Vitamin D and geriatric syndromes


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New evidence suggests a relation between geriatric syndomes and vitamin D exists.

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Vitamin D and geriatric syndromes

  1. 1. SAMIA AHMED ABDUL-RAHMAN Assistant Professor of Geriatrics and Gerontology Faculty of Medicine Ain Shams University 2014 Vitamin D, Geriatric Syndromes & Common Comorbidities: Possible Links
  2. 2. *The autocrine/paracrine functions of vitamin D are becoming increasingly widely recognized. *Several organs possess the enzymatic machinery to convert 25-hydroxyvitamin D, to the active form, 1,25dihydroxyvitamin D, has provided new insights into the function of this vitamin. - Holick MF 2004 Vitamin D: Importance in the prevention of cancers, type 1 diabetes, heart disease and osteoporosis. Am J Clin Nutr 79:362–371. - Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zugel U, Gallo RL, Eisnberg D, Hewison M, Hollis BW, Adams JS, Bloom JR, Modlin RL 2006 Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311:170–173.
  3. 3. Which tissues include vitamin D receptors? Among other tissues; these are the most well known:
  4. 4. * *Yes. *In fact, it controls over 200 genes, including genes responsible for the regulation of: *cellular proliferation, *differentiation, *apoptosis, and *angiogenesis. Iida-Klein A, Guo J, Xie LY et al. Truncation of the carboxyl-terminal region of the rat parathyroid hormone (PTH)/PTH-related peptide receptor enhances PTH stimulation of adenylyl cyclase but not phospholipase C. J Biol Chem 1995; 270: 8458–8465.
  5. 5. Although there is no consensus on optimal levels of 25-hydroxyvitamin D as measured in serum, most experts defined the different vitamin D status as : Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 2006;81:353-73.
  6. 6. * •Normal≥ 30ng/ml 21-29 ng/ml •Deficiency≤ 20 ng/ml
  7. 7. Now what do we all know?!!
  8. 8. * *Musculoskeletal system: *Osteoporosis & osteomalacia *Proximal myopathy *Falls
  9. 9. Osteoporosis and Osteomalacia!!
  10. 10. Muscle function and falls!! - Performance speed, - Proximal and peripheral muscle strength, - Risk of falls.
  11. 11. Non-skeletal systems
  12. 12. Geriatric syndromes possibly linked to vitamin D deficiency
  13. 13. FRAILTY
  14. 14. 25-hydroxyvitamin D deficiency is associated with debilitating chronic diseases and age-related conditions that may influence physical functioning and hence relation to frailty was considered in research. Wilhelm-Leen ER, Hall YN, deBoer IH, Chertow GM. Vitamin D deficiency and frailty in older Americans. J Intern Med 2010; 268: 171–180.
  15. 15. The largest of these studies was that of Wilhelm-Leen and colleagues (2010). Using data from the 3rd National Health and Nutrition Survey (NHANES III), 25- Hydroxyvitamin D deficiency, defined as a serum concentration <15 ng/mL), was associated with a 3.7-fold increase in the odds of frailty amongst whites and a 4-fold increase in the odds of frailty amongst non- whites. - Wilhelm-Leen ER, Hall YN, deBoer IH, Chertow GM. VitaminDdeficiency and frailty in older Americans. J Intern Med 2010; 268:171–180.
  16. 16. *A cross-sectional study on a total of 1,504 community-dwelling men aged 60-79 years- using multinomial logistic regression- found lower levels of 25(OH)D were associated with being pre-frail and frail even after adjustment for confounders. *Among the five frailty phenotypes (FP) criteria, only sarcopenia was not associated with 25(OH)D levels. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. weight loss, muscle weakness, poor endurance, slow motor performance and reduced physical activity
  17. 17. *Its relation to sarcopenia was examined again in the cross-sectional study of Dupuy and colleagues using data from the EPIDOS study. The results again showed no association between low muscle mass and low dietary intakes of vitamin D. *Longitudinal studies are needed to examine if giving vitamin D supplementation or vitamin D rich diet to vitamin D deficient frail persons with sarcopenia has any effect. Charlotte Dupuy, V. Lauwers-Cances, G. Abellan Van Kan, S. Gillette, A. -M. Schott, O. Beauchet, C. Annweiler, B. Vellas, Y. Rolland. Dietary vitamin D intake and muscle mass in older women. Results from a cross-sectional analysis of the EPIDOS study. The journal of nutrition, health & aging 2013, 17(2), 119-124.
