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Vitamin D Intake: Is there a link
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• Discuss the role of Vitamin D in health and disease
• Discuss the causes of Vitamin D deficiency in obesity
• Explain treatment for Vitamin D deficiency in obese children and adolescents
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I have no relevant financial relationships with the manufacturers of any commercial products
and/or provider of commercial services discussed in this CME activity. I do not intend to
discuss an unapproved/investigative use of a
commercial product/device in my presentation.
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The Role of Vitamin D 25(OH)D
1,25(OH)1,25(OH)22DD
BoneBone
Vitamin DVitamin D
Dietary calciumDietary calcium IntestinesIntestines
LiverLiverKidneyKidney
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7-Dehydrocholesterol7-Dehydrocholesterol Pre-Vitamin DPre-Vitamin D33 Vitamin DVitamin D33
EpidermisEpidermis
LatitudeLatitudePollutionPollutionClothingClothingMelanin pigmentationMelanin pigmentationDuration of exposureDuration of exposure
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Causes of Vitamin D Deficiency
• Decreased vitamin D synthesis
– Skin pigmentation
– Physical agents blocking UVR exposure
– Geography
• Decreased nutritional intake
• Decreased maternal vitamin D stores and exclusive breastfeeding
• Malabsorption
• Decreased synthesis or increased degradation of 25(OH)D
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Prevalence of 25(OH)D deficiency in US Children 2001-2004
• Risk Factors: – Older– Obesity (OR 2.0)– Girls (OR 1.9)– Non Hispanic Black (OR
24.2) or Mexican American( OR 3.7)
– Milk intake less than once a week (OR 2.9)
– > 4 hours screen time per day (OR 1.6)
Melamed et al Pediatrics September 2009
25(OH)D <1525(OH)D 15-2925(OH) D > 30
N=6275, age 1-21 yrs
30%
61%
9%
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Prevalence of vitamin D deficiency in children
• More than 50% of Hispanic and African-American adolescents in Boston had 25(OH)D below 20 ng/ml.
• 48% of white preadolescent girls in Maine had 25(OH)D below 20 ng/ml.
Gordon CM, Arch Pediatr Adolesc Med. 2004;158(6):531–537Sullivan SS, J Am Diet Assoc. 2005;105(6):971–974
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How common is vitamin D deficiency in obese children ?
• Olson et al JCEM 2011– 92%of obese subjects had a 25(OH)D level
below 30 ng/ml vs 68% in non overweight children
– 50% of obese subjects were below 20 ng/l vs 22% in non overweight children
• Alemzedeh et al Metabolism 2008– 74% had 25(OH)D levels less than 30 ng/ml
and 32.3% had 25(OH)D < 20 ng/ml
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Causes of Vitamin deficiency in Obese Children
• Poor dietary intake of vitamin D
• Lower sun exposure
• Sedentary lifestyle
• Clothing practices
• Decreased oral absorption
• Decreased cutaneous synthesis
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FoodIU per serving
Percent DV
Cod liver oil, 1 tablespoon 1,360 340
Salmon, cooked, 3.5 ounces 360 90
Sardines, canned in oil, drained, 1.75 ounces 250 63
Tuna fish, canned in oil, 3 ounces 200 50
Milk, nonfat, reduced fat, and whole, vitamin D-fortified, 1 cup 98 25
Yogurt, fortified with 20% of the DV for vitamin D, 6 ounces (more heavily fortified yogurts provide more of the DV)
80 20
Ready-to-eat cereal, fortified with 10% of the DV for vitamin D, 0.75-1 cup (more heavily fortified cereals might provide more of the DV)
40 10
Selected Food Sources of Vitamin D
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Recommendations on Vitamin D Intake for Children
Vitamin IOM AAP Endocrine Society
RDA 600 IU 400 IU 400 IU (0-1 yr)600 IU (>1 yr)
Tolerable Upper Intake
2500 IU (1-3 yr)3000 IU (4-8 yr)4000 IU (>9 yr)
1000 IU (0-6 mo)1500 IU (6-12 mo)2500 IU (1-3 yr)3000 IU (4-8 yr)4000 IU (>8 yr)
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Average Intake of Vitamin D in children
• Age 1-8 years 240 IU• Age 9-18 years Males 240 IU
Females 176 IU• 19-50 years Males 216 IU
Females 168 IU• >51 years Males 212 IU
Females 188 IU
Moore CE, Journal of Nutrition, 2005
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.
Wortsman J et al. Am J Clin Nutr 2000;72:690-693
©2000 by American Society for Nutrition
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.
Wortsman J et al. Am J Clin Nutr 2000;72:690-693
©2000 by American Society for Nutrition
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.
Wortsman J et al. Am J Clin Nutr 2000;72:690-693
©2000 by American Society for Nutrition
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.
Wortsman J et al. Am J Clin Nutr 2000;72:690-693
©2000 by American Society for Nutrition
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What are the implications of low vitamin D levels in Obese
Children ?
