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Shining a Light on Vitamin D Vitamine A
Shining a Light on Vitamin D Vitamine A
Shining a Light on Vitamin D Lisa Pomranky, M.D. Slocum Center for Orthopedics and Sports Medicine Objectives Review the role of Vitamin D and how it relates to our health Discuss replacement and optimal levels What is Vitamin D? The “Sunshine Vitamin” A fat soluble vitamin with an important role in calcium and bone metabolism A vitamin with emerging data and research about previously unknown health benefits A vitamin in which many of us are deficient or insufficient What is Vitamin D? Vitamin D3 (cholecalciferol) is the form produced in humans and animals Supplements made from UVB irradiation of lanolin (wool fat) Vitamin D2 (ergocalciferol) is the plant derived supplement UVB irradiation of ergosterol from yeast Only 30% as effective in raising 25- hydroxyvitamin D level as D3 What is Vitamin D? Vitamin D3 is converted to 25-hydroxyvitamin D in the liver 25-hydroxyvitamin D is the precursor to the active 1,25-dihydroxyvitamin D This conversion takes place mainly in the kidneys Calcium and Bone Metabolism Essential to calcium metabolism primarily by enhancing intestinal absorption of dietary calcium If vitamin D level is low (below 30 ng/ml), calcium absorption is significantly impaired Inadequate Ca absorption leads to osteopenia and osteoporosis Calcium and Bone Metabolism Increased PTH leads to the maturation of osteoclasts, which dissolve mineralized bone matrix to provide calcium, but can result in osteoporosis and osteopenia Increased PTH also results in phosphaturia and lowering of serum phosphorous Calcium and Bone Metabolism Low calcium-phosphorous product leads to inadequate bone mineralization Bone matrix continues to be made but is rubbery and structurally inadequate Rickets In children, inadequate mineralization causes skeletal deformities known as rickets Osteomalacia In adults, inadequate mineralization causes dull, aching bone pain known as osteomalacia Osteoporosis Milder degrees of vitamin D inadequacy can lead to a higher risk of osteoporosis, and an increased likelihood of falling in older adults whose muscles are weakened by a lack of the vitamin. Osteoporosis and Aging A decrease in dietary calcium intake, usually as a result of decreased overall dietary energy intake (e.g. poor appetite, intercurrent illnesses, social and economic factors) A decrease in the intestinal absorption of calcium (exacerbated if vitamin D status is low) A decrease in the capacity of the intestinal cells to adapt to a low calcium intake, and increase their absorptive capacity Osteoporosis and Aging Less frequent exposure to sunlight (e.g. elderly who are housebound, or institutionalized, or have reduced mobility) A decrease in the capacity of the skin to synthesize vitamin D A decrease in the efficiency with which the kidneys can retain calcium, leading to increased calcium loss in the urine A decrease in the capacity of the kidneys to convert vitamin D into the most active form, 1,25- dihydroxyvitamin D Are there other functions of Vitamin D? Most organs in the body (including brain, prostate, breast, colon, heart, pancreas, skin and immune system) have VDR which recognize 1,25-dihydroxyvitamin D Many organs also have enzyme to convert 25-hydroxyvitamin D to active 1,25- dihydroxyvitamin D (similar to kidneys) Functions of Vitamin D 1,25-dihydroxyvitamin D controls more than 200 genes which then: Inhibit cell multiplication Promote cell death and cell maturation