association was seen b CHD, but the number of cases wa Inadequate magnesium intake in the US population may be The primary aim of this ana a risk factor for cardiovascular diseases [1]. There is still association between intake of m controversy on the use of magnesium to prevent CHD because (fatal CHD and non-fatal myoca most of the published data on the protective effects of magne- men participating in the Health P sium involve CHD patients [2–5] and there are limited studies (HPFS). We also assessed the as on prevention among healthy adults. Higher magnesium intake the other minerals, potassium and through water supplies rich in this and other minerals (hard because potassium is metaboli water) has been associated with decreased prevalence of car- [14,15] and zinc deficiency is a su diac mortality in several ecological studies [6 – 8], but these studies did not adjust for possible confounders and the inverse association was not seen in other studies [9 –10]. Magnesium MATERIALS AND M deficiency has been related to coronary spasm and various arrhythmias through the loss of cellular potassium [11]. In a The Health Professionals Fo controlled clinical trial, higher magnesium intake was associated prospective cohort initiated in 1 with a significant antiarrhythmic effect [12]. In the Caerphilly nantly white men 40 to 75 yearig. 1. Magnesium levels and multivariate adjusted* to: Wael K Al-Delaimy, MD, heart Department of Nutrition,according to diabetes status. *(Covariat Address correspondence relative risk of coronary PhD, disease among men Harvard School of Public Health, 665 Huntinge, time period, energy intake, wael@hsph.harvard.edu. history of diabetes, history of high cholesterol, family history of MI, smoking history, aspirin intake, BMI, alcoh take, physical activity, vitamin E intake, trans fatty acids, total protein intake, cereal fiber, folate, omega 3 fatty acid, potassium.) Journal of the American College of Nutrition, Vol. 23, No. 1, 63–70 (2004) Published by the American College of Nutrition
  • 17. MAGNÉSIO E INFLAMAÇÃOSong Y, Li TY, van Dam RM, Manson JE, Hu FB. Am J Clin Nutr. 2007 Apr;85(4):1068-74.
  • 18. 1024 Magnesium Deficiency Produces Insulin Resistance and Magnesium Deficiency Produces Increased Thromboxane Synthesis Insulin Resistance and Increased Thromboxane Synthesis Jerry L. Nadler, Thomas Buchanan, Rama Natarajan, Indra Antonipillai, Jerry L. Nadler, Thomas Buchanan, Rama Natarajan, Indra Antonipillai, Richard Bergman, and Robert Rude Richard Bergman, and Robert RudeEvidence suggestssuggestsmagnesium deficiency may play an an important cardiovascular disease. In disease. In Evidence that that magnesium deficiency may play important role in role in cardiovascularthis study,this study, we evaluated effects ofof amagnesium infusion dietary-induced isolated magnesium magnesium we evaluated the the effects a magnesium infusion and and dietary-induced isolateddeficiency deficiency production Becausethromboxane and may beangiotensin Il-mediated aldosterone synthesis in on the on the production thromboxane andonon associated with altered blood pressure, we also normal human subjects. of of insulin resistance angiotensin Il-mediated aldosterone synthesis innormal human subjects. sensitivity using an intravenous glucose tolerance test withwith altered blood pressure, we also measured insulin Because insulin resistance may be associated minimal model analysis inmeasured six subjects. The magnesium infusion reduced urinary thromboxane concentration minimal model analysis in insulin sensitivity using an intravenous glucose tolerance test with and angiotensinsix subjects. The plasma aldosterone levels. Thecells as urinary thromboxane concentration and II-induced magnesium infusion reducedmagnesium diet reduced both serum magnesium and angiotensin intracellular free magnesium in red blood low determined by nuclear magnetic resonance (186±10II-induced[SEM] to 127±9 mM, p<0.01). Urinary thromboxane concentration measured byboth serum magnesium and plasma aldosterone levels. The low magnesium diet reduced radioimmunoassayintracellular free magnesium indeficiency. Similarly, angiotensin II-induced nuclear magnetic resonance (186±10 increased after magnesium red blood cells as determined by plasma aldosterone concentra-[SEM] to tion increased afterafter magnesium deficiency (3.69±0.6 toconcentration per microunit decrease in 127±9 mM, p<0.01). Urinary thromboxane that all subjects studied had a by millili- insulin sensitivity magnesium deficiency. Analysis showed 2.75±0.5 min~ measured per radioimmunoassayincreased after magnesium deficiency. Similarly, angiotensin II-induced increases thromboxane concentra- terXlO"4, p<0.03). We conclude that dietary-induced magnesium deficiency 1) plasma aldosteronetion increased after magnesium 2) enhances angiotensin-induced aldosterone synthesis. These effects are a decrease in urinary concentration and deficiency. Analysis showed that all subjects studied hadinsulin sensitivity with a decrease in insulin action, suggesting that to 2.75±0.5 min~ per microunit per millili- associated after magnesium deficiency (3.69±0.6 magnesium deficiency may be a commonterXlO"4, factor associated with insulin resistance and vascular disease. (Hypertension 1993;21:1024-1029) p<0.03). We conclude that dietary-induced magnesium deficiency 1) increases thromboxaneurinary concentration • and 2) enhances angiotensin-induced aldosterone synthesis. These effects are KEY WORDS magnesium • angiotensin II • insulin • thromboxanes • aldosteroneassociated with a decrease in insulin action, suggesting that magnesium deficiency may be a common
  • 19. that magnesium intake may have beneficial effects on indi- insulin sensitivit vidual components of the metabolic syndrome. dietary magnesiu Magnesium Intake andthat magnesium may directly Syndrome populatio Experimental data suggest Incidence of Metabolic various Among Young Adults regulate cellular glucose metabolism through its role as a Evidence that cofactor for ScD; Kiang Liu, PhD; Martha L.enzymesMD, PhD; Steven J. Morris,weight regulation Ka He, MD, a number of relevant Daviglus, 28,29 and may PhD; influenceM. Loria, PhD; Linda Van Horn, PhD; Davidwith cellular cal- J. Savage, MD Catherine insulin secretion by interacting R. Jacobs, Jr, PhD; Peter association betw cium homeostasis.6 In addition, epidemiological studies and and sity2 diabetesBackground—Studies suggest that magnesium intake may be inversely related to risk of hypertension type are unclear. have an antiobes clinical trials indicate magnesium may decrease blood triglycerides improve high-density lipoprotein mellitus and that higher intake of that magnesium intake may and increase (HDL) cholesterol levels. However, the longitudinal association of magnesium intake and incidence of metabolic syndrome has not been investigated.Methods and Results—We prospectively examined the relations between magnesium intake and incident metabolic syndrome and its components among 4637 Americans, aged 18 to 30 years, who were free from metabolic syndrome and diabetes at baseline. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III definition. Diet was assessed by an interviewer-administered quantitative food frequency questionnaire, and magnesium intake was derived from the nutrient database developed by the Minnesota Nutrition Coordinating Center. During the 15 years of follow-up, 608 incident cases of the metabolic syndrome were identified. Magnesium intake was inversely associated with incidence of metabolic syndrome after adjustment for major Haza lifestyle and dietary variables and baseline status of each component of the metabolic syndrome. Compared with those total in the lowest quartile of magnesium intake, multivariable-adjusted hazard ratio of metabolic syndrome for participants race in the highest quartile was 0.69 (95% confidence interval [CI], 0.52 to 0.91; P for trend Ͻ0.01). The inverse associations Tabl were not materially modified by gender and race. Magnesium intake was also inversely related to individual component of the metabolic syndrome and fasting insulin levels.Conclusions—Our findings suggest that young adults with higher magnesium intake have lower risk of development of metabolic syndrome. (Circulation. 2006;113:1675-1682.) Key Words follow-up studies Ⅲ magnesium Ⅲ nutrition Ⅲ risk factors Ⅲ syndrome X Downloaded from the pathogenesis of hypertension. on July role for magnesium in circ.ahajournals.org byP eople with metabolic syndrome, characterized by a group 10,11 of metabolic risk factors, have been widely found to be at Although the mechanisms are poorly understood, studieselevated risk of coronary heart disease and type 2 diabetes demonstrate that increased intake of dietary magnesium may 1,2
  • 20. Oral Magnesium supplementation improves insulin sensitivity in non-diabetic subjects with insulin resistance. A double-blind placebo-controlled randomized trialF Guerrero-Romero1, 2 3 A 3 , HE Tamez-Perez , G González-González , AM Salinas-Martínez , 3J Montes-Villarreal3, JH Treviño-Ortiz3, M Rodríguez-Morán1, 2 10S UMMARY R ESUMu u EObjective: Although hypomagnesemia reduces insulin sensitivity, La supplémentation orale en magnésium améliore % 0benefits of magnesium supplementation to non-diabetic insulin resis- 1 la sensibilité à l’insuline chez des sujets non 2 3tant subjects has not been established. Our purpose was to determine diabétiques insulino-résistants. Un essaiwhether oral magnesium supplementation with magnesium chloride randomisé en double insu contrôlé par placebo -10(MgCl2) 2.5 g daily modify insulin sensitivity in non-diabetic subjects.Material and Methods: This study was a 3 months randomized Objectifs : Bien que l’hypomagnésémie réduise la sensibilité à l’insu- line, les bénéfices de la supplémentation en magnésium chez desdouble-blind placebo-controlled trial. Apparently healthy subjects sujets non diabétiques insulino-résistants n’ont pas été établis. Notrewere eligible to participate if they had insulin resistance (HOMA-IR -20index equal or greater than 3.0) and hypomagnesemia (Serum magne- objectif était de déterminer si la supplémentation orale en magnésium avec du chlorure de magnésium (MCl2) 2,5 g par jour modifie la sensi-sium levels equal or lower than 0.74 mmol/l). Subjects were random- bilité à l’insuline chez des sujets non diabétiques.ized to receive either, MgCl2 2.5 g daily or placebo by 3-months. Matériel et méthodes : Nous avons conduit un essai randomisé en -30Results: At baseline there were not significant anthropometric or labo- double insu contrôlé par placeblo pendant 3 mois. Des sujets appa-ratory differences between both groups. At ending of the study, remment sains étaient éligibles pour l’étude s’ils étaient insulinorésis-magnesium-supplemented subjects significantly increased their se- tants (index HOMA-IR supérieur ou égal à 3,0) et hypomagnésémi- -40rum magnesium levels (0.61 ± 0.08 to 0.81 ± 0.08 mmol/l,p < 0.0001) and reduced HOMA-IR index (4.6 ± 2.8 to 2.6 ± 1.1, ques (taux sériques de magnésium inférieurs ou égaux à 0,74 mmol/ l). Les sujets étaient randomisés pour recevoir soit du MgCl2 2,5 g parp < 0.0001), whereas control subjects did not (0.62 ± 0.08 to jour ou un placebo pendant 3 mois.0.61 ± 0.08 mmol/l, p = 0.063 and 5.2 ± 1.9 to 5.3 ± 2.9, p = 0.087). -50Conclusions: Oral magnesium supplementation improves insulin sen- Résultats : Au départ, il n’y avait pas de différence anthropométrique Glucosesitivity in hypomagnesemic non-diabetic subjects. Clinical implica- In suli n HOMA -I R ni biologique signficative entre les deux groupes. À la fin de l’étude, les sujets supplémentés en magnésium ont significativement augmentétions of this finding have to be established. Branco – Magnésio (300 mg) leurs taux sériques de magnésium (0,61 ± 0,08 à 0,81 ± 0,08 mmol/l, Figure 2 Negro - PlaceboKey-words: Magnesium supplementation z Magnesium Chloride z p < 0,0001) et réduit leur index HOMA-IR (4,6 ± 2,8 à 2,6 ± 1,1, p < 0,0001), à la différence des sujets contrôles (0,62 ± 0,08 àInsulin sensitivity z Hypomagnesemia z Insulin resistance. 0,61 ± 0,08 mmol/l, p = 0,063 et 5,2 ± 1,9 à 5,3 ± 2,9, p = 0,087).
  • 21. source of the low serum magnesium levels. However, be- cause the studied population was eligible from the same Oral Magnesium supplementation improves community and were randomize allocated, the source of hy- insulin sensitivity in non-diabetic subjects with insulin resistance. A double-blind placebo-controlled randomized trial F Guerrero-Romero1, 2, HE Tamez-Perez3, G González-González3, AM Salinas-Martínez3, J Montes-Villarreal3, JH Treviño-Ortiz3, M Rodríguez-Morán1, 2 B S UMMARY 40 R ESUMu u E 30 Objective: Although hypomagnesemia reduces insulin sensitivity, La supplémentation orale en magnésium améliore benefits of magnesium supplementation to non-diabetic insulin resis- la sensibilité à l’insuline chez des sujets non 20 tant subjects has not been established. Our purpose was to determine diabétiques insulino-résistants. Un essai whether oral magnesium supplementation with magnesium chloride randomisé en double insu contrôlé par placebo 10 (MgCl2) 2.5 g daily modify insulin sensitivity in non-diabetic subjects. Objectifs : Bien que l’hypomagnésémie réduise la sensibilité à l’insu- Material and Methods: This study was a 3 months randomized 0 line, les bénéfices de la supplémentation en magnésium chez des double-blind placebo-controlled trial. Apparently healthy subjects were eligible to % 1 2 3 4 sujets non diabétiques insulino-résistants n’ont pas été établis. Notre participate if they had insulin resistance (HOMA-IR -10 index equal or greater than 3.0) and hypomagnesemia (Serum magne- objectif était de déterminer si la supplémentation orale en magnésium avec du chlorure de magnésium (MCl2) 2,5 g par jour modifie la sensi- sium levels equal or lower than 0.74 mmol/l). Subjects were random- -20 ized to receive either, MgCl2 2.5 g daily or placebo by 3-months. bilité à l’insuline chez des sujets non diabétiques. Matériel et méthodes : Nous avons conduit un essai randomisé en Results: At baseline there were not significant anthropometric or labo- -30 ratory differences between both groups. At ending of the study, double insu contrôlé par placeblo pendant 3 mois. Des sujets appa- remment sains étaient éligibles pour l’étude s’ils étaient insulinorésis- -40 magnesium-supplemented subjects significantly increased their se- tants (index HOMA-IR supérieur ou égal à 3,0) et hypomagnésémi- rum magnesium levels (0.61 ± 0.08 to 0.81 ± 0.08 mmol/l, ques (taux sériques de magnésium inférieurs ou égaux à 0,74 mmol/ -50 p < 0.0001) and reduced HOMA-IR index (4.6 ± 2.8 to 2.6 ± 1.1, l). Les sujets étaient randomisés pour recevoir soit du MgCl2 2,5 g par p < 0.0001), whereas control subjects did not (0.62 ± 0.08 to jour ou un placebo pendant 3 mois. 0.61 ± 0.08 mmol/l, p = 0.063 and 5.2 ± 1.9 to 5.3 ± 2.9, p = 0.087). Cholesterol HDL Conclusions: Oral magnesium supplementation improves insulin sen- RésultatsDAu départ, il n’y rig lycerdifférence anthropométrique L:L T avait pas de ides ni biologique signficative entre les deux groupes. À la fin de l’étude, les sitivity in hypomagnesemic non-diabetic subjects. Clinical implica- sujets supplémentés en magnésium ont significativement augmenté tions of this finding have to be (300 mg) Branco – Magnésio established. leurs taux sériques de magnésium (0,61 ± 0,08 à 0,81 ± 0,08 mmol/l, Negro - Placebo p < 0,0001) et réduit leur index HOMA-IR (4,6 ± 2,8 à 2,6 ± 1,1, p <1.8%), insulin levelsHypomagnesemia z InsulinMagnesium Chloride z and HOMA-IR index (– 43.5% Insulin sensitivity z (– 32.0% versus – 1.0%), Key-words: Magnesium supplementation z resistance. 0,0001), à la différence des sujets contrôles (0,62 ± 0,08 à 0,61 ± 0,08 mmol/l, p = 0,063 et 5,2 ± 1,9 à 5,3 ± 2,9, p = 0,087).
  • 22. DEFICIÊNCIAS DE MICRONUTRIENTES EM ATLETAS % DE GINASTAS < 2/3 DA DDR 75 50 25 0 B2 B1 B12 C A P Ca Mg E Fe Ác. F. B6 Zn MICRONUTRIENTES 97 Adolescentes 11-14 Anos Loosli AR, Benson J. Pediatr Clin North Am. 1990 Oct;37(5):1143-52.
  • 23. DEFICIÊNCIAS DE MICRONUTRIENTES EM ATLETAS Nutriente % atletas que não atinge DDR Fósforo 33 Vit A 18 Zinco 13 39 atletas de:ü  Ginástica Rítmicaü  Ginástica artísticaü  Ballet Soric M, Misigoj-Durakovic M, Pedisic Z. Int J Sport Nutr Exerc Metab. 2008 Jun;18(3):343-54.
  • 24. DEFICIÊNCIAS DE MICRONUTRIENTES EM ATLETASNutriente % DDR DDR % DDR DDR (Homens) (Japão) (Mulheres) (Japão)Cálcio 64,5 600 mg 76,9 600 mgFerro 97,6 12 mg 68,1 12 mgFósforo 96,8 1300 mg 72,3 1300 mgMagnésio 51,5 300 mg 37,7 300 mgVit B2 78,1 0,55 85,7 0,55 mg/1000 kcal mg/1000 kcal KARATECAS JAPONESES: 29 H 16 M Teshima K, et al. J Physiol Anthropol Appl Human Sci. 2002 Jul;21(4):205-11
  • 25. DEFICIÊNCIAS DE MAGNÉSIO EM ATLETAS !Modalidades % DDR ReferênciasBasquetebol 66 Hickson JF Jr, Schrader J, Trischler LC.(Mulheres) J Am Diet Assoc 1986;86: 251–3Ginástica 66 Hickson JF Jr, Schrader J, Trischler LC. J Am Diet Assoc 1986;86: 251–3(Mulheres)Futebol Americano 69 Hickson JF, et al. Nutr Res 1987;7:27–34.Futebol 90 Hickson JF, et al. Nutr Rep Int 1986;34:85–91Atletismo 53 Zierath J, Kaiserauer S, Snyder AC.(Mulheres com Med Sci Sports Exerc 1986; 18(suppl):S55–6amenorreia)Atletismo 89 Zierath J, Kaiserauer S, Snyder AC.(Mulheres sem Med Sci Sports Exerc 1986; 18(suppl):S55–6amenorreia)Triatlo (Homens) 91 Worme JD, et al. Am J Clin Nutr 1990;51:690–7 Adaptado de Lukaski HC. Am J Clin Nutr. 2000 Aug;72(2 Suppl):585S-93S
  • 26. DEFICIÊNCIAS DE ZINCO EM ATLETAS !Modalidades % DDR ReferênciasAtletismo 86 Deuster PA, et al. Am J Clin Nutr 1989;49:1295–301(Mulheres)Maratonistas 73 Lukaski HC. Am J Clin Nutr. 2000 Aug;72(2 Suppl): 585S-93S(Mulheres)Velocistas 81 Lukaski HC. Am J Clin Nutr. 2000 Aug;72(2 Suppl): 585S-93S(Mulheres)Triatlo 88 Worme JD, et al. Am J Clin Nutr 1990;51:690–7(Mulheres)Triatlo (Homens) 91 Worme JD, et al. Am J Clin Nutr 1990;51:690–7 Adaptado de Lukaski HC. Am J Clin Nutr. 2000 Aug;72(2 Suppl):585S-93S
  • 27. ESCOLHAS ! Alimentos Dose Qtd de Zinco (mg) Ostras 6 médias (cozidas) 43,4 Bife de vaca 90 g (cozido) 5,8 Caranguejo 90 g (cozido) 4,6 Perú (coxa e asa) 90 g (cozido) 3,5 Galinha (coxa e asa) 90 g (cozido) 2,4 Carne de porco 90 g (cozido) 2,2 Feijão cozido ½ chávena 1,8! Grão de bico ½ chávena 1,3 Leite 240 ml 1 Amêndoas 30 g 1 Queijo 30 g 0,9 Amendoins 30 g 0,9 Bland et al. Clinical Nutrition: A functional approach. The Institute for Functional Medicine, 2004
  • 28. ESCOLHAS ! Alimentos Dose Qtd de Selénio (mcg) Castanha do 30 g (6 a 8 unidades) 839 Maranhão Caranguejo 90 g 40 Salmão 90 g 40 Camarão pequeno 90 g (10 a 12 unidades) 34 Bife de porco 90 g 33 Peito de galinha 90 g 20! Arroz integral cozido 1 chávena 19 Bife de vaca 90 g 17 Pão de trigo integral 2 fatias 15 Leite 240 ml 5 Nozes 30 g 5 Bland et al. Clinical Nutrition: A functional approach. The Institute for Functional Medicine, 2004
  • 29. TOTAL ANTIOXIDANTES EM ALIMENTOS VEGETAIS (Redução de Fe3+ para Fe2+) ! 0,8 0,75 7 6,3 0,7 0,64 6 0,6 0,560,58 5Mmol/100 g Mmol/100 g 0,5 4 3,67 0,38 0,4 3 0,3 0,19 2 0,2 n=4 n=11 0,1 n=8 n=17 n=4 n=9 n=22 n=31 1 0 0 Raízes/Tubérculos Cereais Oleaginosas/Sementes Bagas Bagas selvagens Leguminosas Fruta Hortaliças Halvorsen BL et al. J Nutr 2002;132:461-71
  • 30. DENSIDADE DE NUTRIENTES POR GRUPOS DE ALIMENTOS (POR 100 KCAL) Cereais Leite Integrais Inteiro Fruta Vegetais Peixe Carne Oleaginosas Vitamina B12 (µg) 0.004 0.585 0.004 0.004 7.427 0.636 0.004 Vitamina B3 (mg) 1.124 0.141 0.893 2.735 3.196 4.737 0.352 Fósforo (mg) 903 1525 331 1576 2197 1514 802 Vitamina B2 (mg) 0.052 0.266 0.093 0.337 0.094 0.145 0.041 Vitamina B1 (mg) 0.125 0.061 0.113 0.267 0.082 0.186 0.124 Folato (µg) 10.34 8.12 25.06 208.37 10.83 3.81 11.05 Vitamina C (mg) 0.01 1.54 74.26 93.67 1.95 0.12 0.43 Ferro (mg) 0.904 0.081 0.692 2.597 2.076 1.105 0.863 Vitamina B6 (mg) 0.093 0.071 0.205 0.427 0.194 0.326 0.082 Vitamina A (RE) 22 505 946 6877 324 11 23 Magnésio (mg) 32.64 21.92 24.63 54.57 36.16 18.01 35.85 Calcio (mg) 7.62 194.37 43.04 116.86 43.15 6.11 17.53 Zinco (mg) 0.674 0.623 0.251 1.045 7.67 1.96 0.62 Pontuação 42 43 47 82 66 51 39 Cordain L et al. Am J Clin Nutr. 2005 Feb;81(2):341-54.
  • 31. FONTES DE CALCIO NÃO LÁCTEAS! Nº de doses necessárias Alimento Dose Cálcio para = Cálcio absorvido a (mg) partir de 225 ml de leite Leite 225 ml 300 1 Feijão vermelho ½ chávena 41 9,7 Feijão branco ½ chávena 113 3,9 Couve chinesa * ½ chávena 239 1,3 Brócolo * ½ chávena 35 4,5 Couve Galega * 65 g 47 3,5 Repolho chinês * 55 g 79 2,3 Espinafre ½ chávena 115 16,3 Ruibarbo ½ chávena 174 9,5* As Brássicas são uma anomalia entre as plantas, pois não acumulam oxalatos como mecanismo para desentoxicar excesso de cálcio, de modo a prevenir a morte celular Institute for Functional Medicine. Clinical Nutrition – A functional approach. IFM, 2004Shils M.E., Shike M., Ross A.C. et al. Modern Nutrition in Health and Disease. Lippincott Williams & Wilkins, US; 10Rev Ed edition, 2005
  • 32. CA E COMPOSIÇÃO CORPORALhttp://lpi.oregonstate.edu/infocenter/minerals/calcium/capth.html
  • 33. ADIPOSITY AND CALCIUM INTAKE I CÁLCIO E CONTROLO DE PESO! source for t•  .! ! tion increas ! ! 72-h fecal co ! also signific ! terol by 13% compared w controlled tr (as calcium HDL-LDL r gests that th long lasting plementatio 24 subjects c was supplem cium carbon dependent f of total fat i with 2 g Ca Parikh SJ, Yanovski JA. Calcium intake and adiposity. Am J Clin Nutr. 2003 Feb;77(2):281-7 Increased fa FIGURE 6. Proposed mechanisms through which decreased dietary excretion o
  • 34. Role of Dairy Foods in Weight Management MARRS protein: membrane- associated rapid response to steroid Fig. 1. An integrated summary of mechanisms. Zemel MB. The role of dairy foods in weight management. J Am Coll Nutr. 2005 Dec;24(6 Suppl):537S-46Sion in energy balance, it required a larger level of cal- chain amino acid content of dairy protein and specific bioactive
  • 35. DIETA FORNECE TODOS OS MICRONUTRIENTES ?!
  • 36. TÉCNICAS AGRÍCOLAS E FACTORES ! AMBIENTAIS !
  • 37. SOLOS EMPOBRECIDOS EM SELÉNIO, IODO, ZINCO E MAGNÉSIO. ! Kohrle J. Biochimie. 1999;81(5):527-33. Maksimovic Z, et al. J Environ Pathol Toxicol Oncol. 1998;17(3-4):221-7. Clark LC, Cantor KP, Allaway WH. Arch Environ Health. 1991;46(1):37-42 Shambaugh GE Jr. Am J Otol. 1989;10(2):156-60. Miron W, Sobaniec-Lotowska M, Sulkowski S. Wiad Lek. 1989;42(19-21):1033-7
  • 38. TRANSPORTE E ARMAZENAMENTO DOS ALIMENTOS
 !
  • 39. PERDA DE 40 % DE VITAMINA C EM VEGETAIS DESDE O MOMENTO DA COLHEITA Carlson BL, Tabacchi MH. J Am Diet Assoc. 1988;88:65-67.
  • 40. COUVES DE BRUXELAS CONGELADAS DURANTE 6 MESESAPRESENTAM MENOS 14 A 32% DE VITAMINA C EM RELAÇÃO AO MOMENTO DA COLHEITA.! ! ! Kmiecik W, Lisiewska Z. Rocz Panstw Zakl Hig. 1989;40(3):215-22.
  • 41. CONFECÇÃO DOS ALIMENTOS !
  • 42. PERDA DE 40 A 50% DE TIAMINA (B1) NACONFECÇÃO DO ARROZ E VEGETAIS DE FOLHA VERDEKimura M, Itokawa Y, Fujiwara M. J Nutr Sci Vitaminol (Tokyo). 1990;36(Suppl 1):S17-24.
  • 43. bic acid content when it is affected by different pressure levels. They determinedthat after low pressures the Ascorbic acid content was greater than after highpressures. J. Nutr. Sci. Vitaminol., 36, S7-S15, 1990 Of course, cooking duration and the type of foodstuff play an important role asshown by some of our unpublished tests. Products, which need a long cookingperiod, like cabbage and Vitamin soup, showed a higher Ascorbic acid content after Comparison of bean Losses in Vegetables Due to Variouspressure cooking than after steaming. On the other hand, products, which require Cooking Methodsonly a short cooking period, like spinach and kohlrabi in slices, contained a higherconcentration of Ascorbic acid after steaming rather than after pressure cooking D. RUMM-KREUTER and I. DEMMEL(Rumm-Kreuter, 1986). Alfa Institut Eltville (FDG) Further interesting cooking methods are stirfrying and microwave cooking. Summary Preparing vegetables with heat the contents of their con Table 1.stituents will acid contents (mg/100g) in fresh spinach and in spinach after Ascorbic change to a various extend. Particularly the water-soluble different and the heat-sensitive vitamins are affected. At an early stage the vitamin cooking methods. C losses were investigated, because of vitamin Cs indicating function for oxidations and leaching-out processes (1, 2, 7, 11-13, 15, 17). The degree of vitamin losses is influenced by various factors, for example the type of food, variety of vegetables, the way of cutting, preparation, duration and method of cooking. The influence of the various cooking methods with regard to the losses of certain water-soluble vitamins will be discussed. Key Words cooking methods, ascorbic acid, folic acid, thiamine, ribo flavin, niacin, pyridoxine Blumenthal (1980). J. Nutr. Sci. Vitaminol. Foods are prepared in order to become edible and enjoyable. The choice of the cooking method depends on the individual or cultural dietary habits. By preparing food with heat, not only alterations in carbohydrates, fats and
  • 44. J. Nutr. Sci. Vitaminol., 36, S7-S15, 1990 Comparison of Vitamin Losses in Vegetables Due to Various Cooking Methods D. RUMM-KREUTER and I. DEMMEL Alfa Institut Eltville (FDG) COMPARISON OF VITAMIN LOSSES IN VEGETABLES S9 Summary Preparing vegetables with heat the contents of their conTable 2. Ascorbic change contents (%)extend. Particularly green beans after different stituents will acid to a various in broccoli and the water-soluble and the heat-sensitive vitamins are affected. At an early stage the vitamincooking methods. C losses were investigated, because of vitamin Cs indicating function for oxidations and leaching-out processes (1, 2, 7, 11-13, 15, 17). The degree of vitamin losses is influenced by various factors, for example the type of food, variety of vegetables, the way of cutting, preparation, duration and method of cooking. The influence of the various cooking methods with regard to the losses of certain water-soluble vitamins will be discussed. Key Words cooking methods, ascorbic acid, folic acid, thiamine, ribo flavin, niacin, pyridoxine Eheart (1965).Table 3. Foods are prepared in order to acid and edible and enjoyable. Thespinach. of the Mean reduced Ascorbic become Folic acid content of choice cooking method depends on the individual or cultural dietary habits. By preparing food with heat, not only alterations in carbohydrates, fats and
  • 45. Each value is mean±SD of three replicate samples. Values 580 Yuan et al. / J Zhejiang Univ Sci B 2009 10(8):580-588not sharing a common letter are significantly different at Journal of Zhejiang University SCIENCE B ISSN 1673-1581 (Print); ISSN 1862-1783 (Online) www.zju.edu.cn/jzus; www.springerlink.com E-mail: jzus@zju.edu.cnP<0.05. Cooking methods: 1. Raw; 2. Boiled; 3. Streamed; Effects of different cooking methods on health-promoting4. Microwaved; 5. Stir-fried;of6. Stir-fried/boiled compounds broccoli * Gao-feng YUAN1, Bo SUN1, Jing YUAN1, Qiao-mei WANG†‡1,2 120 (1Department of Horticulture, Zhejiang University, Hangzhou 310029, China) a 2 ( Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou 310029, China) Crú † a E-mail: qmwang@zju.edu.cn Vapor Received Feb. 24, 2009; Revision accepted Apr. 20, 2009; Crosschecked July 14, 2009 Micro- 100 b Abstract: The effects of five domestic cooking methods, including steaming, microwaving, boiling, stir-frying, and stir-frying Ondas followed by boiling (stir-frying/boiling), on the nutrients and health-promoting compounds of broccoli were investigated. The c results show that all cooking treatments, except steaming, caused significant losses of chlorophyll and vitamin C and significant Frito decreases of total soluble proteins and soluble sugars. Total aliphatic and indole glucosinolates were significantly modified by allVitamin C content 80 d cooking treatments but not by steaming. In general, the steaming led to the lowest loss of total glucosinolates, while stir-frying and Cozido (mg/100 g FW) Cozido stir-frying/boiling presented the highest loss. Stir-frying and stir-frying/boiling, the two most popular methods for most homemade dishes in China, cause great losses of chlorophyll, soluble protein, soluble sugar, vitamin C, and glucosinolates, but the steaming method appears the best in retention of the nutrients in cooking broccoli. e e frito Key words: Broccoli, Cooking, Glucosinolates, Vitamin C, Chlorophyll, Soluble sugar 60 doi:10.1631/jzus.B0920051 Document code: A CLC number: S635 INTRODUCTION ferent compartments of the plant cells to separate 40 Broccoli (Brassica oleracea var. italica) con- from glucosinolates. When plant tissues are damaged, myrosinase rapidly hydrolyzes the glucosinolates to tains high levels of vitamins, antioxidants, and anti- glucose and other unstable intermediates, which carcinogenic compounds and has been described as a spontaneously rearrange to a variety of biologically vegetable with high nutritional value. Glucosinolates, active products, including isothiocyanates, thiocy- 20 a diverse class of sulfur- and nitrogen-containing anates, epithionitriles, or nitriles depending on secondary metabolites, are found in Brassica vegeta- chemical conditions (Jia et al., 2009). The hydrolysis bles including broccoli. These compounds have products vary depending largely upon the level and gained renewed interest in recent years due to the activity of myrosinase, presence of specifier protein, 0 chemoprotective properties of their major hydrolysis e.g., epithiospecifier protein, and hydrolysis condi- products, isothiocyanates. Glucosinolates are chemi- tions, e.g., pH, metal ions and temperature, and these 14 cally stable until they come in contact J Zhejiang Univ can be 2009 10(8):580-588 cultivar, and cooking Yuan et al. with the deg- Sci B influenced by species, cohydrolase, EC 3.2.1.147), which is stored in dif- a radation enzyme myrosinase ( -thioglucoside glu- time and conditions (Verkerk et al., 2008). Epidemi- ological studies and experimental researches with cell
  • 46. Nursal/Yucecan: Vitamin C losses in frozen vegetables ¨ Vitamin C losses in some frozen vegetables due to various cooking methods zen vegetables B. Nursal and S. Yucecan ¨ eading from the first one. The Frozen spinach,2. Vitamin and okra were commercially 42.1, and 28.2% vitaminfrozen vegetables the losses in Table peas, green beans C levels (dry weight basis) of C loss, respectively. Besides,oducibility between standards cooked in three differentto cookingbased stainless steel, teflon, cooking processes were accelerated in thawed vegetables with the according stewpans (double pans and methods. tendency; that is more destruction occurred in samples boiled in pyrex) with and without thawing. The vitamin C levels were effected same tructed by plotting absorbance both by cooking methods and stewpans. Frozen peas were found to be pyrex pan (60.3% loss in spinach, 40.8% loss in peas, 48.4% loss in rsus concentration of standard the least (3.5% loss), and frozen green beans were foundlto be the green beans,Thawedcooking is uselessLossthe results,vitamin Frozen Unthawed (x Loss and 41.6% loss in okra). According to most (19.6% loss) effected vegetables by thawing. In all of the stew- found that thawing before (x l and causes more it was same manner; their ascorbic pans, vegetables spinach,SEM) [mg/100 g] than[%]loss. Therefore,prevent vegetablesg] not[%] using double double based stainless steel pan retained more vitamin C the others. While boiling C SEM)frozen vitamin must be thawed before cook- peas, green beans, and okra without ing. In order to [mg/100 C from destruction, ording to standard curve plot- thawing resulted 46.5, 25.2, 18.2, and 21.6% vitamin C loss in double based stainless steel pan, minimum amount of water and cooking of based stainless steel pan, boiling them in pyrex pan resulted 58.5, 36.0, frozen vegetables are recommended.%). Spinach 362.1 l 101.7 0.0 305.4 l 50.9 15.7 DBSS 193.4 l 58.2 46.5 182.5 l 54.8 50.0 Teflon 177.1 l 66.8 51.1 160.2 l 79.2 55.8 1 Introduction Table 1. The types and characteristics of stewpans used for cooking Pyrex 150.4 l 47.3 58.5 vegetables. l 43.7 frozen 143.6 60.3 each sample, and vitamin C In recent years, throughout the catering systems like hotels, weight bases. We thought that restaurants, hospitals, schools, army corps lquality foods hygi- 0.0 types 58.5[cm]6.3 [cm] Peas enic, standardized, inexpensive and good 60.6 and factories, have Pan 7.9 meter l Bottom dia- Top diameter 3.5 Thickness Height [cm] [mm] DBSS 45.3 l 7.9a accurate when discussing the become very important. Changes in food consumption patterns25.2 DBSS 36.6 l 5.4a 19.3 39.6 16.4 10.0 4.0 zen samples were measured resulted in[1]. For these reasons, in order demanda, b ready to32.5 eat foods Teflon variability and 40.9 l 5.1 for quality Teflon product a great to keep best Pyrex 36.7 l 4.2a 18.7 39.4 17.4 13.4 8.5 4.0 a 17.8 7.5 5.0 Pyrex 38.8 l 5.6 b els which were found before and extend shelf life, different food protection technics are36.0 35.9 l 6.2 40.8 being applied [2]. It is obvious that cooling and freezing are one of the best methods available in the food industry for pre- Green beans 139.1 l serving food products of high quality [3 – 5]. 3.9 116.5 l 52.0 0.0 Cooking procedures 2.1 19.6 Vitamin C, which is found in 113.8 l 36.0 fruits in DBSS most vegetables and 90.9 l 25.9 18.2A kitchen oven working with natural gas 34.7 during cooking was used detectable levels, is often used as an indicator vitamin, because the samples. The smallest fireplace was chosen in order to cook 100 g it is veryTeflon to air contact,96.7 l of water, cooking of each sample. The samples were dropped into boiling water (150 ml sensitive amount 28.2 30.5 88.8 l 27.0 36.2 time and Pyrextype of stewpans80.5 l 26.3 lid is open distilled water), and boiled for 5 min, and then fire was held in mild method, and whether the 42.1 71.8 l 20.4 48.4 tightly cov- ge of triplicate experiments. or closed during cooking [6, 7]. These effects are also valid for condition till the end of cooking (30 min). The pans werefor unthawed ered during boiling process. This procedure was repeated frozen vegetables. Vitamin losses can increase by cooking and and erformed on the data in order leaching effects, unless no losses152.5 l 21.0 storage. 0.0 thawed 138.7Thawingfor spinach, green beans, peas and okra Okra occur during frozen samples. l 25.1 was done at room temperature (22.3 l 2 8C). Thawing times process 9.6 es. 119.6 l 7.7 21.6The cooked sampleslwere immediately 33.1 in ice-water and It is well known that, generally, losses during cooking depends were 5, 4, 3, and 3 h, respectively. DBSS on variety, species, initial vitamin C level before freezing, pH, 102.0 11.9 cooled surface to mass ratio, cooking time and l 7.0 of cooking homogenized in a Waring 11.4 for 1 min 36.7 ml of 3% meta- Teflon 113.8 amount 25.4 96.5 l Blender with 100 water [8 – 10]. phosphoric acid (HPO3) solution and analysed without waiting. This The purpose of the present study was tol 9.5 Pyrex 89.0 l times 109.5 determine the vita-28.2 was repeated three9.1 for each sample. process 41.6 min C losses of some commercially frozen vegetables after ion cooking (with and without thawing) in three different stewpans 2.2 Ascorbic acid analyses S. 451 – a (double based stainless values are significantly different C levels were measured all2,6-dichlorophenolindophenol Vitamin C steel (DBSS), teflon, and pyrex). Nr. 6,Vitamin (p453 0.05) in by kinds of Nahrung 44 (2000) method (50 mg dye/100 ml distilled water) [11, 12], using a 8700 vegetables, except bearing the same superscripts (a, b) within the same Model Spectrophotometer. process showed that some In order to determine the ascorbic acid levels, 10 g of each homoge- column.
