VITAMIN D DEFICIENCY Review article New England Journal of Medicine, July 19, 2007 Michael F. Holick, M.D.Ph.D. Prepared by Cendrella Hojeily, MD.

What is Vitamin D? A compound required in tiny amounts for metabolic reactions in an organism Fat soluble Maintains normal blood levels of calcium and phosphorus

What are the sources of Vitamin D?

DEFINITION AND PREVALENCE OF VITAMIN D Vit D deficiency: 25(OH)D<20ng/ml Vit D intoxication: 25(OH)D>150ng/ml Journal Percentage Category Place Vit(OH)D Mayo Clin Proc, 2006 40-100% Elderly men & women US & Europe 25(OH)D<20ng/ml J Clin Endocrinol Metab, 2005 >50% Post- menopausal 25(OH)D<30ng/ml Arch Pediatr Adolesc Med, 2004 52% Hispanic & African American adolescents Boston J Am Diet Assoc, 2005 48% Caucasian pre-adolescent girls Maine Am J Med, 2002 32% Healthy students, physicians, residents Boston Hospital Am J Clin Nutr, 2005 30-50% General population Saudi Arabia, UAE, Australia, Turkey, India, Lebanon N Eng J Med, 2006 78-80% Pregnant women & their children Philadelphia

OSTEOPOROSIS AND FRACTURE 33% of women 60-70 y/o have OP 66% of women > 80 y/o have OP 47% of women > 50 y/o will have one osteoporotic fracture 22% of men > 50 y/o will have one osteoporotic fracture

Osteoporosis and fracture Journal Intake: Ca/Vit D vs placebo Risk of fracture N Engl J Med, 1992 1200mg Ca + 800 IU Vit D daily for 3 years Hip fx: 43% Non vert fx: 32% Metaanalysis 400 IU Vit D daily No benefit Women’s Health 400 IU Vit D+1000mg Ca daily Am J Clin Nutr, 2006 700-800 IU Vit D Hip fx: 26% Non vert fx: 23% Record Trial, 2005 800 IU Vit D daily (no exclusion criteria) 25(OH)D: 15-24 No benefit?

Proximal weakness 800 IU Vit D/day  reduces the risk of fall by 35% (OR0.65/CI 0.4-1).Am J clin Nutr, 2006 400 IU Vit D/day  no benefit. Am J Clin Nutr, 2006 800 IU Vit D + Ca/day  reduces the risk of fall by 72% (OR: 0.28/ CI 0.1-0.7). J Amgeriatr soc, 2007

Cancer and Vit D People living at higher latitudes are at increased risk for cancer J of Steriod Biochem Mol Bio, 2005 Journal Condition Incidence of cancer J Natl Cancer Inst, 2006 Vit D deficiency: 25(OH)D < 20 30-50% increase (colon, prostate, breast) J Steroid Biochem Mol Bio, 2005 Intake: 6-94 IU vs. 233-652 IU Decrease in colorectal cancer p < 0.05 J Natl Cancer Inst, 2005 Sunlight exposure 40% decrease in NHL, Decrease in melanoma mortality

Diseases and Vit D Living at higher altitudes increases the risk of DMI, MS, and Crohn’s Toxicology, 2002 African-Americans are at higher risk of developing TB Science, 2006 Journal Intake (per day) Risk Neurology, 2004 400 IU MS + OA + RA 42% Lancet, 2001 2000 IU DMI 81% (children) Diabetes Care, 2006 1200 Ca + 800 IU vs. < 600 Ca + 400 IU DMII 33%

Cardiovascular and Vit D Living at higher altitudes increases risk of HTN/CAD. Prog Biophys Mol Bio, 2006 Vit D deficiency a/w CHF + inflammatory factors (CRP). Annal Cardiology, 2003 Patients with HTN exposed to UVB 3x/week for 3 months  25(OH)D increases and BP becomes normal (reduced by 6 mmHg: both systolic and diastolic). Lancet, 1998

Vit D deficiency and Psychiatric Disorders Vit D deficiency has been linked to increase incidence of schizophrenia and depression. Schizophr Res, 2002 Maintaining sufficient Vit D in utero and in early life may be important for brain dev as well as for maintenance of mental function later in life. J Chem Neuroanat, 2005

Vit D deficiency and Lung Function Men and women with 25(OH)D>35ng/ml have 176 ml increase in the forced expiratory volume in 1 second. Chest, 2005 Children of women who had Vit D deficiency during pregnancy are at increased risk for wheezing illnesses. Am J Clin Nutr, 2007

Vit D Intoxication 25(OH)D > 150ng/ml Caused by ingestion of > 50,000 IU/day Caution: people predisposed to hypercalcemia (granulomatous diseases)

CONCLUSION Serum 25-hydroxyVitamin D is not only a predictor of bone health, but is also an independent risk predictor for cancer and other chronic diseases 1,25(OH)D should never be used for detecting Vit D deficiency

DISCUSSION Should we use 25(OH)D as a screening test? 25(OH)D assay is costly and may not be always available so screening is not recommended! Adequate Vit D intake is recommended 800 IU Vit D/day guarantees Vit D sufficiency unless there are other conditions

“You’ve got a rare condition called ‘good health “You’ve got a rare condition called ‘good health.’ Frankly, we’re not sure how to treat it.”