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“You Light Up My Life”The Importance of Vitamin D and Sunshine to Our Health.

George Guthrie MD MPH CDE CNS

www.aclm-articles.net

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What is Vitamin D

Sun Energy

UV-B 290-315 nm

Lumisterol, Tachysterol, and Previtamin D

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What is Vitamin DC

MA

J April 25, 2006 174:9

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Primary Vitamin D Deficiency Dz

Rickets Osteomalacia Osteoporosis

Fraser, D. and Scriver, C

.R. Endocrinology, G

rune and Stratton, 1994.

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Hyperparathyroidism

GastrointestinalGastrointestinal: Thirst, polydipsia, : Thirst, polydipsia, polyuria,ulcers,pancratitis, constipation, polyuria,ulcers,pancratitis, constipation, vomiting, weight loss. vomiting, weight loss. MusculoskeletalMusculoskeletal: spontaneous fracture, : spontaneous fracture, vertebral collapse, osteoporosis, arthralgia, vertebral collapse, osteoporosis, arthralgia, gout, pseudo gout, calcifications.gout, pseudo gout, calcifications.Neurological:Neurological: Fatigue, apathy, anxiety, Fatigue, apathy, anxiety, depression, psychosis, somnulence, coma, depression, psychosis, somnulence, coma, muscle fatigue, weakness, hypotonia,.muscle fatigue, weakness, hypotonia,.CardiovascularCardiovascular: hypertension, short QT : hypertension, short QT intervalinterval

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Psoriasis

In vehicle-controlled clinical trials, calcitriol 3 microg/g ointment has been shown to significantly improve the symptoms of psoriasis with a low incidence of adverse effects and without affecting calcium homeostasis

Gold LF, Calcitriol ointment: optimizing psoriasis therapy. J Drugs Dermatol. 2009 Aug;8(8 Suppl):s23-7.

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Type 1 DM Prevention

The Finnish Type 1 Diabetes Prediction and Prevention

Study - 31 years

2000 IU of Vitamin D per day given to Finnish Children

Decreased Type 1 Diabetes by 80%.

Hypponen E, et al. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001;358:1500-3.

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Decreased CA Risk

Cancers - Colon, Breast, Prostate, Ovarian, Lymphoma, Leukemia.

Garland CF, et al. 25-hydroxy-vitamin D and colon cancer: eight-year prospective study. Lancet 1989 Nov 18;2(8673):1176-8

80% reduction in Colon Cancer with Vitamin D levels 33-41 ng/ml

75% reduction in Colon Cancer with Vitamin D levels 27-32 ng/ml

In 25,620 individuals followed from August, 1975, to

January, 1983

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Decreased CA Risk

1179 Rural Post Menopausal females - Nebraska 4yr double-blind, Randomized Placebo Controlled Trial. Outcomes: Primary - osteoporosis - Secondary Cancer Ca (14-1500 mg); Ca + Vit D (1100 IU); Placebo Results

Ca + D RR =.402 (P=.01)Ca RR =.532 (P=.06)

Restriction to Cancers after 12 monthsCa + D RR =.232 (CI: .09,0.60, P<0.005)

Lappe JM, et al. Vit D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007;85:1586-91.

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Kaplan Meier Curves - CA

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Lappe JM, et al. Vit D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007;85:1586-91.

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Multiple SclerosisProspective, nested case-control study in 7 million US Military Personnel

257 cases identified - matched with 2 othersWhite 145, black 77, hispanic/other 32Serum samples - 2-3Control for latitude and UV index - residence at entry

Whites only - Lowest to highest quintile - serum vit 25 OH D0.38 (CI .19-.75) 62% reduction in incidenceLow 6-9.6 ng/cc: 39.7-81.3 ng/cc High - p trend.02

Munger KL, et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA, 2006 Dec 20;296(23):2832-8

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Rheumatoid Arthritis

Rheumatoid Arthritis - Iowa Women’s Health Study - 29,38630-35% reduction in RA in women 55-69

years over 11 years. Highest vs lowest tertile of Vitamin D intake - Supplements > Dairy

Merlino LA. Et al, Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women's Health Study. Arthritis & Rheumatism. 50(1):72-7, 2004 Jan.