  • 47. Mean values were significantly different from those of the raw food (paired t test: ***P, 0·005, ****P, 0·0001.† ‘Typical’ cooking procedures were established from the results of a consumer questionnaire (for details see p. 682).‡ Times shown reflect the duration required to cook the food item (determined from preliminary experiments, i.e. not ‘undercooked’ or ‘overcooked’; for details,Journal of Nutrition (2002), 88, 681–688 British see p. 683). q The Authors 2002 DOI: 10.1079/BJN2002733§ To avoid differences in moisture content as a result of different cooking procedures, spinach, broccoli and beef were weighed raw before cooking and values therefore given per 100 g raw weight. Values for potatoes relate to whole potatoes (skin and flesh) and are given per 100 g raw or cooked weight as appropriate (for details of procedures see p. 682). The effect of different cooking methods on folate retention in various foods that are amongst the major contributors to folate intake in the UK diet Derek J. McKillop, Kristina Pentieva*, Donna Daly, Joseph M. McPartlin, Joan Hughes, J. J. Strain, John M. Scott and Helene McNulty Northern Ireland Centre for Food and Health (NICHE), University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK (Received 14 January 2002 – Revised 04 July 2002 – Accepted 15 August 2002) COZIDO A VAPOR Folate intake is strongly influenced by various methods of cooking that can degrade the natural forms of the vitamin in foods. The aim of the present study was to determine the effect of different cooking methods on folate retention in various foods that contribute to folate intake in the UK diet. Typical purchasing and cooking practices of representative food folate sources were determined from a questionnaire survey of local shoppers (n 100). Total folate was deter- mined by microbiological assay (Lactobacillus casei NCIMB 10463) following thermal extrac- tion and tri-enzyme (a-amylase, protease and conjugase) treatment in raw foods and after typical methods of cooking. Boiling for typical time periods resulted in only 49 % retention of folate in spinach (191·8 and 94·4 mg/100 g for raw and boiled spinach respectively; P, 0·005), and only 44 % in broccoli (177·1 and 77·0 mg/100 g for raw and boiled broccoli respectively, P, 0·0001). Steaming of spinach or broccoli, in contrast, resulted in no significant decrease in folate content, even for the maximum steaming periods of 4·5 min (spinach) and COZIDO EM ÁGUA 15·0 min (broccoli). Prolonged grilling of beef for the maximum period of 16·0 min did not result in a significant decrease in folate content (54·3 and 51·5 mg/100 g for raw and grilled beef respectively). Compared with raw values, boiling of whole potatoes (skin and flesh) for 60·0 min did not result in a significant change in folate content (125·1 and 102·8 mg/100 g for raw and boiled potato respectively), nor was there any effect on folate retention whether or not skin was retained during boiling. These current results show that the retention of folate in various foods is highly dependent both on the food in question and the method of cook- ing. Thus, public health efforts to increase folate intake in order to improve folate status should incorporate practical advice on cooking. Food folate retention: Cooking methods: Food folates: Dietary folate intake ESPINAFRE Optimal folate status may have a role in the prevention of 400 mg folic acid/d in addition to normal dietary folate cardiovascular disease via plasma homocysteine-lowering intake to prevent the occurrence of neural tube defects. (Boushey et al. 1995), and possibly in the prevention of However, more recent studies suggest that an additional certain cancers (Branda & Blickenderfer, 1993; Kim et al. intake of 200 mg folic acid/d may be optimal both for the 1997; Jacob et al. 1998; Choi & Mason, 2000). However, prevention of neural tube defect occurrence (Daly et al. the most compelling evidence for the benefit of optimal 1997) and for the lowering of plasma homocysteine
  • 48. British Journal of Nutrition (2002), 88, 681–688 DOI: 10.1079/BJN2002733 q The Authors 2002 The effect of different cooking methods on folate retention in various foods that are amongst the major contributors to folate intake in the UK diet Derek J. McKillop, Kristina Pentieva*, Donna Daly, Joseph M. McPartlin, Joan Hughes, J. J. Strain, John M. Scott and Helene McNulty Northern Ireland Centre for Food and Health (NICHE), University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK (Received 14 January 2002 – Revised 04 July 2002 – Accepted 15 August 2002) COZIDO A VAPOR Folate intake is strongly influenced by various methods of cooking that can degrade the natural forms of the vitamin in foods. The aim of the present study was to determine the effect of different cooking methods on folate retention in various foods that contribute to folate intake in the UK diet. Typical purchasing and cooking practices of representative food folate sources were determined from a questionnaire survey of local shoppers (n 100). Total folate was deter- mined by microbiological assay (Lactobacillus casei NCIMB 10463) following thermal extrac- tion and tri-enzyme (a-amylase, protease and conjugase) treatment in raw foods and after typical methods of cooking. Boiling for typical time periods resulted in only 49 % retention of folate in spinach (191·8 and 94·4 mg/100 g for raw and boiled spinach respectively; P, 0·005), and only 44 % in broccoli (177·1 and 77·0 mg/100 g for raw and boiled broccoli respectively, P, 0·0001). Steaming of spinach or broccoli, in contrast, resulted in no significant decrease in folate content, even for the maximum steaming periods of 4·5 min (spinach) and COZIDO EM ÁGUA 15·0 min (broccoli). Prolonged grilling of beef for the maximum period of 16·0 min did not result in a significant decrease in folate content (54·3 and 51·5 mg/100 g for raw and grilled beef respectively). Compared with raw values, boiling of whole potatoes (skin and flesh) for 60·0 min did not result in a significant change in folate content (125·1 and 102·8 mg/100 g for raw and boiled potato respectively), nor was there any effect on folate retention whether or not skin was retained during boiling. These current results show that the retention of folate in various foods is highly dependent both on the food in question and the method of cook- ing. Thus, public health efforts to increase folate intake in order to improve folate status should incorporate practical advice on cooking. Food folate retention: Cooking methods: Food folates: Dietary folate intakeBRÓCOLO Optimal folate status may have a role in the prevention of 400 mg folic acid/d in addition to normal dietary folate cardiovascular disease via plasma homocysteine-lowering intake to prevent the occurrence of neural tube defects. (Boushey et al. 1995), and possibly in the prevention of However, more recent studies suggest that an additional certain cancers (Branda & Blickenderfer, 1993; Kim et al. intake of 200 mg folic acid/d may be optimal both for the 1997; Jacob et al. 1998; Choi & Mason, 2000). However, prevention of neural tube defect occurrence (Daly et al. Fig. 2. The effect of duration and method of cooking on folate retention in: (a), spinach; the most compelling evidence for the benefit of optimal 1997) and for the lowering of plasma homocysteine
  • 49. British Journal of Nutrition (2002), 88, 681–688 DOI: 10.1079/BJN2002733 q The Authors 2002 The effect of different cooking methods on folate retention in various foods that are amongst the major contributors to folate intake in the UK diet6 D. J. McKillop et al. Derek J. McKillop, Kristina Pentieva*, Donna Daly, Joseph M. McPartlin, Joan Hughes, J. J. Strain, John M. Scott and Helene McNulty Northern Ireland Centre for Food and Health (NICHE), University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK (Received 14 January 2002 – Revised 04 July 2002 – Accepted 15 August 2002) Folate intake is strongly influenced by various methods of cooking that can degrade the natural forms of the vitamin in foods. The aim of the present study was to determine the effect of different cooking methods on folate retention in various foods that contribute to folate intake in the UK diet. Typical purchasing and cooking practices of representative food folate sources were determined from a questionnaire survey of local shoppers (n 100). Total folate was deter- mined by microbiological assay (Lactobacillus casei NCIMB 10463) following thermal extrac- tion and tri-enzyme (a-amylase, protease and conjugase) treatment in raw foods and after typical methods of cooking. Boiling for typical time periods resulted in only 49 % retention of folate in spinach (191·8 and 94·4 mg/100 g for raw and boiled spinach respectively; P, 0·005), and only 44 % in broccoli (177·1 and 77·0 mg/100 g for raw and boiled broccoli respectively, P, 0·0001). Steaming of spinach or broccoli, in contrast, resulted in no significant decrease in folate content, even for the maximum steaming periods of 4·5 min (spinach) and 15·0 min (broccoli). Prolonged grilling of beef for the maximum period of 16·0 min did not result in a significant decrease in folate content (54·3 and 51·5 mg/100 g for raw and grilled beef respectively). Compared with raw values, boiling of whole potatoes (skin and flesh) for 60·0 min did not result in a significant change in folate content (125·1 and 102·8 mg/100 g for raw and boiled potato respectively), nor was there any effect on folate retention whether or not skin was retained during boiling. These current results show that the retention of folate in various foods is highly dependent both on the food in question and the method of cook- ing. Thus, public health efforts to increase folate intake in order to improve folate status should incorporate practical advice on cooking. Food folate retention: Cooking methods: Food folates: Dietary folate intake Optimal folate status may have a role in the prevention of 400 mg folic acid/d in addition to normal dietary folate cardiovascular disease via plasma homocysteine-lowering intake to prevent the occurrence of neural tube defects. (Boushey et al. 1995), and possibly in the prevention ofATATA B However, more recent studies suggest that an additional certain cancers (Branda & Blickenderfer, 1993; Kim et al. intake of 200 mg folic acid/d may be optimal both for the 1997; Jacob et al. 1998; Choi & Mason, 2000). However, prevention of neural tube defect occurrence (Daly et al.g. 3. Impact of preparation the most compelling evidence forretentionofduring boiling. and fordetails of samples and procedures, of potatoes on folate the benefit optimal 1997) For the lowering of plasma homocysteine see p. 682. Values
  • 50. Vitamin C c 60 580 Yuan et al. / J Zhejiang Univ Sci B 2009 10(8):580-588 (mg/100 g Journal of Zhejiang University SCIENCE B ISSN 1673-1581 (Print); ISSN 1862-1783 (Online) www.zju.edu.cn/jzus; www.springerlink.com 40 E-mail: jzus@zju.edu.cn Effects of different cooking methods on health-promoting 20 compounds of broccoli* Gao-feng YUAN1, Bo SUN1, Jing YUAN1, Qiao-mei WANG†‡1,2 0 (1Department of Horticulture, Zhejiang University, Hangzhou 310029, China) 14 2 ( Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou 310029, China) Micro- a † a E-mail: qmwang@zju.edu.cn Crú Vapor Ondas a Received Feb. 24, 2009; Revision accepted Apr. 20, 2009; Crosschecked July 14, 2009 a Frito 12Total carotenoid content Cozidob Abstract: The effects of five domestic cooking methods, including steaming, microwaving, boiling, stir-frying, and stir-frying followed by boiling (stir-frying/boiling), on the nutrients and health-promoting compounds of broccoli were investigated. The (mg/100 g FW) results show that all cooking treatments, except steaming, caused significant losses of chlorophyll and vitamin C and significant Cozido 10 decreases of total soluble proteins and soluble sugars. Total aliphatic and indole glucosinolates were significantly modified by all cooking treatments but not by steaming. In general, the steaming led to the lowest loss of total glucosinolates, while stir-frying and c e frito stir-frying/boiling presented the highest loss. Stir-frying and stir-frying/boiling, the two most popular methods for most homemade dishes in China, cause great losses of chlorophyll, soluble protein, soluble sugar, vitamin C, and glucosinolates, but the steaming 8 method appears the best in retention of the nutrients in cooking broccoli. Key words: Broccoli, Cooking, Glucosinolates, Vitamin C, Chlorophyll, Soluble sugar 6 doi:10.1631/jzus.B0920051 Document code: A CLC number: S635 INTRODUCTION ferent compartments of the plant cells to separate 4 Broccoli (Brassica oleracea var. italica) con- from glucosinolates. When plant tissues are damaged, myrosinase rapidly hydrolyzes the glucosinolates to tains high levels of vitamins, antioxidants, and anti- glucose and other unstable intermediates, which 2 carcinogenic compounds and has been described as a spontaneously rearrange to a variety of biologically vegetable with high nutritional value. Glucosinolates, active products, including isothiocyanates, thiocy- a diverse class of sulfur- and nitrogen-containing anates, epithionitriles, or nitriles depending on 0 secondary metabolites, are found in Brassica vegeta- chemical conditions (Jia et al., 2009). The hydrolysis bles including broccoli. These compounds have products vary depending largely upon the level and 1 2 3 4 gained renewed interest in recent years due to the activity of myrosinase, presence of specifier protein, chemoprotective properties of their major hydrolysis e.g., epithiospecifier protein, and hydrolysis condi- 5 6 products, isothiocyanates. Glucosinolates are chemi- tions, e.g., pH, metal ions and temperature, and these Cooking method cally stable until they come in contact J Zhejiang Univ can be 2009 10(8):580-588 cultivar, and cooking Yuan et al. with the deg- Sci B influenced by species, radation enzyme myrosinase ( -thioglucoside glu- time and conditions (Verkerk et al., 2008). Epidemi- cohydrolase, EC 3.2.1.147), which is stored in dif- ological studies and experimental researches with cell
  • 51. PERDA DE 30 A 35% DE β-CAROTENO NA CONFECÇÃO DE VEGETAIS Sweeney JP, Marsh AC. J Am Diet Assoc. 1971;59:238-43.
  • 52. 580 Yuan et al. / J Zhejiang Univ Sci B 2009 10(8):580-588ntil a color- stir-fried/boiled, stir-fried, and microwaved broccoli Journal of Zhejiang University SCIENCE B se was col- was reduced by 27%, 23%, 18%, and 16%, respec- ISSN 1673-1581 (Print); ISSN 1862-1783 (Online) www.zju.edu.cn/jzus; www.springerlink.com E-mail: jzus@zju.edu.cnfter washed tively (P<0.05), while it was almost unchanged in Effects of different cooking methods on health-promoting were made steamed broccoli. compounds of broccoli*ether. Total Gao-feng YUAN1, Bo SUN1, Jing YUAN1, Qiao-mei WANG†‡1,2cording the 2 (1Department of Horticulture, Zhejiang University, Hangzhou 310029, China) ( Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou 310029, China) Chlorophyll content (mg/g FW) 0.7 Vapor aometer. To- Crú † E-mail: qmwang@zju.edu.cn a Received Feb. 24, 2009; Revision accepted Apr. 20, 2009; Crosschecked July 14, 2009 0.6 Micro- FW. Ondas Frito Cozido Abstract: The effects of five domestic cooking methods, including steaming, microwaving, boiling, stir-frying, and stir-frying b b followed by boiling (stir-frying/boiling), on the nutrients and health-promoting compounds of broccoli were investigated. The b e frito results show that all cooking treatments, except steaming, caused significant losses of chlorophyll and vitamin C and significant Cozido b 0.5 decreases of total soluble proteins and soluble sugars. Total aliphatic and indole glucosinolates were significantly modified by all cooking treatments but not by steaming. In general, the steaming led to the lowest loss of total glucosinolates, while stir-frying and stir-frying/boiling presented the highest loss. Stir-frying and stir-frying/boiling, the two most popular methods for most homemade 0.4 dishes in China, cause great losses of chlorophyll, soluble protein, soluble sugar, vitamin C, and glucosinolates, but the steaming method appears the best in retention of the nutrients in cooking broccoli.ccording to doi:10.1631/jzus.B0920051 0.3 Key words: Broccoli, Cooking, Glucosinolates, Vitamin C, Chlorophyll, Soluble sugar Document code: A CLC number: S635 Chemists 0.2 INTRODUCTION ferent compartments of the plant cells to separate-dichloroin- 0.1 Broccoli (Brassica oleracea var. italica) con- from glucosinolates. When plant tissues are damaged, myrosinase rapidly hydrolyzes the glucosinolates to0). Vitamin tains high levels of vitamins, antioxidants, and anti- glucose and other unstable intermediates, which carcinogenic compounds and has been described as a spontaneously rearrange to a variety of biologically 0 vegetable with high nutritional value. Glucosinolates, active products, including isothiocyanates, thiocy- 1 2 3 4 a diverse class of sulfur- and nitrogen-containing anates, epithionitriles, or nitriles depending on secondary metabolites, are found in Brassica vegeta- chemical conditions (Jia et al., 2009). The hydrolysis 5 6 Cooking method bles including broccoli. These compounds have products vary depending largely upon the level and gained renewed interest in recent years due to the activity of myrosinase, presence of specifier protein, chemoprotective properties of their major hydrolysis e.g., epithiospecifier protein, and hydrolysis condi- Fig.1 The chlorophyll content in broccoli cooked by products, isothiocyanates. Yuan et al. J Zhejiang Univ tions, e.g., pH, metal ions and temperature, and these Glucosinolates are chemi- Sci B 2009 10(8):580-588 cally stable until they come in contact with the deg- can be influenced by species, cultivar, and cookingonverted to different methods radation enzyme myrosinase ( -thioglucoside glu- time and conditions (Verkerk et al., 2008). Epidemi- cohydrolase, EC 3.2.1.147), which is stored in dif- ological studies and experimental researches with cell
  • 53. Research Article Received: 21 September 2009 Revised: 8 January 2010 Accepted: 20 February 2010 Published online in Wiley Interscience: (www.interscience.wiley.com) DOI 10.1002/jsfa.3967 Vitamin C, total phenolics and antioxidative activity in tip-cut green beans (Phaseolus vulgaris) and swede rods (Brassica napus var. napobrassica) processed by methods used in catering Pernille Baardseth,a∗ Frøydis Bjerke,b Berit K Martinsena and Grete Skredea Abstract BACKGROUND: Retention of nutrients in vegetables during blanching/freezing, cooking and warm-holding is crucial in the preparation of both standard and therapeutic diets. In the present study, conventional cooking in water, and cooking by pouch technology (boil-in-bag, sous vide) were compared in their ability to retain vitamin C, total phenolics and antioxidative activityPERDE-SE 13 – 42 % DA VITAMINA C E COMPOSTOS (DPPH and FRAP) in industrially blanched/frozen tip-cut green beans and swede rods. RESULTS: After conventional cooking, 50.4% total ascorbic acid, 76.7% total phenolics, 55.7% DPPH and 59.0% FRAP were recovered in the drained beans. After boil-in-bag cooking, significantly (P < 0.05) higher recoveries were obtained, i.e. 80.5% FENÓLICOS NA ÁGUA DA COZEDURA total ascorbic acid, 89.2% total phenolics, 94.8% DPPH and 92.9% FRAP. Recoveries after sous vide cooking were comparable to those of boil-in-bag cooking. By conventional cooking, 13.5–42.8% of the nutrients leaked into the cooking water; by sous vide about 10% leaked to the exuded liquid, while no leakage occurred by boil-in-bag cooking. Warm-holding beans after cooking reduced recoveries in all components. Recoveries in swede rods were comparable but overall slightly lower. CONCLUSION: Industrially blanched/frozen vegetables should preferably be cooked by pouch technology, rather than conventional cooking in water. Including cooking water or exuded liquid into the final dish will increase the level of nutrients in a meal. Warm-holding of vegetables after cooking should be avoided. c 2010 Society of Chemical Industry Keywords: green beans; swede; cooking; boil-in-bag; sous vide; warm-holding; vitamin C; total phenolics; DPPH; FRAP INTRODUCTION conventional cooking in water,6,10 – 17 baking in oven,10 heating by Consumption of vegetables rich in nutrients and phytochemicals microwave,6,10,11,13 – 15,17,18 steam,7,11,13,15 stir-frying,6,10,12,14,16,17 is today recommended as a means to ensure a health-beneficial cook–chill,8,19 or the more recent technologies of sous vide20 diet.1 – 3 Many vegetables are consumed fresh, but others are and boil-in-bag21 cooking. Both intentional19,22 and unintentional processed to various extents in the catering and foodservice warm-holding after cooking are also practised in many cases. The industries or in the private home prior to consumption. Processing pouch technologies, boil-in-bag and sous vide, will most likely
  • 54. Cereal Grains: Humanity’s Double-Edged Sword Simopoulos AP (ed): Evolutionary Aspects of Nutrition and Health. Diet, Exercise, Genetics and Chronic Disease. World Rev Nutr Diet. Basel, Karger, 1999, vol 84, pp 19–73 Loren Cordain ............................ Department of Exercise and Sport Science, Colorado State University, Fort Collins, Cereal Grains: Colo., USA Humanity’s Double-Edged Sword ‘Here is bread, which strengthens man’s heart, and therefore called the staV of life’ Loren Cordain (Mathew Henry: 1662–1714, Commentary on Psalm 104) yet, Department of Exercise and Sport Science, Colorado State University, Fort Collins, Colo., USA ‘Man cannot live on bread alone’ (Bible, Matthew 4:4) ‘Here is bread, which strengthens man’s heart, and therefore called the staV of life’ Contents (Mathew Henry: 1662–1714, Commentary on Psalm 104) yet,20 Introduction ‘Man cannot live on bread alone’ (Bible, Matthew 4:4)22 Archaeological Perspective24 Dietary Imbalances of Cereal Grains Contents26 Vitamins A, C and Beta-Carotene27 20B Vitamins Introduction29 22Minerals Archaeological Perspective34 24Essential Imbalances of Cereal Grains Dietary Fatty Acids 26 Vitamins A, C and Beta-Carotene36 Amino Acids 27 B Vitamins41 Antinutrients in Cereal Grains 29 Minerals43 34Alkylresorcinols Acids Essential Fatty43 36Alpha-Amylase Inhibitors Amino Acids44 41Protease Inhibitors Antinutrients in Cereal Grains 43 Alkylresorcinols45 Lectins 43 Alpha-Amylase Inhibitors47 Autoimmune Diseases and Cereal Grain Consumption 44 Protease Inhibitors48 45Autoimmunity Lectins49 47Molecular Mimicry and Cereal Grain Consumption Autoimmune Diseases49 48Genetic and Anthropological Factors Autoimmunity 49 Molecular Mimicry51 49 Autoimmune Diseases Associated with Cereal Grain Consumption Genetic and Anthropological Factors56 Psychological and Neurological Illnesses Cereal Grain with Cereal Grain Consumption 51 Autoimmune Diseases Associated with Associated Consumption58 Conclusions 56 Psychological and Neurological Illnesses Associated with Cereal Grain Consumption60 58 Conclusions Acknowledgments 60 Acknowledgments60 References 60 References
  • 55. ELEVADO CONSUMO DE CEREAIS !!ÁCIDO FÍTICO !!DIMINUI A ABSORÇÃO DE:! ü  Ferro! ü  Zinco! ü  Cálcio! ü  Magnésio! ! !! ! Cordain L. World Rev Nutr Diet 1999; 84:19-73. ! Bohn T, et al. Am J Clin Nutr. 2004 Mar;79(3):418-23.
  • 56. BIODISPONIBILIDADE DA B6 EM CEREAIS É BAIXA! ü  Pode chegar a ser de 25-20%! ü  Nos alimentos de origem animal: biodisponibilidade de quase 100%! ü  Baixo status de vitamina B6 em vegetarianos!! Cordain L. World Rev Nutr Diet 1999; 84:19-73.
  • 57. CONSUMO ELEVADO DE ALIMENTOS BOCIOGÉNICOS: ! (MILLET, MILHO, SOJA, MANDIOCA, BATATA-DOCE, BRÁSSICAS, ALHO, CEBOLA)! ! ! PODEM CAUSAR DÉFICE DE IODO, MESMO COM INGESTÃO DE 100% DA DDR! Gaitan E. Annu Rev Nutr 1990;10:21–39. Lakshmy R, et al. Horm Metab Res 1995;27:450–4. Rao PS, Lakshmy R. Indian J Med Res 1995;102:223– 6.! Doerge DR, Sheehan DM. Environ Health Perspect 2002;110(suppl):349 –53.
  • 58. FACTORES QUE AUMENTAM AS NECESSIDADES !
  • 59. EXERCÍCIO
  • 60. SESSÃO DE! BASQUETEBOL (2 H)! ! ! !à PERDA DE Ca (SUOR) DE 400 MG. ! !! ! ! ! !. !Kiesges RC, et al. JAMA. 1996 Jul 17;276(3):226-30
  • 61. PERDA DE FERRO: !ü  SUOR: 0.4 A 0.6 MG/HORA!ü  HEMÓLISE: 0.25 a 0.75 mg!ü  HEMORRAGIA GASTROINTESTINAL, ACIDOSE E PEROXIDAÇÃO DAS MEMBRANAS CELULARES POR RL: 0.5-1 MG/DIA! ! ! Colgan, M. Sports nutrition guide – Minerals, vitamins & antioxidants for athletes. Apple Publications, 2002 SHILS, M.E. et al. Modern Nutrition in Health and Disease. 10 ed. Lippincott Williams & Wilkins, 2005.
  • 62. FERRO!NECESSIDADES DE ATLETAS EM TREINO INTENSO:!ü  HOMENS = 3,25 MG (PERDAS) + 1 MG (FUNÇÕES BÁSICAS) = 4,25MG/DIA!ü  MULHERES = 3,25 MG (PERDAS) + 1 MG (FUNÇÕES BÁSICAS) + 0.5MG (MENSTRUAÇÃO) = 4,75MG/DIA! ! ! ABSORÇÃO: ENTRE 1 A 25% Colgan, M. Sports nutrition guide – Minerals, vitamins & antioxidants for athletes. Apple Publications, 2002 SHILS, M.E. et al. Modern Nutrition in Health and Disease. 10 ed. Lippincott Williams & Wilkins, 2005.
  • 63. PERDA DE Zn: !ü SUOR: 3 A 12 MG/DIA!ü UTILIZAÇÃO NA FORMAÇÃO DE SOD! ! Colgan, M. Sports nutrition guide – Minerals, vitamins & antioxidants for athletes. Apple Publications, 2002
  • 64. CONCENTRAÇÕES DE ELECTRÓLITOS NO SORO E SUOR, E CONCENTRAÇÕES DE HC E ELECTRÓLITOS EM ALGUMAS BEBIDAS COMUNS. ! Na+ K+ Ca2+ Mg2+ Cl- Osmolalidade CHO (mEq.L-1) (mEq.L-1) (mEq.L-1) (mEq.L-1) (mEq.L-1) (mOsm.L-1 ) (g.L-1 )Plasma 140 4,5 2,5 1,5-2,1 110 300 -Suor 60-80 4,5 1,5 3,3 40-90 170-220 -Coca-Cola 3,0 - - - 1,0 650 107Gatorade 23,0 3,0 - - 14,0 280 62Sumo Fruta 0,5 58,0 - - - 690 118Pepsi Cola 1,7 Vestigios - - Vestígios 568 81Àgua Vestígios Vestígios - - Vestígios 10-20 - McArdle W, Katch F, Katch V. Sports & Exercise Nutrition, 2nd Edition. Lippincott Williams & Wilkins, 2005
  • 65. TABACO!
  • 66. smokers had significantly lower plasma ␤-carotene concentra-smokers and nonsmokers, but in neither case were the concentra- tions than did the nonsmokers. The smokers and passive smok-tions in the passive smoking group significantly different from ers had higher plasma ␥-tocopherol concentrations than did the Smoking and exposure to environmental tobacco smoke decreasethose in either of the other groups. In summary, after adjustment for race, age, sex, BMI, alco- nonsmokers. All of these comparisons were significant with the use of Tukey-Kramer’s correction with a 5% procedure-wise some plasma antioxidants and increase ␥-tocopherol in vivo afterhol intake, fruit and vegetable intakes, the respective dietary error rate.antioxidant, and triacylgycerol (for lipid-soluble antioxidants 1–3 The importance of other covariates on plasma antioxidant con- adjustment for dietary antioxidant intakesonly), the smokers had significantly lower plasma concentra- centrations is also notable. BMI was highly significant for severaltions of ␤-carotene, total ascorbic acid, ␤-cryptoxanthin, and carotenoids (data not shown), consistent with earlier findings on Marion Dietrich, Gladys Block, Edward P Norkus, Mark Hudes, Maret G Traber, Carroll E Cross, and Lester Packerlutein and zeaxanthin than did the nonsmokers. The passive the importance of body weight to plasma ascorbic acid status (40). ABSTRACT radicals cause oxidative damage to macromolecules such as lipids, Background: Free radicals in cigarette smoke may cause oxida-TABLE 3 proteins, and DNA, they are believed to be involved in the patho-Plasma antioxidant concentrations in the 159 subjects byto cardiovascular tive damage to macromolecules, contributing study group after adjustment for race, age, sex, body mass index, alcohol intake, fruit and genesis of cardiovascular diseases and cancer (2–5). Free radicals 1vegetable intake, the respective dietaryplasma antioxidant concentrations diseases and cancer. Decreased antioxidant, and triacylglycerol concentrationCS deplete some plasma antioxidants in vitro (4, 6), and several in may indicate cigarette smoke–related oxidative stress. Nonsmokers Passive smokers lower plasma antioxidant concentrations in smok- studies found Smokers Objective: We compared the effects on plasma antioxidant con- (n = 36) ers (n = 40) (7–13). Less information is available on the effect 2of in vivo (n = 83) P centrations in cotinine-confirmed active and passive smokers with CS exposure on plasma antioxidant concentrations in passive␣-Tocopherol (␮mol/L) 30.0 30.4 29.7 0.933 those in nonsmokers, independent of differences in dietary intakes␥-Tocopherol (␮mol/L) 6.5a smokers b(14–18). 7.8 7.8b 0.032 and other covariates.Total ascorbic acid (␮mol/L) 54.5 b It 54.6b been difficult to determine whether differences in has 43.6 a 0.014 Design:(␮mol/L) samples from 83 smokers, 40 passive smokers,␣-Carotene Plasma 0.05 plasma antioxidants between smokers and nonsmokers are 0.210 0.04 0.04 actu-␤-Carotene nonsmokers were analyzed for total ascorbic and 36 (␮mol/L) 0.24 bacid, ␣- and ally due to 0.15 a the effect of CS exposure or are due instead to dif- 0.17 a 0.026 ␥-tocopherols, 5 carotenoids, retinol, and cotinine. Groups wereTotal carotenoids (␮mol/L) 1.80 ferences in dietary antioxidant intakes or in other covariates [eg, 1.60 1.53 0.141 compared by using analysis of variance with adjustment for sex,␤-Cryptoxanthin (␮mol/L) 0.16b body 0.16b index (BMI; in kg/m 2a Epidemiologic studies mass 0.12)]. 0.034 b a,b aLutein and zeaxanthin (␮mol/L) 0.41 age, race, body mass index, alcohol intake, triacylglycerol con- 0.36 0.33 showed that cigarette smokers consume fewer fruits and vegeta- 0.047Lycopene (␮mol/L) and vegetable intakes, and dietary antioxidants. centration, fruit 0.71 0.70 0.71 bles than do nonsmokers (19–23). In addition, cigarette smok- 0.977Retinol (␮mol/L) adjustment for dietary antioxidant intakes and other Results: After 2.15 2.15 2.26 ers consume fewer vitamin supplements than do nonsmokers 0.549 covariates, smokers and passive smokerswas performed for lipid-soluble antioxidants only. Valueshabitssame row with different superscript letters 1 Adjustment for triacylglycerol concentration had significantly lower (24–26). The dietary in the of passive smokers were found to beare plasma ␤-carotene at a 5% procedure-wise did nonsmokers (0.15, significantly different concentrations than error rate. intermediate between those of smokers and nonsmokers (27). 2 Overall general linear model. 0.17, and 0.24 ␮mol/L, respectively) and significantly higher Few of the existing studies of the effect of smoking on plasma ␥-tocopherol concentrations (7.8, 7.8, and 6.5 ␮mol/L, respec- antioxidant status adjusted for dietary or supplement intake (8, tively). Smokers had significantly lower plasma ascorbic acid and 9), and only one study on passive smokers did so (17). As a ␤-cryptoxanthin concentrations than did nonsmokers and passive result, the in vivo effect of smoking or passive smoking on smokers (ascorbic acid: 43.6, 54.5, and 54.6 ␮mol/L, respectively; plasma antioxidant status remains unclear. ␤-cryptoxanthin: 0.12, 0.16, and 0.16 ␮mol/L, respectively) and In this study, we confirmed active smoking, passive smoking, or significantly lower concentrations of lutein and zeaxanthin than nonsmoking status with plasma cotinine measures, excluded cur- did nonsmokers (0.33 compared with Dietrich M, et TheAm J Clin Nutr. 2003 Jan;77(1):160-6. 0.41 ␮mol/L). al. P values rent or recent vitamin supplement users, and adjusted for dietary for all the differences described above were < 0.05. No significant antioxidant intakes and other covariates. This permitted us to differences in plasma concentrations of ␣-tocopherol, ␣-carotene,
  • 67. min C during the 3-mo period among nonsmokers who received fruit and vegetables. A substantial proportion of the US popula- LUND UNIVERSITY on November 24, 2011the supplement. As is often seen in studies like this, a (3, 4) that cause damage to cellular functions (5–7). The this dietary recommendation (13–15). This ABSTRACT radicals nonsignifi- tion does not meet Background: Lack of reliable dietary data has hampered the high oxidant content of smoke explains the low antioxidant statuscant trend to effectivelyadistinguish diet could of smoking and and increased oxidative stress and damage that is a potentially severe health problem because low fruit ability toward better between effects be observed by slight overall constitutes consistently Downloaded from www.ajcn.org at LUND UNIVERSITY on November 24, 2011 Ascorbate is depleted by smoking and repleted by moderateincreases in fruit and vegetable intake,total dietary that smokers in particular would and vegetable intake diet on plasma antioxidant status. As confirmed by analyses though subjects were On this basis, it has been suggested has been associated with an increased risk of even of observed in smokers (8, 9). comprehensive food-frequency questionnaires, the benefit from increasing theirasked intakes of fruit and vegetables and of dietary and smoking habitsintake of antioxidants (10,several diseases such as atherosclerosis (19) and cancer (16–18). to maintain their usual diet antioxidants were dietary during the 11). supplementation: a study in male smokers and nonsmokers withsupplementationdifferent betweenof the effect of smoking. withfruit andchanges currently recommend 5–9that only athe consequences of inadequate micronutrient not significantly the study groups in the present period. Two-way ANOVA study, thereby enabling isolation Dietary guidelines To indicate servings/d of the vegetables (12). Recent studiesinvestigate rel- in 1–4 matched dietary antioxidant intakesdietary intakes as the was to investigate the effect of smoking supplementationof the US population routinely has population was selected for a low intake of fruit Objective: Our objective response and smoking and atively small proportion intake, the study an on plasma antioxidant status by measuring ascorbic acid, ␣-toco- intake in the recommended range (13–15). Like smoking, a lowas factors showed no␤-carotene, of either smoking or supplementation pherol, ␥-tocopherol, effects and lycopene, and subse- daily intake of fruit and vegetables has been associated with an assumed that by selecting for low fruit and and vegetables. Wefor anymoderate-dose vitamin of a 3-mo dietary supplementation with increasedand atherosclerosis (19).vegetablesuch as cancer would isolate a cohort with inadequate vita- quently, to test the effect of the variables. risk of developing chronic diseases intakes, we a cocktail. Jens Lykkesfeldt,placebo-controlled design, the effect ofregimen ondiets than nonsmokers (20–25).have been found inJacob, and and possibly, vitamin E intakes. As (16–18) Stephan Christen, Lynn M Wallock, Harry H min C, ␤-carotene, lycopene, Bruce N Ames The effect double-blind,3-mo supplementation Design: In a of the have poorer plasma Chang,This difference to Smokers Robert A a vitamin cocktail containing 272 mg vitamin C, 31 mg all-rac-␣- dietary habits has so far made it difficult to distinguish betweenTAA, tocopheryl acetate, and and ␥-tocopherol in smokers the effects of diet and smoking per se on plasma antioxidants in 1, the compiled food-frequency question- ␣-tocopherol, 400 ␮g folic acid on plasma antioxidants and nonsmokers summarized in Table ABSTRACT a populationCompared = 37) and non- population studies.is summarized38). The population was selected for a low intake of was determined inTable 3. of smokers (n with baseline, a 43% increase in naire data showed an cause damage to cellular functions (5–7).and radicals (3, 4) that average of only 2.7 servings/d of fruit The smokers (n = In the present study, we investigated antioxidant status in ain TAA wasvegetables and recruited from the San Francisco Bay cohort whereas the the vegetables total ascorbicpresent smoke explains the low antioxidant status Background: Lack of reliable dietary data hasof hampered fruit and observed for supplemented nonsmokers smokers and nonsmokers by high oxidant content of cohort of smokers and nonsmokers. measuring for thesupplemented smokers was significantly depleted byincrease solubleof the same ability to effectively distinguish between effects area. Results: Only ascorbic acid showed a 194% smoking acid (TAA;smoking and during The increased oxidative stress and damage orange consistently and most common fruit choices were that is juice and ascorbic acid + dehydroascorbic acid) and the lipid- antioxidants ␣-tocopherol, ␥-tocopherol, ␤-carotene, and diet on< plasma the 3-mo supplementation period, ascor- lycopene in blood plasma. of subjects were selected for an most 9). On this basis, it has been suggested antioxidant status. As confirmed by analyses The bananas, whereas the (8, common vegetables were fried pota-period. Plasma ␣-tocopherol, both corrected and uncorrected for per se (P 0.01). After observed in smokers bic acid was efficiently repleted in smokers (P < 0.001). Plasma equally low daily intake of fruit and vegetables. A consequence comprehensive food-frequency increased signi- ␣-tocopherol and the ratio of ␣- to ␥-tocopherol questionnaires, the total dietary that smokers in particular would benefit from increasing their intakes both fruit and groups (P < 0.05).and of dietary antioxidants were ficantly in of supplemented vegetables 1 dietary intake of antioxidants (10, 11). Conclusions: Our data suggest that previous reports of lower From the Department of Molecular and Cell Biology, University ofTABLE 3significantly different between the study groups Berkeley, the Western Human Nutrition Research Center, US not concentrations of plasma vitamin E and carotenoids in smokers California, in the present Dietary guidelines currently recommend 5–9 servings/d of Department of Agriculture, Davis, CA; and the Royal Veterinary and Agri- study,nonsmokers may primarily have been caused by differ- supplementation regimen in smokers and nonsmokers1 than plasma antioxidants of isolation of the effect of smoking.Effect on in thereby enabling a 3-mo multivitamin cultural University, Department of Pharmacology and and vegetables (12). Recent studies indicate that only a rel- fruit Pathobiology, Copen- ences in dietary habits between study groups. Plasma ascorbic Objective: Our objective was to investigate the effect Berne, Switzerland. acid was depleted by smoking and repleted by moderate supple- of smoking atively small proportion of the US population routinely has an hagen; and University of Berne, Institute of Medical Microbiology (Infec- mentation. Placebocompany or product name does not imply approval or tious Diseases), Am J Clin Nutr 2000;71:530–6. measuring ascorbic acid, ␣-toco- Supplement on plasma antioxidant status by 2 Reference to a intake in the recommended range (13–15). Like smoking, a low pherol, ␥-tocopherol, ␣-tocopherol, ␥-tocopherol, lycopene, others that may be Smokersdaily intake of fruit and vegetables has been associated with an KEY WORDS Ascorbic acid, ␤-carotene, and Nonsmokersrecommendation of the product by the US Department of Agriculture to the Nonsmokers exclusion of and subse- suitable. Smokers quently, lycopene, folic acid, smoking,aBaseline San supplementation InstituteRelated Diseases Researchgrantrisk of developing chronic diseases such as d to test the effect of plasma antioxidants, 90 dSupported in part by Tobacco Outstanding90 d ProgramBaseline 3-mo dietary 7RT-0178, National Baseline 90 d Baseline 90 cancer 3 ␤-carotene, grant population study, dietary supplementation, poor diet, Cancer with increased CA39910 Investigator aFrancisco Bay area moderate-dose vitamin cocktail. (n = 21) and NIEHS Center grant ESO1896 (to= 19) (16–18) and atherosclerosis (19). Smokers have = 18) found to (n BNA), Danish Natural Science Research (n = 17) (n been Council grant SNF9502434 (to JL), and a fellowship from the Swiss Founda- Design: In double-blind, placebo-controlled tion 18.8 the effect of (to SC).have31.7 Corporation ± 25.6 nonsmokers (20–25). 16.0 difference 3inTotal ascorbic acida(␮mol/L) 41.7 ± 25.2 35.3 design, 30.4 ± Stipends 34.0 ± poorer41.1 than 58.7 ± 29.22 23.4 ± This 68.8 ± 37.9 ± for Medical-Biological 23.0 The Pharmavite diets (Mission Hills, CA) provided the vitamin supplement and placebo. INTRODUCTION␣-Tocopherol (␮mol/L) containing 272 mg vitamin C,Addressmg 22.5 ± to BN Ames, 21.1 ± of California, 23.2 ± 5.4 far made it difficult to±distinguish between a vitamin cocktail 23.0 ± 5.7 24.1 ± 6.7 reprint requests 5.5 4 31 all-rac-␣- University 7.1 habits has so dietary Depart- 25.7 ± 5.24 20.2 5.1 22.9 ± 5.45 Long-term smoking is known to be associated with an 4 4 5 Corrected for total neutralcancer,400 ␮g folic acid on bnames@uclink4.berkeley.edu. tocopheryl acetate, and cardiovascular 0.7 and 4.0 plasma antioxidants increased risk of developing lipids 3.7 ± disease, ± 0.8 3.7 ± 0.6 3.4 ±effects of3.9 ± 0.9 smoking 0.7 se on plasma antioxidants in the 0.9 ment of Molecular and Cell Biology, 401 Barker Hall, Berkeley, CA. E-mail: diet and 4.4 ± per 3.6 ± 0.5 4.1 ± 0.84␥-Tocopherol (␮mol/L) in (1, population of smokers ±Received37) 5.01999. was numberchronic diseases a such Tobaccoand ± 1.6 many other determined 2). 3.9smoke contains a 3.7 (n = Januaryand±August 18, 1999.4.4 ± 2.6 1.5 20, 2.6 non- population studies. 3.7 ± 1.2 3.0 ± 0.95 3.7 ± 1.9 3.1 ± 1.74 large of toxic chemicals as NOx other oxidizing Accepted for publication 4 Corrected for (n = neutral lipids smokers total 38). The population was selected±for a low 0.8 ± 0.3 0.6 ± 0.2 0.6 0.2 intake of 0.7 In0.3 present study, we investigated0.7 ± 0.3 ± the 0.6 ± 0.2 0.5 ± 0.1 antioxidant 0.6 ± 0.34 a status in 5␣-Tocopherol:␥-tocopherol and recruited from Nutr 2000;71:530–6. Printed in USA.Bay American Society2.3Clinical Nutrition ± 2.1 nonsmokers by measuring total ascorbic fruit and vegetables 530 7.0 ± 3.3 J Clin the ± 3.3 Francisco 2.2 Am 7.5 San 5.2 ± © 2000 5.6 ± for of smokers and cohort 6.7 9.5 ± 4.6 6.2 ± 2.3 9.8 ± 6.6 1– xarea. ± SD. acid (TAA; ascorbic acid + dehydroascorbic acid) and the lipid- 2 Different from baseline, P acid was significantlysignificantly different from baseline, P < 0.0001 (two-way ANOVA). Results: Only ascorbic = 0.058 (paired t test); depleted by smoking soluble antioxidants ␣-tocopherol, ␥-tocopherol, ␤-carotene, and 3–5 Significantly different from baseline supplementation 0.001, 4 ascor- 5 < 0.01. 3 per se (P < 0.01). After the 3-mo (paired t test): P < period, P < 0.05, Plycopene in blood plasma. The subjects were selected for an bic acid was efficiently repleted in smokers (P < 0.001). Plasma equally low daily intake of fruit and vegetables. A consequence ␣-tocopherol and the ratio of ␣- to ␥-tocopherol increased signi- ficantly in both supplemented groups (P < 0.05). 1 Conclusions: Our data suggest that previous Am J Clin lower 2000;71:530–6 Department of Molecular and Cell Biology, University of reports of Nutr From the California, Berkeley, the Western Human Nutrition Research Center, US concentrations of plasma vitamin E and carotenoids in smokers Department of Agriculture, Davis, CA; and the Royal Veterinary and Agri- than in nonsmokers may primarily have been caused by differ- cultural University, Department of Pharmacology and Pathobiology, Copen-
  • 68. OUTROS FACTORES !
  • 69. FOLATOMiller AL, Kelley GS. Altern Med Rev. 1996;1(4):220-235
  • 70. CICLO DO FOLATO CICLO DA METIONINA REMETILAÇÃO TRANSMETILAÇÃO Serina THFGlicina Metionina Dimetil- glicina ...S-adenosil metionina Aceptor Metionina 5,10 MTHF sintetase Betaína B12 Aceptor MetiladoNADPH 5,10 MTHF Colina S-adenosil redutase homocisteína 5 Me-THF Homocisteína NADP+ NH2 Cistationa Serina B6 sintetase CH3 S CH2 CH2 CH COOH METIONINA TRANSULFURAÇÃO Cistationina NH2 HS CH2 CH2 CH COOH B6 Cistationina HOMOCISTEÍNA liase NH2 Cisteína HS CH2 CH COOH MTHF = Metileno-tetra-hidro-folato CISTEÍNA “A remetilação aumenta em resposta a uma dieta pobre em metionina” Dennis and Robinson,1996
  • 71. GENE MTHFR Ingestão ≅ 254mcg/dia ≅ 254mcg/dia ≅ 254mcg/dia “Indivíduos com genótipo TT necessitam maioringestão de folato (>400mcg/dia) para manutenção de níveis de folato e homocisteína mais próximos daqueles c/ genótipo CT ou CC” [Hcis 8,1µmol/L (nos CC e CT) vs. 9,5µmol/L (TT)] Ashfield-Watt PAL et al. Am J Clin Nutr 2002;76:180-6.