  19. 19. * Urinary continence requires coordinated muscle function with relaxation of the bladder detrusor allowing the bladder to fill, followed by detrusor contraction with concomitant sphincter relaxation at a time controlled by the individual.
  20. 20. Since bladder musculature possesses vitamin D receptors and responds to vitamin D analogues, vitamin D deficiency perhaps could influence bladder/pelvic floor dysfunction. - Crescioli C, Morelli A, Adorini L, Ferruzzi P, Luconi M, Vannelli GB, Marini M, Gelmini S, Fibbi B, Donati S, Villari D, Forti G, Colli E, Andersson KE, Maggi M 2005 Human bladder as a novel target for vitamin D receptor ligands. J Clin Endocrinol Metab 90:962–972. - Schroder A, Colli E, Maggi M, Andersson KE 2006 Effects of a vitamin D3 analogue in a rat model of bladder outlet obstruction. BJU Int 98:637–642.
  21. 21. Pelvic floor dysfunction in females is common, and its prevalence increases with age. The prevalence of UI varies by definition but has been reported to range between 13- 49%. • Nygaard I, Barber MD, Burgio KL, Kenton K, Meikle S, Schaffer J, Spino C, Whitehead WE, Wu J, Brody DJ (2008) Prevalence of symptomatic pelvic floor disorders in US women. JAMA 300 (11):1311–1316 • Sung VW, Hampton BS (2009) Epidemiology of pelvic floor dysfunction. Obstet Gynecol Clin N Am 36:421–443 • Melville JL, Katon W, Delaney K et al. (2005) Urinary incontinence in US women: a population-based study. Arch Intern Med 165(5):537–42 • Dooley Y, Kenton K, Cao G et al. (2009) Urinary incontinence prevalence: results from the National Health and Nutritional Examination Survey. J Urol 179(2):656–61 • Irwin DE, Milsom I, Hunskaar S et al. (2006) Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol 50(6):1306–14
  22. 22. Previously; research suggested a relation between osteoporosis and pelvic floor muscles function exists and so the idea to study its relation to vitamin D deficiency seems rational. Holick MF, Chen TC, Lu Z, Sauter E. Vitamin D and skin physiology: a D-lightful story. J Bone Miner Res 2007;22(suppl 2):V28–33.
  23. 23. Prospective cohort or randomized studies investigating the relationship between vitamin D nutritional status and PFD symptoms are lacking but observational studies show a possible link.
  24. 24. *One study including more than 1800 adult women showed that as many as 82% of the participants had low levels of vitamin D. *However those who had pelvic floor disorders and/or incontinence had levels significantly lower than those of the rest of the group. Badalian, S. and Rosenbaum PF.Vitamin D and Pelvic Floor Disorders in Women: Results From the National Health and Nutrition Examination Survey Obstetrics & Gynecology, April 2010; vol 115: pp 795-803.
  25. 25. *This is not limited to women with UI. *Studies on males with UI showed significantly lower levels of vitamin D as well. *A cross-sectional study on 2387 men with lower urinary tract symptoms including UI. Although it included all age groups starting from 20 yet 85% had vitamin D levels below 30ng/ml and 55% of them had levels below 20 ng/ml. *Results showed an association between vitamin D deficiency and moderate/severe UI. Vaughan CP1, Johnson TM 2nd, Goode PS, Redden DT, Burgio KL, Markland AD. Vitamin D and lower urinary tract symptoms among US men: results from the 2005-2006 National Health and Nutrition Examination Survey. Urology. 2011 Dec;78(6):1292-7.
  26. 26. * *Still, 2 case studies are available; the first was a 78-year-old woman with UUI symptoms who had vitamin D deficiency [25(OH) D010 ng/ml] who claims her UI resolved with vitamin D supplementation. *The second reported case was a 59-year-old woman with stress urinary incontinence symptoms who had a 25(OH)D level of 13 ng/ml. These symptoms resolved even before normalization of her serum vitamin D level. Gau JT. Urinary incontinence resolved after adequate vitamin D supplementation: a report of two cases.J Am Geriatr Soc. 2010 Dec;58(12):2438-9.
