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.

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

What is Vitamin D?What is Vitamin D?A compound required A compound required in tiny amounts for in tiny amounts for metabolic reactions in metabolic reactions in an organism an organism

Fat solubleFat soluble

Maintains normal Maintains normal blood levels of calcium blood levels of calcium and phosphorus and phosphorus

What are the sources of What are the sources of Vitamin D?Vitamin D?

DEFINITION AND PREVALENCE DEFINITION AND PREVALENCE OF VITAMIN DOF VITAMIN D

Vit D deficiency: 25(OH)D<20ng/mlVit D deficiency: 25(OH)D<20ng/ml

Vit D intoxication: 25(OH)D>150ng/mlVit D intoxication: 25(OH)D>150ng/ml

Journal Journal PercentagePercentage CategoryCategory Place Place Vit(OH)DVit(OH)D

Mayo Clin Proc, Mayo Clin Proc, 20062006

40-100%40-100% Elderly men & womenElderly men & women US & EuropeUS & Europe 25(OH)D<20ng/ml25(OH)D<20ng/ml

J Clin Endocrinol J Clin Endocrinol Metab, 2005Metab, 2005

>50%>50% Post- menopausalPost- menopausal US & EuropeUS & Europe 25(OH)D<30ng/ml25(OH)D<30ng/ml

Arch Pediatr Arch Pediatr Adolesc Med, 2004Adolesc Med, 2004

52%52% Hispanic & African American Hispanic & African American adolescentsadolescents

BostonBoston 25(OH)D<20ng/ml25(OH)D<20ng/ml

J Am Diet Assoc, J Am Diet Assoc, 20052005

48%48% Caucasian pre-adolescent Caucasian pre-adolescent girlsgirls

MaineMaine 25(OH)D<20ng/ml25(OH)D<20ng/ml

Am J Med, 2002Am J Med, 2002 32%32% Healthy students, physicians, Healthy students, physicians, residentsresidents

Boston HospitalBoston Hospital 25(OH)D<20ng/ml25(OH)D<20ng/ml

Am J Clin Nutr, Am J Clin Nutr, 20052005

30-50%30-50% General populationGeneral population Saudi Arabia, UAE, Saudi Arabia, UAE, Australia, Turkey, Australia, Turkey, India, LebanonIndia, Lebanon

25(OH)D<20ng/ml25(OH)D<20ng/ml

N Eng J Med, 2006N Eng J Med, 2006 78-80%78-80% Pregnant women & their Pregnant women & their childrenchildren

PhiladelphiaPhiladelphia 25(OH)D<20ng/ml25(OH)D<20ng/ml

OSTEOPOROSIS AND FRACTUREOSTEOPOROSIS AND FRACTURE

33% of women 60-70 y/o have OP33% of women 60-70 y/o have OP

66% of women > 80 y/o have OP66% of women > 80 y/o have OP

47% of women > 50 y/o will have 47% of women > 50 y/o will have one osteoporotic fractureone osteoporotic fracture

22% of men > 50 y/o will have one 22% of men > 50 y/o will have one osteoporotic fractureosteoporotic fracture

Osteoporosis and fractureOsteoporosis and fractureJournal Journal Intake: Ca/Vit D vs Intake: Ca/Vit D vs

placeboplaceboRisk of fractureRisk of fracture

N Engl J Med, 1992N Engl J Med, 1992 1200mg Ca + 1200mg Ca +

800 IU Vit D daily for 3 800 IU Vit D daily for 3 yearsyears

Hip fx: 43%Hip fx: 43%

Non vert fx: 32%Non vert fx: 32%

MetaanalysisMetaanalysis 400 IU Vit D daily400 IU Vit D daily No benefitNo benefit

Women’s HealthWomen’s Health 400 IU Vit D+1000mg 400 IU Vit D+1000mg Ca dailyCa daily

No benefitNo benefit

Am J Clin Nutr, 2006Am J Clin Nutr, 2006 700-800 IU Vit D700-800 IU Vit D Hip fx: 26%Hip fx: 26%

Non vert fx: 23%Non vert fx: 23%

Record Trial, 2005Record Trial, 2005 800 IU Vit D daily800 IU Vit D daily

(no exclusion criteria)(no exclusion criteria)

25(OH)D: 15-2425(OH)D: 15-24

No benefit?No benefit?

Proximal weaknessProximal weakness800 IU Vit D/day 800 IU Vit D/day reduces the risk of fall reduces the risk of fall by 35% (OR0.65/CI by 35% (OR0.65/CI 0.4-1).0.4-1).Am J clin Nutr, 2006Am J clin Nutr, 2006

400 IU Vit D/day 400 IU Vit D/day no no benefit. benefit. Am J Clin Nutr, 2006Am J Clin Nutr, 2006

800 IU Vit D + Ca/day 800 IU Vit D + Ca/day reduces the risk of reduces the risk of fall by 72% (OR: 0.28/ fall by 72% (OR: 0.28/ CI 0.1-0.7). CI 0.1-0.7). J Amgeriatr soc, 2007J Amgeriatr soc, 2007

Cancer and Vit DCancer and Vit D

People living at higher latitudes are at People living at higher latitudes are at increased risk for cancer increased risk for cancer J of Steriod Biochem Mol Bio, 2005J of Steriod Biochem Mol Bio, 2005

Journal Journal ConditionCondition Incidence of cancerIncidence of cancer

J Natl Cancer Inst, 2006J Natl Cancer Inst, 2006 Vit D deficiency: 25(OH)D < 20Vit D deficiency: 25(OH)D < 20 30-50% increase (colon, 30-50% increase (colon, prostate, breast)prostate, breast)

J Steroid Biochem Mol Bio, 2005J Steroid Biochem Mol Bio, 2005 Intake: 6-94 IU vs.Intake: 6-94 IU vs.