  • 72. Photodegradation of 5-methyltetrahydrofolate: Biophysical Aspects Arnfinn Hykkerud Steindal* , ? Asta Juzeniene, Anders Johnsson and Johan Moan13 Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310Oslo, Norway 2Department of Physics, Norwegian University of Science and Technology - NTNU, N-7491 Trondheim, Norway 3Department of Physics, University of Oslo, N-0316 Oslo, Norway Received 09 June 2006; accepted 24 July 2006; published online 31 July 2006 DOI: 10.1562/2006-06-09-RA-915 Photochemistry and Photobiology, 2006, 82: 1651-1 655 ABSTRACT MATERIALS AND METHODS Chemicals. (6R,S)-5-methyl-5,6,7,8-tetrahydrofolate calcium salt and (6R,S)- 5-methyltetrahydrofolate(SMTHF) absorbs UV radiation and Photodegradation of 5-methyltetrahydrofolat 5-methyl-5,6-dihydrofolateammonium salt was purchased from Schircks has an absorption coefficient of 24250 f 1170 M- cm- at Laboratories (JoM, Switzerland), while p-aminobenzoyl-L-glutamicacid 290 nm.It has a weak fluorescence emission in the wavelength was purchased from Sigma Chemical Co. (St. Louis, MO). Dulbeccos Arnfinn Hykkerud Steindal*, ? Asta Juzeniene, Anders Johnss region around 360 nm. Our data demonstrated induction of 5methyldihydrofolate by exposure to UVB and, after con- ü  5MTHF absorve UVB, sendo phosphate buffered saline (PBS) was purchased from PAA Laboratories GmbH (Paschmg, Austria).Departmentwere Radiation Biology, Institute for Cancer Research, The Norw The solutions of freshly made in PBS before the instability N-0310Oslo, Norway tinues irradiation,p-aminobenzoyl-L-glutamic acid was found. oxidado a 5MDHF each experiment. Because ofMontebello, of the compounds, the solutions were always kept on ice before use. 2Department of Physics, Norwegian University of Science and Technology The photodegradation of SMTHF follows a first order kinetic UVIVis absorption and fluorescence measurements. Absorption spectmOslo, N-0316 Oslo, Norway I 3Department of Physics, University of with a degradation rate constant of 9.2 X min- under were registered with a Perkin-Elmer Lambda 40 UVPis spectrometer 1 poaH our conditions (fluence rate of 2.15 mW crn-, exposure wave- (Shelton, CT). Fluorescence emission and June 2006; accepted 24 July 2006; published online 31 July 2006 Received 09 excitation spectra were recorded lJV lengths from 280 to 350 nm). Our results indicate that a direct ü  5MDHF não volta a entrar no by means of a Perkin-Elmer LS5OB luminescence spectrometer equipped with a Hamamatsu R-928 photomultiplier (Iwata, Japan). All measurements degradation of SMTHF by UV exposure in humans in vivo is were performed in standard 10 mm quartz cuvettes. rather unlikely. 5MTHF mainly absorbs, and is degraded by, ciclo de folato ABSTRACT Photoolysis. Solutions of 5MTHF were exposed to UV radiation in closed quartz cuvettes (1 mL). The radiation source was a broad-band UVB lamp MATER UVB and UVC, radiation that does not penetrate the earths Chemicals. ( with five Philips TL 2OW/12 RS UVB tubes (Amsterdam).(SMTHF) absorbs UV radiation and 5-methyltetrahydrofolate The fluence rate atmosphere and the human skin well. after each experiment with an UVB 24250 of the lamp was measuredhas an absorption coefficient of detector f 1170 M- cm- at 5-methyl-5,6 Laboratories 500 INTRODUCTION ü  UVA, através de ROS (PMA2106) connected to a photometer (PMA2200), both from Solar Light 290 nm.It at the sample position was 2.15 Co. (Philadelphia, PA). The intensity has a weak fluorescence emission in the wavelength region around 360innm. wavelength region Our data demonstrated induction of was purchas phosphate b mW an-*, the radiation was emitted mainly the and Folate is an important vitamin for human health (1). Folate defi- produzidos por 280-350 nm with a maximum at 3 12 nm. The temperaturesexposure to UVB and, after con- 5methyldihydrofolate by of the samples were approximately 25 to tinues irradiation,p-aminobenzoyl-L-glutamic 30°C. All experiments were performed in con- acid was found. GmbH (Pasc each experimon spectra of 5 ciency, or impairment of the folate metabolism in an organism, were always20 and 150 min. leads to several diseases, including megaloblastic anemia (1) and fotosensibilizadores (ex: stant dim light in order to avoid photodegradation of SMTHF follows a first order kinetic The external, uncontrolled light exposure. One point that must be stressed is the fact that our UV source contains with a degradation rate constant of 9.2 X min- under UVIVis ab were registe complications arising in pregnancy, such as neural tube defects (2). radiationthat is not present in the solar radiation (9). In the starting phase of or the emission Folate deficiency may also increase the risk of developing cardio- flavinas, porfirinas, our project we used a narrow-band UVB lamp (Phillips TL 20W/01mW crn-, exposure wave- our conditions (fluence rate of 2.15 RS, lengths from 280 to broad-band UVB lamp, 312 nm peak). The results were the same as for the 350 nm). Our results indicate that a direct (Shelton, CT by means o vascular diseases (3) and cancer (4). with a Hama It has been suggested that exposure to large doses of solar bilirrubina, etc), oxida 5MTHF because 5MTHF SMTHF at UV exposure but the process was slower degradation ofabsorbs lessby 312 nm than at in humans in vivo is shorter wavelengths. SMTHF is rather unstable in vibo, mainly absorbs, and is degraded by, rather unlikely. 5MTHF so we decided to were perform Photoolysiexcitation and Unknown molecule + radiation may lead to folate deficiency, and that sun-induced folate degradation may play a key role in evolution of human skin color. use the broad-band UVB lamp. UVB and UVC, radiation that does not penetrate the earths quartz cuvet with five Ph atmosphere and the human skin well. of the lampVB exposure. This hypothesis was first proposed by Branda and Eaton (5) and Ha further developed by Jablonski and Chaplin (6). No definite con- RESULTS AND DISCUSSION (PMA2106)radiation, the Absorption measurements INTRODUCTION Co. (Philad Figure 8. A possibleclusion about theAs a first step folate photodegradation inproblem, scheme of thepossibility of in the elucidation of this vivo has photodegradation of SMTHF. mW an-*, aat at least one been drawn yet. Folate is an concentrations of 5MTHF are health (1). Folate defi- The absorption spectra of different important vitamin for human 280-350 nm investigations of the photophysics and photochemistry of folate in were approx than SMTHF simple model systems would be of great value. shown in Fig. 2. SMTHF absorbs radiation in the the folate metabolism in an organism, ciency, or impairment of UV region and stant dim lig has an absorption peak at 290 to several diseases, including megaloblastic anemia (1) and leads nm. At wavelengths longer than 340 One poin constant is five times larger than that ofofan unirradiated solution of the The photodegradation folic acid (FA), a synthetic form nm, the absorption is weak. The insert shows apregnancy, such as neural tube defects (2). complications arising in linear plot of the radiationthaes higher than (1.8 x folate, has been thoroughly studied (7,s). 5-methyltetrahydrofolate min-I). (SMTHF) belongs to the naturally occurring folates. In the present absorbance at 290 nm as a function of concentration. The the risk of developing cardio- Folate deficiency may also increase linear our project 312 nm pea y explain the In Fig. 8 a scheme workSMTHF photodegradation is proposed. of we have investigated the photodegradation kinetic of SMTHF relationship between absorbancediseases (3) and cancer (4). that vascular and concentration indicates but the proc the absorbance of SMTHF follows the Beer-Lambert exposure to large doses of solar It has been suggested that law, thus shorter wav F and then the The unknown molecule is probably a reduced form of a chemical by absorption and fluoresence measurements. The pterin. struc- radiation may lead to folate deficiency, and that sun-induced folate aggregation plays no major role. use the broa ture of SMTHF is shown in Fig. 1. It consists of three groups:
  • 73. Human skin pigmentation as an adaptation to UV radiation Human skin pigmentation as an adaptation to Nina G. Jablonski1 and George Chaplin UV radiation Department of Anthropology, Pennsylvania State University, University Park, PA 16802 Nina G. Jablonski1 and George Chaplin Human skin pigmentation is the product of two clines produced by Department of Anthropology, Pennsylvania State University, University Park, PA 16802 color was part of this package (4). The association of dark skin natural selection to adjust levels of constitutive pigmentation to pigmentation with intense sunshine and heat was further devel- Human skin pigmentation is the product of two clines produced by color was part of this package (4). The association of dark skin levels of UV radiation (UVR).to adjust levels of constitutive pigmentation to pigmentation withAristotle andand heat was further devel- of a comprehensive natural selection One cline was generated by high UVR oped by intense sunshine his followers as partTable 1. near the equator and equator and ledand UVB on of dark, photoprotective, the selective mechanisms involved in a comprehensive features, dispositions, Summary of the effects of UVA to the evolution human body and oped by Aristotle and his relatedwhich related dispositions, of levels of led to the(UVR). One cline was generated by high UVR UV radiation evolution of dark, photoprotective, “climatic theory,” followers as part of human the evolution pigmentation. natural selection operatingbyby the and lighten which the environment. By numbers of “+” eumelanin-rich near thepigmentation. The estimated strength of eumelanin-rich pigmentation. The other was produced darken “climatic theory,” The other was produced to the and culturescultures to human features, and to the pigmentationthe indicated by the mid-18th century, nat- environment. By is mid-18th century, nat- requirement for UVB photons to sustain cutaneous photosynthesisand “−” signs, respectively. See text for references for proposed mechanisms. requirement for UVB photons to sustain cutaneous photosynthesis uralists such as John Mitchell and, later, Samuel Stanhope Smith uralists such as John Mitchell and, later, Samuel Stanhope Smith recognized a pronounced latitudinal gradient of skin pigmenta- of vitamin D3 in low-UVBin low-UVB environments, and resulted inthe evolu- recognized a pronounced latitudinal gradient of skin pigmenta- of vitamin D3 environments, and resulted in the evolu- Strength and of depigmented skin. As hominins dispersed outside of the tion among the world’s peoples—from dark near the equator to tion tion of depigmentedthey experienced different dispersed outside mix- the toward among the world’sit peoples—from dark near the equator to tropics, skin. As hominins intensities and seasonal of tionAgent direction of selection and UVB. Extreme UVA throughout the year and two light selectivepoles—and related at different latitudes (5, 6). Proposed heatthe mechanism(s) mainly to differences in tropics, they experienced different intensities and seasonal mix- tures of UVA sunshinelight toward the people experienced by poles—and related it mainly to differences inUVA tures of UVA and UVB. Extreme UVA throughout to protect folate by an influence inuniformity in the effect,”same and by “indicatesthe presence equinoctial peaks of UVB prevail within the tropics. Under these +++ conditions, the primary selective pressure was the year and two “This general Photolysis of folate (as 5-methyltetrahydrofolate [5MTHF] in experienced by people at in Smith wrote, sunshine heat serum) directly circumstances, will climate, that, under the ROS different latitudes (5, 6). maintaining dark pigmentation. Photolysis of folate Under these of flavins and porphyrins, resulting reduction generalavailable for in the effect,” Smith wrote, “indicates operate folate uniformity p. division equinoctial peaks of UVB prevail within the tropics. and its main in always“Thisof in the same manner” (5,cell34). It is thus sur-UVA the primary of 5-methylhydrofolate caused by increased folate prising that Darwin,damage so keen to identify adaptationssame in Competition for folate: UVR and folate needs for DNA who was repair and asunder thedonor circumstances, will conditions,++ serum form selective pressureiswas to protect by reac- by an influence in climate, that, rejected a causal 1-carbon of tive oxygen species generated by UVA. Competition for folate organisms to “different conditions of life,” between the needs for cell division, DNA repair, and melanogenesis folate needed for melanogenesisclimate in favor of(5, p. 34). It is thus sur- maintaining dark pigmentation. Photolysis of folate and its main always operate in the same manner” the methylation of DNA competing with association of skin pigmentation withUVA serum form of 5-methylhydrofolate is ofconditions and is exacerbated by notionprising thatintyrosinase to high levels of ROS identify adaptations of ++ is severe under stressful, high-UVR melanin production because of sensitivity of Darwin, had evolved primarily through Disruption caused by UVR and by reac- that variations skin color who was so keen to + species generated only once during the year. The populations cancer that Selectionto Relation Writingconditions Descent Malignant melanoma (as the only skin theMan, and causes death (1). to Sex (1), 1871 inreproductive age) agency of sexual selection organisms in “different in he stated: of life,” rejected a causal to individuals of The dietary insufficiency. Outside of tropical latitudes, UVB levels areUVA tive oxygen generally low and peak by UVA. Competition for folate ofUVA between the needs for cell division, DNA repair,excess vitamin D3 to inactive metabolites skin pigmentation with climate in favor of the + exhibiting maximally depigmented skin of those melanogenesis Photoconversion are and inhabiting envi- association of “If, however, we look to the races of man, as distributed over the world,UVB +++ ronments with the lowest annual and summer peak levels of UVB. by we notion that their characteristic differencescolorbe accounted Production of cyblobutane pyrimidine dimersmust infer that variations in skin cannot repair resulting from is severe under Developmenthigh-UVR conditions and is exacerbated stressful, of facultative pigmentation (tanning) was important and damaged nucleotides requiring had evolved primarily through dietary insufficiency. Outside DNA absorption23° and 46° , where levels are of folate-dependent DNA repair of (1). Writing to populations settling between roughly of photons; levels of tropical latitudes, UVB activation for the agency of sexual conditionsprocesses after expo-in 1871 in The Descent by the direct action of different selectionlife, even sure to them for an enormous period of time” (p 246). “It can further beUVB generally low+ and peak onlyDirect during season. folate (as 5MTHF in serum), that the differencesamount in races of man, as in colour, cell division of UVB varied strongly according to the year. The populations shewn Man, and Selection the Relation to Sex for he stated: once photolysis of Depigmented and tan- of reducing the between of folate available (1), nable skin evolved numerous times in hominin evolution via inde- and regulation those inhabiting envi- melanogenesisfeatures, &c., are of the nature which it might have of tyrosinase activity in hairyness, form of exhibiting maximally genetic pathways under positive selection. pendent depigmented skin are been expected would have been acted on by sexual selection” (p 250).UVB ronments with Competition for folate: increased folate needs for DNA damage look to andraces of man, donor in + the lowest annual and summer peak levels of UVB. “If, however, we repair the as 1-carbon as distributed over the world, methylation of Development of facultative pigmentation (tanning) was important we must infer that their characteristic differences cannot be accounted folate | vitamin D | melanin | tanning | UVB DNA competing with folate needed for melanogenesis Darwin’s preference for sexual selection in matters of humanUVB No effect Sunburn variation blinded him to the importance of natural selection in of life, even after expo- for by the direct action of different conditions to populations settling between roughly 23° and 46° , human poly- producing the attributes of human skin.* Human skin is func- ariation in skin color is the most noticeable of where levelsUVB V Damage to DNA and its repair system tionally naked and them for an enormous period of time” (p 246). “It can further be sure to as such served forsystem leadthousands of of UVB varied strongly according todominant mammals, we readilyand tan- alterations of thethe differences between the races of man, as in colour, No effect morphisms. As visually season. Depigmented notice and shewn that immune hundreds of to progressive years as the sole interface between our bodies and the environ- nable skin evolved numerous genetic alterations evolutionuniquely ment. Lacking the covering ofcancers hair that are of the nature which it might have differences in skin color in each other. As primates whoformation of nonmelanoma skin times in hominin and the via inde- − use language to create categories, we readily give names to these D3 mammals and exposed form myriad physical, chemical, and bio- hairyness, of features, &c., protects other dense bodyUVB Cutaneous photosynthesis of vitamin pendent genetic pathways under positive selection. has been the differences. Since the mid-18th century, skin color to the been expected would have dimorphismon by sexual selection” (p 250). been acted in pigmentation;UVB − Greater need for vitamin D in females probably causing increasing sexual single most important physical trait used to define human groups, logical challenges of the environment, human skin evolved under including variously named varieties, races,sexual selection in some populations natural selection. The hairless condition itself exaggerated by subspecies, and species. intense pressures of | | | Charles Darwin observed UVB | folate vitamin D melanin tanning variation in human skin color while did not evolve because of a partiality forfor sexualasselection in matters of human Darwin’s preference smooth skin, averred by abroad during the voyage of the H.M.S. Beagle (1831–1836), but he Darwin, but primarily because of the needthe importance of natural selection in variationduring exertion and underlose body heat from blinded him to to hot environmental soundly rejected the notion that physical differences such as skin the skin’s surface Vmediate pigment darkening (IPD) andthe basis for distinguishing separatehuman poly-long distances awayattributes of to eccrine sweat is Human skin is func- ariation incolor constitutedisthe delayednoticeable of human travel conditions (7, 8). Cooling by evaporation of go on skin.* to sunny skin color the most tanning reaction spe- producing the from home human vacation cies (1). Darwin’s dominant mammals,distinct human places nortionally naked and as such served for hundreds of thousands of(DTR). IPD involves an immediate darkening rejection ofof the skin of we readily spe- impeded by thick body hair tanning parlors. Tanning is viewed by the existence following morphisms. As visually his observation that human groups “graduate notice did they go to (9); the primary selective pressure cies was based uponNG, Chaplin G. Proc Natl Acad Sci U S A. 2010 May 11;107 Suppl 2:8962-8exposure differences in skineach other, and that other. As nm (68). The clearmodern clinicians as an imperfect adaptation to UVR because the environ- Jablonski to UVA, with maximum in each it isat 340possible to discover uniquely into color induction hardly primates who dis- years as the sole interface between our bodies and it use language to create categories, we readily give aversion todamages the the Light ofconnective Human Condition,” dense system, that protects othereffect produced by IPD tinctive character between them” (1, p. light Hisnames to the is transient and is visible on 226). skin as these ment. Lacking the covering of held December 10–12, Colloquium immune body hair This paper results from the Arthur M. Sacklertissues, of the National Academy of and DNA, Sciences, “In skin’s Evolution IV: The separation of humans into discrete species was also motivated by his thus leads to progressive changes resulting in skin cancer (76). and bio-blotchy gray or bluishSince coloration to slavery, which skin lifetime was defended the atmammals and exposed to Nationalmyriadofphysical, chemical, and the the differences. gray the aversion appearing on sun-exposed been 2009, the ArnoldIrvine,Mabel Beckman Center of and audio filesAcademies Sciences vehement mid-18th century, in his color has and and Engineering in CA. The complete program of most presentations
  • 74. Production but This Does Not Affect Folate with Also, an increasing FR-autoantibody titer was associated systems such as the proton-co The Journal of Nutrition Nutritional ImmunologyStatus in Spanish Men and significantly 1,2¼ 0.118). We may increased tHcy, although not Women (P specific tissues (32). It appe have lacked sufficient statistical powerIncreased Risk High Milk Consumers Have an due to the small number these routes are sufficient to o 3,4 M. Murphy,3–5* Santiago Ceruelo,3,4,6 Edward V. Quadros,7Maria Isabel Berrocal-Zaragoza,of Michelle Receptor Blocking Autoantibody of FR-autoantibody carriers in our population. FolateJeffrey M. Sequeira,7 and Joan D. Fernandez-Ballart3–5 folate transport at the FR leve Production but This Does Not Affect Folate The mean FR-autoantibody and Women1,2 population is con- Status in Spanish Men titer in our Ramaekers et al. (23) pro3 4 Area of Preventive Medicine and Public Health, Faculty of Medicine and Health Sciences, and Institut d’Investigacio Sanitaria ´ ` siderably lower than Spain; Centro Murphy, * Santiago Ceruelo, en Red Quadros,have been previously reported ´ titers that 3,4 5 3–5Pere i Virgili, Universitat Rovira i Virgili,Maria Isabel Berrocal-Zaragoza, Michelle M.de Investigacion Biomedica Edward V. Fisiopatologıa de la 43201 Tarragona, ´ 3,4,6 ´ 7digestive tract to bovine milk 7 3–5 ´ associated Jeffrey M. Sequeira, and Joan D. Fernandez-Ballart ` rea Basica de Salut El Morell, Institut Catala de la Salut,Obesidad y Nutricion (CB06/03), Instituto de Salud Carlos III, Spain; Aconditions such as subfertility, neural 7 with pathological 6 `43760 Tarragona, Spain; and Department of Medicine/Cell Biology, State University of New York, Downstate Medical Center, 3 ` Area of Preventive Medicine and Public Health, Faculty of Medicine and Health Sciences, and 4Institut d’Investigacio Sanitaria ´ ` of FR-autoantibodies. NinetyBrooklyn, NY 11203 tube defect pregnancy, or CFD in infancy (18–21,23). Folate status Pere i Virgili, Universitat Rovira i Virgili, 43201 Tarragona, Spain; 5Centro de Investigacion Biomedica en Red Fisiopatologıa de la ` ´ ´ ´ Obesidad y Nutricion (CB06/03), Instituto de Salud Carlos III, Spain; 6Area Basica de Salut El Morell, Institut Catala de la Salut, ´ ` ` 43760 Tarragona, Spain; and 7Department of Medicine/Cell Biology, State University of New York, Downstate Medical Center, milk consumption at a simila Downloaded from jn.nutrition.org at Colorado St Univ Lib on April 16, 2009 Brooklyn, NY 11203 (33) but inferior to that of oth Downloaded from jn.nutrition.org at Colorado St Univ Lib on April 16, 2009Abstract Abstract results show that consumers Folate receptor (FR)-blocking autoantibodies (FR-autoantibodies) have been reported in women with neural tube defect- affected pregnancies and subfertility and in children with progressive neurodevelopment disorders. We investigated theirFolate receptor (FR)-blocking autoantibodies (FR-autoantibodies) have been reported in women with neural tube defect- milk, irrespective of whether prevalence and association with folate status and milk intake in adults unexposed to folic acid fortification. A cross-affected pregnancies and subfertility and in children with progressive neurodevelopment disorders. We investigated their sectional study of a randomly selected representative sample of a Spanish population (aged 18–75 y) stratified by age risk of having FR-autoantibo and gender was performed. Plasma and red cell folate, plasma cobalamin, fasting plasma total homocysteine (tHcy)prevalence and association with folate status and milk intake in adults unexposed to folic acid fortification. A cross- concentration, methylenetetrahydrofolate reductase C677T polymorphism, and FR-autoantibody titer were determined in population. Given that milk c blood samples from 787 fasting participants. Lifestyle data were collected and milk intake estimated from a 3-d dietarysectional study of a randomly selected representative sample of a Spanish population (aged 18–75 y) stratified by age record. FR-autoantibody prevalence was 7.2% [0.30 6 0.27 nmol (mean 6 SD) FR blocked/L], equally affecting men and population but only a smaland gender was performed. Plasma and red cell folate, plasma cobalamin, fasting plasma total homocysteine (tHcy) women of all ages. Plasma and red cell folate and tHcy did not differ between carriers and noncarriers of FR- autoantibodies. Milk intake was higher in carriers (225 6 199 g/d) than in noncarriers (199 6 147 g/d) (P , 0.01). The risk ofconcentration, methylenetetrahydrofolate reductase C677T polymorphism, and FR-autoantibody titer were determined in having FR-autoantibodies increased progressively with increasing quintile of milk intake and was significant in the highest either large amounts need to quintile ($307 g/d) compared with the lowest (#67 g/d) [odds ratio (OR), 2.41 [95% CI: 1.02, 5.69]; P , 0.05; linear trend,blood samples from 787 fasting participants. Lifestyle data were collected and milk intake estimated from a 3-d dietary P ¼ 0.02]. We concluded that FR-autoantibodies occur in men and women of all ages and do not affect indicators of folate antibodies or other unknown status such as plasma and red cell folate and tHcy. Higher milk intake is associated with increased risk of having FR-record. FR-autoantibody prevalence was 7.2% [0.30 6 0.27 nmol (mean 6 SD) FR blocked/L], equally affecting men and autoantibodies. J. Nutr. 139: 1037–1041, 2009. of this immune response. Bowomen of all ages. Plasma and red cell folate and tHcy did not differ between carriers and noncarriers of FR- ously, it has been proposedautoantibodies. Milk intake was higher in carriers (225 6 199 g/d) than in noncarriers (199 6 147 g/d) (P , 0.01). The risk of Introduction immune system might play ahaving FR-autoantibodies increased progressively with increasing quintile of milk supply andand was significant in the highest intake transport to the cell. Folate-binding proteins (FBP) Cellular integrity and division, DNA synthesis and methylation, 8 (5) are one of various transport mechanisms. The folate receptor (FR) is a 1.02, 5.69]; P , to the linear trend,quintile ($307 g/d) compared with the lowest (#67 g/d) [odds ratio (OR), 2.41 [95% CI:form of FBP that is attached0.05;plasma membrane by and fasting plasma total homocysteine (tHcy) all depend on associated with milk intake i folate status (1–4). Cellular folate availability depends on folate a glycosylphosphatidylinositol anchor (6). It is widely expressedP ¼ 0.02]. We concluded that FR-autoantibodies occur in men and women of all ages and dothe choroid plexus for transport of folate across in tissues such as not affect indicators of folate that form an important pa the blood-brain barrier (7). Three different protein isoforms (a,status such as plasma and red cell folate and tHcy. Higher milk intake is associated with increased risk expressed in numerous 1 b, and g) have been described and are of having FR- Supported by the Spanish Ministry of Health (Instituto de Salud Carlos III, epithelial tissues (8), in the placenta, hematopoietic cells, and Fondo de Investigaciones Sanitarias) projects 00/0954, 03/0870, 05/1839, immune system are rich in ´ G03/140 and RD06/0045; the Fundacio Caixa Sabadell 2006, Spain and NIHautoantibodies. J. Nutr. 139: 1037–1041, 2009. grant no. HD051880. 2 mature peripheral blood neutrophils (9–11) and in hematopoi- etic tissues, the spleen, and bone marrow (12,13), respectively. Author disclosures: M. I. Berrocal-Zaragoza, M. M. Murphy, S. Ceruelo, E. V. transported from the gut lume The gene coding a 4th isoform (d) has also been described (14). Quadros, J. M. Sequeira, and J. D. Fernandez-Ballar, no conflicts of interest. 8 The presence of autoantibodies capable of binding to the Abbreviations used: BP, folate-binding protein; CFD, cerebral folate deficiency folate binding site of the FR [FR-blocking autoantibodies syndrome; CRP, C-reactive protein; FBP, Folate-binding protein; FR, folate immune system at this point receptor; FR-autoantibody, folate receptor-blocking autoantibody; HTL, homo- (FR-autoantibodies)] has been reported in mothers with neural cysteine thiolactone; MTHFR, methylenetetrahydrofolate reductase; OR, odds ratio; tHcy, fasting plasma total homocysteine. tube defect-affected pregnancies (14–17). They have been asso- specialized dendritic cells and * To whom correspondence should be addressed. E-mail: michelle.murphy@ciated with subfertility in women (18) and also with progressiveIntroduction urv.cat. neurodevelopment disorders, such as idiopathic cerebral folate cretion of IgA provides addit 0022-3166/08 $8.00 ª 2009 American Society for Nutrition. supply and transport to the cell. Folate-binding proteins (FBP) Manuscript received November 20, 2008. Initial review completed January 1, 2009. Revision accepted February 9, 2009.Cellular integrity and division, DNA synthesis and methylation, (5) are one of various transport mechanisms. The folate receptor First published online March 12, 2009; doi:10.3945/jn.108.102475. tigens (36,37). Any aberration 1037 Risk (OR [95% CI]) of FR-autoantibodies for eachis attached to the plasma early infancy either due to 8 quintile FIGURE 2 Risk (OR all depend of (FR) is a form of FBP thatand fasting plasma total homocysteine (tHcy) [95% CI])on FR-autoantibodies for each quintile membrane byfolate status (1–4). Cellular folate availability depends onlowest quintile of milk intake in men and (6). It is widely expressed compared with the folate a glycosylphosphatidylinositol anchor compared with the lowest quintile of milk intake the men and women. women in tissues such as in choroid plexus for transport of folate across factors could trigger an immu the blood-brain barrier (7). Three different protein isoforms (a, 1040 Berrocal-Zaragoza et al. J. Nutr. 139: 1037–1041, 20091 Supported by the Spanish Ministry of Health (Instituto de Salud Carlos III, b, and g) have been described and are expressed in numerousFondo de Investigaciones Sanitarias) projects 00/0954, 03/0870, 05/1839, epithelial tissues (8), in the placenta, hematopoietic cells, and ´G03/140 and RD06/0045; the Fundacio Caixa Sabadell 2006, Spain and NIH mature peripheral blood neutrophils (9–11) and in hematopoi-
  • 75. 16 8 Blocking autoantibody p=0.013 (pmoles/ml serum) 614 4 p=0.0212 2 010 Initial Milk- Re- free exposure Ramaekers VT, et al. Dev Med Child Neurol. 2008 May;50(5):346-528
  • 76. Acknowledgements This work was supported by NIH grant Swiss National Science Foundation gra p=0.492 0.16 p<0.001 References 1. Ramaekers VT, Hausler M, Opladen Psychomotor retardation, spastic pa 0.15 and dyskinesia associated with low 5 cerebrospinal fluid: a novel neurompmoles folate receptor blocked responding to folinic acid substituti 33: 301–08. 0.14 2. Ramaekers VT, Blau N. Cerebral fola Neurol 2004; 46: 843–51. 3. Holm J, Hansen SI, Hoier-Madsen M binding in human choroid plexus. C 0.13 p<0.001 radioligand binding, immunoreacti and hydrophobic domain of the bin 1991; 280: 267–71. 0.12 4. Spector R, Johanson C. Micronutrie choroid plexus and kidney: implica Res 2006; 23: 2515–24. 5. Rothenberg SP da Costa MP Sequeir , , 0.11 against folate receptors in women w by a neural-tube defect. N Engl J Med 6. Ramaekers VT, Rothenberg SP Sequ , 0.1 to folate receptors in the cerebral fo 0 N Engl J Med 2005; 352: 1985–91. Human Human Bovine Goat 7. Schwartz RS. Autoimmune folate de placenta milk milk milk of ‘horror autotoxicus’. N Engl J Med Source of purified folate receptor 8. Jefferis R, Reimer CB, Skvaril F, et al. antibodies having specificity for hum an IUIS/WHO collaborative study. ImFigure 3: Cross-reactivity of folate receptor autoantibodies 9. Hamilton RG, Reimer CB, Rodkey LSagainst folate receptor from different species (n=9; mean and monoclonal antibodies using isoeleSEM). The p values were determined by paired t-test. immunoblot analysis. Hybridoma 1Ramaekers VT, et al. Dev Med Child Neurol. 2008 May;50(5):346-52 Folate Receptor Autoimmunity in CFD Syndrome Vin
  • 77. EXCREÇÃO UCA Jajoo R, et al. J Am Coll Nutr. 2006 Jun;25(3):224-30.
  • 78. CARGA ÁCIDA ASSOCIADA A > EXCREÇÃO DE C A E MG
  • 79. PRAL DE ALGUNS ALIMENTOS ACIDIFICANTES ALCALINIZANTES PRAL(mEq/100 kcal) PRAL (mEq/100 kcal) Peixe 14,6 Oleaginosas -1,1 Carne 12,4 Fruta -5,2 Aves 7,8 Tubérculos -5,4 Ovo 7,3 Cogumelos -11,2Marisco 7,3 RaízesQueijo 3,3 (Cenoura, nabo) -17,1 Leite 1,3 Tomate -17,5Cereais 1,1 Hortaliças -23,4NEUTROS PAEL (mEq/100 kcal)Leguminosas -0,4 Frassetto L.A. et al. J Nephrol. 2006 Mar-Apr;19 Suppl 9:S33-40.
  • 80. CLORO NACL DETERMINA ~ 50% DA PAELFrassetto LA, Morris RC Jr, Sebastian A. Am J Physiol Renal Physiol. 2007 Aug;293(2):F521-5
  • 81. SERÃO AS DDRS ADEQUADAS !
  • 82. of around 3 days. The kinetic of the half-life of MK-7 -glutamyl carboxylation of coagulation factors.is biphasic; within the first 1.5h it lasts 6-8h, where- However, vitamin K2 has a more wide-spread tissueas in a second phase the half-life is around 50h, sug- distribution and is thus also involved in the car-gesting initial redistribution and tissue uptake followed boxylation of osteocalcin and MGP. Osteocalcin (OC),by the incorporation of vitamin K2 in lipoproteins and also called bone Gla-protein (BGP), is exclusivelyFigure 1The Vitamin-K-Cycle (from Stafford, 2005) Krueger T. Port J Nephrol Hypert 2008; 22(2): 143-148
  • 83. 0.07 Mean transvalvular gradient 24 Ϯ 12 21 Ϯ 14 0.37 0.0001 (mm Hg) 0.23 Peak aortic velocity (m/s) 3.14 Ϯ 0.72 2.93 Ϯ 0.85 0.31 0.61 0.14 Data are presented as numbers (percentages) or means Ϯ SDs. 1.00 * Peak aortic velocity between 2 and 3 m/s. † 0.47 Peak aortic velocity between 3.1 and 3.9 m/s. ‡ 0.63 Peak aortic velocity Ն4 m/s. 0.79 es). Table 3 Valvular and coronary calcium scores assessed by multislice spiral computed tomography stratified by anticoagulation statusts using a Variable Oral Anticoagulants pVingmed, Valuecardiogra- Yes (n ϭ 23) No (n ϭ 63)al area ofrtic valve Valvular Agatston 2,409.9 Ϯ 1,758.5 1,070.1 Ϯ 1,084.6 0.002 score0 m/s on Coronary Agatston 1,561.3 Ϯ 1,140.5 738.2 Ϯ 977.5 0.024 of Otto et scorebetween 2h a peak Koos R, et al. Am J Cardiol. 2005 Sep 15;96(6):747-9.aortic ste- tion for OAC therapy was chronic atrial fibrillation in 16 ad severe patients (70%), cardiomyopathy with a low ejection fraction
  • 84. ORIGINAL ARTICLE E n d o c r i n e C a r e — B r i e f R e p o r t Reduced Bone Mineral Density Is Associated with Breast Arterial Calcification Jhansi Reddy, John P. Bilezikian, Suzanne J. Smith, and Lori Mosca Department of Obstetrics, Gynecology, and Reproductive Biology (J.R.), Brigham and Women’s Hospital, Boston, Massachusetts 02115; 210 Reddy et al. of Medicine (J.P.B., L.M.), Pharmacology (J.P.B.), and Radiology (S.J.S.), Columbia University College of Physicians and Departments Bone Density and Arterial Calcification J Clin Surgeons, New York, New York 10032 Background: Arterial calcification, a marker of atherosclerosis, results from a complex process of cohort than the general p biomineralization resembling bone formation. Breast arterial calcification (BAC) has been associ- TABLE 2. Multivariate adjusted odds ratios (OR) and 95% ated with angiographic and clinical cardiovascular disease. The purpose of this study was to de- confidence intervals (CI) for predictors of BAC generalized to the popula termine the association between reduced bone mineral density (BMD) and BAC, which may share a common pathophysiology. data were ascertained fro Methods: We conducted a retrospective study ofOR women (55% 95% CI Variable 228 Hispanic, mean age 64 a physician’s diagnosis o Ϯ10 yr) who had both mammography and BMD evaluation at Columbia University Medical Center from Age (10 2001–2003. Each mammogram was reviewed for the presence of BAC using standardized methods. the systematic d yr) 1.5 1.0 –2.2 cluded HispanicBMD was measured using dual-energy x-ray absorptiometry and categorized as normal, low bone 3.1 1.5– 6.3 particular the diagnosis o density (osteopenia), or osteoporosis as defined by the World Health Organization. Univariate and Menopause 4.1 0.8 –21association between multivariate logistic regression analyses were performed to evaluate the 23 study participants. O mellitusa Diabetesreduced BMD and BAC. 1.6 0.7–3.7 Hypertensiona The prevalence of BAC, low bone density (osteopenia), and osteoporosis was 39, and BAC, however, were Results: 0.9 0.5–1.7 42, and Bone densityrespectively. Women with BAC were significantly more likely to be older, Hispanic, and 29%, was limited to white and Low bone density and have osteoporosis as compared with women1.1– 6.8 In age-adjusted not be generalized postmenopausal (osteopenia) 2.7 without BAC. may analyses, women with BAC were more likely to have reduced BMD (odds ratio 3.0, P Ͻ 0.01) as Osteoporosis with women without BAC. Furthermore, osteoporosis was strongly associated with the compared 4.4 1.6 –12 significance of the correl presence of BAC (odds ratio 3.5, P Ͻ 0.01). a Total n ϭ 205 due to missing data on 23 patients. who may need further ev Conclusion: These data suggest that osteoporosis and arterial calcification are strongly and inde- pendently correlated. Reduced BMD may identify women at risk of vascular disease. (J Clin Endo- The paradigm of CV sclerosis measured 93: 208carotid artery ultrasound and reduced crinol Metab on –211, 2008) replaced by the growing r bone density. et al. J Clin Endocrinol Metab 93: 208–211, 2008 Reddy J, risk. It is important to iC ardiovascular disease (CVD) and osteoporosis are signifi- Several studies have suggested that BAC is an at risk of future clinical cardiovas- cant causes of morbidity and mortality among older testing may identify women cular events (6 –9). independent vascular disease so optim
  • 85. Bolland MJ, et al. BMJ. 2008 Feb 2;336(7638):262-6
  • 86. VITAMINA K1 E OSTEOCALCINA! Binkley NC. Am J Clin Nutr. 2002 Nov;76(5):1055-60.
  • 87. Alimentos Vitamina K1 (mcg)Couve Galega cozida (130 g) 1146Espinafre cozido (180 g) 888Couve-de-Bruxelas cozida (155 g) 300Brócolo cozido (156) 220Cebola crua (100 g) 207 USDA National Nutrient Database for Standard Reference, Release 20
  • 88. 2/121 (hip); 0/120 (hip); 5/121 (nonspine) 1/120 (nonspine) 52 (0) 52 (0) NA NA 1.1 (spine) neral density; CI, confidence interval; NA, not applicable.s who underwent follow-up for outcome. rate. ns low to de- OR % t asymmetry Study Favors Vitamin K Favors Control (95% Cl) WeightPvertebral = .61; Hipl inspection Sato et al,33 1998 0.36 (0.02 to 5.90) 6.3 Shiraki et al,36 2000 0.26 (0.03 to 2.55) 9.4 no evidence Sato et al,34 2002 0.19 (0.05 to 0.75) 26.4 ).24 In terms Ishida and Kawai,26 2004 0.37 (0.02 to 5.90) 6.3 Sato et al,35 2005 0.22 (0.08 to 0.59) 51.6only 2 stud- Subtotal 0.23 (0.12 to 0.47) 100.0 ey had used Vertebralg the alloca- Sasaki et al,32 2005 0.35 (0.02 to 6.00) 2.9 Shiraki et al,36 2000 0.39 (0.20 to 0.75) 54.4ion, another Iwamoto et al,29 2001 0.32 (0.07 to 1.46) 10.4 ranged from Ishida and Kawai,26 2004 0.47 (0.20 to 1.10) 32.3 Subtotal 0.40 (0.25 to 0.65) 100.0 All Nonvertebral Sato et al,33 1998 0.36 (0.02 to 5.90) 4.5 NTS Shiraki et al,36 2000 0.26 (0.05 to 1.30) 13.4 Sato et al,34 2002 0.17 (0.05 to 0.58) 23.0 serious ad- Ishida and Kawai,26 2004 0.22 (0.03 to 1.56) 8.9 Sato et al,35 2005 0.18 (0.08 to 0.41) 50.2d with vita- Subtotal 0.19 (0.11 to 0.35) 100.0 gastrointes-reported by 0.05 0.1 0.2 0.5 1 2 5 10 20 OR Figure 2. Meta-analysis of treatmentArch Intern Med. 2006;166:1256-1261 effects on fractures. Peto odds ratios (ORs) with 95% confidence intervals (CIs).