  27. 27. *In a small cohort study of patients with fecal incontinence, it was shown that all patients had hypovitaminosis D (60% had vitamin deficiency and 40% with relative vitamin D insufficiency). The mean vitamin D level in patients with fecal incontinence was 17 ng per milliliter (range 5.4–22.2 ng per milliliter) wither significantly higher prevalence than the general population. Amer A. Alkhatib • Ashok K. Tuteja. High Prevalence of Vitamin D Deficiency Among Patients with Fecal Incontinence Dig Dis Sci (2010) 55:3632–3633
  28. 28. DEMENTIA AND COGNITIVE IMPAIRMENT (MCI) Dementia and cognitive impairment
  29. 29. *Research in the last 10 years has yielded a large amount of knowledge regarding vitamin D and its previously unknown role in brain development and function. *For example, the distribution of the vitamin D receptor (VDR) has been mapped in human brain. D.W. Eyles, S. Smith, R. Kinobe et al.Distribution of the vitamin D receptor and 1 alpha- hydroxylase in human brain Journal Of Chemical Neuroanatomy, 29 (2005), pp. 21–30
  30. 30. *Hypovitaminosis D has been associated with cognitive decline in the elderly, Parkinson’s disease and Alzheimer’s disease patients. • Evatt ML, DeLong MR, Khazai N, et al. Prevalence of vitamin D insufficiency in patients with Parkinson disease and Alzheimer disease. Archives of Neurology; 65: 1348–1352, 2008. • Jorde R, Sneve M, Figenschau Y et al. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. Journal of Internal Medicine; 264: 599–609, 2008. • Llewellyn DJ, Lang IA, Langa KM, et al. Vitamin D and risk of cognitive decline in elderly persons. Archives of Internal Medicine; 170: 1135–1141, 2010. • May HT, Bair TL, Lappe DL, et al. Association of vitamin D levels with incident depression among a general cardiovascular population. American Heart Journal; 159: 1037–1043, 2010.
  31. 31. *Direct evidence for an association of vitamin D deficiency with Alzheimer’s disease (AD) is limited. *However, low vitamin D levels have been frequently associated with cognitive impairment in the elderly and prospectively with cognitive decline. • J.S. Buell, B. Dawson-Hughes, T.M. Scott, D.E. Weiner, G.E. Dallal, W.Q. Qui, P. Bergethon, I.H. Rosenberg, M.F. Folstein, S. Patz, R.A. Bhadelia, K.L. Tucker, 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services, Neurology 74 (2010) 18–26. • M.L. Evatt, M.R. Delong, N. Khazai, A. Rosen, S. Triche, V. Tangpricha, Prevalence of vitamin D insufficiency in patients with Parkinson disease and Alzheimer disease, Arch. Neurol. 65 (2008) 1348–1352. • E. Pogge, Vitamin D and Alzheimer’s disease: is there a link? Consult. Pharm. 25 (2010) 440–450. • J.W. Miller, Vitamin D and cognitive function in older adults: are we concerned about vitamin D-mentia? Neurology 74 (2010) 13–15. • D.J. Llewellyn, I.A. Lang, K.M. Langa, G. Muniz-Terrera, C.L. Phillips, A. Cherubini, L. Ferrucci, D. Melzer, Vitamin D and risk of cognitive decline in elderly persons,Arch. Intern. Med. 170 (2010) 1135–1141.
  32. 32. *Results of 2 large cross-sectional studies (one on 6,257 and one on 498 subjects) showed an association between cognitive decline and vitamin D deficiency. *4 year follow up of these cohort revealed the same finding. Slinin Y, Paudel M, Taylor BC, et al. Association Between Serum 25(OH) Vitamin D and the Risk of Cognitive Decline in Older Women. J Gerontol A Biol Sci Med Sci ; 67 (10): 1092-1098, 2012. Annweiler C, Rolland Y, Schott AM, et al. Higher Vitamin D Dietary Intake Is Associated With Lower Risk of Alzheimer’s Disease: A 7-Year Follow-up. J Gerontol A Biol Sci Med Sci; 67 (11): 1205-1211, 2012.
  33. 33. *Another large prospective study showed that cognitive decline and the rate of decline were increased in subjects deficient in 25(OH)D (<25 nM). Llewellyn DJ, Lang IA, Langa KM, et al. Vitamin D and risk of cognitive decline in elderly persons. Archives of Internal Medicine; 170: 1135–1141, 2010.
