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Vitamin D

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  1. Vitamin D Swedish Weight Loss Services Dharti Shah (Volunteer Research Assistant) October 2010

  2. Discoverers… Elmer McCollum Marguerite Davis Edward Mellanby

  3. A vitamin? A hormone? • Sources: • Skin synthesis through UVB • 270-300 nm • Diet • Supplementation • Hormone

  4. Forms • Ergocalciferol (vitamin D2, plants, algae) • Cholecalciferol (vitamin D3, mammals) • 25- hydroxycholecalciferol (25(OH)D3 circulating form) • 1, 25 dihyroxycholecalciferol (1,25 (OH)2D3 – active form)

  5. 7- dehydrocholesterol (skin) Ultraviolet B Vitamin D3 (cholecalciferol) Liver enzyme 25-hydroxylase 25-hydroxycholecalciferol {25 (OH)D3, calcidiol, circulating form} Kidney enzyme 25(OH)-D-1α-hydroxylase 1,25-dihydroxycholecalciferol {1,25 (OH)2D3,calcitriol, active form} Production?

  6. “D” action… Vitamin D VDBP Vitamin D receptor (VDR) D D Retinoid X receptor (RXR) D Vitamin D Response Elements(VDRE’s) Gene transcription

  7. Multifunctional

  8. Deficiency • Cut-off values (Dynacare/Know your D) • Optimal levels ≥ 32-100 ng/dl • Insufficiency – 20-32 ng/ml • Deficiency • < 20 ng/ml – very low • <8 ng/ml – extremely low

  9. Deficiency in the Pacific Northwest

  10. Implications • Obesity • Diabetes • Cardiovascular diseases • Cancer • Compromised bone health • Multiple Sclerosis • Depression

  11. Obesity Adiposity, Cardiometabolic Risk, and Vitamin D Status: The Framingham Heart Study • Causal relationship • Type of obesity • Visceral • Subcutaneous • BMI • Parathyroid hormone Cheng S et.al. Diabetes Platinum Periodicals Jan 2010 59,1, pg.432

  12. BMI and vitamin D status BMI is inversely correlated to vitamin D status Wortsman. J. et. al. Am J Clin Nutr 2000;72:690-3

  13. Parathyroid hormone(PTH) PTH Phospholipase C-β Free intracellular Ca2+ insulin catecholamines Fatty acid synthase Dephosphorylation of GLUT4 Lipolysis Lipogenesis Glucose uptake in adipocytes Fatty acid storage Insulin resistance Metabolic syndrome Mccarty MF, ThomasCA. Medical Hypotheses 2003; 61(5-6) 535-542

  14. Vitamin D/calcium on Insulin Secretion Sensitivity • Pancreatic β cells • Vitamin D receptors • 1-α-hydroxylase enzyme • Vitamin D response element in insulin gene promoter • Intracellular (nM)/extracellular (mM) calcium pools - Calbindin • Transcription of insulin gene • VDR in skeletal muscle • Expression of insulin receptors, responsiveness • Activates PPAR-δ – regulates fatty acid metabolism • Optimal insulin action dependent on a very specific and narrow range of calcium • Insulin receptor phosphorylation is also calcium dependent

  15. Diabetes • β-cell function defect - autoimmune • Insulin resistance • Disturbances in Ca2+ pools • Inflammation • Cytokines – β-cell apoptosis • Interleukin-2, TNF-α, interferon-gamma

  16. Diabetes • NHANES (1988-1994) • Serum samples – 6228 subjects • 2766 – non-Hispanic whites • 1736 – non-Hispanic blacks • 1726 – Mexican Americans • Age > 20y • Results were ethnic-specific Scragg R. Sowers M. Bell C. Diabetes Care 2004 27:2813-2818

  17. Results Non- Hispanic Non-Hispanic black Mexican American white 25(OH)D nmol/L Fasting glucose N OR Y Y N OR Y N OR

  18. Effect of Bariatric surgery • Vitamin D levels corrected after surgery and supplementation • BPD • Morbidly obese women followed 5 and 10 years after BPD • Supplemented with 400,000 IU D2 every 2 weeks • Results • Hypovitaminosis • 76% - obese state • 91% after 5 years • 89% after 10 years • Increase in whole-body glucose uptake • Conclusion • Fat mass and BMI are predictors of 25(OH)D • Hypovitaminosis does not imply insulin resistance Manco M. Calvani M. et.al. Obesity Research 2005 Vol.13 No.10 pg:1692-1700

  19. Supplementation • D2 and D3 potency evaluated • Single dose of 50,000 IU of each calciferol administered • Followed time course for rise in 25(OH)D levels over 28 days Armas L.A.G. Hollis B. Heany. R J Clin Endocrinol Metab Nov 2004 89(11):5387-5391

  20. Vitamin D levels – Bariatric patients

  21. Medical patients

  22. Other effects.. • Multiple Sclerosis • Increases anti-inflammatory cytokines • Cancer • Cell differentiation • CVD • NHANES III – 13,131 individuals • Followed for mortality through yr. 2000 • Follow-up period – 3,266 deaths • Premature deaths – 1,066 • Deaths from CVD accounted for 34% of PD • Heart failure deaths – 101 • Rate of vitamin D def. among heart failure deaths – 37% • Low vit. D levels – 3.4 times more likely to die from heart failure

  23. Summary • BMI and fat mass are inversely correlated with vit. D status • PTH is implicated in MS, adipogenesis • Adequate vit. D levels may prevent or delay the progress of diseases