Vitamin D

Swedish Weight Loss Services

Dharti Shah (Volunteer Research Assistant)

October 2010

Discoverers…

Elmer McCollum

Edward Mellanby

Marguerite Davis

A vitamin? A hormone?

Sources:Skin synthesis through UVB

• 270-300 nm

DietSupplementation

Hormone

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)

Production?

7- dehydrocholesterol (skin)

Vitamin D3

(cholecalciferol)

Ultraviolet B

Liver enzyme 25-hydroxylase

25-hydroxycholecalciferol {25 (OH)D3, calcidiol, circulating form}

Kidney enzyme25(OH)-D-1α-hydroxylase

1,25-dihydroxycholecalciferol {1,25 (OH)2D3,calcitriol, active form}

“D” action… Vitamin DVDBP

Retinoid X receptor (RXR)

Vitamin D receptor (VDR)

D

D

D

Gene transcriptionVitamin D Response Elements(VDRE’s)

Multifunctional

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

Deficiency in the Pacific Northwest

Implications

Obesity Diabetes Cardiovascular diseases Cancer Compromised bone health Multiple Sclerosis Depression

Obesity

Causal relationship

Type of obesity Visceral Subcutaneous

BMI Parathyroid

hormone

Cheng S et.al. Diabetes Platinum Periodicals Jan 2010 59,1, pg.432

Adiposity, Cardiometabolic Risk, and Vitamin D Status: The Framingham Heart Study

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

Parathyroid hormone(PTH)

PTH

Phospholipase C-β Free intracellular Ca2+

catecholamines

Lipolysis

Fatty acid synthase

Lipogenesis

Dephosphorylation of GLUT4

insulin

Glucose uptake in adipocytes

Fatty acid storage

Insulin resistance Metabolic syndromeMccarty MF, ThomasCA. Medical Hypotheses 2003; 61(5-6) 535-542

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

Diabetes

β-cell function defect - autoimmune Insulin resistance

Disturbances in Ca2+ pools Inflammation

Cytokines – β-cell apoptosis• Interleukin-2, TNF-α, interferon-gamma

Diabetes

NHANES (1988-1994)Serum samples – 6228 subjects

• 2766 – non-Hispanic whites• 1736 – non-Hispanic blacks• 1726 – Mexican Americans

Age > 20yResults were ethnic-specific

Scragg R. Sowers M. Bell C. Diabetes Care 2004 27:2813-2818

ResultsFasting glucose

Y N OR Y N OR Y N OR

Non- Hispanic Non-Hispanic black Mexican American white

25(OH)Dnmol/L

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

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

Vitamin D levels – Bariatric patients

Medical patients

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

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