1. Vitamin D Intake: Is there a link

2. 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

3. 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.

4. The Role of Vitamin D 25(OH)D 1,25(OH) 2 D Bone Vitamin D Dietary calcium Intestines Liver Kidney

5. 7-Dehydrocholesterol Pre-Vitamin D 3 Vitamin D 3 Epidermis LatitudePollutionClothing Melanin pigmentation Duration of exposure

6. 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

7. 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 <15 25(OH)D 15-29 25(OH) D > 30 N=6275, age 1-21 yrs 30% 61% 9%

8. 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):531–537 Sullivan SS, J Am Diet Assoc. 2005;105(6):971–974

9. 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

10. 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

11. Food IU per serving Percent DV Cod liver oil, 1 tablespoon1,360340 Salmon, cooked, 3.5 ounces36090 Sardines, canned in oil, drained, 1.75 ounces25063 Tuna fish, canned in oil, 3 ounces20050 Milk, nonfat, reduced fat, and whole, vitamin D-fortified, 1 cup9825 Yogurt, fortified with 20% of the DV for vitamin D, 6 ounces (more heavily fortified yogurts provide more of the DV) 8020 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) 4010 Selected Food Sources of Vitamin D

12. Recommendations on Vitamin D Intake for Children VitaminIOMAAPEndocrine Society RDA600 IU400 IU400 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)

13. 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

14. . Wortsman J et al. Am J Clin Nutr 2000;72:690-693 ©2000 by American Society for Nutrition

15. . Wortsman J et al. Am J Clin Nutr 2000;72:690-693 ©2000 by American Society for Nutrition

16. . Wortsman J et al. Am J Clin Nutr 2000;72:690-693 ©2000 by American Society for Nutrition

17. . Wortsman J et al. Am J Clin Nutr 2000;72:690-693 ©2000 by American Society for Nutrition

18. What are the implications of low vitamin D levels in Obese Children ?

19. Typical Signs of Vitamin D deficiency in Infants and Toddlers Rickets (bone deformities) Delayed motor development Muscle weakness, aches and pains Fractures Hypocalcemic seizures

20. Vitamin D Deficiency Rickets Misra M et al. Pediatrics 2008;122:398-417

21. 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.

22. Vitamin D Status in Pediatric Outpatients Johnson et al, Journal of Pediatrics 2010

23. r = -0.2 P<0.001 25(OH)D Levels Correlate Inversely with Fasting Glucose in Children Johnson et al, Journal of Pediatrics 2010

24. r = 0.41 P<0.001 25(OH)D and HDL Cholesterol levels correlate positively in Children Johnson et al, Journal of Pediatrics 2010

25. 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

26. 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( 26 ng/ml) Hypertension 2.36 Fasting hyperglycemia 2.54 Low HDL 1.54 Metabolic syndrome 3.88 Reis et al, Pediatrics September 2009

27. 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

28. 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

29. What doses of vitamin D should be used in obese children ?

30. 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

31. 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

32. What should be the target 25(OH)D level ?

33. What should be the ideal 25(OH)D level IOMAAPEndocrine Society Minimum Level 20 ng/mL 30 ng/mL Optimal Range 20-50 ng/mL 20-100 ng/mL 30-100 ng/mL

34. Relationship of calcium absorption fraction to vitamin D nutritional status Heaney R P CJASN 2008;3:1535-1541

35. Correlation of Serum PTH with serum 25(OH)D Holick M F et al. JCEM 2005;90:3215-3224

36. 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

37. Thank you