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Fructose and the link to the metabolic syndrome - di Piero Portincasa e Leonilde Bonfrate

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Fructose and the link to the metabolic syndrome - di Piero Portincasa e …

Fructose and the link to the metabolic syndrome - di Piero Portincasa e
Leonilde Bonfrate. 31 maggio 2012. Corso di formazione "valore nutrizionale e salutistico di prodotti agroalimentari” - Università degli studi di Bari.

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  • NAFLD: Associated with Metabolic Syndrome NAFLD is associated with the metabolic syndrome. The metabolic syndrome is a constellation of disorders, including obesity, type 2 diabetes and dyslipidemia, that often cluster together. The prevalence of insulin resistance is very high in individuals with the metabolic syndrome. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003;37:917-923. Shirai K. Obesity as the core of the metabolic syndrome and the management of coronary heart disease. Curr Med Res Opin 2004;20:295-304. Miller JL. Insulin resistance syndrome. Description, pathogenesis, and management. Postgrad Med 2003;Spec No:27-34.
  • Il sonnellino (1982 - olio su tela)
  • 2 TI The effect of fruit and vegetable intake on risk for coronary heart disease. AU Joshipura KJ; Hu FB; Manson JE; Stampfer MJ; Rimm EB; Speizer FE; Colditz G; Ascherio A; Rosner B; Spiegelman D; Willett WC SO Ann Intern Med 2001 Jun 19;134(12):1106-14.     BACKGROUND: Many constituents of fruits and vegetables may reduce the risk for coronary heart disease, but data on the relationship between fruit and vegetable consumption and risk for coronary heart disease are sparse. OBJECTIVE: To evaluate the association of fruit and vegetable consumption with risk for coronary heart disease. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study and the Health Professionals' Follow-Up Study. PARTICIPANTS: 84 251 women 34 to 59 years of age who were followed for 14 years and 42 148 men 40 to 75 years who were followed for 8 years. All were free of diagnosed cardiovascular disease, cancer, and diabetes at baseline. MEASUREMENTS: The main outcome measure was incidence of nonfatal myocardial infarction or fatal coronary heart disease (1127 cases in women and 1063 cases in men). Diet was assessed by using food-frequency questionnaires. RESULTS: After adjustment for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake had a relative risk for coronary heart disease of 0.80 (95% CI, 0.69 to 0.93) compared with those in the lowest quintile of intake. Each 1-serving/d increase in intake of fruits or vegetables was associated with a 4% lower risk for coronary heart disease (relative risk, 0.96 [CI, 0.94 to 0.99]; P = 0.01, test for trend). Green leafy vegetables (relative risk with 1-serving/d increase, 0.77 [CI, 0.64 to 0.93]), and vitamin C-rich fruits and vegetables (relative risk with 1-serving/d increase, 0.94 [CI, 0.88 to 0.99]) contributed most to the apparent protective effect of total fruit and vegetable intake. CONCLUSIONS: Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C-rich fruits and vegetables, appears to have a protective effect against coronary heart disease.   AD Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. PMID 11412050 3 TI Legume consumption and risk of coronary heart disease in US men and women: NHANES I Epidemiologic Follow-up Study. AU Bazzano LA; He J; Ogden LG; Loria C; Vupputuri S; Myers L; Whelton PK SO Arch Intern Med 2001 Nov 26;161(21):2573-8.     BACKGROUND: Soybean protein and dietary fiber supplementation reduce serum cholesterol in randomized controlled trials. Consumption of legumes, which are high in bean protein and water-soluble fiber, may be associated with a reduced risk of coronary heart disease (CHD). METHODS: A total of 9632 men and women who participated in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (NHEFS) and were free of cardiovascular disease (CVD) at their baseline examination were included in this prospective cohort study. Frequency of legume intake was estimated using a 3-month food frequency questionnaire, and incidence of CHD and CVD was obtained from medical records and death certificates. RESULTS: Over an average of 19 years of follow-up, 1802 incident cases of CHD and 3680 incident cases of CVD were documented. Legume consumption was significantly and inversely associated with risk of CHD (P =.002 for trend) and CVD (P =.02 for trend) after adjustment for established CVD risk factors. Legume consumption 4 times or more per week compared with less than once a week was associated with a 22% lower risk of CHD (relative risk, 0.78; 95% confidence interval, 0.68-0.90) and an 11% lower risk of CVD (relative risk, 0.89; 95% confidence interval, 0.80-0.98). CONCLUSIONS: Our study indicates a significant inverse relationship between legume intake and risk of CHD and suggests that increasing legume intake may be an important part of a dietary approach to the primary prevention of CHD in the general population.   AD Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, 1430 Tulane Ave, SL18, New Orleans, LA 70112, USA. jhe@tulane.edu PMID 11718588