  • 89. Clin Drug Invest 2009; 29 (7): 4 7 M 7 9 ORIGINAL RESEARCH ARTICLE 1173-2563/09/0007-0471 /S49,95/0 © 2009 Adls Data Infarmatlon BV. All rights resen/ed. Efficacy of Menatetrenone (Vitamin K2)Anti-Fracture Efficacy of Menatetrenone in Patients with Neurological Diseases 47 against Non-Vertebral and Hip Fractures in Patients with Neurological Diseases Meta-Analysis of Three Randomized, Controlled Trials Jun Iwamoto, Hideo Matsumoto and Tsuyoshi Takeda IncidenceIntegrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan Institute for of hip fractures Relative risk Reference Study (95% CI) menatetrenone non-treatmentand objective: Patients with neurological diseases Abstract Background such as Alz- heimers disease, stroke and Parkinsons disease have been reported to have Alzheimers 2/90 15/88 K deficiency secondary to malnutrition, which increases the risk of vitamin 0,13(0,03,0,55) 11 non-vertebral and hip fractures. The purpose of the present study was to disease clarify the efficacy of menatetrenone (vitamin K2) against non-vertebral and hip fractures in patients with neurological diseases. Parkinsons 1/56 8/54 2008hterature search was conducted on PubMed from of use of1995 Methods: A to July 0,12 (0,02,0,93) 12 to identify randomized controlled trials (RCTs) January me- disease natetrenone against non-vertebral and hip fractures in patients with neuro- logical diseases. A meta-analysis of all RCTs meeting these criteria was then performed. Stroke 0/51 1/48 Three RCTs of patients with Alzheimers disease (n= 178, mean age Results: 0,31 (0,01,7,53) 13 78 years), stroke (n = 99, mean age 66 years) and Parkinsons disease (n= 110, mean age 72 years) met the criteria for meta-analysis. These RCTs did not include placebo controls but did have non-treatment controls. According to Pooied data 3/197 24/190 0,14(0,05,0,43) the meta-analysis, the overall relative risks (95% confidence intervals) for non-vertebral and hip fractures with menatetrenone treatment compared with non-treatment were 0.13 (0.05, 0.35) and 0.14 (0.05, 0.43), respectively, in patients with neurological diseases. No severe adverse events were reported Test for heterogeneity: x^ = 0,28 (p =menatetrenone treatment. with 0,8702) 0,10,01 10 Conclusion: The present meta-analysis of three RCTs suggests that there is Test for overaii effect: x^ = 11 -97 efficacy 0,0005) (p < for menatetrenone treatment against non-vertebral and hip fractures Arch Intern Med. 2006;166:1256-1261 among patients with neurological diseases. Further larger placebo-controlledFig, 2. Effectof menatetrenone on the incidence of are needed to confirm the results of the present study. trials hip fractures in patients with neuroiogicai diseases. The reiative risks (95% Cis) of ththree randomized controiied triais (RCTs) are shown. Since the event rates for hip fractures were low and there was a zero event rate in som
  • 90. utrition.org by on May 3, 2009intake of alcohol, SFA, PUFA, flavonols (quercetin, myricetin, and kaempferol), and calcium. 4 CHD comprises fatal and nonfatal MI, sudden cardiac death, and other forms of acute and chronic ischemic heart disease (ICD-10 codes I20 –I25and I46). 5 CHD events followed by death within 28 d after the onset of symptoms.in France and the Mediterranean countries may possibly ac- quantify endogenous menaquinone synthesis. Dietary intake of CALCIFICAÇÃO DA AORTAcount for lower prevalences of CHD. Menaquinone is also menaquinone is reflected in serum levels. In healthy Japaneseproduced by the intestinal flora, but the absorption seems to be subjects who consumed fermented soybean (natto) high inlimited (27). In our study, however, it was not possible to menaquinone (especially MK-7), serum concentrations of TABLE 4 Association of aortic calcification with intake of menaquinone in 4473 Dutch men and women aged 55 y and over1,2 Energy-adjusted menaquinone intake (␮g/d) Ͻ21.6 21.6–32.7 Ͼ32.7 P for trendn 1468 1493 1512Median intake, ␮g/d 15.1 26.9 40.9Moderate calcification Controls, n 916 958 1000 Cases, n 454 452 453 OR, model 13 1 0.93 (0.79, 1.10) 0.94 (0.80, 1.11) 0.49 OR, model 24 1 0.91 (0.77, 1.09) 0.93 (0.76, 1.12) 0.45Severe calcification Controls, n 916 958 1000 Cases, n 98 83 59 OR, model 1 1 0.75 (0.54, 1.03) 0.56 (0.39, 0.80) 0.001 OR, model 2 1 0.71 (0.50, 1.00) 0.48 (0.32, 0.71) Ͻ0.001 1 Aortic calcification was graded according to the length of the calcified area, i.e., no/mild (reference), Յ1 cm; moderate, Ͼ1 and Ͻ5 cm; severe,Ն5 cm. 2 OR obtained by multivariate logistic regression, with 95% CI in parentheses and P for linear trend across the tertiles. 3 Model includes age, gender, and total energy intake. 4 Model includes age, gender, total energy intake, BMI, smoking status, pack-years of cigarette smoking, diabetes, education (3 categories), andintake of alcohol, SFA, PUFA, flavonols (quercetin, myricetin, and kaempferol), and calcium.
  • 91. Alimentos (100 g) Vitamina K2 (mcg)Natto 1103Paté de fígado de Ganso 369Queijos envelhecidos 76,3Queijos gordos 56Gema de ovo 15-32Coxa de Ganso 21Manteiga 15Fígado de Galinha 14Coxa de Galinha 8,5Bife de vaca 8,1 Elder SJ, et al. J Agric Food Chem. 2006; 54: 463-467 Schurgers LJ, Vermeer C. Haemostasis. 2000; 30: 298-307.
  • 92. Solar UVB radiation Solar UVB radiation 7-Dehydrocholesterol Previtamin D3 (290–315 nm) Inactive photoproducts Skin t io n Heat radia r UVB Sola Vitamin D3 Chylomicrons Diet Vitamin D Fat cellVitamin D2 CH3 Circulation Vitamin D3 Vitamin D-25-hydroxylase Circulation CH2 LiverHO CH2 Reference range <20 ng/ml 20–100 ng/ml >150 ng/ml 25(OH)D HO (major circulating metabolite) Deficiency Preferred range Intoxication Phophorus, calcium, 30–60 ng/ml FGF-23, and other factors +/– 1-OHase _ Holick M. NEJM 2007;357:266-81. 1,25(OH)2D Kidneys 1,25(OH)2D 24-OHase Calcitroic acid Calcium Resorption _ + Calcium Absorption + Preosteoclast CaBP Osteoblast Bile Parathyroid hormone VDR–RXR RANK VDR–RXR Excreted RANKL TRPV6 Calcium Osteoclast Bone Ca2+ and HPO42− Parathyroid glands Ca2+ and HPO42− Intestine Calcification Absorption Blood calcium and phosphorus COLOR FIGURE
  • 93. 1,25(OH)2D3 PTH vitamin D3 or vita provide a significa In general, age-rel levels and lower bones29,30, which (OH)2D3 to redres also reduces 1,25-( Kidney VDR levels in bon there has been ev has some anabolic Intestine Bone Pth- and Cyp27b1 Analogues of v ties have been prep (2-methylene-19- which is at least (OH)2D3 in stimu activity, resulting in rats35–37. Howev Neuro- Plasma Ca2+ Mineralization well as formation a muscular bone mass in post There is no dou important in patieFigure 2 | Depiction of 1α,25-dihydroxyvitamin D3 activities and target organs in some countries Plum LA, DeLuca HF. Nat Rev Drug Discov. 2010 Dec;9(12):941-55involved in maintaining plasma calcium homeostasis. 1α,25-dihydroxyvitamin D3 beneficial effects o(1,25-(OH)2D3) works in conjunction with parathyroid hormone (PTH) to release calcium treating osteoporo Furthermore, vitam
  • 94. Holick MF. J Clin Invest. 2006 Aug;116(8):2062-72 ×
  • 95. 3, Vol 78 Musculoskeletal Pain and Severe Hypovitaminosis D 1463vere Hypovitaminosis D in PatientsNonspecific Musculoskeletal Pain Vol 78 Mayo Clin Proc, December 2003, Musculoskeletal Pain andF, Original Article MD, MTS, AND JOANNA M. QUIGLEY, BAmine the prevalence of hypovita- whom were younger than 30 years. Five patients, 4 of whomcare outpatients with persistent, were aged 35 years or younger, had vitamin D serum levels Prevalence of Severe Hypovitaminosis D in Patientsetal pain syndromes refractory to below the level of detection. The severity of deficiency was disproportionate by age for young women (P<.001), by sexds: In this cross-sectional study, for East African patients (P<.001), and by race for African With Persistent, Nonspecific Musculoskeletal Pain consecutively between February h persistent, nonspecific muscu- American patients (P=.006). Season was not a significant factor in determining vitamin D serum levels (P=.06).mmunity University Health Care • Conclusion: All patients with persistent, nonspecific iliated inner city primary care musculoskeletal pain are at high risk for the consequences nn (45 north). Immigrant (n=83) of unrecognized and untreated severe hypovitaminosis D. G REGORYto A. P ) persons of both sexes, aged 10 LOTNIKOFF , MD, MTS, J AND OANNA This risk extends to those considered at low risk for vita- M. QUIGLEY, BA ethnic groups were screened for min D deficiency: nonelderly, nonhousebound, or nonimmi- 25-hydroxyvitamin D levels were grant persons of either sex. Nonimmigrant women of unoassay. childbearing age with such pain appear to be at greatest • Objective: To misdiagnosis or delayed diagnosis. Because osteo-can American, East African, His-dian patients, 100% had deficient risk for determine the prevalence of hypovita- malacia is a known cause of persistent, nonspecific muscu- whom were younger than 30 yeng/mL). Of all patients, 93% (140/D in primary screening all outpatients with such pain for minosis loskeletal pain, care outpatients with persistent, were aged 35 years or younger, nonspecific musculoskeletal pain standard practicerefractory toof vitamin D (mean, 12.08 ng/mL; hypovitaminosis D should be syndromes in clinical below the level of detection. Th , 11.18-12.99 ng/mL). Nonimmi- care. standard therapies.evels as deficient as immigrants Mayo Clin Proc. 2003;78:1463-1470 disproportionate by age for yo • Patients and Methods:of In thisCI = confidence interval; study,n D in men were as deficient as in tients, 28% (42/150) had severely ANOVA = analysis variance; cross-sectional for East African patients (P<.0 150 patients presented consecutively between February ls (≤8 ng/mL), including 55% of PTH = parathyroid hormone American patients (P=.006). S
  • 96. Clin Rheumatol (2007) 26:1895–1901DOI 10.1007/s10067-007-0603-4 ORIGINAL ARTICLEHypovitaminosis D in female patients with chroniclow back painAhmed Lotfi & Ahmed M. Abdel-Nasser &Ahmed Hamdy & Ahmed A. Omran &Mahmoud A. El-RehanyReceived: 7 October 2006 / Revised: 4 March 2007 / Accepted: 5 March 2007 / Published online: 22 March 2007# Clinical Rheumatology 2007Abstract Chronic low back pain (LBP) is an extremely had significantly lower 25 OHD levels (p<0.05)common problem in practice, where it is often labeled significantly higher PTH (p<0.05) and ALP (p<0.idiopathic. No sufficient studies have been conducted to than controls, although there were no significant ganalyze the contribution of hypovitaminosis D to the eti- differences in calcium and phosphorus. Hypovitaminos
  • 97. International Journal of Rheumatic Diseases 2010; 13: 340–346 ORIGINAL ARTICLEAssociation between nonspecific skeletal pain and vitaminD deficiencyBehzad HEIDARI,1 Javad Shokri SHIRVANI,1 Alireza FIROUZJAHI,2 Parnaz HEIDARI3 andKarim O. HAJIAN-TILAKI41 Deparment of Medicine, Division of Rheumatology, 2Deparment of Pathology and Laboratory Medicine, Rouhani Hospital, BabolUniversity of Medical Sciences, Babol, 3Faculty of Medicine, Islamic Azad University, Tehran and 4Department of Social Medicine,Babol University of Medical Sciences, Babol, Iran Abstract Background: Deficiency of vitamin D has been reported in patients with many types of musculoskeletal pain.
  • 98. Fracture Prevention WithVitamin D SupplementationA Meta-analysis of Randomized Controlled TrialsHeike A. Bischoff-Ferrari, MD, MPH Context The role and dose of oral vitamin D supplementation in nonvertebral fWalter C. Willett, DrPH ture prevention have not been well established.John B. Wong, MD Objective To estimate the effectiveness of vitamin D supplementation in prevEdward Giovannucci, ScD ing hip and nonvertebral fractures in older persons.Thomas Dietrich, MPH Data Sources A systematic review of English and non-English articles using MEDL and the Cochrane Controlled Trials Register (1960-2005), and EMBASE (1991-20Bess Dawson-Hughes, MD Additional studies were identified by contacting clinical experts and searching biblF raphies and abstracts presented at the American Society for Bone and Mineral Rese RACTURES CONTRIBUTE SIGNIFI- (1995-2004). Search terms included randomized controlled trial (RCT), controlled c cantly to morbidity and mortal- cal trial, random allocation, double-blind method, cholecalciferol, ergocalciferol, ity of older persons. Hip frac- hydroxyvitamin D, fractures, humans, elderly, falls, and bone density. tures increase exponentially Study Selection Only double-blind RCTs of oral vitamin D supplementation (cwith age so that by the ninth decade of lecalciferol, ergocalciferol) with or without calcium supplementation vs calcium suplife, an estimated 1 in every 3 women mentation or placebo in older persons (Ն60 years) that examined hip or nonverteand 1 in every 6 men will have sus- fractures were included.tained a hip fracture.1 With the aging Data Extraction Independent extraction of articles by 2 authors using predefof the population, the number of hip data fields, including study quality indicators.fractures is projected to increase world- Data Synthesis All pooled analyses were based on random-effects models. Five Rwide.2 The consequences of hip frac- for hip fracture (n=9294) and 7 RCTs for nonvertebral fracture risk (n=9820) mettures are severe: 50% of older persons inclusion criteria. All trials used cholecalciferol. Heterogeneity among studies for bothhave permanent functional disabili- and nonvertebral fracture prevention was observed, which disappeared after pooling Rties, 15% to 25% require long-term with low-dose (400 IU/d) and higher-dose vitamin D (700-800 IU/d), separately. Anursing home care, and 10% to 20% die tamin D dose of 700 to 800 IU/d reduced the relative risk (RR) of hip fracture by 26% JAMA. 2005;293:2257-2264within 1 year.3-6 Besides the personal RCTs with 5572 persons; pooled RR, 0.74; 95% confidence interval [CI], 0.61-0.88)burden, hip fractures account for sub- any nonvertebral fracture by 23% (5 RCTs with 6098 persons; pooled RR, 0.77; 9
  • 99. Figure 2. Comparing the Risk of the Risk of Hip and Nonvertebral Fractures Between Vitamin D (700-800 IU/d) and Controlre 2. Forest PlotsForest Plots ComparingHip and Nonvertebral Fractures Between Vitamin D (700-800 IU/d and 400IU/d and 400 IU/d) and Conps Groups Hip Fracture Hip Fracture Nonvertebral Fracture Nonvertebral Fracture Favors Vitamin D Favors Control Favors Vitamin D Favors Control Favors Vitamin D Favors Control Favors Vitamin D Favors Control Source Source Source Source Vitamin D 700-800 IU/d 700-800 IU/d Vitamin D Vitamin D 700-800 IU/d D 700-800 IU/d Vitamin 17 Pfeifer et al,15 2000 Chapuy et al,17 Chapuy et al, 2002 2002 Pfeifer et al,15 2000 Chapuy et al,17 2002 Chapuy et al,17 2002 12 Chapuy et al,12 Chapuy et al, 1994 1994 Chapuy et al,12 1994 Chapuy et al,12 1994 14 Dawson-HughesDawson-Hughes et al, 1997 18 Trivedi et al,18 2003 et al, 2003 Trivedi et al,14 1997 Trivedi et al,18 2003 Trivedi et al,18 2003 Pooled Pooled Pooled Pooled 0.2 0.2 0.5 1.0 0.5 1.0 5.0 5.0 0.2 0.5 0.2 1.0 0.5 1.0 5.0 5. Vitamin D 400 Vitamin D 400 IU/d IU/d Vitamin D 400 IU/d Vitamin D 400 IU/d Meyer et al,16 2002 et al,16 2002 Meyer Meyer et al,16 2002 Meyer et al,16 2002 Lips et al,13 1996 et al,13 1996 Lips Lips et al,13 1996Lips et al,13 1996 Pooled Pooled Pooled Pooled 0.2 0.5 0.2 1.0 0.5 1.0 5.0 5.0 0.2 0.5 0.2 1.0 0.5 1.0 5.0 5. Relative Risk (95% CI) Risk (95% CI) Relative Relative Risk (95% CI) Risk (95% CI) Relative JAMA. 2005;293:2257-2264es represent relative risks (RRs) and size(RRs) and sizeproportionalis proportionalthe the size of the trials. Error 95%represent 95% confidenceTrials are sortedTrials are so Squares represent relative risks of squares is of squares to the size of to trials. Error bars represent bars confidence intervals (CIs). intervals (CIs). by 12,17,18 12,17,18
  • 100. RECEPTORES EM VÁRIAS CÉLULAS !Catelicidina Holick MF. J Clin Invest. 2006 Aug;116(8):2062-72
  • 101. Canada Epidemiol. Infect. (2006), 134, 1129–1140. f 2006 Cambridge University Press3 doi:10.1017/S0950268806007175 Printed in the United Kingdom Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism,National Institutes of Health, Bethesda, MD Epidemiol. Infect. (2006), 134, 1129–1140. f 2006 Cambridge University Press4 REVIEW ARTICLE Departments of Medicine and Physiology, Boston United Kingdom School of Medicine, Boston, MA, USA doi:10.1017/S0950268806007175 Printed in the University5 Epidemic influenza and vitamin D SUNARC, San Francisco, CA, USA6 Atmospheric Chemistry Division,ARTICLE REVIEW National Center for Atmospheric Research, Boulder, CO, USA7 Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, USA8 Epidemic influenza and vitamin D Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA J. J. C A N N E L L 1*, R. V IE T H 2, J. C. U M H A U 3, M. F. H O L IC K 4, W. B. G R A N T 5,(Accepted 5 August S. M A D R O N I C H 6, C. F. G A R LA N D 7 A N D E. G I O V A 2006)C I 8 2006, first published online 7 September N N U C 1 Atascadero State Hospital, 10333 El Camino Real, Atascadero, CA, USA 2 J. J. C A NNHospital, PathologyT H 2Laboratory Medicine,, Department of IC K 4, W. B. GR A NT 5, Mount Sinai E L L 1*, R. V IE and , J. C. UM H A U 3 M. F. H O L Medicine, Toronto, Ontario, CanadaSUMMARY S. M A D R O N I C H 6, C. F. G A R LA ND 7 A N D E. G I O V A N N U C C I 8 3 Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 10333 El Camino Real, Atascadero, CA, USA 1 Atascadero State Hospital, Bethesda, MD 4In 1981, R. Edgar Hope-Simpson proposed that a ‘ seasonal stimulus ’ intimately associated with 2 5 Departments of Medicine and Physiology, Boston University School of Medicine, Boston, MA, USA Mount Sinai Hospital, Pathology and Laboratory Medicine, Department of Medicine, Toronto, Ontario, SUNARC, San Francisco, CA, USA Canadasolar radiation explained the remarkable seasonality of epidemic influenza. Solar radiation triggers 6 3 Atmospheric Chemistry Division, National Center for Atmospheric Research, Boulder, CO, USA 7 Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, USA National Institutes of Health, Bethesda, MDrobust seasonal vitamin D production in the skin ; vitamin D deficiency is common in the winter, 8 4 Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA Departments of Medicine and Physiology, Boston University School of Medicine, Boston, MA, USA 5 SUNARC, San Francisco, CA, USAand activated vitamin D, 1,25(OH) D, a steroid hormone, has profound effects on human 2 (Accepted 5 August 2006, first published Center for Atmospheric Research, Boulder, CO, USA 6 Atmospheric Chemistry Division, National online 7 September 2006) 7immunity. 1,25(OH) D acts as an immune system modulator, preventing excessive expression Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, USA 8 2 Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USAof inflammatory cytokinesR Y increasing the ‘ oxidative burst ’ potential of macrophages. Perhaps SUMMA and (Accepted 5Edgar Hope-Simpson proposed that a ‘ seasonal stimulus ’ intimately associated with In 1981, R. August 2006, first published online 7 September 2006)most importantly, it dramatically stimulates the expression ofinfluenza. Solar radiation triggers peptides, solar radiation explained the remarkable seasonality of epidemic potent anti-microbialwhich exist in neutrophils, R Y vitamin D production in the skin ; vitamin D deficiencyepithelial the winter, S U M M A monocytes, natural killer cells, and in is common in cells lining the robust seasonal and activated vitamin D, 1,25(OH) D, a steroid hormone, has profound effects on human 2respiratory tract where they play D acts as an immune system a ‘seasonal stimulus ’ intimately associated with Volunteers In 1981, R.1,25(OH) a major role in that modulator, preventing excessive expression immunity. Edgar Hope-Simpson proposed protecting the lung from infection. 2inoculated with livesolar radiation explained the remarkable seasonality of burst ’ potential of macrophages. Perhaps serological of inflammatory cytokines and increasing the ‘ oxidative epidemic influenza. Solar radiationand attenuated influenza virus are more likely to develop fever triggers robust seasonal vitamin D production in the skin ; vitamin of potent anti-microbial peptides, most importantly, it dramatically stimulates the expression D deficiency is common in the winter,evidence of an immune response in the winter.steroid hormone, hasinprofound effectslining the which exist in vitamin D, monocytes, a Vitamin D deficiency predisposes children to and activated neutrophils,1,25(OH) D,natural killer cells, and epithelial cells on human 2respiratory infections. UltravioletDradiation (either protecting the preventinginfection. Volunteers sunlight) reduces immunity. 1,25(OH) they play a immune system modulator, lung from excessive or from respiratory tract where acts as an major role in 2 from artificial sources expression of inflammatory cytokines and influenza virus ‘oxidative burst ’ potentialfever and serological inoculated with live attenuated increasing the are more likely to develop of macrophages. Perhapsthe incidence of viral respiratory dramatically stimulates the expression of potent(which children to vitamin D). An most importantly, it infections, as does codD deficiency predisposes contains evidence of an immune response in the winter. Vitamin liver oil anti-microbial peptides,interventional study showedof viral respiratory infections, as doesfromliver oilinsourcesof cells vitamin D). An which exist infections.vitamin radiation (either the artificial epithelial fromlining the reduces respiratory in neutrophils, monocytes, natural killer cells, and that Ultraviolet D reduces cod incidence contains sunlight) infections in or respiratory respiratory tract where they play a major role in protecting the (which the incidence lung from infection. Volunteerschildren. We conclude thatwith live attenuated influenza D reducesmoreincidence of respiratory and serological inoculated vitamin D, orvitamin virus aremay likelyHope-Simpson’s ‘ seasonal stimulus ’. interventional study showed that lack of it, the be to develop fever infections in evidence of an immune response in D, or lack of it, may D deficiency predisposes children to ’. children. We conclude that vitamin the winter. Vitamin be Hope-Simpson’s ‘ seasonal stimulus respiratory infections. Ultraviolet radiation (either from artificial sources or from sunlight) reduces the incidence of viral respiratory infections, as does cod liver oil (which contains vitamin D). An INTRODUCTION … the characteristic microbe of a disease might be aINTRODUCTION symptom of respiratory infections microbe of a … the characteristic in interventional study showed that vitamin D reduces the incidence instead of a cause. disease might be a children. wishes to investigate medicine properly of it, may besymptom instead of stimulus ’. Bernard Shaw Whoever We conclude that vitamin D, or lack should Hope-Simpson’s ‘seasonal a cause. George proceed thus : in the first place to consider the seasons of the
  • 102. Latitude zone Quarter 1 Quarter 2 Quarter 3 Quarter 4 1200 Jan·Feb·Mar Apr·May·Jun Jul·Aug·Sep Oct·Nov·Dec Monthly percentage of total epidemic months in each zone N. temperate 30 1000 Influenza case rates/100 000 N. 30° + 20 800 10 0 600 20 tical solar radi N. tropical ver ati of 23·5° N o 10 th n N. 0–29° 400 Pa 0 0° Equator 0° 20 S. tropical 200 10 S. 0–29° 0 23·5° S 23·5° S 0 S. temperate 40 S O N S. 30° + 30 1968 20 Fig. 2. Weekly c 10 clinically as influ 0 turns to the GenThe Fig. 1. The seasonal and latitudinal of outbreaks of type A seasonal and latitudinal distribution distribution of College of Gene influenza in the world, 1964–1975 outbreaks of type A influenza in the world, 1964–1975, practices in vario summarized from the Weekly Epidemiological Record of the serving a populat
  • 103. Virology Journal 2008, 5:29 VITAMINA D E GRIPE 25 cr N = 104 Placebo vs 104 Vit D ex 20 m 15 th a 10 se 5 of 0 Winter Spring Summer Autumn In Placebo 800 IU/d 2000 IU/d apFigureseason 2Incidence of reported cold/influenza symptoms according to InIncidence ofJJ, Zasloff M, Garland CF, Scragg R, Giovannucci E. Virol symptoms Cannell reported cold/influenza J. 2008 Feb 25;5:29. luaccording to season. The 104 subjects in the placebo m
  • 104. J Mol Med (2010) 88:441–450Fig. 2 Proposed mechanism for vitamin D’s influence on the develop- environmental trigger of clinical disease. Left untreated,ment and progression of autoimmunity. 1,25(OH)2D regulates DC matu- vitamin D deficiency will continue as many autoimmuneration and the differentiation and activity of CD4+ T cells to prevent the several medications used to treat them lead to sun avoloss of self-tolerance. In a genetically predisposed individual, it is more photosensitivity. The role of vitamin D status in the natulikely that autoantibodies will develop and proliferate in the setting of autoimmunity warrants further investigationvitamin D deficiency. Ultimately, deficiency of vitamin D may act as anT lymphocytes, B lymphocytes, and dendritic cells [43, 44]. and suppresses IL-12p70, IL-23p19, and furthe
  • 105. THYROID Volume 21, Number 8, 2011 ª Mary Ann Liebert, Inc. DOI: 10.1089/thy.2009.0200 Relative Vitamin D Insufficiency in Hashimoto’s Thyroiditis Gonca Tamer,1 Safiye Arik,2 Ismet Tamer,3 and Damla Coksert 2894 TAMER ET AL. Background: Vitamin 3. Characteristics of Patients’ Groupsof 25-hydroxyvitamin D [25(OH)D3] lower than Table D insufficiency, defined as serum levels Versus Healthy Controls 30 ng/mL, has been reported to be prevalent in several autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus. The goal of the presentwith HT OHP study was to assess whether vitamin D insufficiency is also aHealthy SHP with HT EP with HT feature of Hashimoto’s thyroiditis (HT). controls Methods: We performed a prevalence 50) (n ¼ case–control study that included 161 cases with HT and 162 (n ¼ 162) p-Value (n ¼ 45) p-Value (n ¼ 66) p-Value healthy controls. Serum levels of 25(OH)D3, calcium, phosphorus, and parathyroid hormone were measured in all 323Calcium (mIU/mL) 9.4 Æ 0.4 0.97 9.2 Æ 0.5 0.004 9.4 Æ 0.3 0.78 9.4 Æ 0.4 subjects.Phosphorus (mIU/mL) 3.5 Æ 0.7 0.04 3.5 Æ 0.4 0.17 3.5 Æ 0.5 0.28 3.6 Æ 0.5 Results: The prevalence of vitamin DÆ 29.2 <0.0001 HT cases (148 of 161, 92%) was18.1 <0.003 higher Æ 14PTH (mIU/mL) 61.4 insufficiency in 59.3 Æ 22.6 <0.0001 50.9 Æ significantly 43.2 than that observed in healthy controls (102 Æ 9.3 63%, p < 0.0001). Among HT cases, the prevalence rate of vitamin D25(OH)D3 level (ng/mL) 15.4 of 162, 0.003 15.7 Æ 7.4 0.018 17.4 Æ 12.9 0.006 29.6 Æ 25.5Rate of vitamin D insufficiencytrend to be higher in patients with(97.77%) <0.0001 57 (86.36%) 94%) or subclinical insufficiency showed a [n (%)] 47 (94%) <0.0001 44 overt hypothyroidism (47 of 50, <0.001 102 (63%) hypothyroidism (44 of 45, 98%) than in those with euthyroidism (57 of 66, 86%), but the differences were not All p-values are vs. control group. significant ( p ¼ 0.083). Conclusion: Vitamin D insufficiency is associated with HT. Further studies are needed to determine whetherp < 0.0001, and D¼ 0.003, respectively) (Table 3). Serum PTH (9,16). 1,25(OH)2D3 decreases the proliferation of purified Th vitamin p insufficiency is a casual factor in the pathogenesis of HT or rather a consequence of the disease.levels of OHP were significantly higher than EP ( p ¼ 0.016). cells and decreases the production of IFN-g, IL-2, IL-5, andEPs had the lowest PTH levels in all patients with HT (Table tumor necrosis factor-a. In Th2 cells, 1,25(OH)2D3 increases2); however, their PTH levels were significantly higher than the production of IL-4 (9,16) and transforming growth factor Tamer G, Arik S, Tamer I, Coksert D. Thyroid. 2011 Aug;21(8):891-6those of CG ( p ¼ 0.003) (Table 3). There were no significant production, which in turn may suppress inflammatory T-cell Introductiondifferences between serum PTH levels of SHP and OHP activity (8). In another study, 25(OH)D3 is inactive1,25(OH)2D3 insufficiency (3,5). Vitamin the effectiveness of and must be( p ¼ 0.53) and between those of SHP and EP ( p ¼ 0.055). forconverted in of autoimmune disease in vivo was shownD suppression the kidneys to 1,25-dihydroxy vitamin to
  • 106. ARTHRITIS & RHEUMATISM Vol. 50, No. 1, January 2004, pp 72–77 DOI 10.1002/art.11434 © 2004, American College of Rheumatology Vitamin D Intake Is Inversely Associated With Rheumatoid Arthritis Results From the Iowa Women’s Health Study Linda A. Merlino,1 Jeffrey Curtis,2 Ted R. Mikuls,3 James R. Cerhan,4 Lindsey A. Criswell,5 and Kenneth G. Saag2 Objective. Vitamin D is a potent regulator of apparent for both dietary (RR 0.72, 95% CI 0.46–1.14, Pcalcium homeostasis and may have immunomodulatory for trend ‫ )61.0 ؍‬and supplemental (RR 0.66, 95% CIeffects. The influence of vitamin D on human auto- 0.43–1.00, P for trend ‫ )30.0 ؍‬vitamin D. No individualimmune disease has not been well defined. The purpose food item high in vitamin D content and/or calcium wasof this study was to evaluate the association of dietary strongly associated with RA risk, but a composite mea-and supplemental vitamin D intake with rheumatoid sure of milk products was suggestive of an inversearthritis (RA) incidence. association with risk of RA (RR 0.66, 95% CI 0.42–1.01, Methods. We analyzed data from a prospective P for trend ‫.)60.0 ؍‬
  • 107. Sensitivity analysis. In four of the eight toward thregions, Western Australia (WA), South Research | Articles and thu Environ Health Perspect 2003; 111:518–523Australia (SA), Victoria (VIC), and Australian Ecologic Analysis of Some Immune-Related Disorders, Including Type 1 Similarly, Diabetes, in Australia: Latitude, Regional Ultraviolet Radiation, and DiseaseCapital Territory (ACT), at least 70% of the Prevalence Judith A. Staples, Anne-Louise Ponsonby, Lynette L-Y. Lim, and Anthony J. McMichael significan National Center for Epidemiology and Population Health, The Australian National University, Canberra, Australian Capital Territory, Australia immune and autoimmune processes involved The apparent immune-suppressive effect of ultraviolet radiation (UVR) has suggested that this in the etiology of such immune disorders environmental exposure may influence the development of immune-related disorders. Self-reported (McMichael and Hall 1997). Type 1 diabetes Type 1 diabetes prevalence rates of type 1 diabetes mellitus, rheumatoid arthritis (RA), eczema/dermatitis, and 8 asthma, from the 1995 Australian National Health Survey, were therefore examined by latitude and ambient level of UVR. A positive association of type 1 diabetes mellitus prevalence was found with and RA were therefore chosen for ecologic analysis to determine whether these disorders showed environmental gradients similar to 160 APrevalence (per 1,000) both increasing southern latitude of residence (r = 0.77; p = 0.026) and decreasing regional annual those observed for MS in Australia. Prevalence (per 1,000) ambient UVR (r = –0.80; p = 0.018); a 3-fold increase in prevalence from the northernmost region By downregulating Th1-mediated immu- to the southernmost region was evident. In contrast, asthma correlated negatively with latitude (r = nity, UVR has been thought to effect a shift –0.72; p = 0.046), although the change in asthma prevalence from the north to the south of from Th1- to Th2-mediated processes Australia was only 0.7-fold. For both RA and eczema/dermatitis, there were no statistically signifi- cant associations between latitude/UVR and disease prevalence. These ecologic data provide some (Clydesdale et al. 2001). Th2 cells are respon- sible for immediate-type hypersensitivity to 120 G support for a previously proposed beneficial effect of UVR on T-helper 1–mediated autoimmune G allergens such as dust mites; UVR may thus disorders such as type 1 diabetes. The inverse association of type 1 diabetes prevalence with UVR is have the potential to exacerbate allergic disease consistent with that previously reported for another autoimmune disease, multiple sclerosis, in G (Selgrade et al. G 1997). However, recent work G G 4 Australia, and also with type 1 diabetes latitudinal gradients in the Northern Hemisphere. The finding also accords with photoimmunologic evidence of UVR-induced immunosuppression and has cast doubt on the mutual antagonism of Th1 and Th2 cytokine expression, particularly 80 may suggest a beneficial effect of UVR in reducing the incidence of such autoimmune conditions. in humans (Davidson and Diamond 2001; G In light of this study, analytic epidemiologic studies investigating risk of immune disorders in rela- Mackay 2000; Platts-Mills 2002; Platts-Mills G tion to personal UVR exposure in humans are required. Key words: asthma, Australia, autoimmune et al. 2001). Ultraviolet B, particularly disease, ecologic analysis, eczema/dermatitis, immune disorders, latitude, rheumatoid arthritis, through interleukin 10, can inhibit both Th1- type 1 diabetes, ultraviolet radiation. Environ Health Perspect 111:518–523 (2003). and Th2-mediated immune responses in mice doi:10.1289/ehp.5941 available via http://dx.doi.org/ [Online 19 December 2002] (Garssen et al. 1999). In children, asthma can 40 r = 0.77 coexist with Th1-type disorders such as type 1 diabetes, RA, and celiac disease, suggesting a Autoimmune diseases such as type 1 diabetes mellitus, multiple sclerosis (MS), and (Hammond et al. 2000; Miller et al. 1990). In Australia, however, where the opportunity p = 0.026 common environmental influence (Kero et al. 2001). A recent randomized controlled trial in 0 rheumatoid arthritis (RA) are immune sys- exists to study gradients in rates across a the United Kingdom on adult atopic eczema tem disorders that share common features of self-reactive T cells and the presence of auto- large-area population that is less ethnically and genetically diverse than across Europe, has shown UVR, particularly narrow-band ultraviolet B, to also have a beneficial effect 0 antibodies; as a group they affect some 5% of analyses for other immune-related disorders (Reynolds et al. 2001). Eczema/dermatitis, 10 the population (Davidson and Diamond 2001). Although their precise etiologies are 20 30 have not been done previously. Ultraviolet radiation (UVR) reaching the 40 50 together with asthma, were therefore chosen to be similarly analyzed for regional prevalence 10 Latitude (degrees south) unknown, these autoimmune disorders are earth’s surface varies inversely with latitude; gradients to compare with any associations generally agreed to reflect interactions of UVR is thus a prominent latitude-related evident for type 1 diabetes and RA. polygenic traits with various ill-defined environmental factor. Recent photoimmuno- We have examined the association between environmental factors (Cantorna 2000; logic work shows that UVR downregulates latitude and prevalence of the immune-related Dahlquist 1998; Hayes et al. 1997; Karges et cellular immunity (Damian et al. 1998; Kelly disorders type 1 diabetes mellitis, RA, 60 al. 1995; Weinshenker 1996). Descriptive epidemiology may further elucidate the role et al. 1998), attenuating T-helper (Th)1 T- cell–mediated immune responses (Clydesdale eczema/dermatitis, and asthma in Australia, a country with a relatively genetically homoge- 60
  • 108. hat biased prevalence was inversely correlated with allssociation three ambient UVR measures, it was more Research | Articles Environ Health Perspect 2003; 111:518–523ion of r. closely correlated with average or midwinter Ecologic Analysis of Some Immune-Related Disorders, Including Type 1 statistical solar-noon UVR than with midsummerDisease Diabetes, in Australia: Latitude, Regional Ultraviolet Radiation, and UVR Prevalence[from p = (Table 3). Judith A. Staples, Anne-Louise Ponsonby, Lynette L-Y. Lim, and Anthony J. McMichael National Center for Epidemiology and Population Health, The Australian National University, Canberra, Australian Capital Territory, Australia 8 immune and autoimmune processes involved Type 1 diabetes The apparent immune-suppressive effect of ultraviolet radiation (UVR) has suggested that this in the etiology of such immune disorders environmental exposure may influence the development of immune-related disorders. Self-reported (McMichael and Hall 1997). Type 1 diabetes Prevalence (per 1,000) prevalence rates of type 1 diabetes mellitus, rheumatoid arthritis (RA), eczema/dermatitis, and and RA were therefore chosen for ecologic asthma, from the 1995 Australian National Health Survey, were therefore examined by latitude and analysis to determine whether these disorders ambient level of UVR. A positive association of type 1 diabetes mellitus prevalence was found with showed environmental gradients similar to both increasing southern latitude of residence (r = 0.77; p = 0.026) and decreasing regional annual those observed for MS in Australia. ambient UVR (r = –0.80; p = 0.018); a 3-fold increase in prevalence from the northernmost region By downregulating Th1-mediated immu- to the southernmost region was evident. In contrast, asthma correlated negatively with latitude (r = nity, UVR has been thought to effect a shift –0.72; p = 0.046), although the change in asthma G prevalenceG from the north to the south of from Th1- to Th2-mediated processes Australia was only 0.7-fold. For both RA and eczema/dermatitis, there were no statistically signifi- (Clydesdale et al. 2001). Th2 cells are respon- G cant associations between latitude/UVR and disease prevalence. These ecologic data provide some G sible for immediate-type hypersensitivity to support for a previously proposed beneficial effect of UVR on T-helper 1–mediated autoimmune G G allergens such as dust mites; UVR may thus 4 disorders such as type 1 diabetes. The inverse association of type 1 diabetes prevalence with UVR is consistent with that previously reported for another autoimmune disease, multiple sclerosis, in have the potential to exacerbate allergic disease (Selgrade et al. 1997). However, recent work Australia, and also with type 1 diabetes latitudinal gradients in the Northern Hemisphere. The has cast doubt on the mutual antagonism of G finding also accords with photoimmunologic evidence of UVR-induced immunosuppression and G Th1 and Th2 cytokine expression, particularly may suggest a beneficial effect of UVR in reducing the incidence of such autoimmune conditions. in humans (Davidson and Diamond 2001; G In light of this study, analytic epidemiologic studies investigating risk of immune disorders in rela- Mackay 2000; Platts-Mills 2002; Platts-Mills tion to personal UVR exposure in humans are required. Key words: asthma, Australia, autoimmune et al. 2001). Ultraviolet B, particularly disease, ecologic analysis, eczema/dermatitis, immune disorders, latitude, rheumatoid arthritis, through interleukin 10, can inhibit both Th1- type 1 diabetes, ultraviolet radiation. Environ Health Perspect 111:518–523 (2003). and Th2-mediated immune responses in mice r = –0.80 doi:10.1289/ehp.5941 available via http://dx.doi.org/ [Online 19 December 2002] (Garssen et al. 1999). In children, asthma can coexist with Th1-type disorders such as type 1 p = 0.018 diabetes, RA, and celiac disease, suggesting a 0 Autoimmune diseases such as type 1 diabetes (Hammond et al. 2000; Miller et al. 1990). common environmental influence (Kero et al. r = –0.72 mellitus, multiple sclerosis (MS), and rheumatoid arthritis (RA) are immune sys- In Australia, however, where the opportunity exists to study gradients in rates across a 2001). A recent randomized controlled trial in the United Kingdom on adult atopic eczema p = 0.046 tem disorders that share common features of self-reactive T cells and the presence of auto- large-area population that is less ethnically and genetically diverse than across Europe, has shown UVR, particularly narrow-band ultraviolet B, to also have a beneficial effect 100 antibodies; as a group they affect some 5% of the population (Davidson and Diamond 150 200 analyses for other immune-related disorders have not been done previously. 250 (Reynolds et al. 2001). Eczema/dermatitis,300 together with asthma, were therefore chosen 2001). Although their precise etiologies are Ultraviolet radiation (UVR) reaching the to be similarly analyzed for regional prevalence 50 Regional solar-noon UVR (mW/m2) unknown, these autoimmune disorders are generally agreed to reflect interactions of earth’s surface varies inversely with latitude; UVR is thus a prominent latitude-related gradients to compare with any associations evident for type 1 diabetes and RA. polygenic traits with various ill-defined environmental factor. Recent photoimmuno- We have examined the association between environmental factors (Cantorna 2000; logic work shows that UVR downregulates latitude and prevalence of the immune-related Dahlquist 1998; Hayes et al. 1997; Karges et cellular immunity (Damian et al. 1998; Kelly disorders type 1 diabetes mellitis, RA, 160 al. 1995; Weinshenker 1996). Descriptive et al. 1998), attenuating T-helper (Th)1 T- eczema/dermatitis, and asthma in Australia, a epidemiology may further elucidate the role cell–mediated immune responses (Clydesdale country with a relatively genetically homoge-
  • 109. Diabetologia (2008) 51:1391–1398 1393 45 Sardinia, Italy 40 Finland 35 Aberdeen, UKDiabetes incidence rate per 100,000 30 Prince Edward Island, Sweden Canada 25 Canterbury, New Zealand Alberta, Canada Norway Oxford, Tierra del Fuego, Argentina 72 20 77 UK Kuwait Puerto Rico Plymouth, 40 61 64 UK Alabama, 71 15 US Virgin Islands USA 48 New South Wales, Lux . 97 68 49 The Netherlands Australia 45 50 44 10 Montevideo, 3 38 Estonia Uruguay 2 62 43 52 Lithuania 67 Sao Paulo, Brazil 63 Latvia Bogota, Dominica Cordoba, Argentina 31 39 59 36 Columbia Sudan 8 4 5 80 5 Oran, 65 Wielkopolska, 82 Barbados Algeria Poland Cuba 9 32 33 Santiago, Chile 87 7 29 34 23 16 10 88 90 25 17 21 0 –60 –50 –40 –30 –20 –10 0 10 20 30 40 50 60 70 Latitude (º)Fig. 1 Age-standardised incidence rates of type 1 diabetes per Madeira Island, Portugal; 64. Portalegre, Portugal; 65. Bucharest,100,000 boys <14 years of age, by latitude, in 51 regions worldwide, Romania; 67. Slovakia; 68. Catalonia, Spain; 71. Leicestershire, UK;2002. Data points are shown by dots; names shown adjacent to the 72. Northern Ireland, UK; 77. Allegheny, PA, USA; 80. Avellaneda,
  • 110. ting, for a few minutes each day may achieve similar serum bles levels with smaller oral intake. If desired, the serum level of erse 25(OH)D can be readily monitored by widely available ions blood tests. Monitoring can help with choice of antural appropriate combination of oral intake and modest sunlight exposure. Pending further research, oral vitamin D intake ofstent infants <1 year old should not exceed 6.25 μg (250 IU)/day rine [28]. The vitamin D status of pregnant women generally hieu may be kept within an appropriate range with modest 1,25 supplementation of 10–15 μg (400–600 IU)/day [28].uced Physicians and nutritionists should advise parents thatbetic children ≥1 year who live more than approximately 30°mals’ from the equator should consume 25–50 μg (1,000–mice, 2,000 IU)/day of vitamin D3, especially during winter, tovels. substantially reduce their risk of childhood type 1 diabetes. 1,25 Further epidemiological studies would be desirable on p to the effect of serum 25(OH)D levels and oral intake of
  • 111. births. 10 821 (91% of those alive) children weresupplementation is ARTICLESfollowed up at age 1 year.8 Data obtained during the diabetes. Ensuring children’s visits to child welfare centres (on average 10 Intake of during the D and risk of supplemented with infants could help to visits vitamin first year) was type 1 diabetes: a birth-cohortncidence of type 1 information recorded at examinations done by public- studyhealth nurses and family doctors. Written consent from all children was asked for in connection with a follow-up survey done in 1997–98. Permission to collect outcome data using national registers was obtained form the Elina Hyppönen, Esa Läärä, Antti Reunanen, Marjo-Riitta Järvelin, Suvi M Virtanen ministry of social welfare and health. The ethics Summary committee of the faculty of medicine, University of Oulu, Introduction approved the study. Exactly what causes the destruction of insulin secreting Background Dietary vitamin D supplementation is associated ␤ cells in the pancreas, and thus the development of type with reduced risk of type 1 diabetes in animals. Our aim was Protocol 1 diabetes, remains unknown, though cytokines, T cells, ARTICLES to ascertain whether or not vitamin D supplementation or and macrophages have all been implicated.1 In vitro, deficiencyFrequency of vitamin D supplementation invitamin D acts as an immunosuppressive agent, reducing in infancy could affect development of type 1 the first year diabetes. of life was recorded as regular, irregular, orlymphocyte the none, on proliferation and cytokine production.2Biostatistics, Institute basis of information provided by the mothers atof the Type 1 diabetes Time at risk (years) years risk Furthermore, 100animals, the administration of vitamin D Incidence per in 000 RR (95% CI) RR (95% CI)* Adjusted infants. Information on rickets, suspected by the health-seems to prevent development of type 1 Methods A birth-cohort study was done, in which all pregnant ppönen PhD); and ofwomen D supplements in Oulu and Lapland, northern Finland, Use vitamin (n=12 055) (1,25 (OH)2D3) diabetes.3,4 None careto personnel,1966 were enrolled. Data wasthe child’s health can(reference) risk of (reference)th, Imperial College who were due give birth in 2 was obtained from 981 Factors in infancy 1 affect the 204 1 development of MD); Tampere School collected records. year of life about frequency and dose Irregularly in the first The 12 daily dose of vitamin D dependent on later life. The (0·04–0·72) a large(0·04–0·74) 36 143 of diabetes in the 33 0·16 results of 0·16 case-control Regularly 67 276 235pere, Finland study suggest that 0·12 (0·03–0·47) 0·12 (0·03–0·51) 24 product used was calculated, and we noted whether it was vitamin D supplementation during vitamin D supplementation and presence of suspected Dose of vitamin D† primary outcome measure was diagnosis of rickets. Our early childhood can prevent type 1 diabetes.5 Another f Paediatrics, Tampere 1 diabetes by(Ͻ2000 IU daily), within 2 093 IU daily), alsoabove an inverse relation between maternal use Low type below end of2December, 1997. (2000 96 or found study 1 (reference) 1 (reference)Departments of Recommended (Ͼ2000 IU daily) the recommended dose. 24 children 63 259 779 84 0·20 (0·05–0·84) 0·22 (0·05–0·89) High 2 13 245 of 15 liver oil during pregnancy and the0·14 (0·02–1·01) cod 0·14 (0·02–0·97) frequency of typed Public Health Findings who were givenrepresented live births, and 12 058 of 12 231 cod liver oil were classified as having 1 diabetes in their children. Our aim was to ascertain 6 Suspected821 (91% of those alive) children were followed-up at age 10 rickets‡ whether or not dietary supplementation with vitamin D inUniversity of Oulu, No received the recommended 306 945 77 dose. Information was ki (A Reunanen MD, 1 year. Of the 10 366 children included in analyses, 81 were infancy could reduce the(reference) 25 1 1 (reference) risk of type 1 diabetes. Yes available on 4 whether a child had received an increased diagnosed with diabetes during the study. Vitamin D 6 414 62 2·6 (1·0–7·2) 3·0 (1·0–9·0) dose of vitamin D during the first year of life. However, *Adjusted for sex, neonatal (parity, gestational and maternal age), length of maternal education, social status, and standardised birth weight, and growth rate in supplementation was associated with a decreased frequency Methods infancy (suspected rickets adjusted in addition to the increased dose of vitamin D); †In children recieving vitamin D supplementation regularly. Table anthropometric, and socialratioconcentrations of 25the use of D3 weresupplements and suspected rickets in infancy of type data diabetes when adjusted for neonatal, 2: Incidence rate andserum (RR) of type 1 diabetes by for on rate (OH)Participants not 1 characteristics (rate ratio [RR] vitamin D All women (n=12 055) living in Oulu and Lapland, available. regular vs no supplementation 0·12, 95% CI 0·03–0·51, and northern Finland, whose pregnancy continued after the vitamin D, irrespective of dose, had 0·16, 0·04–0·74. Children to daylight, and thus vitamin Dfor whom the estimated date irregular vs no supplementation a lower rate of type 1 24th week of gestation, and production in the skin, is diabetes than thosetook the not. In children whoof vitamin D lowof delivery fell with more southern areas. Vitamin D who regularly who did recommended dose received by comparison during 1966 were enrolled.7 Between vitamin DIU supplementation 0·22 (0·05–0·89) compared with supplementation is, therefore,of gestation, the women were (2000 the 24th and 28th week probably more important in daily) had a RR of regularly, the risk was 358 • November 3, 2001 THE LANCET • Vol those about 80% if received had than the recommended thisasked to fill in a questionnaire to obtain background reduced by who regularly the child less received at least the population than in others. However, supplementation recommended dose compared of having rickets during less. first with vitamin D is generally recommended forbirth and the amount. Children suspected with those receiving the information. A questionnaire about the prevention Adjustment life had a RR for 3·0 (1·0–9·0) comparedonly those of rickets of breast fed infants,filled in by case-control year of of results of social factors had with a status in the neonate was 17 and in a the attending 7
  • 112. PREVALENCIA DE EM POR 100.000 HABITANTESPrevalencia de EM en Australia y Nova Zelandia Rosati G. Neurol Sci. 2001 Apr;22(2):117-39 van der Mei IA, et al. Neuroepidemiology. 2001 Aug;20(3):168-74.