Stimulate insulin secretion from the pancreas Modulate immune function Inhibit renin production Vitamin D Metabolism Plethora of Recent Research Meta-analysis of 18 RCTs with 57,311 participants over average of 5 years showed 7% reduction in all cause mortality Average dose vit D 528 IU (300-2000) Ref: Autier and Gandini. Arch Intern Med Sep 2007 Osteoporosis Osteoporosis and risk of fractures Clinical trials show that vitamin D3 supplementation of 800 IU daily along with adequate calcium can reduce the risk of hip and non-vertebral fractures by 20-40% (need to reach 25 (OH)vit D levels above 30 ng/ml) Vitamin D and Muscle Muscle weakness and risk of falls Skeletal muscles have VDR and may require vit D for maximum function Performance speed and proximal muscle strength markedly improved when 25 (OH)vit D levels were raised from 4-16 to 40 ng/ml Meta-analysis of 5 trials showed 35% reduction in falls in the elderly on 800 IU D3 and calcium In one study of NH patients, falls reduced by 72% with Vit D 800 IU and calcium Vitamin D and Cancer Vitamin D level below 20 ng/ml associated with 30-50% increased incidence of colon, prostate, and breast cancer In one 4 year study of 1179 post-menopausal women in Nebraska showed that women taking vit D3 1100 IU and calcium 1500mg daily had 60% lower risk of developing cancer compared to placebo group Ref: Am J Clin Nutr 2007:1586-91 Vitamin D and DM Increased insulin resistance and decreased insulin production Raising vit D level from 10ng/ml to 30ng/ml, increased insulin sensitivity 60% In one study, vit D 800 IU and Ca 1200mg lowered risk of developing DM Type II by 33% compared to vit D 400 IU and Ca 600mg Vitamin D and Type I Diabetes Increased risk of Type I Diabetes In a large study of 10,366 children in Finland for 31 years Children with vit D deficiency had RR 3 of developing Type 1 DM Risk of developing Type I DM was reduced 80% over 30 years in children given vit D 2000 IU daily in first year of life Ref: Lancet 2001:358: 1500-3 Vitamin D and Pregnancy Pregnancy: low level of 25 (OH) vit D has been associated with: Impaired fetal skeletal formation Higher incidence of pre-eclampsia Normal vit D levels may be necessary for fetal “imprinting” for neurodevelopment, immune function Vitamin D and MS Living north of 37° latitude increases risk of developing MS 100% Higher levels of 25 (OH) vit D associated with lower risk of MS (JAMA 2007) Taking a MVI with 400 IU of vit D reduces risk 40% Vitamin D and CVD In one study of 1,739 Framingham offspring without CV disease, those with vit D level lower than 15ng/ml had twice the risk of MI, CVA, CHF than those with higher than 15 over 5 year period (Circulation 2008 Jan 29) Increasing 25 (OH) vit D with UVB for 3 months lowered systolic blood pressure 6 mmHg Vit D and calcium supplement lowered systolic blood pressure 9.3% What is an Optimal Vitamin D Level? Normal = 32-100 ng/ml (75-100 nmol/L) Insufficiency = 20-29 ng/ml (52-72 nmol/L) Deficiency = < 20 ng/ml (50 nmol/L) Toxic = > 150 ng/ml (374 nmol/L) Optimal = ?? Prevalence of Vitamin D Deficiency Estimated 1 billion worldwide 52% of Hispanic and black adolescents in Boston study 32% of young men and women 18-29 in Boston 76% of mother-infant pairs in Boston 75% ambulatory older adults in Denver Etiology for Deficiency Medications: seizure medicine, steroids Heritable disorders Vitamin D-resistant rickets Primary hyperparathyroidism Granulomatous disorders – sarcoidosis, TB, some lymphomas Hyperthyroidism Chronic renal disease Etiologies for Deficiency