Shining a Light on Vitamin D Vitamine A by benbenzhou


Shining a Light on Vitamin D Vitamine A

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									Shining a Light on
    Vitamin D
         Lisa Pomranky, M.D.
 Slocum Center for Orthopedics
         and Sports Medicine

   Review the role of Vitamin D and how it
    relates to our health
   Discuss replacement and optimal levels
What is Vitamin D?
   The “Sunshine Vitamin”
   A fat soluble vitamin with an important role in
    calcium and bone metabolism
   A vitamin with emerging data and research
    about previously unknown health benefits
   A vitamin in which many of us are deficient or
What is Vitamin D?
   Vitamin D3 (cholecalciferol) is the form
    produced in humans and animals
       Supplements made from UVB irradiation of lanolin
        (wool fat)
   Vitamin D2 (ergocalciferol) is the plant
    derived supplement
       UVB irradiation of ergosterol from yeast
       Only 30% as effective in raising 25-
        hydroxyvitamin D level as D3
What is Vitamin D?
   Vitamin D3 is converted to 25-hydroxyvitamin
    D in the liver
   25-hydroxyvitamin D is the precursor to the
    active 1,25-dihydroxyvitamin D
       This conversion takes place mainly in the kidneys
Calcium and Bone Metabolism
   Essential to calcium metabolism primarily by
    enhancing intestinal absorption of dietary
   If vitamin D level is low (below 30 ng/ml),
    calcium absorption is significantly impaired
   Inadequate Ca absorption leads to
    osteopenia and osteoporosis
Calcium and Bone Metabolism
   Increased PTH leads to the maturation of
    osteoclasts, which dissolve mineralized bone
    matrix to provide calcium, but can result in
    osteoporosis and osteopenia
   Increased PTH also results in phosphaturia
    and lowering of serum phosphorous
Calcium and Bone Metabolism
   Low calcium-phosphorous product leads to
    inadequate bone mineralization
   Bone matrix continues to be made but is
    rubbery and structurally inadequate
   In children, inadequate mineralization causes
    skeletal deformities known as rickets
   In adults, inadequate
    mineralization causes
    dull, aching bone pain
    known as osteomalacia
   Milder degrees of vitamin D inadequacy can
    lead to a higher risk of osteoporosis, and an
    increased likelihood of falling in older adults
    whose muscles are weakened by a lack of
    the vitamin.
Osteoporosis and Aging
   A decrease in dietary calcium intake, usually
    as a result of decreased overall dietary
    energy intake (e.g. poor appetite, intercurrent
    illnesses, social and economic factors)
   A decrease in the intestinal absorption of
    calcium (exacerbated if vitamin D status is
   A decrease in the capacity of the intestinal
    cells to adapt to a low calcium intake, and
    increase their absorptive capacity
Osteoporosis and Aging
   Less frequent exposure to sunlight (e.g. elderly who
    are housebound, or institutionalized, or have
    reduced mobility)
   A decrease in the capacity of the skin to synthesize
    vitamin D
   A decrease in the efficiency with which the kidneys
    can retain calcium, leading to increased calcium loss
    in the urine
   A decrease in the capacity of the kidneys to convert
    vitamin D into the most active form, 1,25-
    dihydroxyvitamin D
Are there other functions of
Vitamin D?
   Most organs in the body (including brain,
    prostate, breast, colon, heart, pancreas, skin
    and immune system) have VDR which
    recognize 1,25-dihydroxyvitamin D
   Many organs also have enzyme to convert
    25-hydroxyvitamin D to active 1,25-
    dihydroxyvitamin D (similar to kidneys)
Functions of Vitamin D
   1,25-dihydroxyvitamin D controls more than
    200 genes which then:
       Inhibit cell multiplication
       Promote cell death and cell maturation
       Stimulate insulin secretion from the pancreas
       Modulate immune function
       Inhibit renin production
Vitamin D Metabolism
Plethora of Recent Research
   Meta-analysis of 18 RCTs with 57,311
    participants over average of 5 years showed
    7% reduction in all cause mortality
   Average dose vit D 528 IU (300-2000)
Ref: Autier and Gandini. Arch Intern Med Sep 2007
   Osteoporosis and risk of fractures
       Clinical trials show that vitamin D3
        supplementation of 800 IU daily along with
        adequate calcium can reduce the risk of hip and
        non-vertebral fractures by 20-40% (need to reach
        25 (OH)vit D levels above 30 ng/ml)
Vitamin D and Muscle
   Muscle weakness and risk of falls
       Skeletal muscles have VDR and may require vit D
        for maximum function
       Performance speed and proximal muscle strength
        markedly improved when 25 (OH)vit D levels were
        raised from 4-16 to 40 ng/ml
       Meta-analysis of 5 trials showed 35% reduction in
        falls in the elderly on 800 IU D3 and calcium
       In one study of NH patients, falls reduced by 72%
        with Vit D 800 IU and calcium
Vitamin D and Cancer
   Vitamin D level below 20 ng/ml associated
    with 30-50% increased incidence of colon,
    prostate, and breast cancer
   In one 4 year study of 1179 post-menopausal
    women in Nebraska showed that women
    taking vit D3 1100 IU and calcium 1500mg
    daily had 60% lower risk of developing
    cancer compared to placebo group