  • 113. MS) IS 25-hydroxyvitamin D levels either by 2mmon partment of Defense Serumsome as yet Multiple sclerosis cases were identified through Repository. unknown effect on vita- 3ses in Army and Navy physical disabilitymetabolismfor 1992 through 2004, and diagnoses collection min D databases or, more likely, by Age at first serum sample ecting Serum 25-Hydroxyvitamin D Levels were confirmed by medicalchanges in behavior—because heat matched to 2 con- (%) unless o record review. Each case (n=257) was *Data are expressed as No. trols by age, sex, race/ethnicity, and dates of blood collection. Vitamin“Methods”to 100% of text forof mis commonly exacerbates MS symp- ‡See D status was †Does not total because Statesvailing and Risk of Multiple Sclerosis estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum samples col- lected before the date of initial multiple sclerosis symptoms. section definine dis- Kassandra L. Munger, MSc Main Outcome Measures Odds ratios of multiple sclerosis evidence suggests thatcon- D Among W Context Ratios of MS and experimental associated with high Figure. Odds Epidemiologicalby Quantile of Serum 25-Hydroxyvitaminlevels of vi-ent or Lynn I. Levin, PhD, MPH tinuous or categorical levels (quantilespotent immunomodulator, may decrease the risk of multiple25- tamin D, a or a priori–defined this hypothesis. of serum sclerosis. There categories) are no prospective studies addressingnflam- Bruce W. Hollis, PhD hydroxyvitamin D within each racial/ethnic group. 3.0 Whites Objective To examine whether levels of 25-hydroxyvitamin D are associated withtion of Noel S. Howard, MD Results AmongDrPH (148 cases, multiple sclerosis. the risk of multiple sclerosis signifi- Alberto Ascherio, MD, whites risk of 296 controls), M cantly decreased with increasing levelsSetting, and military personnelD (oddsnested case-control studythe De- Design, ofmillion US Participants Prospective, serum samples for a in among 25-hydroxyvitamin who have ratio [OR] stored 1.36 al dis- ULTIPLE SCLEROSIS (MS) IS more than 7 1.07 1.07 50-nmol/L increase in 25-hydroxyvitaminDefense Serum Repository. Multipleinterval, 0.36-0.97). through among the most common partment of 1.0 0.59; 95% confidence sclerosis cases were identified 1 D, crease In categorical analyses using the lowest quintile (Ͻ63.3 nmol/L) as the 1992 through the ORs diagnoses neurological diseases in Army and Navy physical disability databases0.74 reference, 2004, and for 0.75 Odds Ratiotitude, young adults, affecting were confirmed by medical record review.(P=.02 (n = 257) was across to 2 con- Each case for each subsequent quintile were 0.57, 0.57, 0.74, and0.57 dates of blood collection. Vitamin D status was 0.57 0.38 for trend matched trols by age, sex, race/ethnicity, anduator.3 350 000 individuals in the United States estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum samples col- quintiles). Only the OR for the highest quintile, corresponding to 0.40 25-hydroxyvitamin D 0.38 and 2 million worldwide.1 Prevailing lected before the date of initial multiple sclerosis symptoms. 0.30 0.30utes to thought higher thanautoimmune dis- was significantly different from 1.00 (OR, 0.38; 95% con- levels is that MS is an 99.1 nmol/L, in MS fidence interval, 0.19-0.75; or Main Outcome Measures Odds ratios of multiple sclerosis risk was with con- tinuous or categorical relation with multiple sclerosis associated order whereby an unknown agent P=.006). The inverse levels (quantiles or a priori–defined categories) of serum 25- 0.19 agents triggers astrong for 25-hydroxyvitamin D levels measured before age 20 years. Among particularly T cell–mediated inflam- hydroxyvitamin=D within each racial/ethnic group. ple of matory attack, causing demyelination of P .02 for Trend blacks and Hispanics (109 cases, 218 0.1 Among whites (148 cases, 296 controls), the risk of multiplelev- signifi- Resultscontrols), who had lower 25-hydroxyvitamin D sclerosisports a central nervous system tissue.2 els than whites, nothe global dis- associations between vitamin D and84.9-99.1 99.2-152.9 ratio [OR] for a A striking feature of 15.2-63.2 63.3-75.3 75.4-84.8 significant cantly decreased with increasing levels of 25-hydroxyvitamin D (odds risk multiple sclerosis ne po- were found. Quintile of 25-Hydroxyvitamin D, nmol/L 50-nmol/L increase in 25-hydroxyvitamin D, 0.59; 95% confidence interval, 0.36-0.97). 9 tribution of MS is a multifold increase In categorical analyses using the lowest quintile (Ͻ63.3 nmol/L) as the reference, the ORs a po- in incidence with increasing latitude, forCases subsequent quintile were 0.57, 0.57, 0.74, and 0.3818 each 41 29 27 33 (P=.02 for trend across Cts hor- Conclusion The results of ourquintiles).suggest that60 highest63 both north and south of the equator. 3 study Only56 OR for the circulating 57 Controls the high quintile, corresponding60 25-hydroxyvitamin D levels of vitamin D to C Genetic predisposition contributes to levelsmultiple 99.1 nmol/L, was significantly different from 1.00 (OR, 0.38; 95% con- are associated with a lower risk of higher than sclerosis.mental this variation,4 but the change in MS bars indicate 95% confidence intervals. inverse relation with multiple sclerosis risk was Error fidence interval, 0.19-0.75; P=.006). The JAMA. 2006;296:2832-2838 www.jama.com(EAE), risk with migration among people of particularly strong for 25-hydroxyvitamin D levels measured before age 20 years. Among e food common ancestry5 strongly supports a blacks and Hispanics (109 Association. All rights reserved. ©2006 American Medical cases, 218 controls), who had lower 25-hydroxyvitamin D lev- els than whites, no significant associations between vitamin D and multiple sclerosis risk
  • 114. Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Vitamin D Metabolite (nmol/litre) 20 4.5 4 30 Vitamin D Metabolite (nmol/litre) 3.5 40 3 MS Lesions 50 2.5 R2 = 0.8491 R2 = 0.7931 60 2 1.5 70 1 80 0.5 90 0 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec MS Lesions Vitamin D metabolite level nmol/litre MS lesion activity Curves are best fit third order polynomials for the two data sets Figure 1. Embry et al. Embry AF, Snowdon LR, Vieth R. Ann Neurol. 2000 Aug;48(2):271-2Figure Caption
  • 115. RIESGO DE QUEDAS RELATIVO AJUSTADO PARA A IDADE EM 124 IDOSOS
  • 116. NÍVEL IDEAL DE 25OHD PARA ÓPTIMA FUNÇÃO MUSCULAR NOS MEMBROS INFERIORES
  • 117. the growt Prostate cell inhibit pr1α,25(OH)2D3 25(OH)D3 Review line that TRENDS in Endocrinology and Metabolism Vol.14 No.9 November 2003 to the SV Mitochondria DU145 ce 1α-OHase Vitamin D and prostate cancer 25(OH)D3 1α,25(OH)2D3 of 24-OHa of Liaroz prevention and treatment 24-hydrox half-life o Tai C. Chen and Michael F. Holick Nucleus 1a,25(OH 1α,25(OH)D3 University School of Medicine, Boston, MA 02118, USA and in cel Vitamin D, Skin and Bone Research Laboratory, Section of Endocrinology, Diabetes and Nutrition, Department of Med VDR RXR might be Human prostate cells contain receptors for 1a,25-dihy- and prodifferentiation activities of 1a,25(OH droxyvitamin D, the active form of vitamin D. Prostate Apoptotic analogs in prostate cells in vitro and in vivo [ Gene transcription we summarize recent findings of: (1 cancer cells respond to vitamin D3 with increases in Here Under so differentiation and apoptosis, and decreases in prolifer- ation between vitamin D deficiency, UVR expo ation, invasiveness and metastasis. These findings risk of prostate cancer; (2) the mechanism of a induces 1 strongly support the use of vitamin D-based therapies Cell-cycle arrest Apoptosis Differentiation action; (3) the identification of terminal 1a-OHase in for prostate cancer and/or as a second-line therapy CDK2, p21, p27, p53, the evaluation of anti Bcl-2, Bcl-XL, Mcl-1 PSA, AR if and its implications; (4) BAG1L, deprivation fails. The association between Ki67, E-Cadherin 2D3 and itsnick in pro androgen XIAP, cIAP1 activity of 1a,25(OH) analogs end either decreased sun exposure or vitamin D deficiency cIAP2 risk of prostate cancer at an earlier culture, in animal models and inassociation be and the increased controversy that surrounds the clinical trials cytometri age, and with a more aggressive progression, indicates Blutt et polymorphism and the risk of prostate cancer that adequate vitamin D nutrition should be a priority TRENDS in Vitamin D Metabolism LNCaP c for men of all ages. Here we summarize recent advancesEndocrinology &deficiency, UV exposure and the in epidemiological and biochemical studies of the endo- prostate cancer downregu crine and autocrine systems associated with vitamin D An association between vitamin D deficiency a
  • 118. 453 death Table 3 The estimated relationship between serum calcidiol and deatharately from prostate cancer among patients receiving hormone therapy (n ¼ 97)III RR Model I Model II Model IIICI) Variables RR (95%CI) RR (95%CI) RR (95%CI) Calcidiol (nmol lÀ1) Low (< 50) 1.00 (ref) 1.00 (ref) 1.00 (ref) Medium (50-80) 0.39 (0.19 – 0.81) 0.35 (0.17 – 0.73) 0.18 (0.07 – 0.46)– 0.77) High (> 80) 0.29 (0.12 – 0.68) 0.20 (0.08 – 0.50) 0.09 (0.03 – 0.27)– 0.43) Group status 0.08 (0.04 – 0.16) 0.06 (0.02 – 0.13)– 0.10) Age (1 year) 1.00 (0.94 – 1.03) Clinical Studies– 1.03) Functional status Good 1.00 (ref) Less good 1.19 (1.04 – 1.61)– 5.06)– 25.7) Differentiation gradea High 1.00 (ref) Moderate 0.85 (0.23 – 3.18) Low 5.63 (1.42 – 22.3)– 1.50) a British Journal of Cancer (2009) 100, 450 – 454 Differentiation grade of tumour tissue; WHO three-grade system. & 2009 Cancer Research UK All rights reserved 0007 – 0920/09 $32.00 www.bjcancer.com
  • 119. VITAMIN D FOR CANCER PREVENTION 470 Garland et al.arland et al. AEP Vol. AEP No. 7 No. 7 19, Vol. 19, TAMIN D FOR VITAMIN D FOR CANCER PREVENTION CANCER PREVENTION July 2009: 468–483 468–483 July 2009: 1.0 1.0 1.0 1.0 0.93 0.95 0.93 1.0 0.95 0.93 0.9 p trend = 0.02 p trend = 0.02 0.9 0.9 0.8 0.8 0.8 0.8 0.7 0.68 0.8 0.68 Relative risk 0.7 Relative risk 0.6 0.6 0.7 Relative risk 0.6 0.5 Relative risk RR=0.44 Relative risk 0.4 0.6 RR = 0.28 0.5 0.4 RR=0.44 0.6 RR = 0.28 p < 0.05 RR=0.28 0.4 0.3 0.2 p < 0.05 0.3 0.2 RR=0.28 0.5 0.20 0.4 0.08 0.1 RR = 0.28 0.11 0.0 0.2 0.20 0.4 0.08 < 62.5 nmol/L > 62.5 nmol/L 0.1 p < 0.05 < 50 nmol/L 50 to <80 nmol/L0.11 > 80 nmol/L FIGURE 1. Relative risk of breast cancer mortality, by baseline FIGURE 3. Relative risk of colon cancer mortality, by baseline 0.3 < 62.5 nmol/L > 62.5 nmol/L serum 25(OH)D concentration, divided at the median, 0.2 1988–2000. (Source: Drawn from data in serum nmol/L 50 to <80 nmol/L > 80 nmol/L < 50 25(OH)D concentration, in tertiles, NHANES cohort, NHANES III cohort,E 1. Relative risk of breast cancer mortality, by baseline FIGURE 3. Relative (Source: Drawn from data in Freedman et al. [56].) 0.2 1988-2000. risk of colon cancer mortality, by baseline Freedman et al. [56].) divided at the median,25(OH)D concentration, serum 25(OH)D concentration, 0.08in tertiles, NHANES cohort,ES III cohort, 1988–2000. (Source: Drawn from data in 25(OH)D and0.1 1988-2000. (10) found that physicians whoseet al. [56].) by quantiles of serum 25(OH)D provided a clear linear dose- (Source: Drawn from data in Freedman n et al. [56].) 0.0 1,25(OH)2D levels were both below the median, response gradient (61) (Fig. 4). A serum 25(OH)D level tiles of serum than 38 ng/mL (95 a clear<(top quintile) 62.5 nmol/L asso- greater25(OH)D providednmol/L)linear dose- was (10) found that of 28 ng/mL (70 nmol/L) and 1,25(OH)2D of 25(OH)D physicians whose 25(OH)D and > 62.5 nmol/L ciated with an odds ratio of 0.45 (95% CI 0.28–0.69), cor- 32 pg/mL (77 pmol/L) had twice the incidence of aggressivee gradient (61) (Fig. 4). A serum 25(OH)D level 1,25(OH)2D levels were both below the median, risk Relative risk of 25(OH)D prostateng/mL (odds ratioby and 1,25(OH) p ! 0.05) as responding to 55% lower1. of colorectal cancer compared FIGURE quintile) was asso- breast cancercancer (70 nmol/L) the median. 2D of FIGURE of 28 mortality, 2.1, 95% CI 1.2–3.4, baselinethan 38to individuals with 25(OH)D of less than 16 ng/mL (40 ng/mL (95 nmol/L) (top men whose levels were above serum 25(OH)D concentration, divided case-control incidence ofKaiser Foundation 25(with an nmol/L) (bottom quintile) CI 0.28–0.69), cor- odds ratio of 0.45 (95% (61). 32 pg/mL (77In a nested at the study of 90 aggressive serum pmol/L) had twice the median, prostate cancer (odds controls 95% CI 1.2–3.4, p ! 0.05) of serum NHANES III cohort, 1988–2000. (Source: ratio 2.1,matched on age, race, and dayas 1988-2000 ing to 55% lower risk of colorectal cancer compared cases and 91Drawn from data inviduals with 25(OH)D of less et al. [56].) (40 men whose levels were above the median. of prostate cancer was storage, the estimated relative risk Prostate Freedman than 16 ng/mL Cancer In a nested (not significant) in men inKaiser Foundation serum 0.41 case-control study of 90 the top quartile of) (bottom quintile) (61). Observational studies of the inverse association of prediag- and 91 controls metabolites, specifically, 25(OH)Dserum than cases vitamin D matched on age, race, and day of greater
  • 120. AEP Vol. 19, No. 7 July 2009: 468–483 470 Garland et al. arland et al. AEP Vol. AEP No. 7 No. 7 19, Vol. 19, TAMIN D FOR VITAMIN D FOR CANCER PREVENTION CANCER PREVENTION July 2009: 468–483 468–483 July 2009: 1.0 1.0 0.95 1.0 0.95 0.93 1.0 0.95 0.93 0.9 p = 0.02 0.9 0.9 p trend = 0.02= 0.02trend p trend 0.8 0.8 0.8 0.68 0.7 0.8 0.68 Relative risk 0.7 Relative risk 0.6 0.6 Relative risk 0.7 0.6 0.5 0.68 RR=0.44 0.4 RR = 0.28 Relative risk 0.5 0.4 RR=0.44 0.6 RR = 0.28 p < 0.05 0.4 0.3 RR=0.28 0.2 p < 0.05 0.2 RR=0.28 0.5 0.3 RR=0.44 0.20 0.08 0.1 0.11 0.2 0.20 0.0 < 62.5 nmol/L 0.4 0.08 > 62.5 nmol/L 0.1 < 50 nmol/L 50 to <80 nmol/L0.11 > 80 nmol/L 0.3 > 62.5 nmol/L FIGURE 1. Relative risk of breast cancer mortality, by baseline FIGURE 3. Relative risk ofRR=0.28 mortality, by baseline colon cancer < 62.5 nmol/L serum 25(OH)D concentration, divided at the median, serum nmol/L 50 to <80 nmol/L > 80 nmol/L < 50 25(OH)D concentration, in tertiles, NHANES cohort,E 1. Relative risk of breast cancer mortality, by baseline from data in NHANES III cohort, 1988–2000. (Source: Drawn 0.2 FIGURE 3. Relative (Source: Drawn from data in Freedman et al. [56].) 1988-2000. risk of colon cancer mortality, by baseline Freedman et al. [56].) divided at the median,25(OH)D concentration, 0.20 serum 25(OH)D concentration, in tertiles, NHANES cohort,ES III cohort, 1988–2000. (Source: Drawn from data in 0.1 1988-2000. (10) found that physicians whoseet al. [56].) (Source: Drawn from data in Freedman 25(OH)D and by quantiles of serum 25(OH)D provided a clear linear dose- n et al. [56].) 0.11 response gradient (61) (Fig. 4). A serum 25(OH)D level 1,25(OH)2D levels were both below the median, greater25(OH)D providednmol/L)linear dose- was (10) found that of 28 ng/mL (70 nmol/L) and 1,25(OH)2D of than 38 ng/mL (95 a clear (top quintile) asso- 25(OH)D physicians whose 25(OH)D and L of serum with an odds ratio of 0.45 (95% CI 0.28–0.69), cor- 50 to <80 nmol/L tiles ciated < 50 nmol/L 32 pg/mL (77 pmol/L) had 80 nmol/L > twice the incidence of aggressive e gradient (61) (Fig. 4). A serum 25(OH)D level 1,25(OH)2D levels were both below the median, responding to 55% lower risk of colorectal cancer compared prostate cancer (odds ratio 2.1, 95% CI 1.2–3.4, p ! 0.05) asby baseline (95 nmol/L) (top quintile) Relative risk(40 colon cancer(70 nmol/L) and 1,25(OH)2D of FIGURE 3. than 16 than 38to individuals with 25(OH)D of lesswas asso- ng/mL of ng/mL 25(OH)D men whose levels were above the median. of 28 ng/mL mortality, by baselinewith an nmol/L) (bottom serum CI 0.28–0.69), cor- 32 pg/mL (77 pmol/L) had twice the incidence of aggressive median, of 0.45 (95% (61). odds ratio quintile) 25(OH)D concentration, In a tertiles, NHANES 90 Kaiser Foundation in nested case-controlCI 1.2–3.4,cohort, of study of p ! 0.05) prostate cancer (odds ratio 2.1,matched on age, race, and dayas serum 95% ing to 55% lower risk of colorectal cancer compared cases and 91 controls m data in 1988-2000. (Source: Drawn whose levels wereestimated relativeet al. prostate cancer wasviduals with 25(OH)D of less than 16 ng/mL (40 men from data in above the median. of [56].) storage, the Freedman risk Prostate Cancer In a nested (not significant) in men inKaiser Foundation serum 0.41 case-control study of 90 the top quartile of) (bottom quintile) (61). Observational studies of the inverse association of prediag- and 91 controls metabolites, specifically, 25(OH)Dserum than cases vitamin D matched on age, race, and day of greater
  • 121. 450 Grant and MohrINCIDÊNCIAECOLOGICAL STUDIESRENAL CANCER RECENT DE CARCINOMA OF UVB, EM HOMENS (2002) ! NON-H There a vitamin One of have fo irradian latitude regional Mortali with mo cancer ( that in the imp (60–63) Ann Epidemiol 2009;19:446–454 noma inFIGURE 1. Annual standardized incidence rates of renal cancer,by country, males, 2002. Source: Mohr et al .(38) based on GLOBO- tent wit
  • 122. RCT COM VITAMINA Dü N: 1.180 M pós-Menopausaü Administração de 1.000 UI de Vit D vs placebo Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007 Jun;85(6):1586-91.
  • 123. AO FINAL DE 4 ANOS:ü Risco de qualquer Cancro 60% < no grupo da Vit Dü Excluindo os Tumores que foram diagnosticados no 1º ano (podiam estar presentes no início do Estudo): REDUÇÃO DE 77% Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007 Jun;85(6):1586-91.
  • 124. Best Practice & Research Clinical Endocrinology & Metabolism 25 (2011) 681–691 Contents lists available at ScienceDirect Best Practice & Research Clinical Endocrinology & Metabolism journal homepage: www.elsevier.com/locate/beem13Why the minimum desirable serum 25-hydroxyvitamin Dlevel should be 75 nmol/L (30 ng/ml)Reinhold Vieth, Ph.D., F.C.A.C.B., Professor a, b, c, *a Department of Nutritional Sciences, University of Toronto, Canadab Department of Laboratory Medicine and Pathobiology, University of Toronto, Canadac Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, Toronto, Ontario, Canada M5G 1X5Keywords: The Institutes of Medicine (IOM) recently revised the recom- mended dietary allowances (RDA) for vitamin D, to maintain
  • 125. [Dermato-Endocrinology 1:4, 207-214; July/August 2009]; ©2009 Landes BioscienceReviewIn defense of the sunAn estimate of changes in mortality rates in the United States if mean serum 25-hydroxyvitamin Dlevels were raised to 45 ng/mL by solar ultraviolet-B irradianceWilliam B. GrantSunlight, Nutrition and Health Research Center (SUNARC); San Francisco, CA USAKey words: cancer, cardiovascular diseases, melanoma, respiratory infections, skin cancer, vitamin D, ultraviolet-B Emerging scientific evidence strongly supports the beneficial rates of other diseases such as type 2 diabetes mellitus,9,10 coronaryrole of vitamin D in reducing the risk of incidence and death heart disease (CHD)11 and congestive heart failure.12from many chronic and infectious diseases. This study esti- Let us put vitamin D production into the context of humanmates increases in melanoma and nonmelanoma skin cancer history on Earth. The human species originated in the easternmortality rates and decreases in chronic and infectious disease portion of tropical Africa. Skin pigmentation in that region wasmortality rates in the US from the standpoint of approximately very dark to protect against the adverse effects of solar UVR,doubling population doses of solar UVB to increase mean primarily free radical production and DNA damage leading toserum 25-hydroxyvitamin D levels from 16 ng/mL for black melanoma and other skin cancer.13 Because UVB doses wereAmericans and 25 ng/mL for white Americans to 45 ng/mL. high and clothes were not worn, sufficient UVB penetrated the
  • 126. The n e w e ng l a n d j o u r na l of m e dic i n e droxylase Circulation review article Medical Progress Vitamin D Deficiency Michael F. Holick, M.D., Ph.D. O rom the Department of Medicine, Sec- nce foods were fortified with vitamin d and rickets appeared ion of Endocrinology, Nutrition, and Di- to have been conquered, many health care professionals thought the major betes, the Vitamin D, Skin, and BoneResearch Laboratory, Boston University Reference range health problems resulting from vitamin D deficiency had been resolved. How-Medical Center, Boston. Address reprint ever, rickets can be considered the tip of the vitamin D–deficiency iceberg. In fact, <20 ng/ml equests to Dr. Holick at Boston UniversitySchool of Medicine, 715 Albany St., M-1013, 20–100 ng/ml vitamin D deficiency remains common in children and adults. In utero and during >150 ng/ml childhood, vitamin D deficiency can cause growth retardation and skeletal deformi-Boston, MA 02118, or at mfholick@bu.edu. ties and may increase the risk of hip fracture later in life. Vitamin D deficiency in adults etabolite)N Engl J Med 2007;357:266-81. opyright © 2007 Massachusetts Medical Society. can precipitate or exacerbate osteopenia and osteoporosis, cause osteomalacia and muscle weakness, and increase the risk of fracture. Deficiency Preferred range Intoxication The discovery that most tissues and cells in the body have a vitamin D receptor and that several possess the enzymatic machinery to convert the primary circulating form of vitamin D, 25-hydroxyvitamin D, to the active form, 1,25-dihydroxyvitamin D, has 30–60 ng/ml provided new insights into the function of this vitamin. Of great interest is the role it can play in decreasing the risk of many chronic illnesses, including common can- cers, autoimmune diseases, infectious diseases, and cardiovascular disease. In this review I consider the nature of vitamin D deficiency, discuss its role in skeletal and _ nonskeletal health, and suggest M. NEJM 2007;357:266-81. and treatment. Holick strategies for its prevention S ource s a nd Me ta bol ism of V i ta min D
  • 127. PORQUE EXISTE DEFICIÊNCIA
  • 128. Webb AR, Kline L, Holick MF. J Clin Endocrinol Metab. 1988 Aug;67(2):373-8.
  • 129. RADIAÇÃO UV E VITAMINA D 68 Défice de Vitamina D 6 ou + meses/ano! Défice de Vitamina D 1 ou + meses/ano! . .   .  Vitamina D todo o ano! Défice de Vitamina D 1 ou + meses/ano! Défice de Vitamina D 6 ou + meses/ano!Figure 1. The potential for synthesis of previtamin D3 in lightly pigmented human skin computed from annual average UVMED. The highest annualvalues for UVMED are shown in light violet, with incrementally lower values in dark 2000 Jul;39(1):57-106 shades of blue, orange, green and gray Jablonski NG, Chaplin G. J Hum Evol. violet, then in light to dark(64 classes). White denotes areas for which no UVMED data exist. Mercator projection. In the tropics, the zone of adequate UV radiation throughoutthe year (Zone 1) is delimited by bold black lines. Light stippling indicates Zone 2, in which there is not sufficient UV radiation during at least one monthof the year to produce previtamin D3 in human skin. Zone 3, in which there is not sufficient UV radiation for previtamin D3 synthesis on average for
  • 130. Sunlight, UV-Radiation, Vitamin D and Skin Cancer 5Figure 3. Influence of season, time of day in July and latitude on the synthesis of previtaminD3 in Boston (42°N)-o-, Edmonton (52°N)-n-, Bergen (60°) - ^ - . The hour is the end of theone hour exposure time in July. Holick copyright 2007 with permission.cells in the kidneys. l,25(OH)2D is responsible for the maintenance of calcium homeostasis andbone health by increasing the efficiency ofExp Med Biol.calcium absorption, stimulating osteoblast Holick MF. Adv intestinal 2008;624:1-15.function and increase bone calcium resorption. It also enhances the tubular resorption of calciumin the kidneys (Fig. 5).