Reduced skin synthesis – season, northern latitude, sunscreen, aging, pigmented skin Inadequate nutritional intake Malabsorption – celiac disease, Crohns, gastrointestinal bypass surgery Breast feeding exclusively Obesity – sequestration in body fat Vitamin D Level Defined by level of 25-hydroxyvitamin D which is the circulating form of vitamin D (half-life of 10-19 days) “Normal” = Level at which PTH suppression levels off towards nadir and calcium absorption reaches maximum (a physiologic and not population based “normal”) What to Order When measuring for Vitamin D deficiency be sure to order: 25-hydroxyvitamin D Sometimes reported as total with subcomponents of D2 and D3. Use the total level. Do not order 1,25 dihydroxyvitamin D level This is active form of Vitamin D3, produced by kidneys and can remain at normal level in face of overall Vitamin D deficiency. Sources of Vitamin D Sunlight (UVB) Diet Dietary supplements Sources of Vitamin D Solar UVB penetrates skin to convert 7- Dehydrocholesterol to vitamin D3 Sunlight produces 90% of vitamin D Sunscreen SPF 15 reduces capacity 99% Season and time of day important In northern winters, no Vit D production; Pigmented skin and aging skin - >75% reduction in vit D production Vitamin D from the Sun Some of your vitamin D requirement can be attained with adequate sun or UVB (tanning booth) exposure 5-30 minutes of sun exposure (no sunscreen) to arms and face or legs between 10am – 3pm twice a week in summer is usually adequate (with exception of pigmented or older skin) Food Sources of Vitamin D Natural Sources: Vitamin D3 Salmon, wild 600-1000 IU Salmon, farmed 100-250 IU Sardines (canned) 300 IU Tuna (canned) 230 IU Shitake mushrooms Vitamin D2 Fresh 100 IU Sundried 1600 IU Food Sources of Vitamin D? Fortified Foods Vitamin D3 Milk (8 oz) 100 IU Orange juice (8 oz) 100 IU Infant formula (8 oz) 100 IU Cereal (serving) 100 IU Vitamin D Supplements Over the counter Multivitamin 400 IU Cholecalciferol (D3) 400, 800, 1000, 2000 Cod liver oil (1 tsp) 400-1000 IU* Calcium with Vit D 200 IU Prescription Ergocalciferol (D2) 50,000 IU cap Can contain mercury and other toxins Vitamin D Supplements Over the counter D3 Tri Vi Sol 400 IU / ml (A,D,C) Poly Vi Sol 400 IU /ml (A,D,C,Bs) Prescription Ergocalciferol (D2) 8,000 IU/ml Drisdol Vitamin D Dosage Newly evolving recommendations for maintenance dose (to prevent deficiency): Vitamin D3 Children 400-1000 IU Adults 800-1000 IU* Alternatively, 50,000 IU vitamin D2 (ergocalciferol) by Rx once or twice a month Vitamin D Dosage Newly evolving recommendations for maintenance dose (to prevent deficiency): Pregnant/lactating 1000-2000 IU African American 1000-2000 IU Obesity 1000-2000 IU Vitamin D Toxicity Vitamin D intoxication is extremely rare Doses of 50,000 IU a day of Vit D3 would raise levels above the toxic level of 150ng/ml Doses of 10,000 IU Vit D3 for 5 months did not cause toxicity Bottom line: Doses up to 2000 IU Vit D3 daily are quite safe for almost everyone Vitamin D Toxicity Signs and symptoms of toxicity High calcium levels in the blood and urine Confusion Severe increase in urination and thirst Anorexia, vomiting Muscle weakness References Vitamin D: bone and beyond, rationale and recommendations for supplementation. Stechschulte SA, Kirsner RS, Federman DG. Am J Med. 2009 Sep;122(9):793-802. Review. Vitamin D deficiency and risk for cardiovascular disease. Judd SE, Tangpricha V. Am J Med Sci. 2009 Jul;338(1):40-4. Review. References Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. Tarcin O, Yavuz DG, Ozben B, Telli A, Ogunc AV, Yuksel M, Toprak A, Yazici D, Sancak S, Deyneli O, Akalin S. J Clin Endocrinol Metab. 