Ref: Am J Clin Nutr 2007:1586-91
Vitamin D and DM
   Increased insulin resistance and decreased
    insulin production
       Raising vit D level from 10ng/ml to 30ng/ml,
        increased insulin sensitivity 60%
       In one study, vit D 800 IU and Ca 1200mg
        lowered risk of developing DM Type II by 33%
        compared to vit D 400 IU and Ca 600mg
Vitamin D and Type I Diabetes
   Increased risk of Type I Diabetes
       In a large study of 10,366 children in Finland for
        31 years
           Children with vit D deficiency had RR 3 of developing
            Type 1 DM
           Risk of developing Type I DM was reduced 80% over
            30 years in children given vit D 2000 IU daily in first
            year of life

Ref: Lancet 2001:358: 1500-3
Vitamin D and Pregnancy
   Pregnancy: low level of 25 (OH) vit D has
    been associated with:
       Impaired fetal skeletal formation
       Higher incidence of pre-eclampsia
   Normal vit D levels may be necessary for
    fetal “imprinting” for neurodevelopment,
    immune function
Vitamin D and MS
   Living north of 37° latitude increases risk of
    developing MS 100%
   Higher levels of 25 (OH) vit D associated with
    lower risk of MS (JAMA 2007)
   Taking a MVI with 400 IU of vit D reduces risk
Vitamin D and CVD
   In one study of 1,739 Framingham offspring
    without CV disease, those with vit D level
    lower than 15ng/ml had twice the risk of MI,
    CVA, CHF than those with higher than 15
    over 5 year period (Circulation 2008 Jan 29)
   Increasing 25 (OH) vit D with UVB for 3
    months lowered systolic blood pressure 6
   Vit D and calcium supplement lowered
    systolic blood pressure 9.3%
What is an Optimal Vitamin D
   Normal = 32-100 ng/ml (75-100 nmol/L)
   Insufficiency = 20-29 ng/ml (52-72 nmol/L)
   Deficiency = < 20 ng/ml (50 nmol/L)
   Toxic = > 150 ng/ml (374 nmol/L)
   Optimal = ??
Prevalence of Vitamin D
   Estimated 1 billion worldwide
   52% of Hispanic and black adolescents in
    Boston study
   32% of young men and women 18-29 in
   76% of mother-infant pairs in Boston
   75% ambulatory older adults in Denver
Etiology for Deficiency
 Medications: seizure medicine, steroids
 Heritable disorders
    Vitamin D-resistant rickets
 Primary hyperparathyroidism
 Granulomatous disorders – sarcoidosis, TB,
 some lymphomas
 Chronic renal disease
Etiologies for Deficiency
 Reduced skin synthesis – season, northern
 latitude, sunscreen, aging, pigmented skin
 Inadequate nutritional intake
 Malabsorption – celiac disease, Crohns,
 gastrointestinal bypass surgery
 Breast feeding exclusively
 Obesity – sequestration in body fat
Vitamin D Level
 Defined by level of 25-hydroxyvitamin D
 which is the circulating form of vitamin D
 (half-life of 10-19 days)
 “Normal” = Level at which PTH suppression
 levels off towards nadir and calcium
 absorption reaches maximum (a physiologic
 and not population based “normal”)
What to Order
 When measuring for Vitamin D deficiency be
 sure to order:
    25-hydroxyvitamin D
        Sometimes reported as total with subcomponents of
         D2 and D3. Use the total level.
 Do not order 1,25 dihydroxyvitamin D level
    This is active form of Vitamin D3, produced by
     kidneys and can remain at normal level in face of
     overall Vitamin D deficiency.
Sources of Vitamin D