  • 131. alless 34 Geometric mean monthly variations in serum 25- hydroxyvitamin D [25)OH)D] concentration in men (dark shade, n = 3723) and women (light shade, n = 3712) in a 1958he British birth cohort at age 45. 30 28 ng 24 onm- 20e is 16ted 12tu-ate 8za. 4 he 0 vi- Sept Oct Nov Dec Jan Feb Mar Apr May June July Aug Sept Oct Nov Dec Jan Feb Mar Figure [25)OH)D] concentration in Virol a Feb shade, 3723) D1Cannell JJ, ageM,45 CF, Scragg Giovannuccimen J.(dark 25;5:29. n birth and mean Garland tamincohort at Zasloff (light shade,R,n = 3712) in2008 25-hydroxyvi- Geometricwomenmonthly variations inE.serum 1958 British= Geometric mean monthly variations in serum 25-
  • 132. Epidemiol. Infect. (2006), 134, 1129–1140. f 2006 Cambridge University Press doi:10.1017/S0950268806007175 Printed in the United Kingdom Epidemiol. Infect. (2006), 134, 1129–1140. f 2006 Cambridge University Press REVIEW ARTICLE doi:10.1017/S0950268806007175 Printed in the United Kingdom Epidemic influenza and vitamin D REVIEW ARTICLE Epidemic influenza and vitamin D Epidemic influenza and vitamin D J. J. C A N N E L L 1*, R. V IE T H 2, J. C. U M H A U 3, M. F. H O L IC K 4, W. B. G R A N T 5, 1131 S. M A D R O N I C H 6, C. F. G A R LA N D 7 A N D E. G I O V A N N U C C I 8 1 Atascadero State Hospital, 10333 El Camino Real, Atascadero, CA, USA 2 J. J. C A NNHospital, PathologyT H 2Laboratory Medicine,, Department of IC K 4, W. B. GR A NT 5, Mount Sinai E L L 1*, R. V IE and , J. C. UM H A U 3 M. F. H O L Medicine, Toronto, Ontario,ess despite being a 35 Canada S. M A D R O N I C H 6, C. F. G A R LA ND 7 A N D E. G I O V A N N U C C I 8 3 Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism,mmune population National Institutes of Health, 10333 El Camino Real, Atascadero, CA, USA 1 4 2 Atascadero State Hospital, Bethesda, MD Departments of Medicine and Physiology, Boston University School of Medicine, Boston, MA, USA Mount Sinai Hospital, Pathology and Laboratory Medicine, Department of Medicine, Toronto, Ontario, rates increased in 30 5 SUNARC, San Francisco, CA, USA Canada 25(OH)D (ng/ml) 6 3 Atmospheric Chemistry Division, National Center for Atmospheric Research, Boulder, CO, USA 7 Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, USAgressively lower in National Institutes of Health, Bethesda, MD 8 4 Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA 25Departments of Medicine and Physiology, Boston University School of Medicine, Boston, MA, USA 5 SUNARC, San Francisco, CA, USAng until the winter (Accepted 5 August 2006, first published Center for Atmospheric Research, Boulder, CO, USA 6 7 Atmospheric Chemistry Division, National online 7 September 2006) Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, USAmmunity outbreaks 20 8 Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA SUMMARY eaked for several (Accepted 5Edgar Hope-Simpson proposed that a ‘ seasonal stimulus ’ intimately associated with In 1981, R. August 2006, first published online 7 September 2006) 15 solar radiation explained the remarkable seasonality of epidemic influenza. Solar radiation triggerse higher in the sky S U M M A R Y vitamin D production in the skin ; vitamin D deficiency is common in the winter, robust seasonal and activated vitamin D, 1,25(OH)2D, a steroid hormone, has profound effects on humaninfluenza virtually 10 In 1981, R.1,25(OH)2D acts as an immune system a ‘seasonal stimulus ’ intimately associated with immunity. Edgar Hope-Simpson proposed that modulator, preventing excessive expression solar radiation explained the remarkable seasonality of burst ’ potential of macrophages. Perhaps of inflammatory cytokines and increasing the ‘ oxidative epidemic influenza. Solar radiation triggersstice. Clinical case robust seasonal vitamin D production Jan. skin ; vitamin of potentMayJune JulyAug. Aug. Sep. Oct.Nov.Dec. in the Feb. Mar.Apr. anti-microbial in the winter, most importantly, it dramatically stimulates the expression D deficiency is commonpeptides, Month and activated neutrophils,1,25(OH)2D,natural killer cells, and in epithelialeffects on human which exist in vitamin D, monocytes, a steroid hormone, has profound cells lining thea increased from immunity. 1,25(OH)2Dthey play a immune system modulator, preventinginfection. Volunteers respiratory tract where acts as an major role in protecting the lung from excessive expression of inflammatory cytokines and influenza virus ‘oxidative burst ’ potentialfever and serological inoculated with live attenuated increasing the are more likely to develop of macrophages. Perhaps again in the days Fig. 3. Seasonal variation of 25(OH)D levels in a popu- evidence of an immune response in the winter. Vitamin D deficiency predisposes children to most importantly, it dramatically stimulates the expression of potent anti-microbial peptides, which exist infections. Ultraviolet radiation (either from artificial sources or cells lining the reduces respiratory in neutrophils, monocytes, natural killer cells, and in epithelial from sunlight) n though a much lation-based sample of inhabitants of a small southern respiratory tractviral respiratory infections, as does cod liver the (which contains vitamin D). An the incidence of where they play a major role in protecting oil lung from infection. Volunteers German town, aged 50–80 years. (Reproduced/amended inoculated with live attenuated influenza D reducesmore likely to of respiratory and serological interventional study showed that vitamin virus are the incidence develop fever infections inpulation had virus- evidence of an immune response in D, or lack of it, may D deficiency predisposes children to ’. children. We conclude that vitamin the winter. Vitamin be Hope-Simpson’s ‘ seasonal stimulus with respiratory infections. Ultraviolet of Springer artificial sourcesand sunlight) reduces kind permission radiation (either from Science or from Businessning of the lethal the incidence of viral respiratory infections, as does cod liver oil (which contains vitamin D). An Media, R O D U CstudyNS.H., 1998.)D reduces the incidence of respiratory infections in might I N T Scharla, TIO … the characteristic microbe of a disease be a interventional showed that vitamin symptom instead of a cause. e beginning of its children. wishes to investigate medicine properly of it, may be Hope-Simpson’s ‘seasonal stimulus ’. Bernard Shaw Whoever We conclude that vitamin D, or lack should proceed thus : in the first place to consider the seasons of the George
  • 133. Table 4 shows 25(OH)D levels by study centre, for the study(38), where unexpectedly only 3·5 % of the analysedwhole group split by sex. The highest levels were obtained European elderly presented optimum 25(OH)D levels British Journal of Nutrition, page 1 of 10 doi:10.1017/S0007114511003527in Rome, Athens, Vienna q The Authors 2011 and Zaragoza, and the lowest (. 60 nmol/l), public health authorities have been concernedlevels were found in Dortmund, Heraklion and Ghent for about the widespread 25(OH)D deficiency in the Europeanthe whole group, where the sampling procedure adolescents in Europe: the Healthy Lifestyle our knowledge, the data obtained Vitamin D status among went on population. To the best offor most of the academic year. In none of the in Adolescence studythe framework of the HELENA study are the first to aim at in Europe by Nutrition cities were inmean levels above the proposed cut-off of 75 nmol/l. Girls establishing descriptive 25(OH)D status in adolescents at ahad higher mean levels in all Gonzalez-Gross *†, Jara Valtuena †, Christina Breidenassel2level.A.According to the Institute of Medicine report Marcela cities except for Athens, ´ 3 1,2 6 ˜ 1,3 European , Luis8 Moreno4,5,3 7 Marika Ferrari , Matilde Kersting , Stefaan De Henauw , Frederic Gottrand , Elena Azzini ,Pecs and Lille. Deficient levels (,50 nmol/l) were highest Manios11 and Peter vitamin behalf of the for bone health should correspond to Kurt Widhalm9, Anthony Kafatos10, Yannis in 2011, Stehle2 on D intake HELENA Study Group 1 Department of Health and Human Performance, Faculty of Physical Activity and Sport Sciences (INEF), Universidad ´ ´ Politecnica de Madrid, C/Martın Fierro, 7, 28040 Madrid, Spain 40 ¨ 2 ¨ ¨ ¨ Institut fur Ernahrungs- und Lebensmittelwissenschaften – Humanernahrung, Rheinische Friedrich-Wilhelms Universitat, Bonn, Germany 3 National Research Institute on Food and Nutrition, Rome, Italy 4 Growth, Exercise, Nutrition and Development (GENUD) Research Group, Universidad de Zaragoza, Zaragoza, Spain 5 British Journal of Nutrition Escuela Universitaria de Ciencias de la Salud, Universidad de Zaragoza, Zaragoza, Spain 6 ¨ Research Institute of Child Nutrition Dortmund, Rheinische Friedrich-Wilhelms Universitat, Bonn, Germany 7 Department of Public Health, Ghent University, Ghent, Belgium 30 8 Inserm U995, IFR114, University Lille 2, Lille, France 9 Department of Paediatrics, Medical University of Vienna, Vienna, Austria 10 Preventive Medicine and Nutrition Clinic, University of Crete School of Medicine, Iraclion, Crete, Greece 11 Department of Nutrition and Dietetics, Harokopio University, Athens, Greece Subjects (%) (Received 12 November 2010 – Revised 23 May 2011 – Accepted 31 May 2011) 20 Abstract 38·8 An adequate vitamin D status is essential during childhood and adolescence, for its important role in cell growth, skeletal structure and development. It also reduces the risk of conditions such as CVD, osteoporosis, diabetes mellitus, infections and autoimmune disease. As comparable data on the European level are lacking, assessment of vitamin D concentrations was included in the Healthy Lifestyle in 27·4 Europe by Nutrition in Adolescence (HELENA) study. Fasting blood samples were obtained from a subsample of 1006 adolescents (470 males; 46·8 %) with an age range of 12·5– 17·5 years, selected in the ten HELENA cities in the nine European countries participating in this cross-sectional study, and analysed for 25-hydroxycholecalciferol (25(OH)D) by ELISA using EDTA plasma. As specific reference 10 18·9 values for adolescents are missing, percentile distribution were computed by age and sex. Median 25(OH)D levels for the whole popu- lation were 57·1 nmol/l (5th percentile 24·3 nmol/l, 95th percentile 99·05 nmol/l). Vitamin D status was classified into four groups according 15·0 to international guidelines (sufficiency/optimal levels $75 nmol/l; insufficiency 50 –75 nmol/l; deficiency 27·5 – 49·99 nmol/l and severe deficiency ,27·5 nmol/l). About 80 % of the sample had suboptimal levels (39 % had insufficient, 27 % deficient and 15 % severely deficient levels). Vitamin D concentrations increased with age (P,0·01) and tended to decrease according to BMI. Geographical differences were also identified. Our study results indicate that vitamin D deficiency is a highly prevalent condition in European adolescents and should be a matter of concern for public health authorities. 0 Key words: Adolescents: Vitamin D: Prevention: Europe Severe deficiency Deficient Insufficient Sufficient (<27·5 nmol/l) group for malnutrition Adolescents are considered as a risk (27·5–50 nmol/l) (50–756)nmol/l)cognitive function and concen- osteomalacia (4 – , impaired (>75 nmol/l) because of their increasing needs of nutrients and energy tration problems(7), hyperactivity(8) and immune system deficiency(4). Inadequate vitamin D levels have also been for adequate growth and development that vary with 25(OH)D age(1 – 3). Specifically different levels of vitamin D deficiency status groups related to other diseases such as diabetes, multiple sclerosisFig. 1. 25-Hydroxycholecalciferol (25(OH)D) statuscould be considered a risk factor for at these early ages classification. and cancer(9 – 11). One of the most important applications
  • 134. DEFICIÊNCIA DE VITAMINA D EM ATLETAS !Modalidades 25OHD3   Referências ng/mlMulheres  Finlandesas      (corredoras  e   Lehtonen-­‐Veromaa  M,  et  al.     67%:  <  15   Eur  J  Clin  Nutr.  1999;53(9):746–51.ginastas)  GinásFca     77%:  <  35   Willis  KS,  Peterson  NJ,  Larson-­‐Meyer  DE.     Int  J  Sport  Nutr  Exerc  Metab.  2008;18:204–24.(Alemanha)   37%:  <  10GinásFca     83%:  <  30     Lovell  G.  Clin  J  Sport  Med.  2008;18(2):159–61.(EUA  -­‐  Mulheres) 33%:  <  20Ciclistas  franceses       Maïmoun  L,  et  al.    (treino  de  16  h/dia) Média:  32 Int  J  Sports  Med.  2006;27(2):105–11. PERFORMANCE AUMENTA NOS MESES DE VERÃO USO DE RADIAÇÃO UVB EM ATLETAS MELHORA PERFORMANCE Cannell JJ, et al. Med Sci Sports Exerc. 2009 May;41(5):1102-10
  • 135. T-score Documento descargado de http://www.elsevier.es el 19/08/2011. Copia para uso personal, se prohíbe la transmisión de este documento por ± 0,8 0,2 cualquier medio o formato. 0,4 ± 1,2 0,223 Trocánter (g/cm2 ) 0,743 ± 0,104 0,789 ± 0,960 0,722 ± 0,101 0,003 T-score Endocrinol Nutr. 2011;58(6):267—273 0,1 ± 0,8 0,4 ± 1,2 0,189 2 Intertrocánter (g/cm ) 1,138 ± 0,151 1,213 ± 0,134 1,104 ± 0,147 0,001 T-score 0,1 ± 0,8 0,4 ± 1,3 0,218 ENDOCRINOLOGÍA Y NUTRICIÓN www.elsevier.es/endo Tabla 6 Valores de ultrasonidos medidos en el calcáneo QUS ORIGINAL los alumnos Todos Varones Mujeres Valor de p BUA (dB/MHz) 76,8 (13,7) 80,3 (12,8) 75,1 (14) Elevada prevalencia de hipovitaminosis D en los estudiantes de 0,084 T-score —0,2 ± 0,7 —0,2 ± 0,9 0,733 medicina de Gran Canaria, Islas Canarias (Espa˜a) n SOS (m/s) 1.561,8 (24,5) 1.560,4 (25,7) 1.562,5 (24,1) 0,692 T-score —0,2b±Elisa González-Rodríguez a , ± 0,8 a Esther González-Padilla , Adela Soria López , 0,8 —0,1 0,529 a a QUI 102,7 (18) 102,8 (15,7) Marco a , Sabrina García-Santana , Ana Mirallave-Pescador , María del Val Groba102,6 (19,1) 0,960 c T-score Gómez y Manuel Sosa Henríquez a,e,∗ 1 d Pedro Saavedra , José Manuel Quesada —0,1 ± 0,8 —0,1 ± 0,514 a Grupo de Investigación en Osteoporosis y Metabolismo Mineral, Universidad de Las Palmas de Gran Canaria, Gran Canaria, Espa˜a n b Servicio de Bioquímica Clínica, Hospital Universitario Insular, Las Palmas de Gran Canaria, Gran Canaria, Espa˜a n c Departamento de Matemáticas, Universidad de Las Palmas de Gran Canaria, Gran Canaria, Espa˜a n Tabla 7 Prevalencia deUnidad de Investigación,deficiencia de vitamina D (%)Metabolismo Mineral, Servicio de Endocrinología, Hospital d insuficiencia y Iniciativas y Desarrollo, Sanyres y Unidad de Universitario Reina Sofía, RETICEF, Córdoba. Espa˜an e Todos los estudiantes Unidad Metabólica Ósea, Hospital Universitario Insular, Gran Canaria, Espa˜an Varones Mujeres Valor de p Deficiencia (25-HCC < 30 Recibido el 3 de agosto de 2010; aceptado el 9 de marzo de 2011 ng/dl) 32,6 48,3 26,1 0,048 Disponible en Internet el 8 de mayo de 2011 Insuficiencia (25-HCC < 20 ng/dl) 28,6 27,6 29 0,927 Deficiencia e insuficiencia conjuntas 61,2 75,9 55,1 0,081 Valores óptimos (> 30 ng/ml) PALABRAS CLAVE 38,8 Resumen 24,1 44,9 0,081 Vitamina D; Fundamento: Se ha descrito la existencia de deficiencia de vitamina D tanto en la población Deficiencia; general como en un gran número de enfermedades. Sin embargo, se han publicado pocos estu- Insuficiencia; dios realizados en población joven y sana en Espa˜a. Teóricamente no debería encontrarse n Estudiantes; deficiencia de vitamina D entre los estudiantes de Medicina de la Universidad de Las Palmas de Exposición solar; Gran Canaria, porque disponen de todos los medios para evitarla.que fueron estadísticamente Canarias Islas superiores en todos los lugares 25-HCC que es el metabolito utilizado para valorar el estado Objetivo: Estimar la prevalencia de deficiencia de vitamina D en una población de estudiantes de Medicina de ambos sexos de la Universidad de Las Palmas de Gran Canaria. 18,19anatómicos de la extremidad proximal del fémur. de vitamina D en el organismo . Método: Se estudiaron 103 alumnos de Medicina de ambos sexos de la Universidad de Las Palmas Gran Canária: 28º N existe un consenso sobre cuáles son los niveles La tabla 6 muestra los parámetros ultrasonográficos Aunque no de Gran Canaria. A todos se les realizó un cuestionario y una exploración física. Se determinó la vitamina D 25-hidroxicolecalciferol (25-HCC), la hormona paratiroidea, varios marcadoresmedidos en el calcáneo. No se observaron diferencias esta- óptimos de 25-HCC, hoy en día se acepta la clasificación de bioquímicos de remodelado óseo y un estudio bioquímico general. Se estimó la densidad mineraldísticamente significativas entre ambos sexos en ninguno de deficiencia de vitamina D cuando los valores de 25-HCC son ósea por absorciometría radiológica dual en la columna lumbar y en la extremidad proximal del fémur. Asimismo, se midieron los parámetros ultrasonográficos en el calcáneo. 20los parámetros estudiados: BUA, SOS y QUI. inferiores a 20 ng/ml e insuficiencia cuando las cifras de Resultados: Sólo el 38,8% de los estudiantes de Medicina (el 42,1% de los varones y el 44,9% de las mujeres) presentaron niveles de 25-HCC superiores a 30 ng/dl tal y como se recomienda 3,21 Finalmente, en la tabla 7 se muestra la prevalencia 25-HCC están por debajo de 30 ng/ml .de insuficiencia y deficiencia de vitamina D en la pobla- Las personas que viven cerca del Ecuador, expuestas ación estudiada. El 48,3% de los varones y el 26,1% de las la luz solar sin protección, habitualmente tienen unos nive- 3
  • 136. mined by RIA being approximately 6.8 ng/ml higher than by doi: 10.1210/jc.2006-2250 HPLC. Thus, if the Diasorin RIA had been used to determine the prevalence of low vitamin D status (using a cutpoint ofLow 30 ng/ml), fewer individuals would have been classified as Vitamin D Status despite Abundant Sun ExposureN. Binkley, R. Novotny, D. Krueger, T. using the RIA, 25% of this population and “low.” However, even Kawahara, Y. G. Daida, G. Lensmeyer, B. W. Hollis, would be classified as having low vitamin D status. Finally,M. K. DreznerUniversity of Wisconsin Osteoporosis Clinical Research Program (N.B., D.K., T.K., M.K.D.), Madison, Wisconsin 53705;Human Nutrition, Food and Animal Sciences (R.N., Y.G.D.), University of Hawaii at Manoa, Honolulu, Hawaii 96822; Hawai: 21º NLaboratory Medicine (G.L.), University of Wisconsin, Madison, Wisconsin 53792; and Medical University of South Carolina(B.W.H.), Charleston, South Carolina 29425Context: Lack of sun exposure is widely accepted as the primary cause Main Outcome Measures: Serum 25(OH)D concentration was mea-of epidemic low vitamin D status worldwide. However, some individuals sured using a precise HPLC assay. Low vitamin D status was definedwith seemingly adequate UV exposure have been reported to have low as a circulating 25(OH)D concentration less than 30 ng/ml.serum 25-hydroxyvitamin D [25(OH)D] concentration, results thatmight have been confounded by imprecision of the assays used. Results: Mean serum 25(OH)D concentration was 31.6 ng/ml. Using a cutpoint of 30 ng/ml, 51% of this population had low vitamin DObjective: The aim was to document the 25(OH)D status of healthy status. The highest 25(OH)D concentration was 62 ng/ml.individuals with habitually high sun exposure. Conclusions: These data suggest that variable responsiveness toSetting: This study was conducted in a convenience sample of adults UVB radiation is evident among individuals, causing some to havein Honolulu, Hawaii (latitude 21°). low vitamin D status despite abundant sun exposure. In addition, because the maximal 25(OH)D concentration produced by natural UVParticipants: The study population consisted of 93 adults (30 women exposure appears to be approximately 60 ng/ml, it seems prudent toand 63 men) with a mean (SEM) age and body mass index of 24.0 yr (0.7) use this value as an upper limit when prescribing vitamin Dand 23.6 kg/m2 (0.4), respectively. Their self-reported sun exposure was supplementation. (J Clin Endocrinol Metab 92: 2130 –2135, 2007)28.9 (1.5) h/wk, yielding a calculated sun exposure index of 11.1 (0.7).L OW VITAMIN D status1 is extremely common (1– 4), and may contribute to the development of osteopo-rosis and osteomalacia/rickets, as well as increase the risk The high prevalence of low vitamin D status is assumed to result from inadequate sun exposure. Because highly sun- exposed individuals likely possess normal vitamin D statusfor falls (5, 6). Moreover, low vitamin D status may play from an evolutionary standpoint, the use of such individualsa role in nonmusculoskeletal diseases, including a variety to define normal 25(OH)D status has been proposed (19).of cancers, multiple sclerosis, infection, hypertension, and This argument is based on the view that contemporary hu-diabetes mellitus (7, 8). Although it is widely accepted that mans are genetically adapted to the environment of ourvitamin D status is determined by the measurement of the ancestors and that the profound lifestyle changes that havecirculating concentration of 25-hydroxyvitamin D occurred over the past approximately 10,000 yr (importantly[25(OH)D] (9), the cutoff value to define low vitamin D including reduced sun exposure) have been much too rapidstatus and a definition for success of vitamin D repletion for the human genome to adjust (20, 21). The current studytherapy remain controversial (10, 11). This is partially due was designed to assess whether, in fact, people living IGa low Comparison of 25(OH) F at . 4.to the variability2. vitamin D concentration by geograph- FIG. of Low vitamin D status in highly sun-exposed subjects. When haveAlthough the correlation betwee latitude with high amounts of sun exposure adequateical location and differences in assay methodology (12–16). vitamin D status, as expected, D status, a target6.8 ng/ml is present using th and to identifyDespite this controversy, cutpoint of 30 ng/ml is usedof 25(OH)D for use in vitamin D therapy. an accepted clinicians often endeavor to cor- to define low vitamin of value 51% of these subjects (open bars) are low.rect vitamin D deficiency by prescribing high-dose vita- HPLC assay used in this studymin D (17). However, the goal for such therapy is unclearand could include achieving a serum 25(OH)D level Subjects and Methodsgreater than an accepted cutpoint (e.g. 30 ng/ml) or, al- Subjects and study designternatively, The Journal of normal, a value that varies the upper limit of Clinical Endocrinology & Metabolism 92(6):2130–2135 Subjects older than 18 yr were recruited approximately equally frombetween laboratories (18). the University of Hawaii at Manoa (UH) and from patrons of the A’ala Park Board Shop, Honolulu, Hawaii (latitude 21° north), in late March 2005. The A’ala Park Board Shop is a skateboard shop frequented by First Published Online April 3, 2007 young adults. Recruitment was performed by posted notice at the Board
  • 137. ENVELHECIMENTO vitamin D and ellular growth. in the skin ab- (preD3). Once mation to vita- D3 and vitamin g from the diet5(OH)D3 in the eenters the cir- 25(OH)D3 1␣- m phosphorusD. 1,25(OH)2Dmajor target tis- destruction by (24-OHase). FIGURE 4. A: Circulating concentrations of vitamin D3 after a single llular growth. exposure to 1 MED of simulated sunlight, with a sunscreen (SPF 8) or a topical placebo Holick M. Am J Circulating concentrations of vitamin D in re- cream. B: Clin Nutr 2004;80(suppl):1678S– 88S. sponse to whole-body exposure to 1 MED among healthy young and elderly subjects. Reproduced with permission from reference 3.
  • 138. toon- Albedo from lighter-colored ground and, especially, from snow 7).ted UVBonsnin ur-hasernan- calerethe ich of msent ost ol-the Jablonski NG, Chaplin G. Proc Natl Acad Sci U S A. 2010 May 11;107 Suppl 2:8962-8and
  • 139. Pele pouco pigmentada54 mJ/cm2 Pele muito pigmentada Pele muito320 mJ/cm2 pigmentada Holick M. Am J Clin Nutr 2004;80(suppl):1678S– 88S.!
  • 140. Pele pouco pigmentada54 mJ/cm2 Pele muito pigmentada Pele muito320 mJ/cm2 pigmentada Holick M. Am J Clin Nutr 2004;80(suppl):1678S– 88S.!
  • 141. Pele pouco pigmentada54 mJ/cm2 Pele muito pigmentada Pele muito320 mJ/cm2 pigmentada Holick M. Am J Clin Nutr 2004;80(suppl):1678S– 88S.!
  • 142. PROTECTOR SOLAR!ü  SPF de 8 diminui a capacidade de produzir Vitamina D3 em 95%!ü  SPF de 15 diminui a capacidade de produzir Vitamina D3 em 98%! !! !!! !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! !! ! ! ! ! ! ! ! !! Holick M. Am J Clin Nutr 2004;80(suppl):1678S– 88S.!
  • 143. Table 1. Predictors of risk of death from melanoma in a population-based tion. Compared withstudy of residents from Connecticut awareness, individual No. of Hazard ratio lower risk of death fro Total melanoma (95% condence reported skin self-exaVariable no.* deaths interval) P value were not statistically Demographic variables from melanoma (P =Sex When melanoma- Male 272 33 1.0 (referent) .33 multivariable setting Female 256 25 0.8 (0.5 to 1.3) univariate analysis aAge at diagnosis 528 58 1.2 (1.0 to 1.4) .08 death from other cau 10-year increase remained statisticallyEducation anatomic site, Breslo Up to high school 202 28 1.0 (referent) .11 In addition, the point Greater than 326 30 0.7 (0.4 to 1.1) high school tivariable model for i CI = 0.3 to 1.1) and Sun exposure variables CI = 0.4 to 1.1) chaEver severely sunburned (Table 1), but the co No 173 27 1.0 (referent) .02 rose, both to 0.12. In Yes 353 31 0.5 (0.3 to 0.9) the 80% of subjects fIntermittent sun containing nevus cou exposure index count in association w Low 189 27 1.0 (referent) .04 val for melanoma inc High 328 28 0.6 (0.3 to 1.0) value. The point estiSolar elastosis Absent 254 36 1.0 (referent) .02 variables in this mode J Natl Cancer Inst 2005;97:195–9 Present 268 21 0.5 (0.3 to 0.9) Table 2. Screening variables
  • 144. FONTES DE VITAMINA D Alimentos Vit. D (UI)Óleo de Fígado de Peixe (10 g) 1360Sardinha (105 g) 500Atum (105 g) 402Salmão Cozinhado (105 g) 360Ovo (Unidade) 20Fígado de Vitela cozinhado (105 g) 15 Ozkan B. J Clin Res Pediatr Endocrinol. 2010 Dec;2(4):137-43
  • 145. The Journal of Nutrition Symposium: Food-Based Approaches to Combating Micronutrient Deficiencies in Children of Developing Countries Local Cultural Animal Food Contributes High Levels of Nutrients for Arctic Canadian Indigenous Adults and Children1,2 Harriet V. Kuhnlein3,4* and Olivier Receveur5 3 Centre for Indigenous Peoples’ Nutrition and Environment (CINE) and 4School of Dietetics and Human Nutrition, McGill University, Ste. Anne de Bellevue H9X3V9, Canada and 5Department of Nutrition, University of Montreal, Montreal J3C3KS, Canada ´ ´ TF – Alimentos Tradicionais 1 mcg 4 = 40 UI ´ Óleo de Fígado de Peixe: 8400 IUTABLE Vit DMicronutrient intake on days with and without TF for Yukon, Dene/Metis, and Inuit adults and Yukon and Dene children ! Abstract Adults1 Children1 Downloaded from jn.nutrition.org at Lund University Libraries on September 20, 2011 Food systems of Canadian Arctic Indigenous Peoples contain many species of traditional animal and plant food, but the Yukon ´ Dene/Metis Inuit extent of use today is limited because purchased food displaces much of the traditional species from the diet. Frequency Yukon and Dene Days with Days without Days with Days without Days with Days without and 24-h dietary interviews of Arctic adults and children were used to investigate these trends. The most frequently Days with Days withoutNutrient consumed Arctic foods were derived from (n ¼ 661) fish. TF adults 346) foods contributed 6–40%TF daily energy of TF (n ¼ 410) TF (n ¼ 387) TF animals and In (n ¼ these TF (n ¼ 968) of (n ¼ 632) TF (n ¼ 58) TF (n ¼ 40) adults. Children ate much less, 0.4–15% of energy, and .40% of their total energy was contributed by ‘‘sweet’’ and ‘‘fat’’Iron, mg 23.3 6 0.6a 14.1 6 0.7b 26.5 6 0.9a 15.6 6 1.3b 37.4 6 1.1a 15.0 6 1.4b food sources. Nevertheless, for adults and children, even a single portion of local animal or fish food resulted in increased 16 6 0.6a 14 6 0.7bZinc, mg (P , 6 0.9alevels of energy, protein, vitamin D, vitamin E, riboflavin, b vitamin B-6, iron, zinc, copper, magnesium, 27.7 0.05) 13.1 6 1.1b 23.8 6 1.0a 15.4 6 1.3 21.5 6 0.5a 9.5 6 0.6b 11 6 0.5a 8.6 6 0.6bCopper, mg 1655 6 46a phosphorus, 6 53b manganese, 2025 6 89a had 6 122b 2076 6 44a 1041 not b 1163 and potassium; although children 1439similar results for these nutrients, they did6 58reach 1293 6 41a 1066 6 48b significance for energy, vitaminbD, or manganese. Because market foods are the major source of energy in the Arctic,Phosphorus, mg 1602 6 35a 1155 6 40 1759 6 31a 1224 6 43b 1663 6 27a 947 6 36b 1044 6 32a 924 6 37b traditional animal-source foods are extremely important to ensure high dietary quality of both adults and children. J. Nutr. a b a b a b aPotassium, mg 3520 6 76 2608 6 87 3516 6 63 2561 6 86 2997 6 53 1999 6 0 2291 6 86 2043 6 99b 137: 1110–1114, 2007.Magnesium, mg 297 6 6a 240 6 7b 305 6 5a 237 6 7b 597 6 31a 280 6 40b 203 6 5.7a 182 6 6.6bManganese, mg 3.7 6 0.1a 3.3 6 0.1b 3.6 6 0.1a 3.3 6 0.1b 3.3 6 0.1a 2.7 6 0.1b 2.4 6 0.1 2.1 6 0.2 a b a b a b aRiboflavin, mg 2.2 6 0.1 1.5 6 0.1 2.5 6 0.1 1.6 6 0.1 2.9 6 0.1 1.3 6 0.1 1.6 6 0.07 1.2 6 0.08b 6bVitamin B-6, mg Animal-source foods (ASF) are viewed 6 0.1a 3.3 6 0.1a 1.7 6 0.1 3.7 as essential in1.9 6 0.1btheir derivatives0.1a their possible 0.1b most 4.0 6 and 1.4 6 contribution 1.9 the 0.08a to 6 nutrition 1.6 6 0.09b human societies because of their high nutrient content. In food- btransition in developing societies (2,3). In Canadian Arctic food a b a a bVitamin D, mg 7.3 6 0.6 2.1 6 0.7 7.9 6 0.9 based approaches to ameliorating multiple micronutrient defi- 3.5 6 1.3 systems 25.1 6are abundant animals and fish 3.2 6 0.4 there 1.3 8.6 6 1.7 in addition to 2.5 6 0.5Vitamin E, mg 4.8 6 0.1a 3.5 6 0.2b 6.5 6 0.4a use of ASF6 0.5bpurchased foods. Studies of 3.1 6 0.3b Nations, Dene/Metis, ciencies, particularly in developing countries, the 3.9 in 5.4 6 0.2a Yukon First 3.5 6 0.2a ´ 3.1 6 0.2b combination with plant foods is seen as effective and efficacious and Inuit cultural groups demonstrate extensive knowledge of1 Significant differences in nutrient intakes cultural and without TF are represented by are presence offood sources, unique (a, b). Absence of superscripts means results are not (1) provided that with TF and household-level constraints the diverse different superscripts foods with exceptional nutrient Downloaded from jsignificantly different. Adults, P , 0.01;(2). Successful0.05. accommodated children P , efforts to increase intake of ASF quality, and unique patterns of food use incorporating varying have been documented, yet concerns have been expressed about levels of local cultural food with purchased market food (MF)result of fortification of frequently consumed commercial bev- or the amount of saturated fat and additional energy from ASF significantlyarticle, we present data on dietary food sources for phosphorus, (4–9). In this more iron, zinc, copper, magnesium, Kuhnlein HV, Receveur O. J Nutr. 2007 Apr;137(4):1110-4!selected samples of Dene (10,11) adults of these 3 groups anderages (not shown) (8). potassium, vitamin E, riboflavin, and vitamin B-6 than did recall and Inuit children. Presented as part of amounts ‘‘Food-Based Approaches to Combating days with no TF. It is very clear that traditional ASF are For children, even with smallthe symposium of TF being consumed, 1 Micronutrient Deficiencies in Children of Developing Countries’’ given at the Methods of data collection
  • 146. INGESTÃO PROLONGADA DE 100 IU/DIA DE VITAMINA D3RESULTA NUM AUMENTO DE 25(OH)D DE 2,5 NMOL/L (1 NG/ML) Heaney RP. Journal of Steroid Biochemistry & Molecular Biology 103 (2007) 635–641
  • 147. 1550 Clinical Journal of the American Society of Nephrology calcium metabolism lating cellular prolif wide variety of other immune function, m renin and insulin sy although increasing lead to an increase i believed that raising vides an adequate a version of 25(OH)D t cells. Once 1,25(OH) the cell, it then indu creasing the expressi ylase (CYP24R; 24-OFigure 2. Comparison of the percentage increase in serum25(OH)D levels of healthy adults who were in a bathing suit Clinical Uses oand exposed to suberythemal doses (0.5 MED) of ultraviolet B Activity of 1,25radiation once a week for 3 mo with healthy adults who re- Epidermal cells haceived either 1000 IU of vitamin D2 or 1000 IU of vitamin D3 ited by 1,25(OH)2D3daily during the winter and early spring for a period of 11 wk. that 1,25(OH)2D3 coFifty percent increase represented approximately 10 ng/ml skin disorder psoriasfrom baseline 18 Ϯ 3 to 28 Ϯ 4 ng/ml. Skin type is based on the found to be very effFitzpatrick scale: Type IISoc Nephrol. 2008 Sep;3(5):1548-54 Holick MF. Clin J Am always burns, sometimes tans; type III ward toxicity (42). 1always burns, always tans; type IV sometimes burns, always now one of the first-
  • 148. EXPOSIÇÃO SOLAR!Todo o corpo (1 MED): 10 000 – 25 000 UI !             (20 000-50 000 UI em suplemento)!Braços e pernas (0,25 – 0,5 MED): 2 000 – 4 000 UI!!  Mãos e cara: 200 UI! Holick M. The Vitamin D Solution. 2010. Hudson Street Press!
  • 149. TIPOS DE PEL TIPO! DESCRIÇÃO!Tipo I ! Queima-se sempre, nunca se bronzeia, pele muito clara com cabelo louro ou ruivo!Tipo II ! Queima-se rápido, bronzeia-se com dificultade, pele clara!Tipo III ! Queima-se ocasionalmente, bronzeia-se gradualmente (origen mediterrânica e do médio oriente)!Tipo IV! Muito raro queimar-se, bronzeia-se sempre (Médio Oriente, Índia, Paquistão)!Tipo V! África, Sudeste asiático, alguns nativos de India e Paquistão!Tipo VI ! África, Tamils de Ásia (Índia, Sri Lanka), Nativos de Papua-Nova Guiné, Aborígenes Australianos! Holick M. The Vitamin D Solution. 2010. Hudson Street Press!
  • 150. PENÍNSULA IBÉRICA 8-11 H / 15 – 18 HTipo  de  Pele! Nov-­‐Fev ! Mar-­‐Maio ! Jun-­‐Ag ! Sep-­‐Oct !Tipo  1! 15-­‐20  min! 10-­‐15  min! 15-­‐20  min!Tipo  II! 20-­‐30  min! 15-­‐20  min! 20-­‐30  min!Tipo  III! 30-­‐40  min! 20-­‐30  min! 30-­‐40  min!Tipo  IV! 40-­‐60  min! 30-­‐40  min! 40-­‐60  min!Tipo  V  e  VI! 60-­‐75  min! 40-­‐60  min! 60-­‐75  min! Holick M. The Vitamin D Solution. 2010. Hudson Street Press!
  • 151. PENÍNSULA IBÉRICA 11 - 15 HTipo  de  Pele Nov-­‐Fev ! Mar-­‐Maio ! Jun-­‐Ag ! Sep-­‐Oct !Tipo  1 10-­‐15  min! 2-­‐8  min! 10-­‐15  min!Tipo  II   15-­‐20  min! 5-­‐10  min! 15-­‐20  min!Tipo  III   20-­‐30  min! 15-­‐20  min! 20-­‐30  min!Tipo  IV   30-­‐40  min! 20-­‐25  min! 30-­‐40  min!Tipo  V  e  VI   40-­‐60  min! 25-­‐35  min! 40-­‐60  min! Holick M. The Vitamin D Solution. 2010. Hudson Street Press!
  • 152. dSci i ographies published by October 2005. All randomizedelectronic databases and bibli- Data primary and secondary prevention We searched trials involving adults compar- ized Sources and Trial Selection trials. ing beta carotene, vitamin A, vitamin C All randomized vitamin E, and selenium either ographies published by October 2005. (ascorbic acid),electronic databases and bibli- i Trial Selection We searched trials involving adults compar- Data Sources andplacebo or vs no intervention were included in our analysis. Ran- singly or combined vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either ing beta carotene, vs by October 2005. All randomized trials involving adults compar- ographies published and follow-up werefor PrimaryTrials of Antioxidant in the included Mortality in RandomizedSci domization, blinding, placebo or vs no intervention were includedPrevention: singly or combined vs Supplements considered markers of bias and Secondary in our analysis. Ran- IMPLI- ing beta carotene,antioxidantvitamin C (ascorbic acid), vitamin E, and selenium either vitamin A, Systematic Review and Meta-analysis trials. The Online articleof relatedand follow-up were considered markers of bias in the included effect and domization, blinding, 2009. supplements on all-cause mortality was analyzed with random-effects meta-analysesor vs no intervention were mortality wasanalysis. Ran- singly or current as of Januaryvs placeboGoran Bjelakovic; Dimitrinka Nikolova; Liseincluded et al.with 95% confi- combined 8, content and reported as relative risk (RR) our analyzed withan dis- Lotte Gluud; in IMPLI- trials. The effect of antioxidant supplements on all-cause domization, blinding, and follow-up were considered markers of bias in the included ts may JAMA. 2007;297(8):842-857 (doi:10.1001/jama.297.8.842) dence intervals (CIs). Meta-regressionreported as assess the effect ofwith 95% acrossan IMPLI- S dis- random-effects meta-analyses supplements onto relativemortality was analyzed confi- trials. The effect of antioxidant and was used all-cause risk (RR) http://jama.ama-assn.org/cgi/content/full/297/8/842 covariates withdative ts mayman dis- the trials. dence intervals (CIs). Meta-regressionreported as relative risk (RR)of covariates across random-effects meta-analyses andis appended to this PDF assess the effect with 95% confi- was used toants ef- ful maydative the trials. Correction Correction Data Extraction We included 68 randomized trials with 232 606 participants (385 dence intervals (CIs). Meta-regression was used to assess the and also available at http://jama.ama-assn.org/cgi/content/full/jama;299/7/765 effect of covariates across g anti- ful ef-xidative publications). Contact me if this article is corrected. Datatrials. Citations the Extraction We included article has been cited 160 times. trials with 232 606 participants (385 This 68 randomized to im- g anti- mful ef- Contact me when this article is cited. publications). collections We all low- and high-bias Medicine;with 232 606 participants (385 Data Synthesis Whenincluded 68Care; Evidence-Basedrisk trials ofRandomized Controlledsupplements Data Extraction Topic Quality of randomized trials Review; antioxidant Trial; event ng im- to anti- Adverse Effects were pooled together there was no significantare publishedtrialstopic areas. (RR, 1.02; 95% CI, Data Synthesis When all low- and high-bias risk on mortality publications). Contact me when new articles effect in thesexidant of antioxidant supplementsng to im- event 0.98-1.06). Multivariate meta-regressionJAMA. 2007;298(4):400.trialsmortality (RR, 1.02; 95% CI, were pooled together there was noHuang high-bias risk on of antioxidant risk trials (RR, Data Synthesis When all low- and et al.analyses showed that low-bias supplements Related Letters Antioxidant Supplements and Mortality significant effect Demetrius Albanes. armfulpreventxidant 1.16; 95% CI, together there was Hemilä. JAMA. 2007;298(4):401. showed that low-bias risk were (RR, 1.05-1.29) and selenium al. JAMA. 0.998; 95%mortality (RR, 1.02; 95% sig- 0.98-1.06). Multivariate meta-regression analyses Han-Yao (RR, 2007;298(4):401.on CI, 0.997-0.9995) trials CI, JAMA. 2007;298(4):400. were pooled Philip no significant effect Harri R. Taylor et or sec- oxidant armful nificantly associated with mortality. In 47 low-bias trials with 180 938 participants, the 1.16; 95% CI, 1.05-1.29)meta-regression analyses showedCI, 0.997-0.9995) were sig- 0.98-1.06). Multivariate and selenium (RR, 0.998; 95% that low-bias risk trials (RR,ntioxi- harmful or sec- antioxidant supplements mortality. In 47 low-bias trials with 0.997-0.9995) were sig- nificantly associated with significantly increased mortality (RR, 1.05; participants, the 1.16; 95% CI, 1.05-1.29) and selenium (RR, 0.998; 95% CI, 180 938 95% CI, 1.02-n con- y or sec-ntioxi- 1.08). In low-bias risk with significantly 47 low-bias trialstrials,180 1.05; 95% CI, 1.07; Subscribe trials, after exclusion of selenium with beta carotene (RR, 1.02- antioxidant supplements mortality. In increased mortality (RR, 938 participants, the nificantly associated http://jama.com/subscribe Email Alerts http://jamaarchives.com/alertsses. 95% CI, 1.02-1.11), vitamin after exclusion of selenium trials, betavitamin E (RR, 1.04; 1.08). In low-bias risk trials, A (RR, 1.16; 95% CI,mortality (RR, 1.05; 95% CI, 1.02- antioxidant supplements significantly increased 1.10-1.24), and carotene (RR, 1.07; Permissions Reprints/E-printsnantioxi- con- permissions@ama-assn.org reprints@ama-assn.org upple- 95% CI,In low-bias risk trials,or combined,95%seleniumincreased mortality.EVitamin C 95% CI, 1.02-1.11), vitamin A (RR, 1.16; significantly trials, beta carotene (RR, 1.07; 1.08). 1.01-1.07), singly after exclusion of CI, 1.10-1.24), and vitamin (RR, 1.04; http://pubs.ama-assn.org/misc/permissions.dtlses. con- en and selenium had no singly or combined,95% CI, 1.10-1.24), andmortality.(RR, 1.04;C ases. eption 95% CI, 1.02-1.11), significant effect on mortality. 95% CI, 1.01-1.07), vitamin A (RR, 1.16; significantly increased vitamin E Vitamin upple- supple- ificant Conclusions had no significant effect on significantly increased mortality. Vitamin C and selenium Treatment with combined, mortality. A, and vitamin E may increase 95% CI, 1.01-1.07), singly or beta carotene, vitamin eptionxceptionancers mortality. The potentialsignificant effectC and selenium on mortality need further study. and selenium had no roles of vitamin on mortality. Conclusions Treatment with beta carotene, vitamin A, and vitamin E may increase ificantgnificant ty.14,15 Conclusions Treatment with beta carotene, vitamin A, and vitamin E further study. JAMA. 2007;297:842-857 roles of vitamin C and selenium on mortality needmay increase mortality. The potential www.jama.comancers mortality. The potential roles of vitamin C and selenium on mortality need further study. cancers ect14,15 ty. of JAMA. 2007;297:842-857 www.jama.com 14,15 JAMA. 2007;297:842-857 www.jama.com ality.of -cause ect Author Affiliations: The Cochrane Hepato-Biliary reven-of METHODS ffect -cause Group, Copenhagen Trial Unit, Center for Clinical In-
  • 153. Antioxidants prevent health-promoting effects of physical exercise in humans ¨ Michael Ristowa,b,1,2, Kim Zarsea,2, Andreas Oberbachc,2, Nora Klotingc, Marc Birringera, Michael Kiehntopfd, ¨ Michael Stumvollc, C. Ronald Kahne, and Matthias Bluherc,2 aDepartment of Human Nutrition, Institute of Nutrition, University of Jena, Jena D-07743, Germany; bGerman Institute of Human Nutrition, Potsdam-Rehbrucke D-14558, Germany; cDepartment of Medicine, University of Leipzig, Leipzig D-04103, Germany; dInstitute of Clinical Chemistry and ¨ Laboratory Medicine, University of Jena, Jena D-07743, Germany; and eResearch Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215 Contributed by C. Ronald Kahn, March 31, 2009 (sent for review March 14, 2009) Exercise promotes longevity and ameliorates type 2 diabetes olism has been functionally connected with type 2 diabetes (11). mellitus and insulin resistance. However, exercise also increases Mitochondria, however, are also the main source of reactive mitochondrial formation of presumably harmful reactive oxygen oxygen species (ROS), which are inevitable by-products of species (ROS). Antioxidants are widely used as supplements but oxidative glucose metabolism. Muscle is also known to generate whether they affect the health-promoting effects of exercise is free radicals, especially during contraction and physical exercise unknown. We evaluated the effects of a combination of vitamin C (12). It has been suggested that ROS may mediate some health-ion on expression of (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as promoting effects, at least in nonprimate model systems (13–17). measured by glucose infusion rates (GIR) during a hyperinsuline- We here evaluated the possibility that ROS are required for tion of vitamins by mic, euglycemic clamp in previously untrained (n ‫ )91 ؍‬and pre- the insulin-sensitizing capabilities of physical exercise in healthy trained (n ‫ )02 ؍‬healthy young men. Before and after a 4 week humans and that commonly used antioxidants, such as vitamin intervention of physical exercise, GIR was determined, and muscle C and vitamin E, may abrogate the health-promoting effects ofhat physical exercise biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential both physical exercise and oxidative stress in humans. Resultssulin sensitivity irre- influences of vitamins on exercise effects. Exercise increased pa- rameters of insulin sensitivity (GIR and plasma adiponectin) only in Baseline Characteristics. Of the 40 individuals included in thehat this induction is the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled present study, 20 were known to be previously trained, and 20 were previously untrained. Study subject characteristics in thetation. by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisome- preinterventional state are given in Table 1. No significant differences in age, height, body mass index, fat free mass, or VO2 proliferator-activated receptor gamma (PPAR␥), and PPAR␥ coac- maximum were observed within the groups (Table 1) and no tivators PGC1␣ and PGC1␤ only in the absence of antioxidants (P < significant differences in age, height and body mass index were fense Following Phys- 0.001 for all). Molecular mediators of endogenous ROS defense observed between untrained and pretrained groups. Not sur- (superoxide dismutases 1 and 2; glutathione peroxidase) were also prisingly, pretrained individuals had a significantly higher fat The transcriptional induced by exercise, and this effect too was blocked by antioxidant free mass (P ϭ 0.03) and VO2 maximum (P Ͻ 0.001). supplementation. Consistent with the concept of mitohormesis, Half of the previously untrained and previously trained groups only been linked to were randomly assigned to either antioxidant supplementation MEDICAL SCIENCES exercise-induced oxidative stress ameliorates insulin resistance as described in Methods or to no supplementation (creating 4een shown to induce and causes an adaptive response promoting endogenous antiox- idant defense capacity. Supplementation with antioxidants may groups of 10 each) (supporting information (SI) Fig. S1). All involved into detox- preclude these health-promoting effects of exercise in humans. subjects underwent a 4 week exercise training program irrespec- tive of antioxidant supplementation and previous training status. ncluding superoxide aging ͉ hormesis ͉ insulin resistance ͉ oxidative stress ͉ reactive oxygen species One untrained individual withdrew during the study for personal reasons unrelated to the experimental protocol.dase 1 (GPx1) and T ype 2 diabetes mellitus is increasing worldwide at epidemic Induction of Oxidative Stress by Short-Term Exercise. It is well-mical function (20). established that physical exercise increases ROS formation in Fig. rates complications (1). with both microvascular is caused by skeletal muscle (12); however, it is not knownof the health- 3. and is associated Type 2 diabetes mellitus and macro- Mitohormesis links physical exercise and subsequent formation if vascularexercise resulted in a a combination of insulin resistance involving sensitivity promoting effects of exercise are partly due to this effect. To reactive oxygen species to insulin a number of and antioxidant defense. Physical our specific replicate the ROS-inducing capacity of exercise in peripheral tissues, including skeletal muscle (2, 3), and an 2 G and H, Left pair exercise exerts ameliorating effectsincreased experimental set-up, bysubjected previously untrained individ- inadequate ␤-cell response despite normal or even on insulin resistance we increasing mito- uals to 3 days of exercise with muscle biopsy before (Fig. S1,g. 2 I and J, Left pair chondrialcirculating insulin. of reactive oxygen species in skeletal muscle to induceS1, ‘‘early’’). amounts of formation Physical exercise exerts numerous favorable effects on general ‘‘pre’’) and after this short-term intervention (Fig.
