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The Vitamin D “Dilemma”!
This presentation will not involve discussion of unapproved or offlabel, experimental or investigational use.
Michael A. Levine, M.D.
Recent Medical Literature… • Time Magazine “Top 10 medical breakthroughs of 2007” PubMed “HITS” on Vitamin D Using “Title/Abstract”
Michael A. Levine has no financial relationships to disclose or Conflicts of Interest to resolve.
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Vitamin D in Popular Culture… • Dr. Mehmet Oz, Oprah’s
medical advisor, discussing her recent weight gain on 1/7/09: “She had vitamin D deficiency. Why would that be shocking for a darker-skinned person who spends a lot of time in Chicago… And then what does that cause? It causes autoimmune problems. So for her, it takes your thyroid gland.”
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Vitamin D Homeostasis
Vitamin D Homeostasis
UVB (280-315 nm)
Anticonvulsants Rifampicin Glucocorticoids, Vitamin D Anti-retrovirals, bile acids
24,25(OH)2D
Cyp3A4 25-hydroxyvitamin D3
24,25(OH)2D
25-hydroxyvitamin D3
1,25(OH)2D
24,25(OH)2D
Cutaneous Synthesis of Vitamin D • Generation of pre-vitamin
1,25(OH)2D
Vitamin D Deficiency is Common: Rickets Around the World
D3 depends on quantity and wavelength of UVB.
• Time required to produce a given amount of vitamin D depends on skin melanin, distance from the equator, and on season of the year.
Without sunscreen
SPF 8 sunscreen
• 1 MED equals 20,000 IU of vitamin D
• Sunscreens reduce UVB penetration of skin.
Holick MF: Am J Clin Nutr 60:619-630, 1994
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How Common is Vitamin D Insufficiency in U.S.? Serum level of 25(OH)D is below 30 ng/ml in… A. B. C. D.
10% of population 25% of population 50% of population 75% of population
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N = 259/532
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48.7%
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N = 342/642
53.3%
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N = 198/362 ●
54.7%
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P = NS for test of trend. Holick MF et al. J Clin Endocrinol Metab. 2005;90:3215–3224.
Prevalence of Vitamin D Deficiency (25(OH)D < 20 ng/ml) in US, 2001–2006 Adapted from Looker et al.: Vitamin D status: United States, 2001–2006.
Diseases and Associations Linked to Low 25(OH)D Levels • Rickets and osteomalacia • Osteoporosis and fractures • Increased risk of stress fractures • Increased risk of multiple sclerosis • Increased risk of type 1 diabetes mellitus and Crohn disease • Increased risk of infections and cancer
Holick M F et al. JCEM 2012;97:1153-1158
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Biochemical Manifestations of Nutritional Rickets Early sCalcium
Moderate Severe
Low
Normal
↓↓
Normal
↓
↓↓
Alk Phosphatase
↑
↑↑
↑↑↑
PTH
↑
↑↑
↑↑↑
25(OH)D
N or ↓
↓
↓↓
1,25(OH)2D
Normal
N or ↑
↑ N ↓
sPhos
Source: National Academy of Science, 2000 www.beyonddiscovery.org
Lower Limb Deformities
Genu Varum
Genu Valgum
Radiographic Features
Windswept Deformity
Knee
Wrist
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2008: Hope Springs Eternal!
How well are formula-fed babies doing with vitamin D intake? How many formula-fed babies meet 2008 AAP recommendations for 400 U of vitamin D per day? A. B. C. D.
Infants Who Met the 2003 (200 U) or 2008 (400 U) AAP Vitamin D Recommendations Perrine et al, PEDIATRICS Vol. 125 No. 4 April 2010, pp. 627-632 ,
Infant Age, mo (wk)
Total, %
Breast Milk, %
Mixed, %
Formula, %
2003
2008
2003
2008
2003
2008
2003
2008
1 (3 to