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Typical Signs of Vitamin D deficiency in Infants and Toddlers• Rickets (bone deformities)
• Delayed motor development
• Muscle weakness, aches and pains
• Fractures
• Hypocalcemic seizures
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Vitamin D Deficiency Rickets
Misra M et al. Pediatrics 2008;122:398-417
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Extraskeletal Effects of Vitamin D
• Cells containing 25OH-VitD3-1-alpha-OHase– Breast, prostate, lung, skin, lymph nodes, colon, pancreas,
adrenal medulla, brain, placenta» Holllick MF. Am J Clin Nutr. 2004. 79(3):362.» Zehnder et al. J Clin Endocrin Metab. 2001;86(2)
• Cells containing Nuclear VDR– Pancreatic islet cells, monocytes, transformed B cells, activated
T cells, neurons, prostate, ovaries, pituitary, aortic endothelium, placenta, skeletal muscle cells.
» Zittermann A. Br J Nutr. 2003;89(5):552.» Bischoff HA, et al. Histochem J 2001;33:19.
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Vitamin D Status in Pediatric Outpatients
Johnson et al, Journal of Pediatrics 2010
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60
70
80
90
100
110
120
0 10 20 30 40 50 60 70 80
25 OH(D) (ng/mL)
Fas
tin
g G
luco
se (
mg
/dL
)
r = -0.2P<0.001
25(OH)D Levels Correlate Inversely with Fasting Glucose in Children
Johnson et al, Journal of Pediatrics 2010
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20
40
60
80
100
120
140
0 10 20 30 40 50 60 70 80
25 OH(D) (ng/mL)
HD
L (
mg
/dL
)
r = 0.41P<0.001
25(OH)D and HDL Cholesterol levels correlate positively in Children
Johnson et al, Journal of Pediatrics 2010
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Implications of low vitamin D in Obese Children
• 25(OH)D was negatively correlated with homeostasis model assessment of insulin resistance (r = −0.19; P = 0.001) and 2-h glucose (r = −0.12; P = 0.04)
• serum 25(OH) D positively correlated with insulin sensitivity, which was FM mediated, but negatively correlated with HbA1c
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Vitamin D Status and Cardiometabolic Risk Factors in US Adolescent Population
• 25(OH) D levels inversely correlated with systolic blood pressure (P=0.02) and plasma glucose (P=0.01), independent of BMI
• OR for lowest quartile(<15 ng/ml) vs highest quartile(>26 ng/ml)
Hypertension 2.36
Fasting hyperglycemia 2.54
Low HDL 1.54
Metabolic syndrome 3.88
Reis et al, Pediatrics September 2009
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IOM consensus statement
Health benefits beyond bone health—benefits often reported in the media—were from studies that provided often mixed and inconclusive results and could not be considered reliable
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Effects of vitamin D supplementation on metabolic parameters in obese children
• Ongoing study on effect of vitamin D3
supplementation on insulin resistance and cardiometabolic risk markers in obese adolescents
• Ongoing study on effect of vitamin D3 supplementation on endothelial function in obese adolescents
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What doses of vitamin D should be used in obese children ?
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AAP guidelines on Management of
Vitamin D deficiency… • <1 mo old infants: 1000 IU/day of vitamin D2 or D3• 1-12 month old 1000-5000 IU/day • >12 month old 5,000 IU/day
once weekly for 6 weeks followed by 400U/day
• Stoss therapy: 10,000-50,000 IU over 1-5 days
or
50,000 IU once weekly for 8 weeks
Misra et al. Pediatrics 2008, 122:398
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Obese Children Respond Poorly to Traditional Vitamin D Supplementation
• Significant increase in mean 25(OH)D after the initial course of treatment with vitamin D ( 50,000 IU once a week for 608 weeks but 25(OH)D levels normalized in only 28%
• Repeat courses with the same dosage in the other 72% did not significantly change their low vitamin D status
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What should be the target 25(OH)D level ?
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What should be the ideal 25(OH)D level
IOM AAP Endocrine Society
Minimum Level
20 ng/mL
20 ng/mL 30 ng/mL
Optimal Range
20-50 ng/mL
20-100 ng/mL
30-100 ng/mL
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Relationship of calcium absorption fraction to vitamin D nutritional status
Heaney R P CJASN 2008;3:1535-1541
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Correlation of Serum PTH with serum 25(OH)D
Holick M F et al. JCEM 2005;90:3215-3224
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Summary
• Vitamin D deficiency is common in obese children and adolescents.
• Lack of sunlight exposure and inadequate intake of D are major contributors to vitamin D deficiency.
• Vitamin D deficiency in obese children should be treated with 2-3 fold higher doses of vitamin D realtive to non obese children
• Well designed studies are needed to determine the extraskeletal benefits of vitamin D
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Thank you