  • 154. Antioxidants prevent health-promoting effects of physical exercise in humans ¨ Michael Ristowa,b,1,2, Kim Zarsea,2, Andreas Oberbachc,2, Nora Klotingc, Marc Birringera, Michael Kiehntopfd, ¨ Michael Stumvollc, C. Ronald Kahne, and Matthias Bluherc,2 aDepartment of Human Nutrition, Institute of Nutrition, University of Jena, Jena D-07743, Germany; bGerman Institute of Human Nutrition, Potsdam-Rehbrucke D-14558, Germany; cDepartment of Medicine, University of Leipzig, Leipzig D-04103, Germany; dInstitute of Clinical Chemistry and ¨ Laboratory Medicine, University of Jena, Jena D-07743, Germany; and eResearch Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215 Contributed by C. Ronald Kahn, March 31, 2009 (sent for review March 14, 2009) Exercise promotes longevity and ameliorates type 2 diabetes olism has been functionally connected with type 2 diabetes (11). mellitus and insulin resistance. However, exercise also increases Mitochondria, however, are also the main source of reactive mitochondrial formation of presumably harmful reactive oxygen oxygen species (ROS), which are inevitable by-products of species (ROS). Antioxidants are widely used as supplements but oxidative glucose metabolism. Muscle is also known to generate whether they affect the health-promoting effects of exercise is free radicals, especially during contraction and physical exercise unknown. We evaluated the effects of a combination of vitamin C (12). It has been suggested that ROS may mediate some health-ion on expression of (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as promoting effects, at least in nonprimate model systems (13–17). measured by glucose infusion rates (GIR) during a hyperinsuline- We here evaluated the possibility that ROS are required for tion of vitamins by mic, euglycemic clamp in previously untrained (n ‫ )91 ؍‬and pre- the insulin-sensitizing capabilities of physical exercise in healthy trained (n ‫ )02 ؍‬healthy young men. Before and after a 4 week humans and that commonly used antioxidants, such as vitamin intervention of physical exercise, GIR was determined, and muscle C and vitamin E, may abrogate the health-promoting effects ofhat physical exercise biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential both physical exercise and oxidative stress in humans. Resultssulin sensitivity irre- influences of vitamins on exercise effects. Exercise increased pa- rameters of insulin sensitivity (GIR and plasma adiponectin) only in Baseline Characteristics. Of the 40 individuals included in thehat this induction is the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled present study, 20 were known to be previously trained, and 20 were previously untrained. Study subject characteristics in thetation. by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisome- preinterventional state are given in Table 1. No significant differences in age, height, body mass index, fat free mass, or VO2 proliferator-activated receptor gamma (PPAR␥), and PPAR␥ coac- maximum were observed within the groups (Table 1) and no tivators PGC1␣ and PGC1␤ only in the absence of antioxidants (P < significant differences in age, height and body mass index were fense Following Phys- 0.001 for all). Molecular mediators of endogenous ROS defense observed between untrained and pretrained groups. Not sur- (superoxide dismutases 1 and 2; glutathione peroxidase) were also prisingly, pretrained individuals had a significantly higher fat The transcriptional induced by exercise, and this effect too was blocked by antioxidant free mass (P ϭ 0.03) and VO2 maximum (P Ͻ 0.001). supplementation. Consistent with the concept of mitohormesis, Half of the previously untrained and previously trained groups only been linked to were randomly assigned to either antioxidant supplementation MEDICAL SCIENCES exercise-induced oxidative stress ameliorates insulin resistance as described in Methods or to no supplementation (creating 4een shown to induce and causes an adaptive response promoting endogenous antiox- idant defense capacity. Supplementation with antioxidants may groups of 10 each) (supporting information (SI) Fig. S1). All involved into detox- preclude these health-promoting effects of exercise in humans. subjects underwent a 4 week exercise training program irrespec- tive of antioxidant supplementation and previous training status. ncluding superoxide aging ͉ hormesis ͉ insulin resistance ͉ oxidative stress ͉ reactive oxygen species One untrained individual withdrew during the study for personal reasons unrelated to the experimental protocol.dase 1 (GPx1) and T ype 2 diabetes mellitus is increasing worldwide at epidemic Induction of Oxidative Stress by Short-Term Exercise. It is well-mical function (20). established that physical exercise increases ROS formation in Fig. rates complications (1). with both microvascular is caused by skeletal muscle (12); however, it is not knownof the health- 3. and is associated Type 2 diabetes mellitus and macro- Mitohormesis links physical exercise and subsequent formation if vascularexercise resulted in a a combination of insulin resistance involving sensitivity promoting effects of exercise are partly due to this effect. To reactive oxygen species to insulin a number of and antioxidant defense. Physical our specific replicate the ROS-inducing capacity of exercise in peripheral tissues, including skeletal muscle (2, 3), and an 2 G and H, Left pair exercise exerts ameliorating effectsincreased experimental set-up, bysubjected previously untrained individ- inadequate ␤-cell response despite normal or even on insulin resistance we increasing mito- uals to 3 days of exercise with muscle biopsy before (Fig. S1,g. 2 I and J, Left pair chondrialcirculating insulin. of reactive oxygen species in skeletal muscle to induceS1, ‘‘early’’). amounts of formation Physical exercise exerts numerous favorable effects on general ‘‘pre’’) and after this short-term intervention (Fig.
  • 155. 2, shaded of the adipocyte-derived secretory protein adiponectin havengs (12), been shown to be positively correlated with insulin sensitivity in exercise humans and inversely correlated with type 2 diabetes risk (19).tioxidant Antioxidants prevent health-promoting effects We observe an increase in circulating adiponectin levels follow- st 3 days. of physical exercise inpreviously untrained humans ing physicalRistow , Kim Zarse , Andreas Oberbach , Nora Klo¨ting , Marc Birringer , Michaelindividuals exercise in both Michael a,b,1,2 a,2 c,2 c Kiehntopf , a d (Fig. 1C, Left pairC. of bars,and Matthias Blu¨her and pretrained individuals Michael Stumvoll , Ronald Kahn , P Ͻ 0.001) c e c,2g Physical (Fig. 1D, Left pair of bars, P Ͻ 0.001). In contrast, previously aDepartment of Human Nutrition, Institute of Nutrition, University of Jena, Jena D-07743, Germany; bGerman Institute of Human Nutrition, Potsdam-Rehbrucke D-14558, Germany; cDepartment of Medicine, University of Leipzig, Leipzig D-04103, Germany; dInstitute of Clinical Chemistry and ¨ Laboratory Medicine, University of Jena, Jena D-07743, Germany; and eResearch Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215 shown to Contributed by C. Ronald Kahn, March 31, 2009 (sent for review March 14, 2009) tabolism Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases olism has been functionally connected with type 2 diabetes (11). Mitochondria, however, are also the main source of reactivey trained mitochondrial formation of presumably harmful reactive oxygen oxygen species (ROS), which are inevitable by-products of species (ROS). Antioxidants are widely used as supplements but oxidative glucose metabolism. Muscle is also known to generate whether they affect the health-promoting effects of exercise is free radicals, especially during contraction and physical exercise 85 min unknown. We evaluated the effects of a combination of vitamin C (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as (12). It has been suggested that ROS may mediate some health- promoting effects, at least in nonprimate model systems (13–17). (with or measured by glucose infusion rates (GIR) during a hyperinsuline- mic, euglycemic clamp in previously untrained (n ‫ )91 ؍‬and pre- We here evaluated the possibility that ROS are required for the insulin-sensitizing capabilities of physical exercise in healthymeasure- trained (n ‫ )02 ؍‬healthy young men. Before and after a 4 week humans and that commonly used antioxidants, such as vitamin intervention of physical exercise, GIR was determined, and muscle C and vitamin E, may abrogate the health-promoting effects of biopsies for gene expression analyses as well as plasma samples both physical exercise and oxidative stress in humans.R) during were obtained to compare changes over baseline and potential influences of vitamins on exercise effects. Exercise increased pa- Resultscted (5), rameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P < Baseline Characteristics. Of the 40 individuals included in the present study, 20 were known to be previously trained, and 20crease in 0.001) and pretrained (P < 0.001) individuals. This was paralleled were previously untrained. Study subject characteristics in the by increased expression of ROS-sensitive transcriptional regulators preinterventional state are given in Table 1. No significant of insulin sensitivity and ROS defense capacity, peroxisome- differences in age, height, body mass index, fat free mass, or VO2 exercise proliferator-activated receptor gamma (PPAR␥), and PPAR␥ coac- tivators PGC1␣ and PGC1␤ only in the absence of antioxidants (P < maximum were observed within the groups (Table 1) and no significant differences in age, height and body mass index werentrained: 0.001 for all). Molecular mediators of endogenous ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase) were also observed between untrained and pretrained groups. Not sur- prisingly, pretrained individuals had a significantly higher fat ned: Fig. induced by exercise, and this effect too was blocked by antioxidant supplementation. Consistent with the concept of mitohormesis, free mass (P ϭ 0.03) and VO2 maximum (P Ͻ 0.001). Half of the previously untrained and previously trained groups were randomly assigned to either antioxidant supplementation MEDICAL SCIENCES exercise-induced oxidative stress ameliorates insulin resistance findings and causes an adaptive response promoting endogenous antiox- idant defense capacity. Supplementation with antioxidants may as described in Methods or to no supplementation (creating 4 groups of 10 each) (supporting information (SI) Fig. S1). All tivity. By preclude these health-promoting effects of exercise in humans. subjects underwent a 4 week exercise training program irrespec- tive of antioxidant supplementation and previous training status.retrained aging ͉ hormesis ͉ insulin resistance ͉ oxidative stress ͉ reactive oxygen species One untrained individual withdrew during the study for personal reasons unrelated to the experimental protocol. gnificant T ype 2 diabetes mellitus is increasing worldwide at epidemic Induction of Oxidative Stress by Short-Term Exercise. It is well- established that physical exercise increases ROS formation in rates and is associated with both microvascular and macro- r of bars, vascular complications (1). Type 2 diabetes mellitus is caused by a combination of insulin resistance involving a number of skeletal muscle (12); however, it is not known if the health- promoting effects of exercise are partly due to this effect. To physical peripheral tissues, including skeletal muscle (2, 3), and an inadequate ␤-cell response despite normal or even increased replicate the ROS-inducing capacity of exercise in our specific experimental set-up, we subjected previously untrained individ- uals to 3 days of exercise with muscle biopsy before (Fig. S1, ly in the Fig. 1. amounts of circulating insulin. Antioxidants prevent exercise-dependent induction of insulin sensi- Physical exercise exerts numerous favorable effects on general ‘‘pre’’) and after this short-term intervention (Fig. S1, ‘‘early’’).
  • 156. Mari-Carmen Gomez-Cabrera, Elena Domenech, Marco Romagnoli, Alessandro Arduini, Consuelo Borras,one concentrations and increases ˜ a muscle and blood glutathi-oxidative stress, as indicated by alteredFederico V Pallardo, Juan Sastre, and Jose Vinin protein, DNA, and lipid peroxi- beneficial eff exerts processesdation. There is, and increases inC decreases muscle regarding the bene- one concentrations however, considerable debate lipid peroxi-ABSTRACT Oral administration of vitamin protein, DNA, and processes (10) and ha mitochondrial can exert favorable effects and c and mice dation. There is, and hampers training-induced adaptationstheendurance and mice (12). however, considerable debate regarding 9). Thus, ROS genes (8, bene-Background: Exercise practitioners vitamin C supplementation. in process of training adaptation. Up-regulatificial biogenesis 1–3 of often take vitamin C supple- involved in the health effects The m ficial health effects of vitamin C supplementation.endogenous antioxidant systemsThe maximal capa performancements because intense muscular contractile activity can result inObjective: This study was designedglutathi- effect of vitamin C in the preventionduringVtra Objective: This study altered muscle Marcoto study the Arduini, Consuelo Borras,oxidative stress, as indicated by was designed blood and to studyexerts effect of vitamin in responseof chronic˙ di the beneficial effects during exercise is ex C to regular O Mari-Carmen Gomez-Cabrera, Elena Domenech, Romagnoli, Alessandroone concentrations efficiencyprotein, Vina and lipidhumans.on training Vefficiency in ratsrats in humans. on trainingPallardo, Juan Sastre, in and Federico and increases in and Jose DNA, and in peroxi-dation. There is, however, considerable debate regarding the bene- ˜ processes (10) and has also been related to longevity of a and mice (12). limit in flies limit of a person’s or aDesign:The Exercise practitionerssupplementation. double-blindROSofcan exert adaptation.effects and canFour-transport and runnin Design: effectshuman study waswassupple- genes (8, in the process The maximal capacity to take up, during a utilize ox ABSTRACTficial health The human study double-blind and randomized. Four- belevel Background: of vitamin C often take vitamin C involved 9). Thus, and randomized. of training favorable Up-regulation level duri ments because intense muscular contractilestudy the effect of vitamin C activity can result in endogenous antioxidant systems in response to˙regular trainingObjective: Thisstress, as indicated by altered muscle and blood glutathi- 8 wk. Fiveduring exercise is VO2max (13). Endurance is defined as the teen men (27–36designed to were trained for 8 wk. inthepreventionthe diseasestudies of humans wi oxidative study was old) were trained forteenmen (27–36 increases in protein, DNA, and lipid peroxi- exerts beneficial effects Five of longevitymen were to maintain a specific p y y old) of the men were of chronic studies ofon training efficiency and rats and in humans. one concentrations in processes (10) and has also beena person’s or animal’s ability limit of related to in flies (11)Design: The health effects of daily withoral oral dose mice (12).g vitamin C. In the animallow aerobic exesupplemented vitaminwith an anandthe bene- 1 gof 1 capacity to take up, transport and utilize oxygenthat Large-scale epidemio supplemented however,was double-blind dose of and Four- levelIn theaanimal protocol (14). dation. There is, study considerable debate regarding randomized. vitamin C. ficial human daily C supplementation. during running that low The maximal Downloaded from www.ajcn.org by on June 29, 2009teen menObjective: This studywere trained forthe effect of vitamin C men were 2isdifferent protocolsasand without cardiovascular diseasestudy,24 male Wistar ratsrats vitamin exercised or that 2ability to maintain a specific power study,on 24 male Wistar were exercised under (27–36 y old) was designed to study 8 wk. Five of the during exercise VO max (13).of humans with the timemortality than are oth ˙ studies Endurance is definedsupplemented daily withinanwas double-blind and gwereFour-In the animal under low aerobic exercise capacity is an stronger predict limit of a person’s animal’s different protocols mortality 2 training efficiency rats and in humans. 1 oral dose of randomized. C. for 3 and Wistar ratswere trained for 8 wk. Five of the2men were level during running and withoutthan are other established risk factors, such as diab Design:6 wk. study The human Twelve of the rats were treateda withprotocol (14). Large-scale epidemiologicstudy,3 teen men (27–36 y old) were exercised under different studies of humans with a daily dose of showsmoking, hypertensifor andsupplemented daily with anthe rats2wereof C. In the animaldaily doseaerobic exercise capacitycardiovascular diseasedose of 24 and 6 wk. Twelve male 6 C (0.24 of Twelve mg/cm undertreated protocols the rats were treated with an stronger predictor of oral dose of 1 g vitamin surface area). of protocols mortality a daily vitaminwk.male Wistar rats were exercisedbody with a mortality than are other established risk factors, such as diabetes,ease obstructive pulmonary smoking,for 3 2 2 different that low smoking, hypertension, or chronic (15–18). These isvitaminand wk. Twelve body surface area). vitamin C significantlychronic҃ 0.014) dis-impaired regulation for 3 C (0.24 mg/cm study, 24 2 body surface area).ease (P obstructive pulmonaryvitamin C (0.246 mg/cm of the rats were treated with a daily dose of smoking, hypertension, or (15–18). These observations are consistent with the ro Results: The administration of 2 ease (15–Results: Results: The administration of vitamin C significantly (P ҃ 0.014) ҃ vitamin C (0.24 mg/cm body surface area). C significantly (P ease0.014) These observations are consistent with the role ofResults:administration ofcapacity.ofThe C may impaired regulationofmitochondrial(19). The(Paerobic capacity (19). Thefor an impo The vitamin (15–18).hampered endurance capacity. hampered endurance administration of vitamin effects impaired regulation of mitochondrial function as low a hampered enduranceThe adverse effects effects adverseC may significantlylow an҃amongmechanism relations am Thecapacity. The adverse vitamin ofvitamin C low aerobic capacity for may important mechanism for mechanism C relations of vitamin function as 0.014) impairedresult from its capacity to reduce the mitochondrial biogenesis.expression muscle effects ofendurance of C capacity, endurance capacityhamperedits capacity to reduce the to exercise-inducedof adverse oxidativemax, muscle oxidativeforVO2max, muscle ox result resulttranscriptioncapacity exercise-induced expressionexercise-induced2 expression discussed andmay from its factors involved incapacity. The maximal aerobic workload capacity, have been capacity, ˙ endurance reduce the VO capacity vitamin ˙ mechanis from 2 ˙ VO max, of keykey transcription factors involved in mitochondrial biogenesis. maximal aerobic workload capacity have been discusse These factors are peroxisome proliferator–activated receptor co-resultactivator 1, nuclear respiratory prevented mitochondrial transcrip- receptor co-the mitochondrialbiogenesis. al major concluded aerobic oxid key transcription factors to reduce in capacity (ie, from its capacity involved mitochondrial (20). Davies etThese factors are Vitamin C alsofactor 1, andthe exercise-induced ex-the exercise-induced muscle) was a (21)maximalthat O2max, tion factor A. peroxisome proliferator–activated years content of expression of years (20). Davies et al (21) concluded that muscle oxidative ˙ ˙ Vmuscle wo determinant of endurance capacity, whereas VO max was onlyactivator pression of cytochrome C (aperoxisome content) and of transcrip- to endurance capacity thewas directly relatedyears (20). Daviesa e These 1,factors are marker of mitochondrial proliferator–activated receptor co-key transcription factor 1, andtheinvolved exerciserelated capacity (ie, but mitochondrial content of muscle) was m nuclear respiratory factors mitochondrial indirectlyex-mitochondrial biogenesis. in 2 the antioxidant enzymes superoxide dismutase and glutathione per-tion factor A. Vitamin C also prevented exercise-induced intensity.determinant of endurance capacity, whereas VO2max was to In eukaryotic cells, mitochondrial biogen- maximal ˙ activator 1, oxidase. nuclear respiratory factor 1, and requires gene products from 2 physically separated ge-capacity (ie, the mitopression of cytochrome Care peroxisome proliferator–activated receptor co- esis mitochondrial transcrip-These factors it (a marker ofcellular adaptations content) andone contained within the organelle and the other con- capacity but years (20 mitochondrial Conclusion: Vitamin C supplementation decreases training nomes— of indirectly related to endurance was directly re tion factorenzymes superoxide dismutase and glutathione within the nucleus. Peroxisome proliferator–activateddeterminant of endur efficiency A. Vitamin C also prevented the exercise-induced ex- because prevents somethe antioxidant Am J Clin Nutr 2008;87:142–9. to tained per-activator 1, nuclear respiratory factor 1, nuclear receptors. Itrequires induces mRNA eukaryotic cells, mitochondrial biooxidase. exercise. of to exercise intensity. In receptor and mitochondrial transcrip- co-activator 1 (PGC-1) is a recently identified coacti- pression of cytochromeVCmax, antioxidant enzymes,mitochondrial content)factors such as expres-indirectly related to e (a marker of vatorfor important nuclear transcription and of nuclear from 2 physically separated esis powerfully gene products capacityConclusion: Vitamin Vitamin C also prevented the exercise-induced ex-tion factorsupplements, exercise, exhaustion, vitamins,decreases sion factor 1nomes— one contained within the organelle and the other antioxidant A. KEY WORDS Free radicals, ˙ O C supplementation gene ex- training determin 2 the antioxidant it preventsspecies cellular adaptations toandtained and mitochondrial transcriptionPeroxisome proliferator–acti enzymes someefficiency because reactive oxygen pression, hormesis, superoxide dismutase respiratory glutathione per- (NRF-1) within the nucleus. to exercise intensity.pression Am cytochrome C (a marker of mitochondrial content) and ofarequires gene co oxidase. of J Clin Nutr 2008;87:142–9.exercise. 1 receptor co-activator 1 (PGC-1) is recently identified p From the Department of Physiology, Faculty of Medicine, University of Valencia, Valencia, Spain (M-CG-C, ED, AA, FVP, JS, and JV); the Catholic esis indirectly INTRODUCTIONthe WORDSphysicalFreeenzymesmax, antioxidant enzymes, decreasesnuclear receptors. It powerfully inducesexercis antioxidant radicals, VO supplementation Conclusion: Vitamin augmented generation of re- Acute exercise induces C 2 ˙ superoxide dismutase and glutathione nomes— one such as exKEY active oxygen species (ROS) in muscle and in other organs (1–3). vator of training University of Valencia, Valencia, Spain (CB); and the Polytechnic Univer- sity of Valencia, Valencia, Spain (MR). 2 sion for important nuclear transcription per- factors mRNA nu to contain Supported by grants no. SAF 2004-03755 (to JV) and GV06/289 (toantioxidant supplements, exercise, accepted over the pastsome gene ex-oxidase. of that,thehas been generally antioxidants withinvitamins, cellular respiratory factor 1to efficiency because it prevents 20 y adaptations (NRF-1) and mitochondrial the ntained within transcri Because that increasing it concentrations of exhaustion,pression,cle cell should provide greaterClin speciesthese oxidizing hormesis, reactive oxygen Nutr 2008;87:142–9. M-CG-C) and by la Red Tematica de investigacion cooperativa en enveje- ´ ´ cimiento y fragilidad (RETICEF) from the Instituto de Salud Carlos III a mus- esis requ exercise.Conclusion:Am fatigue (4 –7). However, thesupplementation From the Department oftraining of Medicine, Univer J protection C Vitaminagainst functional (ISCIII2006-RED13-027). 3 decreases Physiology, Faculty co-activator receptor nomes— Reprints not available. Address correspondence to J Vina, Department of 1 agents and should reduce Physiology, Faculty of Medicine, Blasco Ibanez, 15, Valencia, Spain 46010. ˜ significance of exercise-induced oxidative stress is open to dis-
  • 157. soreness following muscle-damaging exercise but may delay the recoveryprocess British Journal of Nutrition (2006), 95, 976–981 DOI: 10.1079/BJN20061732 q The Authors 2006Graeme L. Close1*, Tony Ashton2, Tim Cable1, Dominic Doran1, Chris Holloway1, Frank McArdle2 Ascorbic acid supplementation does not attenuate post-exercise muscleand Don P. M. MacLaren1 soreness following muscle-damaging exercise but may delay the recovery1 process Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Henry Cotton Campus, 15– 21Webster Street, Liverpool L3 2ET, UK2 School of Clinical Sciences,L. Close1*, Tony Ashton2, Tim Cable1, Dominic Doran1, Chris Hollowayof Frank McArdle2 Graeme Division of Metabolic and Cellular Medicine, University 1, Liverpool, Liverpool L69 3GA, UK and Don P. M. MacLaren1(Received 7 October 2005 –Research Institute for Sport 2005 – Accepted 19 Liverpool John Moores University, Henry Cotton Campus, 15– 21 1 Revised 15 December and Exercise Sciences, December 2005) Webster Street, Liverpool L3 2ET, UK 2 School of Clinical Sciences, Division of Metabolic and Cellular Medicine, University of Liverpool, Liverpool L69 3GA, UK (Received 7 October 2005 – Revised 15 December 2005 – Accepted 19 December 2005)Exercise involving lengthening muscle actions, such as downhill running, results in delayed onset muscle soreness (DOMS), which may be attribu-table to reactive oxygen species (ROS). Although exercise causes oxidative stress, any link between ROS and DOMS remains speculative. There isemerging evidence to suggest reactiveROS play an important physiological role, inany link between the and DOMS remains speculative. There is Exercise involving lengthening muscle actions, such as downhill running, results delayed onset muscle soreness (DOMS), which may be attribu- table to that oxygen species (ROS). Although exercise causes oxidative stress,assisting in ROS recovery process and protecting the cell from futuredamage; however, this has not been fully established. Despite this uncertainty as tointhe recovery process and protecting the cell from future emerging evidence to suggest that ROS play an important physiological role, assisting the precise role of ROS, attempts to prevent post-exercise ROSproduction through antioxidant intervention been fully established. common. The study investigated precise role of effectsacid supplementation on ROS ROS damage; however, this has not Despite this uncertainty as to the of ROS, attempts to prevent post-exercise production through antioxidantare still common. The study investigated the ascorbic of ascorbic acid supplementation on ROS pro- intervention are still the effects pro-duction and DOMS following and DOMS following downhill running. Subjects were assigned to two groups. The ascorbic acid group (group AA)group (group AA) received 1 g ascorbic duction downhill running. Subjects were assigned to two groups. The ascorbic acid received 1 g ascorbic acid 2 h pre-, and for 14 d post-downhill running, whilst the placebo group (Pl group) received a placebo. Blood samples were drawn pre-sup-acid 2 h pre-, and for 14plement, pre- and post-exercise, and then 1, 2, 3,the7 placebo group (Pl analysis of ascorbate, malonaldehyde and Blood samples were drawn pre-sup- d post-downhill running, whilst 4, and 14 d post-exercise for group) received a placebo. total glutathione.ASCORBIC ACID SUPPLEMENTATION ATTENUATES ROS PRODUCTIONplement, pre- and post-exercise, and then a 2, analogue and 14 d post-exercise for analysis of ascorbate, malonaldehyde and total glutathione. DOMS was assessed using 1, visual3, 4, 7 scale and pressure algometry. Muscle function was assessed using isokinetic dynamometry. Plasma ascorbate was elevated throughout in group AA compared with the Pl group. Downhill running resulted in DOMS in both groups.DOMS was assessed using a visual analogue scale inand groups, although a delayed recovery was noted in group AA. Malonaldehyde increased 4 d isokinetic dynamometry. Muscle function was impaired post-exercise both pressure algometry. Muscle function was assessed using FOLLOWING DOWNHILL RUNNING, WITHOUT AFFECTING DOMS.Plasma ascorbate was elevated throughout in group AA supplementation with the Plproduction following downhill running, without affecting DOMS in both groups. post-exercise in the Pl group only. Ascorbic acid compared attenuates ROS group. Downhill running resulted in DOMS. Furthermore, ascorbic acid supplementation may inhibit the recovery of muscle function.Muscle function was impaired post-exercise in both groups, although a delayed recovery was noted in group AA. Malonaldehyde increased 4 dFURTHERMORE, ASCORBIC ACID SUPPLEMENTATION MAY INHIBIT THEpost-exercise in the Pl group oxygen species: Exercise: Eccentric muscle torque: Antioxidants: Muscle damage Reactive only. Ascorbic acid supplementation attenuates ROS production following downhill running, without affectingDOMS. Furthermore, ascorbic acid supplementation may inhibit the recovery of muscle function. RECOVERY OF MUSCLE FUNCTION. Unaccustomed or excessive exercise often results in the sen- or is an essential physiological process assisting in the recov-Reactive oxygen species: Exercise: Eccentric muscle torque: Antioxidants: Muscle damage sation of muscular discomfort and pain that is characterised ery from the initial trauma. The reason for this is that merely by its delay in onset and has been termed ‘delayed onset the presence of ROS cannot determine if their production is muscle soreness’ (DOMS) (Newham et al. 1983). DOMS is involved in the observed pathology. The only way that ROS often first noticed 24 h post-exercise and presents as a dull can be confirmed to be involved in the pathology is through ache similar to that of a bruise. Despite extensive research specific intervention (Jackson, 1999). Despite this uncertaintyUnaccustomed or excessive exercise often results in the sen- into DOMS, the underlying causes and methods of prevention asor is an essential physiological process assisting in the recov- to the exact role of ROS following contraction-induced remain unresolved (Close et al. 2005). damage, it is common practice for athletes to use antioxidantsation of muscular discomfort and pain that is characterised We have previously demonstrated that 30 min of downhill therapy from the initial trauma. The reason for this is that merely ery to prevent post-exercise ROS production and, further-by its delay in onsetand a significantbeen intensity ‘delayed damage running at a sub-maximaltermed results in muscleonset and has increase in reactive oxygen species (ROS) more, there is still extensive research investigating ways to if their production is the presence of ROS cannot determine prevent DOMS and muscle damage using antioxidant sup-muscle soreness’ (DOMS) (Newham etlipid peroxidation DOMS is production and subsequent al. 1983). in the days fol- plementation (Jakeman & observed pathology. The only way that ROS involved in the Maxwell, 1993; Goldfarb, 1999;often first noticed 24lipidpost-exercise speculated to be due as increase in lowing the exercise (Close et presentsThis a dull h peroxidation was and al. 2004). to phagocyte- Thompson et confirmed to be involved in the pathology is through al. 2001a). can beacid is a water-soluble, dietary antioxidant present Ascorbicache similar to that of a bruise. Despite extensive research derived superoxide (O2z2) production resulting in the sub- in specific intervention the cell and the 1999). Despite this uncertainty the cytosolic compartment of (Jackson, extracellularinto DOMS, the underlying formation is still methods of hydroxyl of ROS sequent causes and unclear ifpotentproduction radical (zOH). However, it of the more this prevention fluid, and is known to be a powerful inhibitor of lipid peroxi- as to the exact role of ROS following contraction-induced dation (Powers et al. 2004), in conjunction with a-tocopherol
  • 158. ys a ory,nses rainwth, andatedROS rain ugh 83]; cor- tiontion, the the s of Fig. 1. The redox homeostasis-associated changes Jan 15;44(2):153-9. single bout of Radak Z, Chung HY, Goto S. Free Radic Biol Med. 2008 as a result of exercise and regular exercise compared to physical inactivity. Sedentary
  • 159. Z. Radak et al. / Ageing Research Reviews 7 (2008) 34–42mesis curve and the effects of exercise. Moderate exercise increases the physiological function of different orgainst diseases and improves quality of life. Physical inactivity and strenuous exercise and overtraining in
  • 160. Pflügers Arch - Eur J Physiol (2002) 443:791–797 DOI 10.1007/s00424-001-0770-0 O R I G I N A L A RT I C L E P. Tauler · A. Aguiló · E. Fuentespina · J. A. Tur A. Pons Diet supplementation with vitamin E, vitamin C and β-carotene cocktail enhances basal neutrophil antioxidant enzymes in athletes 795Table 2 Basal neutrophil glutathione of/ Accepted: 10 October 2001 / Published online: 31 January 2002 Received: 14 June 2001 sportsmen before and after supplementation with antioxidants. The results are the mean ±s.e.m.of ten subjects in the placebo group 2002 ten subjects in the antioxidant-supplemented group © Springer-Verlag and Initial Final ANOVA Abstract Exercise increases oxygen consumption and Introduction causesPlacebo a disturbance of intracellular pro-oxidant-antioxi- Supplemented Placebo Supplemented G×T G T dant homeostasis. Few data are available as to the cumu- Exercise increases oxygen consumption and causes a lative effects of exercise on the antioxidant defenses of disturbance of intracellular pro-oxidant-antioxidant ho-Total glutathione the neutrophil. We studied the effects of 90 days’ supple- meostasis [21]. The mitochondrial electron transportnmol/ml of blood mentation with placebo or2.41±0.09a cocktail of vi- chain [26], 2.36±0.16a 2.34±0.08a an antioxidant 2.06±0.20b polymorphonuclear neutrophils [27],* and * *nmol/109neutrophils tamin E (500 mg/day) and991±37a (30 mg/day) 793±33b 961±33a β-carotene and xanthine oxidase [29] have been identified as major 989±41a * * * the last 15 days also with vitamin C (1 g/day) on sports- sources of intracellular reactive oxygen species (ROS) men’s basal neutrophil antioxidant defenses. We ana- and free radical generation during exercise. The cellularGSH lyzed the activities of catalase, glutathione peroxidase, antioxidant defense systems have demonstrated great ad-nmol/ml of blood 2.18±0.12 the activities 1.99±0.12 2.22±0.10# glutathione reductase and 2.20±0.14 and levels of su- aptation to acute and chronic exercise [32]. However, ex- *nmol/10 9 neutrophils peroxide dismutase, glutathione and glutathione disul- treme physical exercise causes oxidative damage to * 887±33 900±37 700±39 901±48# well- fide in neutrophils purified from antecubital vein blood trained athletes, as indicated by an increase in plasma of sportsmen before and after diet supplementation. Plas- levels of malondialdehyde [22, 28] and conjugated di-GSSG ma vitamin E, β-carotene and vitamin C concentrations enes [28] or by an increase in urine 8-hydroxydeoxygua-nmol/ml of blood in the0.10±0.01 0.10±0.01 0.13±0.01& 0.11±0.01a antioxidant-supplemented group were approxi- nosine (8-OhdG) after an ultra-marathon [41] and as also *nmol/10 9 neutrophils mately 1.6, 10, and 1.2 times higher respectively 52.7±1.3& 44.1±3.3 45.0±2.7 than indicated by46.9±1.6a in erythrocyte catalase activity an increase * those of the placebo group. The antioxidant-supplement- after a duathlon competition [45]: in these situations ofGSH/GSSG ed group presented a significantly higher glutathione strenuous exercise the# antioxidant defenses are over- 20.2±1.9 20.5±2.3 13.8±1.8 19.4±2.0 * versus glutathione disulfide ratio in neutrophils (about whelmed [28]. Recent studies point to negative effects of* Significant effects of20%) than the or the interaction G×Tsupplementation Significant differences between placebo of and supplemented factor G, T placebo one. Antioxidant (two-way # oxidative stress in sportsmen on the functionality dif- enhances the antioxidant enzyme activity of superoxide ferent cells of the immune system [38]. EpidemiologicalANOVA). Factor G representsand catalase antioxidant supplementa- groups (Student’shigher risk of upper respiratory tract in- dismutase the diet in neutrophils. reports suggest a t-test for unpaired data, P<0.05)tion; factor T represents the training and competition period; G×T & Significant differences betweenprolonged and final values (Stu- fection in endurance athletes due to initial exercise,represents the interaction between the two factors. Different letters dent’s t-test for unpaired data, P<0.05)perturbation of Keywords Antioxidants · Exercise · Glutathione · which leads to a transient yet significantindicate significant Neutrophil · values (ANOVA one-way test, different Oxidative stress immune and host defenses [39]. Some studies haveP<0.05) when a significant G×T interaction is observed shown that diet supplementation with vitamin C reduces the risk of upper respiratory tract infection [39]. The phagocytic cell of the immune system, which is
  • 161. ACTIVIDADE FÍSICA DIETA fffffff ! SONO TREINO EXPOSIÇÃO SOLAR DIETA GESTÃO DE STRESS SUPLEMENTOS??? SONO EXPOSIÇÃ O SOLA GESTÃO R DE STR MOTIVAÇ ESSPERFORMANCE S ÃO UPLEME NTOS?? ? Fenótipo “normal” FENÓTIPO “NORMAL”168
  • 162. ERGOGÉNICOS / ANABÓLICOS / OUTROS !
  • 163. situated within the outer mitochondrial membrane oxidation (McGarry & Brown, 1997). Figure 1. A schematic diagram of the metabolic roles of carnitine in skeletal muscle Carnitine’s role in long-chain fatty acid (acyl group) translocation into the mitochondrial matrix, for subsequent J Physiol 581.2 (2007) pp 431–444 β-oxidation is highlighted in red, whereas the role of carnitine as a buffer of excess acetyl-CoA production is highlighted in blue. PDC, pyruvate dehydrogenase complex; TCA, tricarboxylic acid cycle; CAT, carnitine acetyltransferase; CACT, carnitine acylcarnitine translocase; CPT, carnitine palmitoyltransferase; CD36, fatty acid
  • 164. hich permits unrestricted http://www.nutritionandmetabolism.com/content/3/1/35 the original work is properly cited. article is available from: use, distribution, and reproduction in any medium, provided 006 Johnston et al; licensee BioMed Central Ltd. is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 Nutrition & Metabolism BioMed Central ch permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Open Access Background:communication a cofactor in the biosynthesis of carnitine, a molecule required for the Brief Vitamin C is oxidation Marginal vitamin C statusin the ability towith reduced fatcontribute to the reported of fatty acids. A reduction is associated oxidize fat may oxidation Abstract during submaximal vitamin Cin1 young adults exercise inverse relationship betweenCorinne Corte and Pamela D Swan2 To examine this possibility, we status and adiposity. Carol S Johnston*1, Background:preliminary is a cofactor in the biosynthesisvitamin C status on fat oxidation during conducted a Vitamin C trial to evaluate the impact of of carnitine, a molecule required for the oxidation of fatty acids.Nutrition, Arizona State University, Mesa, ability to oxidizeand Wellness, Arizona State University, to the reported submaximal exercise. of A reduction in the USA and Department of Exercise fat may contribute Address: Department Mesa, USA 1 2 inverse relationship between vitaminwas Corte - corinne.corte@asu.edu; Pamela D SwanTo examine this possibility, or Methods:Email: Carolenergy - carol.johnston@asu.edu; Corinne status and adiposity. - pswan@asu.edu marginal (n = 15) we Fat S Johnston* expenditure C determined in individuals with * Corresponding author conducted (n preliminary trial status duringthesubmaximal,vitamin C status on fat oxidation during adequate a = 7) vitamin C to evaluate a impact of 60-minute treadmill test. Subsequently, submaximal exercise. with marginal vitamin C status completed an 8-week double-blind, placebo- eight of the subjects Published: 31 August 2006 Received: 16 June 2006 Methods: Nutrition &energy expenditure with submaximal exercise testing. with marginal (n = 15) or controlled,Fat Metabolism 2006, 3:35 doi:10.1186/1743-7075-3-35 determinedAugust 2006 depletion-repletion trial was Accepted: 31 in individuals This article is available from: http://www.nutritionandmetabolism.com/content/3/1/35 adequate (n 2006 Johnston et al;with BioMedstatus vitamin C status oxidized 25% less fat per kg body weight during Results: Individuals licensee marginal during a submaximal, 60-minute treadmill test. Subsequently, © = 7) vitamin C Central Ltd. eight treadmillispermits unrestricted use,distributed under theindividuals with adequate vitamin 8-week double-blind, placebo- the of thewhich test as with distribution, and reproduction in any medium, provided the original work is properly cited.C status. Fat oxidation during subjects compared to terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), This an Open Access article marginal vitamin C status completed an controlled, depletion-repletion to fatigue submaximal p = 0.009). Vitamin C repletion of vitamin C exercise was inversely related trial with (r = -0.611, exercise testing. Results: IndividualsAbstractmarginal vitamin raised fatoxidized expenditure per kg body weight during depleted subjects (500 mg vitamin C/d) C status energy 25% less fat during exercise 4-fold as with the treadmill test as compared to individuals 0.011). compared to depleted control subjects (p = with adequate vitamin C status. Fat oxidation during Background: Vitamin C is a cofactor in the biosynthesis of carnitine, a molecule required for the oxidation of fatty acids. A reduction in the ability to oxidize fat may contribute to the reported exercise was inversely related to results show-0.611, p vitamin C Vitamin C repletion of vitamin C Conclusion: These preliminary fatigue (r = that low = 0.009). status is associated with reduced inverse relationship between vitamin C status and adiposity. To examine this possibility, we conducted a preliminary trial to evaluate the impact of vitamin C status on fat oxidation during depleted subjects (500 mg vitamin C/d) raised vitamin C status may partially explain the4-fold as fat oxidation during submaximal exercise. Low fat energy expenditure during exercise inverse submaximal exercise. Methods: Fat energy expenditure was relationship depleted controlC status during determined in individuals with marginal (nindividuals are unsuccessful in compared to between vitaminvitamin C status and=a submaximal, 60-minute treadmill test. Subsequently, adequate (n = 7) subjects (p adiposity and why some 0.011). = 15) or their weight loss attempts. eight of the subjects with marginal vitamin C status completed an 8-week double-blind, placebo- Conclusion: These preliminary results with submaximal exercise testing. controlled, depletion-repletion trial show that low vitamin C status is associated with reduced Results: Individuals fat oxidation duringthe treadmill test as withexercise. Low adequate 25% lessCstatus oxidationpartially explain the inverse submaximal marginal vitamin C status oxidized vitamin fatstatus. Fat may during compared to individuals with vitamin C per kg body weight during relationship between vitamin C mg vitamin C/d) raised fat energy expenditure during exercise 4-fold as exercise was inversely status fatigue (radiposity and why repletion of vitamin C depleted subjects (500 related to and = -0.611, p = 0.009). Vitamin C some individuals are unsuccessful in their weight loss attempts. depleted control subjects (p = 0.011). compared toBackground Conclusion: These preliminary results show that low vitamin C status is associated withwaist measurements [6]. The underlyin weight [4,5] and reduced bout 15% of US adults are vitamin between vitamin C status and adiposity and systemic oxidative stress associated with obesity has bee C deficient (plasma fat oxidation during submaximal exercise. Low vitamin C status may partially explain the inverse relationship why some individuals are unsuccessful in
  • 165. Eur J NutrDOI 10.1007/s00394-011-0253-9 REVIEWThe efficacy of long-term conjugated linoleic acid (CLA)supplementation on body composition in overweight and obeseindividuals: a systematic review and meta-analysis of randomizedclinical trialsIgho J. Onakpoya • Paul P. Posadzki •Leala K. Watson • Lucy A. Davies •Edzard ErnstReceived: 17 February 2011 / Accepted: 26 September 2011Ó Springer-Verlag 2011Abstract Keywords Obesity Á Body weight Á Body fat ÁIntroduction Numerous supplements containing conju- Weight loss Á Fat loss Á Meta-analysisgated linoleic acid (CLA) are presently being promoted forbody weight reduction. The aim of this systematic reviewis to evaluate the evidence for or against the long-term Introductionefficacy of CLA.Methods Electronic searches were conducted to identify The prevalence of overweight and obesity has increasedrelevant randomized clinical trials (RCTs). No restrictions dramatically over the last few decades [1]. Different weightin age, time, or language were imposed. Studies had to be management options are available, and a variety of dietaryat least 6 months in duration. Three reviewers indepen- supplements is being sold as slimming aids. However, thedently determined the eligibility of studies. Two reviewers efficacy of some of these supplements is not proven. Oneindependently extracted data and assessed the reporting such supplement is conjugated linoleic acid (CLA).