233-652 IU233-652 IUDecrease in colorectal cancer Decrease in colorectal cancer

p < 0.05p < 0.05

J Natl Cancer Inst, 2005J Natl Cancer Inst, 2005 Sunlight exposureSunlight exposure 40% decrease in NHL,40% decrease in NHL,

Decrease in melanoma mortalityDecrease in melanoma mortality

Diseases and Vit DDiseases and Vit D

Living at higher altitudes increases the risk of DMI, MS, and Crohn’sLiving at higher altitudes increases the risk of DMI, MS, and Crohn’s Toxicology, Toxicology,

20022002

African-Americans are at higher risk of developing TB African-Americans are at higher risk of developing TB Science, 2006Science, 2006

Journal Journal Intake (per day)Intake (per day) RiskRisk

Neurology, 2004Neurology, 2004 400 IU400 IU MS + OA + RA 42%MS + OA + RA 42%

Lancet, 2001Lancet, 2001 2000 IU2000 IU DMI 81% (children)DMI 81% (children)

Diabetes Care, 2006Diabetes Care, 2006 1200 Ca + 800 IU vs. 1200 Ca + 800 IU vs.

< 600 Ca + 400 IU< 600 Ca + 400 IUDMII 33%DMII 33%

Cardiovascular and Vit DCardiovascular and Vit D

Living at higher altitudes increases risk of Living at higher altitudes increases risk of HTN/CAD. HTN/CAD. Prog Biophys Mol Bio, 2006Prog Biophys Mol Bio, 2006

Vit D deficiency a/w CHF + inflammatory Vit D deficiency a/w CHF + inflammatory factors (CRP). factors (CRP). Annal Cardiology, 2003Annal Cardiology, 2003

Patients with HTN exposed to UVB 3x/week Patients with HTN exposed to UVB 3x/week for 3 months for 3 months 25(OH)D increases and BP 25(OH)D increases and BP becomes normal (reduced by 6 mmHg: both becomes normal (reduced by 6 mmHg: both systolic and diastolic). systolic and diastolic). Lancet, 1998Lancet, 1998

Vit D deficiency and Psychiatric Vit D deficiency and Psychiatric DisordersDisorders

Vit D deficiency has been linked to Vit D deficiency has been linked to increase incidence of schizophrenia increase incidence of schizophrenia and depression. and depression. Schizophr Res, 2002Schizophr Res, 2002

Maintaining sufficient Vit D in utero and in Maintaining sufficient Vit D in utero and in early life may be important for brain dev early life may be important for brain dev as well as for maintenance of mental as well as for maintenance of mental function later in life. function later in life. J Chem Neuroanat, 2005 J Chem Neuroanat, 2005

Vit D deficiency and Lung FunctionVit D deficiency and Lung Function

Men and women with 25(OH)D>35ng/ml have Men and women with 25(OH)D>35ng/ml have 176 ml increase in the forced expiratory volume 176 ml increase in the forced expiratory volume

in 1 second.in 1 second. Chest, 2005Chest, 2005

Children of women who had Vit D deficiency Children of women who had Vit D deficiency during pregnancy are at increased risk for during pregnancy are at increased risk for wheezing illnesses.wheezing illnesses. Am J Clin Nutr, 2007Am J Clin Nutr, 2007

Vit D IntoxicationVit D Intoxication

25(OH)D > 150ng/ml25(OH)D > 150ng/ml

Caused by ingestion of > 50,000 Caused by ingestion of > 50,000 IU/dayIU/day

Caution: people predisposed to Caution: people predisposed to hypercalcemia (granulomatous hypercalcemia (granulomatous diseases)diseases)

CONCLUSIONCONCLUSION

Serum 25-hydroxyVitamin D is not Serum 25-hydroxyVitamin D is not only a predictor of bone health, but is only a predictor of bone health, but is also an independent risk predictor for also an independent risk predictor for cancer and other chronic diseasescancer and other chronic diseases

1,25(OH)D should never be used for 1,25(OH)D should never be used for detecting Vit D deficiencydetecting Vit D deficiency

DISCUSSIONDISCUSSION

Should we use 25(OH)D as a screening Should we use 25(OH)D as a screening test? test? – 25(OH)D assay is costly and may not be always 25(OH)D assay is costly and may not be always

available so screening is not recommended! available so screening is not recommended!

Adequate Vit D intake is recommendedAdequate Vit D intake is recommended

800 IU Vit D/day guarantees Vit D 800 IU Vit D/day guarantees Vit D sufficiency unless there are other sufficiency unless there are other conditionsconditions

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