Vitamin D: The Hottest Nutrient Under the Sun

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Vitamin D The Hottest Nutrient Under the Sun

• Keli M. Hawthorne, MS, RD, LD
• Baylor College of Medicine
• Childrens Nutrition Research Center
• Texas Childrens Hospital
• kelih_at_bcm.edu

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History of Vitamin D

• Identified in 1919 but improperly named as a
  vitamin
• Actually a prohormone
• Structurally similar to steroid hormones (ie,
  cortisol, estradiol, and aldeosterone)
• 2 main forms D2 (ergocalciferol) and D3
  (cholecalciferol)

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Functions of Vitamin D

• To aid in the intestinal absorption of calcium
  and phosphorus, thereby promoting strong bones
• Role in cellular metabolism
• Antiproliferation, prodifferentiation

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Effects of Deficiency

• Rickets (children)
• Osteomalacia (adults)
• Elevated serum PTH
• Decreased serum phosphorus
• Elevated serum alkaline phosphatase
• Osteoporosis
• Epidemiological evidence of increased risk of
  colon, breast, and prostate cancer

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Measurement

• 1,25(OH)D active metabolite of vitamin D, but a
  poor marker for vitamin D status because it
  doesnt indicate body stores
• 25-hydroxyvitamin D
• 25(OH)D3
• Inactive metabolite but a better indicator of
  vitamin D status
• Should be analyzed with RIA

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PTHVitamin D interaction

• Inverse relationship between 25(OH)D levels and
  PTH
• Increased fractional absorption of calcium is
  associated with increased PTH levels, not 25(OH)
  D levels
• Consequences of low 25(OH) D levels are not
  obvious. Compensation with increased PTH and
  production of 1,25 (OH) D with resultant normal
  calcium absorption appears appropriate
• 1,25 (OH) D levels are pending in this cohort
• However, this sequence may be inadequate under
  stress situations such as low mobility, very low
  dietary calcium, chronic illnesses

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Factors that Affect Production of Vit D from UV-B
Radiation

• Time spent outdoors
• Time of day
• Latitude, altitude
• Season
• Air pollution

• Degree of clothing
• Skin pigmentation
• Age
• Cloud cover
• Ozone column
• Sunscreen

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Let the Sun Shine

• Affect of Sunscreen
• SPF 8 decreases vitamin D production by 95
• No known cases of Vit D toxicity with extreme or
  prolonged sun exposure
• Chronic sun exposure among outdoor workers at the
  end of summer equate to 25(OH)D levels similar to
  2800-5000 IU/d supplementation
• Barger-Lux Heaney. J Clin Endocrinol Metab 2002

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Special Populations

• Dark skin pigmentation
• Elderly
• Infants
• Obese
• Limited Sunlight Exposure

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Individuals with Dark Pigmentation of Skin

• High melanin content in the skin reduces the
  skins ability to produce vit D from sunlight
• Higher risk of deficiency who may benefit even
  more from a supplement (especially older women)

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Elderly

• Vit D deficiency leads to
• Muscle weakness
• Loss of balance
• Decreased lower extremity function
• And therefore, more FALLS and HIP FRACTURES
• At what 25(OH)D level?
• Generally, gt74 nmol/L in Caucasians
• Higher in older adults of darker skin color

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Changing What We Know
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Breastfed Infants

• Breast milk provides 25 IU vit D/L
• DRI recommends 200 IU/d for breastfed infants who
  are not exposed to sunlight (ie, northern
  latitudes)
• AAP recommends 200 IU/d for all breastfed infants
  (with no geographical or racial distinctions)
  beginning in the first 2 months of life unless
  weaned to at least 500 mL infant formula

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Questionable Benefits in Pregnancy

• Low maternal 25(OH)D levels may result in
  decreased whole body BMC (r0.21, p0.009) and
  spine BMC (r0.17, p0.03) when the child is 9
  yrs old
• Javaid et al, Lancet Jan 2006
• Compared to pregnant women with 25(OH)D levels
  lt30 nmol/L, women with 25(OH)D levels gt75 nmol/L
  were not associated with childs body size,
  intelligence, psychological health, or
  cardiovascular system possible increased risk of
  eczema at 9 mo of age (OR 3.26, 95 CI 1.15-9.29,
  plt0.03) and asthma at 9 yrs of age (OR 5.4, 95
  CI 1.09-26.65, plt0.04)
• Gale et al, Eur J Clin Nutr 2008

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Obese

• Vit D is stored in bodys fat cells and is
  unavailable for use
• Even if adequate Vit D is produced in the sun, it
  may not be physiologically available
• No data on recommended amounts to increase based
  on body weight range

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Limited Sunlight Exposure

• Homebound individuals
• Living in northern latitudes
• Wearing robes head coverings for religious
  reasons
• Working in occupations that prevent sun exposure
• Need to be more cognizant of dietary intake or
  consider supplementation

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37o Latitude Cutoff for Vit D
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Vitamin D, PTH and Bone Mass in Late Adolescence
in Finland

• 220 Finnish males, ages 18.3-20.6
• Positive correlation between 25(OH)D level and
  BMC at lumbar spine (P 0.06), femoral neck (P
  0.04) and hip (P 0.02)
• Negative correlation between 25(OH)D level and
  PTH level (r - 0.24, P lt 0.001)

Ville-Valtteri et al, JCEM, 2004
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Vitamin D Levels in Adolescents in Boston
Gordon et al, Arch Pediatr Adolesc Med 158 2004
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Vitamin D Deficiency ( 37 nmol/L) in Boston
Adolescents
N No. deficient() RR
Gordon et al, Arch Pediatr Adolesc Med 1582004
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Vitamin D and PTH in Adolescents in Boston
Gordon et al, Arch Pediatr Adolesc Med 1582004
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Houston, We Have a Problem
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25-(OH)D Levels by Ethnicity

Mean age 12.6 0.1 yrs, p lt 0.01
White Afr-Am Hispanic Asian
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Low Vitamin D Levels ( 50 nmol/L) in Houston

• White 3/44 9
• African-American 8/15 53
• Hispanic 2/20 10
• Asian 2/10 20
• Overall, 17 with low levels. Ethnic groups
  different, p lt 0.01. Question is, what does this
  mean functionally?