  • 166. 23, 25], their treatment groups wereTs reported no significant differenceetween the CLA and placebo groups. CLA E PESO CORPORAL on in the dosages and composition of ! the RCTs. The dosages ranged from Fig. 3 Funnel plot of comparison of the effect of CLA supplemen-3, 26]. All RCTs except one [24] tation on body weightct of) 123
  • 167. CLA E GORDURA CORPORAL ! Eur J4 Forest plot of the effect of CLA supplementation on body fat (kg)5 Forest plot of the effectLA supplementation on circumference (cm)
  • 168. CLA E PERÍMETRO DA CINTURA! e effect of CLA supplementation on body fat (kg) e effectn onm)e effectn on
  • 169. Eur J NutrDOI 10.1007/s00394-011-0253-9 REVIEWThe efficacy of long-term conjugated linoleic acid (CLA)supplementation on body composition in overweight and obeseindividuals: a systematic review and meta-analysis of randomizedclinical trialsIgho J. Onakpoya • Paul P. Posadzki •Leala K. Watson • Lucy A. Davies •Edzard ErnstReceived: 17 February 2011 / Accepted: 26 September 2011Ó Springer-Verlag 2011Abstract Keywords Obesity Á Body weight Á Body fat ÁIntroduction Numerous supplements containing conju- Weight loss Á Fat loss Á Meta-analysisgated linoleic acid (CLA) are presently being promoted forbody weight reduction. The aim of this systematic reviewis to evaluate the evidence for or against the long-term Introductionefficacy of CLA.Methods Electronic searches were conducted to identify The prevalence of overweight and obesity has increasedrelevant randomized clinical trials (RCTs). No restrictions dramatically over the last few decades [1]. Different weightin age, time, or language were imposed. Studies had to be management options are available, and a variety of dietaryat least 6 months in duration. Three reviewers indepen- supplements is being sold as slimming aids. However, thedently determined the eligibility of studies. Two reviewers efficacy of some of these supplements is not proven. Oneindependently extracted data and assessed the reporting such supplement is conjugated linoleic acid (CLA).
  • 170. found in the muscle is stored as phosphocreatine (PCr), while the remaining amount H2N CH COOH + Glycine Ornithine + Guanidinoacetic acid (H2C)3 NH S-adenosylmethionine C NH NH2 COOH Arginine ADP ATP CH2 Phosphocreatine H3C NH ADP ATP HN C NH2 O músculo degrada ~ 1-2% de creatina Creatine como creatinina Pi + H2O (URINA) H2O CreatinineFIGURE 9.1 Chemical structure and biochemical pathway for creatine and creatinine syn-thesis. (From Paddon-Jones, D. et al., J. Nutr., 134, 2888S–2894S, 2004.)Totowa, NJ, 2009 Greenwood M, Kalman D, Antonio J. Nutritional Supplements in Sports and Exercise. Humana Press,
  • 171. VARIAÇÃO DO PESO TOTAL (BM), MASSA MAGRA (FFM) EGORDURA CORPORAL DURANTE AS 12 SEMANAS DE INTERVENÇÃO Volek JS, et al. Med Sci Sports Exerc.1999 Aug;31(8):1147-56.
  • 172. VARIAÇÃO NA ÁREA TRANSVERSAL DAS FIBRAS MUSCULARES APÓS A INTERVENÇÃO Figure4)Deltachangesincross)sec3onalareasofspecific musclefibertypesa:er12wkofheavyresistance trainingincrea3neandplacebosubjects.*P<=0.05 fromcorrespondingchangeintheplacebogroup.Values aremean+/)SE. Volek JS, et al. Med Sci Sports Exerc.1999 Aug;31(8):1147-56.
  • 173. P Group  Time 0.264 0.653 0.385ge of 3-d1 ) carbo-efore and The data BASICces were FIGURE 1—Body mass and composition changes. * Significantly Cribb PJ, Williams AD, Hayes A. Med Sci Sports Exerc. 2007 Nov;39(11):1960-8. different from PRO-CHO; † significantly different from PRO (P G 0.05).th regard
  • 174. FIGURE 3—Changes in muscle fiber CSA (types I, IIa, and IIx).* Significantly different from PRO-CHO; † significantly different from FIGUREPRO (P G 0.05). and 1RM Cribb PJ, Williams AD, Hayes A. Med Sci Sports Exerc. 2007 Nov;39(11):1960-8.
  • 175. up  in CSA across all muscle fiber types (P G 0.05) after theme01011130105t for all FIGURECribb PJ, Williamsstrength Med Sci Sports * Significantly different from 2—1RM AD, Hayes A. changes. Exerc. 2007 Nov;39(11):1960-8. PRO-CHO; † significantly different from PRO (P G 0.05).
  • 176. Journal of the International Societyof Sports Nutrition BioMed CentralCommentary Open AccessInternational Society of Sports Nutrition position stand: creatinesupplementation and exerciseThomas W Buford, Richard B Kreider*, Jeffrey R Stout, Mike Greenwood,Bill Campbell, Marie Spano, Tim Ziegenfuss, Hector Lopez, Jamie Landis andJose AntonioAddress: International Society of Sports Nutrition, 600 Pembrook Drive, Woodland Park, CO 80863, USAEmail: Thomas W Buford - thomas_buford@baylor.edu; Richard B Kreider* - Richard_Kreider@baylor.edu; Jeffrey R Stout - jrstout@ou.edu;Mike Greenwood - Mike_Greenwood@baylor.edu; Bill Campbell - Campbell@coedu.usf.edu; Marie Spano - mariespano@comcast.net;Tim Ziegenfuss - tim@ohioresearchgroup.com; Hector Lopez - hlopezmd@gmail.com; Jamie Landis - jlandis@lakelandcc.edu;Jose Antonio - exphys@aol.com* Corresponding authorPublished: 30 August 2007 Received: 13 August 2007 Accepted: 30 August 2007Journal of the International Society of Sports Nutrition 2007, 4:6 doi:10.1186/1550-2783-4-6This article is available from: http://www.jissn.com/content/4/1/6© 2007 Buford et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
  • 177. been approved by the Research Committee of the Soci- 6. The addition of car ety. been approved by the Research Committee of theto a creatine sup tein Soci- 6. The ety. lar retention tein c of to lar r 5.1.At present, creatine monohydrate effective ergogenic Creatine monohydrate is the most is the most exten- performance measure nutritional 1. Creatine monohydrate is the most effectiveatine monohydrate al supplement currently available of creatine for ergogenic sively studied and clinically effective form to athletes in perfor related terms of increasing high-intensity exercise capacity and to athletes in nutritional supplement currently available use in nutritional supplements in terms of muscle uptake atineent con- lean body mass during training. high-intensity exercise capacity and terms of increasing and ability to increase high-intensity exercise capacity. 7. The quickest met lean body mass during training. 7. Th stores appears to be to ey have 2. Creatine monohydrate supplementation is not only stores atine monohydrate fohe Soci- 6. The addition of carbohydrate or carbohydrate and pro- safe, but possibly beneficial in regard to preventing injury isd not only to mainta 2. Creatine monohydrate supplementation thereafter atine tein to a creatine supplement appears to increase muscu- and/or management possibly beneficial in regard to preventing injury creatine safe, but of select medical conditions when amounts of d ther lar retention of creatine, although the effect on taken within recommended guidelines. and/or management of select medical conditions whenincrease muscle creat amou gogenic performance measures may not be greater than using cre- however, the performhletes in taken within recommended guidelines. atine monohydrate alone. increa 3. There is no scientific evidence that the short- or long- plementation are less howecity and term use of creatine is no scientifichas any detrimental 3. There monohydrate evidence that the short- or long- pleme 7.effects on otherwise healthy individuals. muscle creatine 8. Creatine products a The quickest method of increasing stores appears to be to of creatine monohydrate has any detrimental are reg term use consume ~0.3 grams/kg/day of cre- plement and ot only effects on otherwise healthy individuals. g/ atine monohydrate for at least supervision are provided, 3 days followed by 3–5 8. Cre 4. If proper precautions and Administration (FDA). g injury d supplementation in young athletes is acceptable and may thereafter to maintain elevated stores. Ingesting smaller Bill Clinton signed plemens when amounts aof 4. If proper precautions and 2–3 g/d) will Health and Education creatine monohydrate (e.g., supervision are provided, provide nutritional alternative to potentially dangerous Admin supplementation in young athletes is acceptable and may increase muscle creatine stores over a 3–4 week period, ufacturers/companies anabolic drugs. Bill C however, the performance effects alternative to potentially dangerous provide a nutritional of this method of sup- Healtor long- plementation are less drugs. anabolic supported. ufactuimental
  • 178. Figure 3 The increase in muscle phosphocreatinety of Melbourne on 02/07/11. For personal use only. (PCr) after creatine supplementation is inversely related to presupplementation PCr levels. Reproduced from Volek & Rawson (90), with permission from Elsevier. of supplementation. Decreased urine output exercise, by an average of 37%. Clearly, these during this time has been attributed to water Brosnan ME. Annu Rev Nutr. 2007;27:241-61 in- Brosnan JT, compounds are major osmotically active retention because of the osmotic effects of cre- tracellular solutes. Creatine supplementation atine uptake (97). Creatine is frequently taken does not affect muscle ATP levels (30).
  • 179. FONTES ALIMENTARES DE CREATINA! Alimento  (1  Kg) CreaUna  (grs) Arenque 6,5-­‐10 Porco 5 Salmão 4,5 Bife  (bovino) 4,5 Atum 4 Bacalhau 3 Leite 0,1Greenwood M, Kalman D, Antonio J. Nutritional Supplements in Sports and Exercise. Humana Press, Totowa, NJ, 2009
  • 180. Effects of 7 Days of Arginine-Alpha-Ketoglutarate Supplementation on Blood Flow, Plasma L-Arginine, Nitric Oxide Metabolites, and Asymmetric Dimethyl Arginine After Resistance Exercise Darryn S. Willoughby, Tony Boucher, Jeremy Reid, Garson Skelton, and Mandy Clark “At the dosage used, we have presented data Background: Arginine-alpha-ketoglutarate (AAKG) supplements are alleged to increase nitric oxide produc- tion, thereby resulting in vasodilation appear to refute the alleged effects herein that during resistance exercise. This study sought to determine the of AAKG supplementation on hemodynamics and brachial-artery blood flow and the circulating levels of L-arginine, nitric oxide metabolites (NOx; manufacturers’ claims that and supposition and nitrate/nitrite), asymmetric dimethyl arginine (ADMA), L-arginine:ADMA ratio after resistance exercise. Methods: Twenty-four physically active men underwent 7 “vasodilating supplements” Platinum or placebo (PLC). Before and after days of AAKG supplementation with 12 g/day of either NO containing L-arginine 2 supplementation, a resistance-exercise session involving the elbow flexors was performed involving 3 sets of 15 repetitions with 70–75% of 1-repetition maximum. Datavasodilation, before, immediately are effective at causing were collected immediately thereby after (PST), and 30 min after (30PST) each exercise session. Data were analyzed with factorial ANOVA (p < .05). Results: Heart rate, blood pressure, and blood flow were increased in to groups at PST skeletal resulting in increased blood flow both active (p = .001) but not different between groups. Plasma L-arginine was increased in the NO group (p = .001). NOx was shown muscle during resistance exercise” 2 to increase in both groups at PST (p = .001) and at 30PST (p = .001) but was not different between groups. ADMA was not affected between tests (p = .26) or time points (p = .31); however, the L-arginine:ADMA ratio was increased in the NO2 group (p = .03). Conclusion: NO2 Platinum increased plasma L-arginine levels; however, the effects observed in hemodynamics, brachial-artery blood flow, and NOx can only be attributed to the resistance exercise. Keywords: vasodilation, hemodynamics, amino acid, skeletal muscle International Journal of Sport Nutrition and Exercise Metabolism, 2011, 21, 291-299 Nitric oxide is a gaseous signaling molecule known © 2011 Human Kinetics, Inc. In recent years, various nutritional supplements haveto contribute to the control of vascular tone (Thomas, been developed containing L-arginine and other com-Shaul, Yuhanna, Froehner, & Adams, 2003) and is con- pounds (mainly arginine-alpha-ketoglutarate; AAKG)
  • 181. 
Branched-Chain Amino Acids BCAA! 251 Time to exhaustion at 40% VO2 max in the heat (min) 180 * 150 120 90 60 30 0 PLACEBO BCAA ~30g ingested during exerciseFIGURE 13.6 Time to exhaustion during cycling at 40% VO2max in the heat with or withoutingestion of ~30 g of BCAA. *, p < 0.05 significantly different from placebo. (Data fromMittleman, K.D. et al., Med. Sci. Sports Exerc., 30, 83–91, 1998.) Time to exhaustion at ~75% VO2 max (min) 180
  • 182. Atleta de forçaSíntese proteica Atleta de endurance Indivíduo sedentário 0.5 1.0 1.5 2.0 2.5 Consumo proteico diário (g/Kg peso) Lemon PW. Int J Sport Nutr. 1998 Dec;8(4):426-47.
  • 183. FONTES ALIMENTARES DE BCAA!Alimento Isoleucina Leucina Valina Total(100 Kcal) mg mg mg mgClara de ovo em pó 1200 1791 1352 4343Clara de ovo 1188 1774 1340 4302Proteínas Whey 922 1719 896 3537Carnes (média) 928 1474 967 3369Proteína de soja 886 1481 923 3290Marisco 744 1285 803 2832Leite 323 524 358 1205Cereais (média) 130 303 172 605Fruta (média) 20 31 29 80
  • 184. amino acids (AA), casein isolate (CAS), and whey protein isolate (WP greater than that of ra Table 2 Approximations of Amino TAXA DEAbsorption from Different PARTIR DE Acid ABSORÇÃO DE AA A cooked egg white, pe and slightly greater tha VÁRIAS FONTES PROTEICAS Protein Sources protein. Free amino aci Absorption the same amino acid Protein source rate (g/h) Reference as casein protein elicit transient peak of plasma Egg protein raw 1.3 43 acids, while casein r Pea flour 2.4 41 amino acids slowly ove Egg protein cooked 2.8 43 hours after consumptio is consistent with othe Pea flour: globulins 3.4 42 ies that show free ami & albumins mixtures induce a mor Milk protein 3.5 40 absorption than intact p Soy protein isolate 3.9 46 (49, 50). The two mi tein fractions, micellar Free AA 4.3 39 and the soluble whey Casein isolate 6.1 38 have been synonymou the concept of “slow Free AA (same 7-7.5 39 profile as casein) “fast” digestibility of p A detailed discussion o Whey isolate 8-10 38 two milk protein fractBilsborough & Mann (2006). International Journal of Sport Nutrition and Exercise Metabolism, 16(2), 129-152.
  • 185. Nutrientes Leite Humano Leite de Vaca Proteína Total (g/dl) 0,7-1,6 3,6 Rácio Caseína/PSL 20/80 - 50/50 80/20Chandan RC. Milk composition, physical and processing characteristics. In Hui YH, Chandan RC, Clark S, et al. Handbook of Food ProductsManufacturing – Health, Meat, Milk, Poultry, Seafood, and Vegetables. John Wiley & Sons, 2007, pps 347-377Lonnerdal. Human Milk Proteins. In Pickering LK, et al. Protecting Infants through Human Milk. Kluwer Academic/Plenum Publishers, 2004, pps 11-25
  • 186. LEITE HUMANO VS BOVINO!Proteínas do Soro g/Lt de Leite g/Lt de Leite (PSL) Bovino Humanoβ-Lactoglobulina (A,B,C,D,E,F,G) 3,2 -------α- Lactalbumina (A,B,C) 1,2 2,8Albumina Sérica 0,4 0,6Immunoglobulinas 0,7 1Lactoferrina 0,1 0,2 Mataix J. Nutrición y Alimentación Humana – Tomo I: Nutrientes y Alimentos. Ergon, 2002.
  • 187. CASEÍNA VS WHEY Caseína Whey Tempo (min) FIG. 3. (A) Total Proc Natl Acad rateS A. 1997 Dec 23;94(26):14930-5. exogenous Boirie Y, et al. leucine Sci U of appearance, (B)f the leucine rate of appearance, and (C) endogenous leucine rate ofered appearance after labeled WP ingestion (13C-WP study; open triangles)
  • 188. WPC E GLUTATIONA !ü  Grupo 1 (5 H e 5 M): ! ! !10 g 2 x dia de Imunocal (WPC) !ü  Grupo 2 (5 H e 5 M): ! ! !10 g 2 x dia de Caseína (C)!ü Duração: 3 meses!ü Objectivo: ! !Analisar as concentrações linfocitárias de GSH e !Performance (cicloergómetro durante 30’’)! ! ! !! !! Lands LC, et al. J. Appl. Physiol. 87(4): 1381–1385, 1999. ! ! ! ! ! !!!
  • 189. RESULTADOS% de gordura: Peso (Kg) MG (Kg) MIG (Kg)Grupo WPC: - 4.8 Grupo WPC: - 1 Grupo WPC: - 0.93 Grupo WPC: - 0.07Grupo C: + 5.1 Grupo C: + 0.2 Grupo C: + 0.65 Grupo C: - 0.45
  • 190. J Appl Physiol 107: 987–992, 2009. First published July 9, 2009; doi:10.1152/japplphysiol.00076.2009. HIGHLIGHTED TOPIC Regulation of Protein Metabolism in Exercise and Recovery Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise990 in young men WHEY PROTEIN AND MUSCLE ANABO Jason E. Tang,1 Daniel R. Moore,1 Gregory W. Kujbida,1 Mark A. Tarnopolsky,2 and Stuart M. Phillips1 1 Department of Kinesiology-Exercise Metabolism Research Group, and 2Pediatrics and Neurology, McMaster University, Hamilton, Ontario, Canada Submitted 25 January 2009; accepted in final form 6 July 2009 Tang JE, Moore DR, Kujbida GW, Tarnopolsky MA, Phillips exercise potentiates the anabolic effect of feeding (32, 35). SM. Ingestion of whey hydrolysate, casein, or soy protein isolate: Several studies examining the consumption of whole proteins effects on mixed muscle protein synthesis at rest and following have found that the type of protein, and not simply its amino Downloaded from jap.physiology.org on September 23, 2011 resistance exercise in young men. J Appl Physiol 107: 987–992, 2009. acid composition, can differentially modulate the anabolic First published July 9, 2009; doi:10.1152/japplphysiol.00076.2009.— response (3, 8, 9, 37). For example, it has been suggested that This study was designed to compare the acute response of mixed muscle protein synthesis (MPS) to rapidly (i.e., whey hydrolysate and milk promotes better whole body nitrogen retention at rest (4, soy) and slowly (i.e., micellar casein) digested proteins both at rest 14), and greater skeletal muscle protein accretion after resis- and after resistance exercise. Three groups of healthy young men (n ϭ tance exercise, compared with soy protein (37). The difference 6 per group) performed a bout of unilateral leg resistance exercise in the metabolism of milk and soy proteins has been attrib- followed by the consumption of a drink containing an equivalent uted to their digestion kinetics, wherein milk is digested content of essential amino acids (10 g) as either whey hydrolysate, slower than soy (4). Milk contains two protein fractions, micellar casein, or soy protein isolate. Mixed MPS was determined by whey and casein, which have been characterized based on a primed constant infusion of L-[ring-13C6]phenylalanine. Ingestion of their rate of digestion as “fast” and “slow” proteins, respec- whey protein resulted in a larger increase in blood essential amino tively (3). Soy, on the other hand, contains a single homo- acid, branched-chain amino acid, and leucine concentrations than either casein or soy (P Ͻ 0.05). Mixed MPS at rest (determined in the geneous protein fraction, which is digested in a manner nonexercised leg) was higher with ingestion of faster proteins more similar to whey than casein (4). (whey ϭ 0.091 Ϯ 0.015, soy ϭ 0.078 Ϯ 0.014, casein ϭ 0.047 Ϯ Whey protein is acid soluble and thus is digested quickly and 0.008%/h); MPS after consumption of whey was ϳ93% greater than results in a pronounced aminoacidemia. Data obtained at the casein (P Ͻ 0.01) and ϳ18% greater than soy (P ϭ 0.067). A similar whole body level show that whey induces a transient rise in result was observed after exercise (whey Ͼ soy Ͼ casein); MPS whole body protein synthesis and leucine oxidation at rest (3, following whey consumption was ϳ122% greater than casein (P Ͻ 8, 9). Conversely, casein has a modest effect on whole body 0.01) and 31% greater than soy (P Ͻ 0.05). MPS was also greater with protein synthesis but instead inhibits whole body protein break- soy consumption at rest (64%) and following resistance exercise down (3, 8, 9). Thus, at least at the whole body level, protein (69%) compared with casein (both P Ͻ 0.01). We conclude that the digestion rate appears to be an independent factor regulating feeding-induced simulation of MPS in young men is greater after whey hydrolysate or soy protein consumption than casein both at rest protein anabolism (8). While the data from whole body protein and after resistance exercise; moreover, despite both being fast pro- kinetics point to differential effects of different proteins on teins, whey hydrolysate stimulated MPS to a greater degree than soy synthesis and breakdown (3, 8, 9), skeletal muscle only con- after resistance exercise. These differences may be related to how tributes ϳ25–30% to whole body protein synthesis (25), and its quickly the proteins are digested (i.e., fast vs. slow) or possibly to turnover rate is much lower (on the order of 20ϫ) than that of small differences in leucine content of each protein. more rapidly-turning-over gut (26, 27) and plasma proteins (6). hypertrophy; muscle mass; weightlifting Thus protein turnover measured at the whole body level may or may not be reflective, or even representative, of the anabolism of muscle proteins. At present, only a single study has mea- TWO OF THE MOST POTENT stimulators of skeletal muscle protein sured the chemical net balance of amino acids across a limb synthesis (MPS) are feeding and resistance exercise (29). The following whey and casein ingestion (34), but these data do not postprandial increase in circulating essential amino acids stim- give kinetic results and were equivocal depending on the ulates a marked rise in protein synthesis (7, 15, 35); this effect choice of amino acid tracer studied. Thus to date no study has appears to be due to the amino acids themselves acting as the directly compared changes in skeletal MPS following the stimulus and not an effect due to the modest increases in consumption of isolated proteins with differing rates of diges- insulin that result from amino acid ingestion (16). Resistance tion in humans. The purpose of this study, therefore, was to measure the response of skeletal MPS following the ingestion of three distinct but high-quality proteins (from a dietary Address for reprint requests and other correspondence: S. M. Phillips, Dept. of Kinesiology-Exercise Metabolism Research Group, McMaster standpoint), whey, micellar casein, and soy, at rest and after Univ., 1280 Main St. West, Hamilton, Ontario L8S 4K1, Canada (e-mail: resistance exercise. We chose to measure these responses phillis@mcmaster.ca). following ingestion of similar quantities of these proteins but http://www. jap.org 8750-7587/09 $8.00 Copyright © 2009 the American Physiological Society 987
  • 191. J Appl Physiol 107: 987–992, 2009. First published July 9, 2009; doi:10.1152/japplphysiol.00076.2009. HIGHLIGHTED TOPIC Regulation of Protein Metabolism in Exercise and Recovery Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men Jason E. Tang,1 Daniel R. Moore,1 Gregory W. Kujbida,1 Mark A. Tarnopolsky,2 and Stuart M. Phillips1 1 Department of Kinesiology-Exercise Metabolism Research Group, and 2Pediatrics and Neurology, McMaster University, Hamilton, Ontario, Canada Submitted 25 January 2009; accepted in final form 6 July 2009 Tang JE, Moore DR, Kujbida GW, Tarnopolsky MA, Phillips exercise potentiates the anabolic effect of feeding (32, 35). SM. Ingestion of whey hydrolysate, casein, or soy protein isolate: Several studies examining the consumption of whole proteins effects on mixed muscle protein synthesis at rest and following have found that the type of protein, and not simply its amino Downloaded from jap.physiology.org on September 23, 2011 resistance exercise in young men. J Appl Physiol 107: 987–992, 2009. acid composition, can differentially modulate the anabolic First published July 9, 2009; doi:10.1152/japplphysiol.00076.2009.— response (3, 8, 9, 37). For example, it has been suggested that This study was designed to compare the acute response of mixed muscle protein synthesis (MPS) to rapidly (i.e., whey hydrolysate and milk promotes better whole body nitrogen retention at rest (4, soy) and slowly (i.e., micellar casein) digested proteins both at rest 14), and greater skeletal muscle protein accretion after resis- and after resistance exercise. Three groups of healthy young men (n ϭ tance exercise, compared with soy protein (37). The difference 6 per group) performed a bout of unilateral leg resistance exercise in the metabolism of milk and soy proteins has been attrib- followed by the consumption of a drink containing an equivalent uted to their digestion kinetics, wherein milk is digested content of essential amino acids (10 g) as either whey hydrolysate, slower than soy (4). Milk contains two protein fractions, micellar casein, or soy protein isolate. Mixed MPS was determined by whey and casein, which have been characterized based on a primed constant infusion of L-[ring-13C6]phenylalanine. Ingestion of their rate of digestion as “fast” and “slow” proteins, respec- whey protein resulted in a larger increase in blood essential amino tively (3). Soy, on the other hand, contains a single homo- acid, branched-chain amino acid, and leucine concentrations than either casein or soy (P Ͻ 0.05). Mixed MPS at rest (determined in the geneous protein fraction, which is digested in a manner nonexercised leg) was higher with ingestion of faster proteins more similar to whey than casein (4). (whey ϭ 0.091 Ϯ 0.015, soy ϭ 0.078 Ϯ 0.014, casein ϭ 0.047 Ϯ Whey protein is acid soluble and thus is digested quickly and 0.008%/h); MPS after consumption of whey was ϳ93% greater than results in a pronounced aminoacidemia. Data obtained at the casein (P Ͻ 0.01) and ϳ18% greater than soy (P ϭ 0.067). A similar whole body level show that whey induces a transient rise in result was observed after exercise (whey Ͼ soy Ͼ casein); MPS whole body protein synthesis and leucine oxidation at rest (3, following whey consumption was ϳ122% greater than casein (P Ͻ 8, 9). Conversely, casein has a modest effect on whole body 0.01) and 31% greater than soy (P Ͻ 0.05). MPS was also greater with protein synthesis but instead inhibits whole body protein break- soy consumption at rest (64%) and following resistance exercise down (3, 8, 9). Thus, at least at the whole body level, protein (69%) compared with casein (both P Ͻ 0.01). We conclude that the digestion rate appears to be an independent factor regulating feeding-induced simulation of MPS in young men is greater after protein anabolism (8). While the data from whole body protein whey hydrolysate or soy protein consumption than casein both at rest and after resistance exercise; moreover, despite both being fast pro- kinetics point to differential effects of different proteins on Fig. 4. Plasma (A) and muscl synthesis and breakdown (3, 8, 9), skeletal muscle only con- teins, whey hydrolysate stimulated MPS to a greater degree than soy after resistance exercise. These differences may be related to how tributes ϳ25–30% to whole body protein synthesis (25), and its (tracee-to-tracer ratio; t ⅐ TϪ1) quickly the proteins are digested (i.e., fast vs. slow) or possibly to turnover rate is much lower (on the order of 20ϫ) than that of small differences in leucine content of each protein. more rapidly-turning-over gut (26, 27) and plasma proteins (6). Ex, exercise. hypertrophy; muscle mass; weightlifting Thus protein turnover measured at the whole body level may or may not be reflective, or even representative, of the anabolism of muscle proteins. At present, only a single study has mea- TWO OF THE MOST POTENT stimulators of skeletal muscle protein sured the chemical net balance of amino acids across a limb synthesis (MPS) are feeding and resistance exercise (29). The following whey and casein ingestion (34), but these data do not postprandial increase in circulating essential amino acids stim- ulates a marked rise in protein synthesis (7, 15, 35); this effect give kinetic results and were equivocal depending on the choice of amino acid tracer studied. Thus to date no study has body protein turnover b appears to be due to the amino acids themselves acting as the stimulus and not an effect due to the modest increases in directly compared changes in skeletal MPS following the consumption of isolated proteins with differing rates of diges- of whey hydrolysate and tion in humans. The purpose of this study, therefore, was to in considerably higher insulin that result from amino acid ingestion (16). Resistance measure the response of skeletal MPS following the ingestion of three distinct but high-quality proteins (from a dietary Address for reprint requests and other correspondence: S. M. Phillips, Dept. of Kinesiology-Exercise Metabolism Research Group, McMaster Univ., 1280 Main St. West, Hamilton, Ontario L8S 4K1, Canada (e-mail: standpoint), whey, micellar casein, and soy, at rest and after resistance exercise. We chose to measure these responses casein (i.e., “slow” pr phillis@mcmaster.ca). Blood 8750-7587/09 $8.00 Copyright 2009 amino acids (A) © following ingestion of similar quantities of these proteins butFig. 3. http://www. jap.orgconcentration of essential the American Physiological Society and leucine (B) after 987 casein) and after resistaningestion of whey hydrolysate, casein, or soy protein. Inset: leucine area under our view, these differen
  • 192. of aminoacidemia following ingestion of 36 g of whole whey protein or its hydrolysate (5). While the pattern of peripheral J Appl Physiol 107: 987–992, 2009. First published July 9, 2009; doi:10.1152/japplphysiol.00076.2009.u- aminoacidemia yields no insight into the actual kinetics of HIGHLIGHTED TOPIC Regulation of Protein Metabolism in Exercise and Recovery Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixedoy protein absorption, this fact and following littleexercise muscle protein synthesis at rest is of resistance consequences since the in young meney concentration of amino acids in the peripheral (i.e., non- Jason E. Tang,1 Daniel R. Moore,1 Gregory W. Kujbida,1 Mark A. Tarnopolsky,2 and Stuart M. Phillips1 1 Department of Kinesiology-Exercise Metabolism Research Group, and 2Pediatrics and Neurology, McMaster University, Hamilton, Ontario, Canada Submitted 25 January 2009; accepted in final form 6 July 2009 ty Tang JE, Moore DR, Kujbida GW, Tarnopolsky MA, Phillips SM. Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following exercise potentiates the anabolic effect of feeding (32, 35). Several studies examining the consumption of whole proteins have found that the type of protein, and not simply its amino Downloaded from jap.physiology.org on September 23, 2011 resistance exercise in young men. J Appl Physiol 107: 987–992, 2009. acid composition, can differentially modulate the anabolic b- First published July 9, 2009; doi:10.1152/japplphysiol.00076.2009.— response (3, 8, 9, 37). For example, it has been suggested that This study was designed to compare the acute response of mixed muscle protein synthesis (MPS) to rapidly (i.e., whey hydrolysate and milk promotes better whole body nitrogen retention at rest (4, soy) and slowly (i.e., micellar casein) digested proteins both at rest 14), and greater skeletal muscle protein accretion after resis- tance exercise, compared with soy protein (37). The difference of and after resistance exercise. Three groups of healthy young men (n ϭ 6 per group) performed a bout of unilateral leg resistance exercise in the metabolism of milk and soy proteins has been attrib- followed by the consumption of a drink containing an equivalent uted to their digestion kinetics, wherein milk is digested content of essential amino acids (10 g) as either whey hydrolysate, slower than soy (4). Milk contains two protein fractions, micellar casein, or soy protein isolate. Mixed MPS was determined byon whey and casein, which have been characterized based on a primed constant infusion of L-[ring-13C6]phenylalanine. Ingestion of their rate of digestion as “fast” and “slow” proteins, respec- whey protein resulted in a larger increase in blood essential amino tively (3). Soy, on the other hand, contains a single homo- acid, branched-chain amino acid, and leucine concentrations than either casein or soy (P Ͻ 0.05). Mixed MPS at rest (determined in the geneous protein fraction, which is digested in a manner al nonexercised leg) was higher with ingestion of faster proteins more similar to whey than casein (4). (whey ϭ 0.091 Ϯ 0.015, soy ϭ 0.078 Ϯ 0.014, casein ϭ 0.047 Ϯ Whey protein is acid soluble and thus is digested quickly and 0.008%/h); MPS after consumption of whey was ϳ93% greater than results in a pronounced aminoacidemia. Data obtained at the casein (P Ͻ 0.01) and ϳ18% greater than soy (P ϭ 0.067). A similar whole body level show that whey induces a transient rise inm- result was observed after exercise (whey Ͼ soy Ͼ casein); MPS whole body protein synthesis and leucine oxidation at rest (3, following whey consumption was ϳ122% greater than casein (P Ͻ 8, 9). Conversely, casein has a modest effect on whole body 0.01) and 31% greater than soy (P Ͻ 0.05). MPS was also greater with protein synthesis but instead inhibits whole body protein break- soy consumption at rest (64%) and following resistance exercise down (3, 8, 9). Thus, at least at the whole body level, protein (69%) compared with casein (both P Ͻ 0.01). We conclude that the a digestion rate appears to be an independent factor regulating feeding-induced simulation of MPS in young men is greater after whey hydrolysate or soy protein consumption than casein both at rest protein anabolism (8). While the data from whole body protein and after resistance exercise; moreover, despite both being fast pro- kinetics point to differential effects of different proteins on teins, whey hydrolysate stimulated MPS to a greater degree than soy synthesis and breakdown (3, 8, 9), skeletal muscle only con-ar- after resistance exercise. These differences may be related to how tributes ϳ25–30% to whole body protein synthesis (25), and its quickly the proteins are digested (i.e., fast vs. slow) or possibly to turnover rate is much lower (on the order of 20ϫ) than that of small differences in leucine content of each protein. more rapidly-turning-over gut (26, 27) and plasma proteins (6). hypertrophy; muscle mass; weightlifting Thus protein turnover measured at the whole body level may or ta may not be reflective, or even representative, of the anabolism of muscle proteins. At present, only a single study has mea- TWO OF THE MOST POTENT stimulators of skeletal muscle protein sured the chemical net balance of amino acids across a limb synthesis (MPS) are feeding and resistance exercise (29). The following whey and casein ingestion (34), but these data do not es postprandial increase in circulating essential amino acids stim- give kinetic results and were equivocal depending on the ulates a marked rise in protein synthesis (7, 15, 35); this effect choice of amino acid tracer studied. Thus to date no study has appears to be due to the amino acids themselves acting as the directly compared changes in skeletal MPS following the stimulus and not an effect due to the modest increases in consumption of isolated proteins with differing rates of diges- or insulin that result from amino acid ingestion (16). Resistance tion in humans. The purpose of this study, therefore, was to measure the response of skeletal MPS following the ingestion of three distinct but high-quality proteins (from a dietary Address for reprint requests and other correspondence: S. M. Phillips, standpoint), whey, micellar casein, and soy, at rest and after Fig. 5. Mixed muscle protein fractional synthetic rate (FSR) after ingestion of Dept. of Kinesiology-Exercise Metabolism Research Group, McMasterns Univ., 1280 Main St. West, Hamilton, Ontario L8S 4K1, Canada (e-mail: resistance exercise. We chose to measure these responses phillis@mcmaster.ca). following ingestion of similar quantities of these proteins but whey hydrolysate, casein, or soy protein at rest and after resistance exercise. http://www. jap.org 8750-7587/09 $8.00 Copyright © 2009 the American Physiological Society 987
  • 193. eEF2 phosphorylation (which indicated increased activation) proat the same time point. There were no differences between ap SÍNTESE PROTEICA APÓS UMA DOSE ÚNICA DE WHEY (25 G) tha OU 10 X 2.5 G EM INTERVALOS DE 20 MIN EA ges tha res and rise con app sus pro con (21 pos FIGURE 4. Mean DW, et al. Am J Clin Nutr. 2011 Sep;94(3):795-803. synthesis [fractional West (6SEM) myofibrillar proteinsynthetic rate (FSR)] in the fasted state (Fasted) and after a protein bolus det(BOLUS; 1 · 25 g) and protein pulses (PULSE; 10 · 2.5 g every 20 min) res
  • 194. Eur J Appl Physiol (2006) 97: 225–238 DOI 10.1007/s00421-005-0127-z O R I GI N A L A R T IC L E Stephen P. Bird Æ Kyle M. Tarpenning Frank E. Marino Independent and combined effects of liquid carbohydrate/essential amino acid ingestion on hormonal and muscular adaptations following resistance training in untrained men Received: 8 November 2005 / Accepted: 15 December 2005 / Published online: 24 March 2006 ody composition 5 Ó Springer-Verlag 2006 following 12 weeks ance training. Abstract This investigation examined chronic alteration Keywords Resistance training Æ Supplementation Æant difference 4 of the acute hormonal response associated with liquid Cortisol Æ Insulin Æ Hypertrophy carbohydrate (CHO) and/or essential amino acid (EAA) PLA5) from baseline Delta Body Composition. Treatment group ingestion on 3 hormonal and muscular adaptations fol- CHOpost-training change is lowing resistance training. Thirty-two untrained young Introduction men performed 12 weeks of resistance training twice a EAA ntly different 2 week, consuming $675 ml of either, a 6% CHO solu- Resistance exercise stimulates acute changes in the rate5) from PLA (filled (kg) tion, 6 g EAA mixture, combined CHO + EAA sup- of muscle protein turnover, resulting in an increase in CHO+EAA plement or placebo (PLA). Blood samples were obtained both protein synthesis and protein degradation (Chesley 1 pre- and post-exercise (week 0, 4, 8, and 12), for deter- et al. 1992; Biolo et al. 1995; Phillips et al. 1997). mination of glucose, insulin, and cortisol. 3-Methylhis- However, in the absence of nutritional intake, net tidine excretion and muscle fibre cross-sectional area muscle protein balance (i.e., the difference between 0 (fCSA) were determined pre- and post-training. Post- protein synthesis and degradation) remains negative in exercise cortisol increased (P<0.05) during each train- the early stages of recovery (Biolo et al. 1995). Fur- -1 ing phase for PLA. No change was displayed by EAA; thermore, myofibrillar protein degradation, as deter- CHO and CHO + EAA demonstrated post-exercise mined by 3-methylhistine (3-MH) excretion, has been decreases (P<0.05). All groups displayed reduced pre- shown to remain elevated for 48 h post-exercise fol- -2 exercise cortisol at week 12 compared to week 0 lowing an acute bout of resistance exercise (Bird et al. (P<0.05). Post-exercise insulin concentrations showed 2005). Collectively, these findings indicate that during no change for PLA; increases were observed for the post-exercise recovery from resistance exercise, catabolic -3 treatment groups (P<0.05), which remained greater for events predominate in determining net protein turnover CHO and CHO + EAA (P<0.001) than PLA. Fat freestatus. This imbalance Fat mass Body mass EAA mass between protein synthesis and and CHO ingestion attenuated 3-methylhistidine excre- degradation is likely facilitated by the antagonisticpes. Following 12 weeks of progressivehinfollowingdecrease (P<0.01), whilerecorded across allbetween the(P<0.05), pre- cortisol. tion 48 resistance exercise bout. CHO + EAA relationship groups hormones insulin and resulted a 26% the strength were PLA dis- The resultant physiological stress associated with played a 52% three Após 12 increased across resistance exercise protocols designed in maximally to post-training. CHO + EAA ingestion resulted tog, a hypertrophic effect was observed for allincrease (P<0.01). fCSAsemanas de Treino de Forçapes across groups. CHO + EAA demonstrated and IIb fibres (P<0.05),in 1-RM leg press strength groups (i.e., whole-body; groups for type I, IIa, greater increases with stimulate the major muscle relative toatest relative increase in type I fCSA oftoEAA (2.8) theThese datagains in[210.0 (16.4) compared to 151.3 often produces hy- CHO + relative 23.4 displaying the PLA group fCSA moderate volume, high(CORT) >500 nmol lÀ1 (Tar- PLA (P<0.05). greatest indicate that persecretion of cortisol intensity) (12.2) pared to PLA and EAA [7.1 (1.3) and 13.1 (1.6) kg; P<0.05). anabolism penning the PLA Bird et al. 2005; Kraemer et al. CHO + EAA ingestion enhances muscle Additionally, et al. 2001; and treatment
  • 195. ESTUDOS A TESTAR P+CHO EM ATLETAS ! Timing Resultados Referências Zawadzki KM, Yaspelkis BB 3rd, Ivy JL.Imediatamente / > Replecção J Appl Physiol. 1992 May;72(5):1854-9.4 h após de Glicogénio Ivy JL, e tal. J Appl Physiol. 2002 Oct;93(4):1337-4410 min / 2 h após > Replecção de Glicogénio Berardi JM, et al.Imediatamente / > Replecção Med Sci Sports Exerc. 2006 Jun;38(6):1106-131 h / 2 h após de Glicogénio Rasmussen BB, et al.1 h / 3 h após > Síntese J Appl Physiol. 2000 Feb;88(2):386-92. Proteica Tipton KD, et al.Imediatamente > Síntese Am J Physiol Endocrinol Metab. 2001 Aug;281(2):E197-206antes e após Proteica Miller SL, et al.1 h / 2 h após > Síntese Med Sci Sports Exerc. 2003 Mar;35(3):449-55 Proteica
  • 196. ü  N: 387 recrutas! ü  Duração: 54 dias! ü  Metodologia: ! !Imediatamente após o treino:! ! ü  Grupo Prot: ! 8 grs de HC + 10 grs de P + 3 g de L! ü  Grupo HC: ! 8 grs de HC + 0 grs de P + 3 g de L! ü  Grupo Placebo: ! 0 grs de HC + 0 grs de P + 0 g de L! !! !!Flakoll PJ, et al.. J Appl Physiol. 2004 Mar;96(3):951-6
  • 197. Alterações 34º dia vs início Alterações último dia vs inícioFlakoll PJ, et al.. J Appl Physiol. 2004 Mar;96(3):951-6
  • 198. RESULTADO: ! !Grupo Prot registou:!!33% MENOS DE VISITAS AO MÉDICO,!28% MENOS INFECÇÕES VIRAIS EBACTERIANAS, !37% MENOS PROBLEMAS MUSCULARESE ARTICULARES!83% MENOS HIPERTERMIA E MENOR DORMUSCULAR IMEDIATAMENTE APÓS OESFORÇO.! !! Flakoll PJ, et al.. J Appl Physiol. 2004 Mar;96(3):951-6
  • 199. Obrigado 
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