  • 2 TI The effect of fruit and vegetable intake on risk for coronary heart disease. AU Joshipura KJ; Hu FB; Manson JE; Stampfer MJ; Rimm EB; Speizer FE; Colditz G; Ascherio A; Rosner B; Spiegelman D; Willett WC SO Ann Intern Med 2001 Jun 19;134(12):1106-14.     BACKGROUND: Many constituents of fruits and vegetables may reduce the risk for coronary heart disease, but data on the relationship between fruit and vegetable consumption and risk for coronary heart disease are sparse. OBJECTIVE: To evaluate the association of fruit and vegetable consumption with risk for coronary heart disease. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study and the Health Professionals' Follow-Up Study. PARTICIPANTS: 84 251 women 34 to 59 years of age who were followed for 14 years and 42 148 men 40 to 75 years who were followed for 8 years. All were free of diagnosed cardiovascular disease, cancer, and diabetes at baseline. MEASUREMENTS: The main outcome measure was incidence of nonfatal myocardial infarction or fatal coronary heart disease (1127 cases in women and 1063 cases in men). Diet was assessed by using food-frequency questionnaires. RESULTS: After adjustment for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake had a relative risk for coronary heart disease of 0.80 (95% CI, 0.69 to 0.93) compared with those in the lowest quintile of intake. Each 1-serving/d increase in intake of fruits or vegetables was associated with a 4% lower risk for coronary heart disease (relative risk, 0.96 [CI, 0.94 to 0.99]; P = 0.01, test for trend). Green leafy vegetables (relative risk with 1-serving/d increase, 0.77 [CI, 0.64 to 0.93]), and vitamin C-rich fruits and vegetables (relative risk with 1-serving/d increase, 0.94 [CI, 0.88 to 0.99]) contributed most to the apparent protective effect of total fruit and vegetable intake. CONCLUSIONS: Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C-rich fruits and vegetables, appears to have a protective effect against coronary heart disease.   AD Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. PMID 11412050 3
  • TI Fruit and vegetable consumption and stroke: meta-analysis of cohort studies. AU He FJ; Nowson CA; MacGregor GA SO Lancet. 2006 Jan 28;367(9507):320-6.     BACKGROUND: Increased consumption of fruit and vegetables has been shown to be associated with a reduced risk of stroke in most epidemiological studies, although the extent of the association is uncertain. We quantitatively assessed the relation between fruit and vegetable intake and incidence of stroke in a meta-analysis of cohort studies. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library, and bibliographies of retrieved articles. Studies were included if they reported relative risks and corresponding 95% CIs of stroke with respect to frequency of fruit and vegetable intake. FINDINGS: Eight studies, consisting of nine independent cohorts, met the inclusion criteria. These groups included 257,551 individuals (4917 stroke events) with an average follow-up of 13 years. Compared with individuals who had less than three servings of fruit and vegetables per day, the pooled relative risk of stroke was 0.89 (95% CI 0.83-0.97) for those with three to five servings per day, and 0.74 (0.69-0.79) for those with more than five servings per day. Subgroup analyses showed that fruit and vegetables had a significant protective effect on both ischaemic and haemorrhagic stroke. INTERPRETATION: Increased fruit and vegetable intake in the range commonly consumed is associated with a reduced risk of stroke. Our results provide strong support for the recommendations to consume more than five servings of fruit and vegetables per day, which is likely to cause a major reduction in strokes.   AD Blood Pressure Unit, Cardiac and Vascular Sciences, St George's University of London, London, UK. fhe@sgul.ac.uk PMID 16443039
  • . These observations have implications for dietary recommendations in patients in whom fructose malabsorption is suspected since foods that contain fructose may be well tolerated if they also contain glucose but may be less well tolerated if they also contain sorbitol (although sorbitol itself can cause diarrhea). Thus, it is the net amount of fructose that is important. . These observations have implications for dietary recommendations in patients in whom fructose malabsorption is suspected since foods that contain fructose may be well tolerated if they also contain glucose but may be less well tolerated if they also contain sorbitol (although sorbitol itself can cause diarrhea). Thus, it is the net amount of fructose that is important.
  • Metabolic pathways of entry of (A) glucose and (B) fructose into the glycolytic pathway of the CNS. GK, glucokinase; KHK, ketohexokinase; DHAP, dihypoxyacetone; Gald, glyceraldehyde.
  • Proc Natl Acad Sci U S A. November 2008 4; 105(44): 16871–16875. Published online 2008 October 29. doi: 10.1073/pnas.0809255105. PMCID: PMC2579345 Copyright © 2008 by The National Academy of Sciences of the USA Biochemistry Differential effects of central fructose and glucose on hypothalamic malonyl–CoA and food intake Seung Hun Cha,a Michael Wolfgang,a Yuka Tokutake,b Shigeru Chohnan,b and M. Daniel Lanea1 The brain, like the liver, possesses a unique set of enzymes that enables fructose to bypass the rate-limiting step in glycolysis and thereby rapidly deplete ATP in the hypothalamus The central administration of fructose rapidly lowers ATP, increases P-AMPK and P-ACC (acetyl-CoA carboxylase ), and decreases malonyl-CoA in the hypothalamus, whereas centrally administered glucose has the inverse effects.