2009 Oct;94(10):4023-30. Epub 2009 Jul 7. The effect of vitamin D2 and vitamin D3 on intestinal calcium absorption in Nigerian children with rickets. Thacher TD, Obadofin MO, O'Brien KO, Abrams SA. J Clin Endocrinol Metab. 2009 Sep;94(9):3314-21. Epub 2009 Jun 30. Osteoporosis in inflammatory bowel disease. Ali T, Lam D, Bronze MS, Humphrey MB. Am J Med. 2009 Jul;122(7):599-604. Review. Falls in the nursing home: a collaborative approach. Messinger-Rapport B, Dumas LG. Nurs Clin North Am. 2009 Jun;44(2):187-95. Review. References Estimation of the dietary requirement for vitamin D in free-living adults >=64 y of age. Cashman KD, Wallace JM, Horigan G, Hill TR, Barnes MS, Lucey AJ, Bonham MP, Taylor N, Duffy EM, Seamans K, Muldowney S, Fitzgerald AP, Flynn A, Strain JJ, Kiely M. Am J Clin Nutr. 2009 May;89(5):1366-74. Epub 2009 Mar 18. Health effects of vegan diets. aig WJ. Am J Clin Nutr. 2009 May;89(5):1627S-1633S. Epub 2009 Mar 11. Review. Long-term effects of giving nursing home residents bread fortified with 125 microg (5000 IU) vitamin D(3) per daily serving. Mocanu V, Stitt PA, Costan AR, Voroniuc O, Zbranca E, Luca V, Vieth R. Am J Clin Nutr. 2009 Apr;89(4):1132-7. Epub 2009 Feb 25. Vitamin D supplementation during Antarctic winter. Smith SM, Gardner KK, Locke J, Zwart SR. Am J Clin Nutr. 2009 Apr;89(4):1092-8. Epub 2009 Feb 18. References Expanding roles of vitamin D. Giovannucci E. J Clin Endocrinol Metab. 2009 Feb;94(2):418-20. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Wejse C, Gomes VF, Rabna P, Gustafson P, Aaby P, Lisse IM, Andersen PL, Glerup H, Sodemann M. Am J Respir Crit Care Med. 2009 May 1;179(9):843-50. Epub 2009 Jan 29. Vitamin D deficiency in older men. Orwoll E, Nielson CM, Marshall LM, Lambert L, Holton KF, Hoffman AR, Barrett-Connor E, Shikany JM, Dam T, Cauley JA; Osteoporotic Fractures in Men (MrOS) Study Group. J Clin Endocrinol Metab. 2009 Apr;94(4):1214-22. Epub 2009 Jan 27. Vitamin D beyond bones in chronic obstructive pulmonary disease: time to act. Janssens W, Lehouck A, Carremans C, Bouillon R, Mathieu C, Decramer M. Am J Respir Crit Care Med. 2009 Apr 15;179(8):630-6. Epub 2009 Jan 22. Review. References Cod liver oil, vitamin A toxicity, frequent respiratory infections, and the vitamin D deficiency epidemic. Cannell JJ, Vieth R, Willett W, Zasloff M, Hathcock JN, White JH, Tanumihardjo SA, Larson-Meyer DE, Bischoff-Ferrari HA, Lamberg-Allardt CJ, Lappe JM, Norman AW, Zittermann A, Whiting SJ, Grant WB, Hollis BW, Giovannucci E. Ann Otol Rhinol Laryngol. 2008 Nov;117(11):864-70. Review. A vitamin D nutritional cornucopia: new insights concerning the serum 25- hydroxyvitamin D status of the US population. Norman AW. m J Clin Nutr. 2008 Dec;88(6):1455-6. Vitamin D deficiency an important, common, and easily treatable cardiovascular risk factor? Lee JH, O'Keefe JH, Bell D, Hensrud DD, Holick MF. J Am Coll Cardiol. 2008 Dec 9;52(24):1949-56. Review. References Prevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer disease. Evatt ML, Delong MR, Khazai N, Rosen A, Triche S, Tangpricha V. Arch Neurol. 2008 Oct;65(10):1348-52. The "sunshine deficit" and cardiovascular disease. Wallis DE, Penckofer S, Sizemore GW. Circulation. 2008 Sep 30;118(14):1476-85. Review. No abstract available. Erratum in: Circulation. 