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Type 2 Diabetes

Increase in Insulin Secretion*Protein synthesis increased(rats)Pro-insulin to insulin increased

Decrease triglycerides Increase in insulin sensitivity-

60% *

*Chiu KC, et al. Hypovitaminosis D is associated with insulin resistance in Beta cell dysfunction. Am J Clin Nutr 2004; 79:820-5.

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Type 2 DM Prevention & Vit D

Finnish Cohort Study 4097 subjects 40-69yrs old (1978-80) 17 years of follow-up 25 OH vit D quartiles

9.0; 14.2; 19.2; 28.4 ng/ccP for trend = 0.01 adjusted for age, sex month of collection

Matilla C, Et al. Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Diabetes Care 30:2569-2570, 2007

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Type 2 DM Prevention & Vit D

Ely Prospective Study- England 524 randomly chosen non-DM 10 years follow-up Serum vit D <20;20-30;>30

FBS P=0.19 HOMA p=0.0052 hr PP p=.006

Forouhi NG, et al. Baseline serum 25-hydroxy vit D is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990-2000. Diabetes 57:2619-2625, 2008

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Congestive Heart Failure

Low vitamin D leads to increase PTH

Parathyroid hormone (PTH) also activates Protein Kinase - C (via Galphaq) in cardiomyocytes, and provokes the hypertrophic response.

May Result in Congestive Heart Failure

McCarty MF. Nutritional modulation of parathyroid hormone secretion may influence risk for left ventricular hypertrophy. Med Hypotheses. 2005;64(5):1015-21.Zittermann A. Vitamin D insufficiency in congestive heart failure: Why and what to do about it? Heart Fail Rev. 2006 Mar;11(1):25-33.

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Musculoskeletal pain 150 consecutive ED patients in Minneapolis,

MN Feb-June, 2002. (45o lat north) Results:

African American, East African, Hispanic, Native Americans - 100% deficient

All patients - 93% deficient (<20 ng/cc) Diagnoses - fibromyalgia, chronic fatigue,

depression.

Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc 2003;78:1463-70

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Fall Prevention

Falls (Risk Factor in the elderly)

Broe KE, et al. A higher dose of vitamin D reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. J Am Geriatr Soc 2007;55:234-9.

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Performance, speed and proximal muscle strength in elderly population was markedly improved when 25 OH Vit D increased 4-16 ng/cc up to 40 ng/cc

Ilse S. Wicherts1,2, etal. Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrin Metab. First published ahead of print March 6, 2007 as doi:10.1210/jc.2006-1525.

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Vitamin D deficiency and Pregnancy 198 UK pregnancies

31% insufficient18% deficient

Reduced whole body (p=.0088) and LS spine bone-mineral content (p=.03) at 9 years.

Low maternal vit D levels and child bone mass predicted by UVB exposure and supplements

Umbilical vein calcium predicted low childhood bone mass

Javaid MK. Et al. Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study Lancet 2006; 367: 36–43

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Gestational Vit D Deficiency

SchizophreniaAnimal model gene

disruptionEnlarged lateral ventriclesDecreased nerve growth

factorEpidemiologic association

in humans

Levenson CW, Figuerioa SM. Gestational vit D deficiecny: long-term effects on the brain. Nutritional Reviews Vol 66(12):726-729.

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Vitamin D and Survival

0.6

0.7

0.8

0.9

1.0

0 2 4 6 8

Years of Follow-up

Surv

ival

(%)

8 ng/mL13 ng/mL19 ng/mL28+ ng/mL

Serum Vitamin D levels

Archives of Internal Medicine 2008;168:1340-1349

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Seasonal Variation in Vitamin D

Average serum vitamin D levels varied by season: March 12.0 ng/mL August 22.7 ng/mL

This is an 89% difference, showing the need for supplementation during winter months.

12.0

22.7

0

5

10

15

20

25

March August

Serum Vitamin D (ng/mL)

Archives of Internal Medicine 2008;168:1340-1349

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Prevalence of Low Vitamin DIn this study of over 3,200 people: One-fourth were deficient,

less than 10 ng/mL Two-thirds were rated

“insufficient”, less than 20 ng/mL

75% were less than the recommended level, 30 ng/mL

Archives of Internal Medicine 2008;168:1340-1349

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Incidence in Populations Estimated 1 billion people world wide 40-100% elderly men and women 50% of postmenopausal women have levels less than

optimal (<30 ng/cc). 52% of Hispanic and black adolescents in Boston (<20

ng/cc) 48% of white preadolescent girls in Maine (<20ng/cc) 42% of 15-49 y/o in US - NHANES (< 20 ng/cc) 32% of healthy student, physicians and residents in

Boston Hospital despite daily glass of milk, daily multivit and salmon weekly

Holick MF, Vitamin D Deficiency. NEJM 357:3 July 19, 2007. Pp 266-277.