  • Proc Natl Acad Sci U S A. 2008 November 4; 105(44): 16871–16875. Published online 2008 October 29. doi: 10.1073/pnas.0809255105. PMCID: PMC2579345 Copyright © 2008 by The National Academy of Sciences of the USA Biochemistry Differential effects of central fructose and glucose on hypothalamic malonyl–CoA and food intake Seung Hun Cha,a Michael Wolfgang,a Yuka Tokutake,b Shigeru Chohnan,b and M. Daniel Lanea1
  • Nutr Metab (Lond). 2005; 2: 5. Published online 2005 February 21. doi: 10.1186/1743-7075-2-5. PMCID: PMC552336 Copyright © 2005 Basciano et al; licensee BioMed Central Ltd. Fructose, insulin resistance, and metabolic dyslipidemia Heather Basciano,1 Lisa Federico,1 and Khosrow Adeli1
  • Basciano et al. Nutr Metab (Lond). 2005; 2: 5. Published online Basciano et al. Nutr Metab (Lond). 2005; 2: 5. 2005 February 21. doi: 10.1186/1743-7075-2-5. Copyright © 2005; licensee BioMed Central Ltd. Circa il 50-80% dell’APO B dopo essere stato sintetizzato viene degradato. Il processo di degradazione è regolato da una proteina microsomiale, la MTP (microsomial triglYceride transfer protein) che è necessaria all’assemblamento dei trigliceridi con l’APO B100 ed alla secrezione delle VLDL Highly efficient inducer of de novo lipogenesis (high concentrations: unregulated source of acetyl CoA) In contrast to glucose, dietary fructose does NOT stimulate insulin or leptin (which are both important regulators of energy intake and body adiposity). Stimulated triglyceride synthesis is likely to lead to hepatic accumulation of triglyceride So, reduction hepatic insulin sensitivity, as well as increased formation of VLDL particles due to higher substrate availability, increased apoB stability, and higher MTP, the critical factor in VLDL assembly
  • J Hepatol. 2008 June; 48(6): 993–999. Published online 2008 March 10. doi: 10.1016/j.jhep.2008.02.011. PMCID: PMC2423467 NIHMSID: NIHMS52684 Copyright notice and Disclaimer Fructose Consumption as a Risk Factor for Non-alcoholic Fatty Liver Disease Xiaosen Ouyang, MD,1* Pietro Cirillo, MD,1* Yuri Sautin, PhD,1* Shannon McCall, MD,2‡ James L. Bruchette, ASCP,2‡ Anna Mae Diehl, MD,3‡ Richard J. Johnson, MD,1* and Manal F. Abdelmalek, MD3‡
  • Nutr Metab (Lond). 2005; 2: 5. Published online 2005 February 21. doi: 10.1186/1743-7075-2-5. PMCID: PMC552336 Copyright © 2005 Basciano et al; licensee BioMed Central Ltd. Fructose, insulin resistance, and metabolic dyslipidemia Heather Basciano,1 Lisa Federico,1 and Khosrow Adeli1
  • Transcript

    • 1. Fructose and the link to the metabolicsyndrome Piero Portincasa, MD, PhD Leonilde Bonfrate,MD Department of Internal and Public Medicine University of Bari Medical School Bari – Italy p.portincasa@semeiotica.uniba.it
    • 2. NAFLD: Associated with Metabolic Syndrome 17/09/12 Metabolic Syndrome Obesity P. Portincasa, UNIBA Diabetes DyslipidemiaEPIDEMIA DEL III MILLENNIO
    • 3. The “BOTERO Syndrome” 17/09/12 P. Portincasa, UNIBA 329.04.05
    • 4. 17/09/12Food fast! 4 Fast food! P. Porti ncas a, UNI
    • 5. 5FRUITS AND VEGETABLES P. Portincasa, 17/09/1 2 UNIBA
    • 6. 6 P. 17/09/1 Portincasa, 2FRUITS AND VEGETABLES UNIBA • Consumption is inversely related to the risk of coronary heart disease (CHD) and strokeThe effect of fruit and vegetable intake on risk for coronary heart disease. AUJoshipura KJ; Hu FB; Manson JE; Stampfer MJ; Rimm EB; Speizer FE; Colditz G;Ascherio A; Rosner B; Spiegelman D; Willett WC SO Ann Intern Med 2001 Jun19;134(12):1106-14.Legume consumption and risk of coronary heart disease in US men and women:NHANES I Epidemiologic Follow-up Study. AU Bazzano LA; He J; Ogden LG; Loria C;Vupputuri S; Myers L; Whelton PK SO Arch Intern Med 2001 Nov 26;161(21):2573-8.