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Suboptimal Vitamin D levels ( 80 nmol/L) in
Houston

• White 27/44 61
• African-American 14/15 93
• Hispanic 15/20 75
• Asian 9/10 90
• Overall, 65/89 73 suboptimal

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Vitamin D Status of Young Adolescents

• Recent data from US and elsewhere indicate
  possible vitamin D deficiency among adolescents
• New dietary recommendations (US) suggest that a
  level of up to 80 nmol/L for 25(OH)D might be
  optimal
• Physiological consequences of low vitamin D
  levels are not clear for adolescents.

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Vitamin D and PTH in Adolescents in Houston
N 93 Mean age 12.6 0.10 y (SE) Population
50 White, 16 AA, 23 Hispanic and 11 Asian
r -0.41, P lt 0.0001
PTH concentration (pg/ml)
by Intact PTH measured by IRMA (DSL, Inc.)
25 (OH) D concentration (ng/ml)
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Recommendations
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Current Recommendations
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Affect of Supplementation

• For each additional 100 IU/d of D3, serum 25(OH)D
  increases by 1-2 nmol/L
• Fair evidence that 800 IU/d Vit D3 and 1200 mg/d
  calcium can decrease fracture risk in older
  individuals

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Improvements in 25(OH)D with Supplementation
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Are the Current AIs Enough?

• Consensus is NO
• Historically, normal level of Vit D was 30
  nmol/L now considered deficient
• At least 50 nmol/L necessary for proper function
• 78-100 nmol/L for bone health, fracture
  prevention, and chronic disease prevention
• Holick MF. AJCN 2004
• Bischoff-Ferrari et al. AJCN 2006

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Changing What We Know

• 1997 30 nmol/L is sufficient
• Present 80 nmol/L is sufficient

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What should the UL be?

• Current UL is 2,000 IU/d
• Most agree this is far too low
• Discourages food beverage companies from
  fortifying with higher levels of Vit D
• Level to avoid toxicity symptoms
• First symptom appears as hypercalcemia
• Seen with 25(OH)D at 500 nmol/L (but usually
  650-700 nmol/L)

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Changing What We Know

• Current NOAEL 60 mcg/d
• Recommended NOAEL 265 mcg/d

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What should the UL be?

• Report to IOM Food and Nutrition Board
• Reviewed over 20 trials with supplementation
  ranging from 2144-100,000 IU/d
• Concluded that 10,000 IU/d Vit D is safe
• At this level, 25(OH)D concentrations remain well
  below 500 nmol/L

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Sources of Vitamin D

• Few natural food sources
• Fatty fish (salmon and tuna), cod liver oil
• Fortified foods make up 65-87 in US diet
• Milk, cereals, orange juice
• Dietary Supplements
• Adequate sunlight exposure
• Duration of exposure is variable based on skin
  pigmentation and latitude

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Vitamin D Intakes
Calvo Whiting, J Nutr 2006
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Sources of Vitamin D
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Vitamin D Levels Based on Fortified Juice for 1
Year
P lt 0.001 for Never vs other groups, values
corrected for season of measurement (NS) and race
(p lt 0.001).
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Change in Vitamin D Levels After 1 Year
P lt 0.001 for difference between groups and P lt
0.01 for difference from zero. Values corrected
for race and season (both NS).
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Whats on the Food Label?

• Not Vitamin D!
• Lack of Vit D content info on Nutrition Facts
  Food Label is a critical barrier to improving Vit
  D intakes of natural food sources

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Vitamin D and Disease
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Low Vitamin D Status is also associated with

• Reduced lower extremity neuromuscular function
• Increased risk of Type I Diabetes
• Impaired insulin sensitivity
• Increased risk of metabolic syndrome
• Increased risk of Multiple Sclerosis
• With 25(OHD) gt 100 nmol/L, 62 reduction in risk
  for MS compared to patients with 25(OH)D lt 63
  nmol/L
• Impaired immune response
• Increased risk of influenza and respiratory
  infections
• Increased risk and severity of tuberculosis
• Increased risk of various cancers
• Breast, colon, lung, prostate, marrow, lymphoma

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Vitamin D and Cancer Incidence

• Inverse relationship found for 25(OH)D levels and
  risk for all types of non-skin cancers
• With 25(OH)D gt 80 nmol/L, there was a 50
  reduction in colorectal cancer risk
• With 25(OH)D gt 50 nmol/L, there was a 50
  reduction in prostate cancer risk
• Lappe et al, AJCN 2007
• Tuohimaa et al, Int J Cancer 2004

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Vitamin D and Cancer Incidence
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How much vitamin D does the body need to produce
a serum level that protects against disease?
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Reaching Optimal 25(OH)D Levels
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Summary

• Be aware that recommendations for intakes and the
  UL will likely change soon
• Groups at higher risk for vitamin D deficiency
  should emphasize fortified and natural food
  sources in addition to supplementation
• 25(OH)D levels
• Deficient lt50 nmol/L
• Sufficient 50-80 nmol/L
• Vitamin D intakes
• Current UL is 2000 IU/d although new data show
  that 10,000 IU/d is safe