Vitamin D Intake: Is there a link

• 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

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.

The Role of Vitamin D 25(OH)D

1,25(OH)1,25(OH)22DD

BoneBone

Vitamin DVitamin D

Dietary calciumDietary calcium IntestinesIntestines

LiverLiverKidneyKidney

7-Dehydrocholesterol7-Dehydrocholesterol Pre-Vitamin DPre-Vitamin D33 Vitamin DVitamin D33

EpidermisEpidermis

LatitudeLatitudePollutionPollutionClothingClothingMelanin pigmentationMelanin pigmentationDuration of exposureDuration of exposure

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

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%

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

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

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

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

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)

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

.

Wortsman J et al. Am J Clin Nutr 2000;72:690-693

©2000 by American Society for Nutrition

.

Wortsman J et al. Am J Clin Nutr 2000;72:690-693

©2000 by American Society for Nutrition

.

Wortsman J et al. Am J Clin Nutr 2000;72:690-693

©2000 by American Society for Nutrition

.

Wortsman J et al. Am J Clin Nutr 2000;72:690-693

©2000 by American Society for Nutrition

What are the implications of low vitamin D levels in Obese

Children ?

Typical Signs of Vitamin D deficiency in Infants and Toddlers• Rickets (bone deformities)

• Delayed motor development

• Muscle weakness, aches and pains

• Fractures

• Hypocalcemic seizures

Vitamin D Deficiency Rickets

Misra M et al. Pediatrics 2008;122:398-417

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.

Vitamin D Status in Pediatric Outpatients

Johnson et al, Journal of Pediatrics 2010

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

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

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

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

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

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

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

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

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

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

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

Relationship of calcium absorption fraction to vitamin D nutritional status

Heaney R P CJASN 2008;3:1535-1541

Correlation of Serum PTH with serum 25(OH)D

Holick M F et al. JCEM 2005;90:3215-3224

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

Thank you