    • 7. 7 P. 17/09/1 Portincasa, 2The effect of fruit and vegetable intake on risk for coronary heart disease. AU Joshipura KJ; Hu FB; UNIBAManson JE; Stampfer MJ; Rimm EB; Speizer FE; Colditz G; Ascherio A; Rosner B; Spiegelman D;Willett WC SO Ann Intern Med 2001 Jun 19;134(12):1106-14. • The Nurses Health Study and the Health Professionals Follow-Up Study • 84 251 women 34 to 59 yrs of age who for 14 yrs and 42 148 men 40 to 75 yrs followed for 8 yrs • Incidence of nonfatal myocardial infarction or fatal coronary heart disease (1127 cases in women and 1063 cases in men). • Diet assessed by using food-frequency questionnaires • CONCLUSIONS: Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C-rich fruits and vegetables, appears to have a
    • 8. 8 P. 17/09/1 Portincasa, 2Fruit and vegetable consumption and stroke: meta-analysis UNIBA ofcohort studies. He FJ; Nowson CA; MacGregor GA Lancet. 2006Jan 28;367(9507):320-6.  • MEDLINE, EMBASE, the Cochrane Library, and bibliographies of retrieved articles• 8 studies, 9 independent cohorts• 257,551 individuals (4917 stroke events), average follow-up of 13 years• relative risk of stroke was 0.89 (95% CI 0.83-0.97) for those with 3 to 5 servings per day, and 0.74 (0.69-0.79) >5 servings per day.• Fruit and vegetables significant protective effect on both ischaemic and haemorrhagic stroke.
    • 9. 9 P. 17/09/1 Portincasa, 2 UNIBALyn M Steffen Jan 28, 2006, The Lancet, Vol. 367 No. 9507 pp 278-279
    • 10. 10 P. 17/09/1 Portincasa, 2 UNIBA 5 a day!Lancet. 2006 Jan 28;367(9507):320-6.
    • 11. FRUCTOSE........FRIEND… OR ENEMY?
    • 12. Fructose consumption 16–20 grams/day (only fresh fruits) 74%85–100 grams/day Basciano et al; Nutr Metab (Lond). 2005; 2: 5.
    • 13. Dietary fructose monosaccharide Fructose • a free hexose • as the disaccharide (sucrose: glucose-fructose) • in a polymerized form (fructans) Up to one half of the population unable to completely absorb a sucrose load of 25 g 4 Kcal / g Glycemic index: 23 (sucrose: 57)
    • 14. According to the USDA database, foods with more fructose than glucose include: Fructose (grams / Glucose (grams / Food 100 grams) 100 grams) High fructose 55 to 90 45 to 10 corn syrup Sucrose 50 50 (for reference) Honey 40.9 35.7 Raisins 29.8 27.8 Pears 6.2 2.8 Apples 5.9 2.4 Fruit juice e.g. Apples, 5 to 7 2 to 3 Pears Watermelon 3.4 1.6
    • 15. Metabolic pathways of entry of (A) glucose and (B) fructose into the glycolytic pathway of the CNS Cha S H et al. PNAS 2008;105:16871-16875©2008 by National Academy of Sciences
    • 16. Central administration of fructose Fructose exerts an orexigenic effect Seung Hun Cha et al., Proc Natl Acad Sci U S A. November 2008
    • 17.  The brain, like the liver, possesses a unique set of enzymes that enables fructose to bypass the rate- limiting step in glycolysis and thereby rapidly deplete ATP in the hypothalamus The central administration of fructose rapidly lowers ATP, increases P-AMPK and P-ACC (acetyl-CoA carboxylase ), and decreases malonyl-CoA in the hypothalamus, whereas centrally administered glucose has the inverse effects.
    • 18. FRUCTOSE IN THE LIVER  A high flux of fructose to the liver (the main organ capable of metabolizing this simple carbohydrate)1. perturbs glucose metabolism and glucose uptake pathways (Fructose-induced insulin resistance)2. leads to a significantly enhanced rate of de novo lipogenesis and triglyceride (TG) synthesis, driven by the high flux of glycerol and acyl portions of TG molecules from fructose catabolism.
    • 19. MTP (microsomial triglyceride transfer protein)Basciano et al. Nutr Metab (Lond). 2005; 2: 5.
    • 20. Increased fructose intake upregulation ofNAFLD KHK (fructokinase) fructose-induced ATP depletion Hepatic necroinflammation
    • 21. keypointsHigh dietary intake of fructose NAFLD insulindyslipidemia resistance metabolic syndrome