  34. 34. *However, it is unclear if associations between hypovitaminosis D and dementia are causative or circumstantial, but there is some evidence for symptom improvements with vitamin D supplementation. Jorde R, Sneve M, Figenschau Y et al. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. Journal of Internal Medicine; 264: 599–609, 2008.
  35. 35. * DEPRESSION
  36. 36. *Vitamin D has also been linked to depression which is one of the most common mental disorders in elderly populations. *Stumpf and colleagues first suggested that vitamin D may contribute to the higher prevalence of seasonal affective disorders at high latitudes. *However to date, the results of small trials of vitamin D supplements in seasonal affective disorder have been inconclusive Stumpf, W.E., Privette, T.H., 1989. Light, vitamin D and psychiatry. Role of 1,25 dihydroxyvitamin D3 (soltriol) in etiology and therapy of seasonal affective disorder and other mental processes. Psychopharmacology (Berlin) 97, 285–294. Gloth 3rd, F.M., Alam, W., Hollis, B., 1999. Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder. J. Nutr. Health Aging 3, 5–7. Lansdowne, A.T., Provost, S.C., 1998. Vitamin D3 enhances mood in healthy subjects during winter. Psychopharmacology (Berlin) 135, 319–323.
  37. 37. *Even with large cross-sectional studies the results are conflicting. *A number of cross-section studies have reported an association between low vitamin D and depression. *While other cross-sectional studies have failed to find such an association when controlled for potential confounding factors. Pan, A., Lu, L., Franco, O.H., Yu, Z., Li, H., Lin, X., 2009. Association between depressive symptoms and 25-hydroxyvitamin D in middle-aged and elderly Chinese. J. Affect. Disord. 118, 240–243. Nanri, A., Mizoue, T., Matsushita, Y., Poudel-Tandukar, K., Sato, M., Ohta, M., Mishima, N., 2009. Association between serum 25-hydroxyvitamin D and depressive symptoms in Japanese: analysis by survey season. Eur. J. Clin. Nutr. 63, 1444–1447. Zhao, G., Ford, E.S., Li, C., Balluz, L.S., 2010. No associations between serum concentrations of 25- hydroxyvitamin D and parathyroid hormone and depression among US adults. Brit. J. Nutr. 104, 1696– 1702.
  38. 38. *One large, population-based survey of the elderly (n = 2070 participants, aged 65 years and older) reported a significant increased risk of depressive symptoms in those with vitamin D deficiency. Stewart, R., Hirani, V., 2010. Relationship between vitamin D levels and depressive symptoms in older residents from a national survey population. Psychosom. Med. 72, 608–612
  39. 39. *A 6-year prospective study of 954 adults aged 65 years and older examined the association between low vitamin D at baseline and subsequent (incident) depression. *Those with 25(OH)D less than 50 nM at baseline (compared with those with higher levels) experienced significantly higher scores on measures of depression at 3 and 6 year follow-up even after adjustment for confounding factors. Milaneschi, Y., Shardell, M., Corsi, A.M., Vazzana, R., Bandinelli, S., Guralnik, J.M., Ferrucci, L., 2010. Serum 25-hydroxyvitamin D and depressive symptoms in older women and men. J. Clin. Endocrinol. Metab..
  40. 40. *A re-analysis of the Women’s Health Initiative examined the association between dietary vitamin D intake at baseline and depression in a very large sample (n = 81,189). *Those with the highest dietary intake has lower scores on depressive symptoms at the 3 year follow-up, and this persisted after adjustments for potential confounding factors. Bertone-Johnson, E.R., Powers, S.I., et al. 2011. Vitamin D intake from foods and supplements and depressive symptoms in a diverse population of older women. Am. J. Clin. Nutr. 94, 1104–1112.
  42. 42. *Of great interest is the role it can play in decreasing the risk of many chronic illnesses: *Infectious diseases *Malignancies *Cardiovascular disease
  43. 43. Infectious diseases Auto-immune disease IMMUNE SYSTEM
  44. 44. Infectious diseases
  45. 45. *The link between vitamin D deficiency and susceptibility to infection has been suggested for longer than a century. *One of the first clinical trials to use vitamin D for treatment of infections was on patients with pulmonary TB in the 1950s and it’s been demonstrated that vitamin D enhanced bactericidal activity of human macrophages against Mycobacterium tuberculosis. • Khajavi A, Amirhakimi GH. The rachitic lung: pulmonary findings in 30 infants and children with malnutritional rickets. Clin Pediatr (Phila). 1977;16:36-38 • Martineau AR, Honecker FU, Wilkinson RJ, Griffiths CJ. Vitamin D in the treatment of pulmonary tuberculosis. J Steroid Biochem Mol Biol. 2007;103:793-798. • Bhalla AK, Amento EP, Clemens TL, Holick MF, Krane SM. Specific high-affinity receptors for 1,25-dihydroxyvi-tamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J Clin Endocrinol Metab. 1983;57: 1308-1310. • Rook GA, Steele J, Fraher L, et al. Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology. 1986;57: 159-163. • Crowle AJ, Ross EJ, May MH. Inhibition by l,25(OH)2-vitamin D3 of the multiplication of virulent tubercle bacilli in cultured human macrophages. Infect Immun. 1987;55: 2945-2950.