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Emerging Serum Vitamin D Norms

Vitamin D status (ng/dL) (nmol/L)

Deficient(low risk)

<20 <50

Insufficient(moderate risk)

20-29 50-72

Adequate(low risk)

30 or higher 73 or higher

Serum vitamin D test results (25-Hydroxyviamin D) are shown in these two units.

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Sources of Vitamin DDairy Cod liver Oil - eat

lots of fish Supplements

Toxicity - calcifications, HTN, anorexia, nausea, weakness, polyuria, polydypsia, kidney failure, kidney stones, deathChen TC, et al. An update on the vitamin D content of

fortified milk from the United States and Canada. N Eng J Med 1993;329:1507

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Supplements Sources

Vit D2 - ergosterol from yeast - 30% as effective

Vit D3 - 7-dehy- cholesterol from lanolin (Rx in USA)

Holick MF, Vitamin D Deficiency. NEJM 357:3 July 19, 2007. Pp 266-277.

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Sources of Vitamin D Sunlight Never Causes Toxic Levels Whole Body Minimal Erythema Dose gives

10-20,000 IU RDA: 200-400-600 IU Need: 6% of body exposed for 15 min 3

days a week

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Special Situations

Sun Screen - SPF 8 -> 98% decrease in Vit D formation

Winter >35 Degree Latitude

Dark SkinUp to 50X exposure needed30-50% of Black Americans

Deficient (Estimated)

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Special Situations

Giovannucci E, Liu Y, Willett WC. Cancer Incidence and Mortality and Vitamin D in Black and White Male Health Professionals. Cancer Epidemiol Biomarkers Prev. 2006 Nov 28

Black compared to White Health Professionals Black - Low risk for Vit D deficiency

CA RR 95 (CI .6-1.51)Mortality RR 1.55 (CI .91-2.62)

Black - High Risk for Vit D deficiencyCA RR 1.57 (CI 1.15-2.11)Mortality RR 2.27 (CI 2.26-3.28)

“This pattern was even more pronounced for digestive system cancer. Our results suggest that the high frequency of hypovitaminosis D in Blacks may be an important, and easily modifiable, contributor to their higher risk of cancer incidence and mortality.”

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Special Situations Sun Screen - SPF 8 -> 98%

decrease in Vit D formation Winter >35 Degree Latitude Dark Skin

Up to 50X exposure needed30-50% of Black Americans

Deficient (Estimated)

Older Skin - need increases with ageBy 70 y/o there is a 75%

decrease in ability to make Pre-Vitamin D

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Special Situations Obese Individuals

Less Available for Cells Babies

No Vit D in Breast Milk unless Mother has adequate levels

ChildrenRickets25% of children in Saudia Arabia

Deficient in Vit D Fibromyalgia -

40-60% suffer from osteomalacia

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RecommendationsSun every day - 15 + minutesSun block after sun exposure for 15 min.Educate the Public as to risk factors.Supplement in high risk individuals or situations Diagnose and Treat to Target

Deficient < 20 ng/ml Insuficiency 20-30ng/cc

Goal 40-60 ng/mlGoal 40-60 ng/mlSafe up to 150 ng/ml(Lab "Normal" 8-60 ng/ml)

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RecommendationsScreen all High Risk Individuals

Aggressive Replacement for <20 ng/cc

50,000 IU two or three times per week with meals ( 1 tsp oil with meal)

Recheck levels in one to two months

Treat to greater than 30 ng/cc to shut off PTH completely in osteoporisis

Consider Higher levels in special situations - autoimmune disease, malignancy. No toxicity to 150 ng/cc

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Maintenance Recommendations

RDA 200-400-600 IU - Inadequate oral maintenance

Complete oral replacement 1000 IU/day

Safe upper daily limits 2000 IU/day - Present RDA

Recommended increase to optimize health

RDA 1000-2000IU/day

Safe Upper Daily Limit to 10,000/day

Bischoff-Ferrari HA, et al. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 2006;84:18 –28.

The End

www.aclm-articles.net -- Lectures - Vit D 5-09