2009 Jun 2;119(21):e550. Adverse effects of nutritional inadequacy and excess: a hormetic model. Hayes DP. Am J Clin Nutr. 2008 Aug;88(2):578S-581S. Review. Assessing the vitamin D status of the US population. Yetley EA. Am J Clin Nutr. 2008 Aug;88(2):558S-564S. Review. References African Americans, 25-hydroxyvitamin D, and osteoporosis: a paradox. Aloia JF. Am J Clin Nutr. 2008 Aug;88(2):545S-550S. Review. Vitamin D and calcium interactions: functional outcomes. Heaney RP. Am J Clin Nutr. 2008 Aug;88(2):541S-544S. Review. Serum 25-hydroxyvitamin D and functional outcomes in the elderly. Dawson-Hughes B. Am J Clin Nutr. 2008 Aug;88(2):537S-540S. Review. 25-Hydroxyvitamin D: functional outcomes in infants and young children. Greer FR. Am J Clin Nutr. 2008 Aug;88(2):529S-533S. Review. Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcomes from human and animal studies. Kovacs CS. Am J Clin Nutr. 2008 Aug;88(2):520S-528S. Review. References Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health. Cranney A, Weiler HA, O'Donnell S, Puil L. Am J Clin Nutr. 2008 Aug;88(2):513S-519S. Review. Measuring 25-hydroxyvitamin D in a clinical environment: challenges and needs. Hollis BW. Am J Clin Nutr. 2008 Aug;88(2):507S-510S. Review. Vitamin D across the lifecycle: physiology and biomarkers. Prentice A, Goldberg GR, Schoenmakers I. Am J Clin Nutr. 2008 Aug;88(2):500S-506S. Review. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Norman AW. Am J Clin Nutr. 2008 Aug;88(2):491S-499S. Review. References Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M; Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society. Pediatrics. 2008 Aug;122(2):398-417. Review. Issues with vitamin D in routine clinical practice. Jones BJ, Twomey PJ. Rheumatology (Oxford). 2008 Sep;47(9):1267-8. Epub 2008 Jul 25. No abstract available. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm BO, Weihrauch G, Maerz W. Arch Intern Med. 2008 Jun 23;168(12):1340-9. Deficiency of sunlight and vitamin D. Holick MF. BMJ. 2008 Jun 14;336(7657):1318-9. No abstract available. References Vitamin D assessment in population-based studies: a review of the issues. Millen AE, Bodnar LM. Am J Clin Nutr. 2008 Apr;87(4):1102S-5S. Review. Vitamin D deficiency: a worldwide problem with health consequences. Holick MF, Chen TC. Am J Clin Nutr. 2008 Apr;87(4):1080S-6S. Review. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta- analysis. Zipitis CS, Akobeng AK. Arch Dis Child. 2008 Jun;93(6):512-7. Epub 2008 Mar 13. Review. Pharmacokinetics of a single, large dose of cholecalciferol. Ilahi M, Armas LA, Heaney RP. Am J Clin Nutr. 2008 Mar;87(3):688-91. Vitamin D insufficiency in southern Arizona. Jacobs ET, Alberts DS, Foote JA, Green SB, Hollis BW, Yu Z, Martínez ME. Am J Clin Nutr. 2008 Mar;87(3):608-13. References Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women. Prince RL, Austin N, Devine A, Dick IM, Bruce D, Zhu K. Arch Intern Med. 2008 Jan 14;168(1):103-8. Dose response to vitamin D supplementation among postmenopausal African American women. Talwar SA, Aloia JF, Pollack S, Yeh JK. Am J Clin Nutr. 2007 Dec;86(6):1657-62. Response to teriparatide in patients with baseline 25-hydroxyvitamin D insufficiency or sufficiency. Dawson-Hughes B, Chen P, Krege JH. J Clin Endocrinol Metab. 2007 Dec;92(12):4630-6. Epub 2007 Oct 2. Hypocalcaemia and vitamin D deficiency: an important, but preventable, cause of life- threatening infant heart failure. Maiya S, Sullivan I, Allgrove J, Yates R, Malone M, Brain C, Archer N, Mok Q, Daubeney P, Tulloh R, Burch M. Heart. 2008 May;94(5):581-4. Epub 2007 Aug 9.
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