  46. 46. *VDRs are present in cells of the immune system. *Recent studies have demonstrated that vitamin D regulates the expression of specific endogenous antimicrobial peptides in immune cells. *This action leads to a potential role for vitamin D in modulating the immune response to various infectious diseases. Stumpf WE, Sar M, Reid FA, Tanaka Y, DeLuca HE Target cells for 1,25-dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary, and parathyroid. Science. 1979;206:1188-1190. Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311:1770-1773.
  47. 47. *This induces production of cathelicidin- which has broad spectrum antibacterial activity- from macrophages. *It also induces the production of other antimicrobial peptides as β- defensin that works against bacteria, fungi, and viruses. • Ramanathan B, Davis EG, Ross CR, Blecha E Cathelicidins: microbicidal activity, mechanisms of action, and roles in innate immunity. Microbes Infect. 2002;4: 361-372. • Wang TT, Nestel FP, Bourdeau V, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression [published correction appears in J Immunol. 2004;173:following 6489]. J Immun. 2004;173:2909-2912.
  48. 48. *It has been argued through observations that the seasonal variations in vitamin D status could be a major influence on the flu season especially that both β- defensin and cathelicidin play major role in immune defense of the respiratory system.
  50. 50. *An analysis from the Nurses’ Health Study cohort (32,826 subjects) showed that the odds ratios for colorectal cancer were inversely associated with median serum levels of 25(OH)D BUT NOT 1,25(OH)D (the odds ratio at 16.2 ng/ml was 1.0, and at 39.9 ng/ml was 0.53; P"0.01).61 - Feskanich D, Ma J, Fuchs CS, et al. Plasma vitamin D metabolites and risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev 2004;13:1502-8.
  51. 51. *A prospective study of vitamin D intake and the risk of colorectal cancer in 1954 men showed a direct relationship (with a relative risk of 1.0 when vitamin D intake was 6 to 94 IU per day and a relative risk of 0.53 when the intake was 233 to 652 IU per day, P<0.05). - Gorham ED, Garland CF, Garland FC, et al. Vitamin D and prevention of colorectal cancer. J Steroid Biochem Mol Biol 2005; 97:179-94.
  52. 52. *A study of men with prostate cancer, the disease developed 3 to 5 years later in the men who worked outdoors than in those who worked indoors. *Also, pooled data for 980 women showed that the highest vitamin D intake, as compared with the lowest, correlated with a 50% lower risk of breast cancer. - Luscombe CJ, Fryer AA, French ME, et al. Exposure to ultraviolet radiation: association with susceptibility and age at presentation with prostate cancer. Lancet 2001;358:641-2. - Garland CF, Garland FC, Gorham ED, et al. The role of vitamin D in cancer prevention. Am J Public Health 2006;96:252- 61.
  53. 53. *Both prospective and retrospective epidemiologic studies indicate that levels of 25(OH)D below 20 ng/ml are associated with a 30 to 50% increased risk of incident colon, prostate, and breast cancer, along with higher mortality from these cancers. - Ichikawa S, Guigonis V, Imel EA et al. Novel GALNT3 mutations causing hyperostosis-hyperphosphatemia syndrome result in low intact FGF23 concentrations. J Clin Endocrinol Metab 2007. - Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V et al. The parathyroid is a target organ for FGF23 in rats. J Clin Invest 2007; 117: 4003–4008. - Yamazaki Y, Tamada T, Kasai N et al. Anti-FGF23 neutralizing antibodies show the physiological role and structural features of FGF23. J Bone Miner Res 2008; 23: 1509–1518. - Krajisnik T, Bjorklund P, Marsell R et al. Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha- hydroxylase expression in cultured bovine parathyroid cells. J Endocrinol 2007; 195: 125–131.
  55. 55. *Vitamin D deficiency increased insulin resistance, decreased insulin production, and was associated with the metabolic syndrome in one study. *In another; a combined daily intake of 1200 mg of calcium and 800 IU of vitamin D lowered the risk of type 2 diabetes by 33% (relative risk, 0.67; 95% CI, 0.49 to 0.90) as compared with a daily intake of less than 600 mg of calcium and less than 400 IU of vitamin D. - Chiu KC, Chu A, Go VLW, Saad MF. Hypovitaminosis D is associated with insulin resistance and ! cell dysfunction. Am J Clin Nutr 2004;79:820-5. - Pittas AG, Dawson-Hughes B, Li T, et al. Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care 2006;29:650-6.
  57. 57. Laboratory studies indicate that 1,25- dihydroxyvitamin D suppresses renin expression and vascular smooth muscle cell proliferation. Vitamin D deficiency is associated with blood levels of inflammatory markers, including C-reactive protein and interleukin-10.
  58. 58. *Clinical studies demonstrate an inverse association between ultraviolet radiation exposure and blood pressure. *Patients with hypertension were exposed to ultraviolet B radiation three times a week for 3 months, 25-hydroxyvitamin D levels increased by approximately 180%, and blood pressure became normal (both systolic and diastolic blood pressure reduced by 6 mm Hg). - Krause R, Buhring M, Hopfenmuller W, Holick MF, Sharma AM. Ultraviolet B and blood pressure. Lancet 1998;352:709- 10. - Thomas KK, Lloyd-Jones DM, Thadhani RI, et al. Hypovitaminosis D in medical inpatients. N Engl J Med 1998;338:777- 83. - Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Körfre R, Stehle P. Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol 2003;41:105-12. - Zittermann A. Vitamin D and disease prevention with special reference to cardiovascular disease. Prog Biophys Mol Biol 2006;92:39-48
  59. 59. *Other studies on vitamin D supplementation to patients with hypertension showed similar results.
  61. 61. *Vitamin D supplementation intake recommendations are controversial based upon the targeted condition. *The Institute of Medicine (IOM) published the “2011 report” on dietary reference intakes for vitamin D to be: *600 IU/day for ages 1 to 70 years, and *800 IU/day for those older than 71 years in musculoskeletal conditions. Ross AC, Manson JE, Abrams SA et al. (2011) The 2011 repor on dietary reference intakes for Calium and Vitamin D from the Institute of medicine: what clinicans need to know. J Clin Endocrinol Metab 96:53–58
  62. 62. * Nevertheless, there is ample evidence that vitamin D doses above these recommendations are well tolerated. Brazier M, Grados F, Kamel S, et al. (2005) Clinical and laboratory safety of one year's use of a combination calcium + vitamin D tablet in abmulatory elderly women with vitamin D insufficiency: results of a multicenter, randomized, double-blind, placebo-controlled study. Clin Ther 27:1885–93 Trivedi DP, Doll R, Khaw KT (2003) Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomized double blind controlled trial. BMJ 326:469
  63. 63. *Yet, due to the lack of conclusive level I evidence, the IOM concluded that recommendations for vitamin D supplementation to address any other condition-specific goal must await larger epidemiologic or randomized studies.
  65. 65. *Several problems are inevitably connected with the use of plasma 25(OH)D to assess vitamin D status.
  66. 66. *One important problem is that plasma 25(OH)D level depends on: *Unchangeable ecological factors (season, local weather conditions and latitude), *Modifiable individual lifestyle factors (clothing, dietary habits, etc.), and *Unmodifiable individual factors (race, pigmentation, skin thickness and age). Mosekilde, L., Hermann, A.P., Beck-Nielsen, H., Charles, P., Nielsen, S.P. & Sorensen, O.H. (1999) The Danish Osteoporosis Prevention Study (DOPS): project design and inclusion of 2016 normal perimenopausal women. Maturitas, 31, 207209
  67. 67. So, most guidelines for elderly population recommend vitamin D and calcium supplementation for the elderly without previous testing of vitamin D status. Ross AC, Manson JE, Abrams SA et al. (2011) The 2011 repor on dietary reference intakes for Calium and Vitamin D from the Institute of medicine: what clinicans need to know. J Clin Endocrinol Metab 96:53–58