 Sunlight (UVB)
 Dietary supplements
Sources of Vitamin D
 Solar UVB penetrates skin to convert 7-
 Dehydrocholesterol to vitamin D3
 Sunlight produces 90% of vitamin D
 Sunscreen SPF 15 reduces capacity 99%
 Season and time of day important
    In northern winters, no Vit D production;
 Pigmented skin and aging skin - >75%
 reduction in vit D production
Vitamin D from the Sun
 Some of your vitamin D requirement can be
 attained with adequate sun or UVB (tanning
 booth) exposure
    5-30 minutes of sun exposure (no sunscreen) to
     arms and face or legs between 10am – 3pm twice
     a week in summer is usually adequate (with
     exception of pigmented or older skin)
Food Sources of Vitamin D
 Natural Sources:        Vitamin D3
    Salmon, wild        600-1000 IU
    Salmon, farmed      100-250 IU
    Sardines (canned)   300 IU
    Tuna (canned)       230 IU
    Shitake mushrooms   Vitamin D2
        Fresh           100 IU
        Sundried        1600 IU
Food Sources of Vitamin D?
 Fortified Foods             Vitamin D3
    Milk (8 oz)             100 IU
    Orange juice (8 oz)     100 IU
    Infant formula (8 oz)   100 IU
    Cereal (serving)        100 IU
Vitamin D Supplements
 Over the counter
    Multivitamin             400 IU
    Cholecalciferol (D3)     400, 800, 1000, 2000
    Cod liver oil (1 tsp)    400-1000 IU*
    Calcium with Vit D       200 IU
    Ergocalciferol (D2) 50,000 IU cap

Can contain mercury and other toxins
Vitamin D Supplements
 Over the counter D3
   Tri Vi Sol            400 IU / ml
  Poly Vi Sol            400 IU /ml
   Ergocalciferol (D2)   8,000 IU/ml
Vitamin D Dosage
 Newly evolving recommendations for
 maintenance dose (to prevent deficiency):
                    Vitamin D3
    Children       400-1000 IU
    Adults         800-1000 IU*

Alternatively, 50,000 IU vitamin D2
 (ergocalciferol) by Rx once or twice a month
Vitamin D Dosage
 Newly evolving recommendations for
 maintenance dose (to prevent deficiency):
    Pregnant/lactating   1000-2000 IU
    African American     1000-2000 IU
    Obesity              1000-2000 IU
Vitamin D Toxicity
 Vitamin D intoxication is extremely rare
 Doses of 50,000 IU a day of Vit D3 would
 raise levels above the toxic level of 150ng/ml
 Doses of 10,000 IU Vit D3 for 5 months did
 not cause toxicity
 Bottom line: Doses up to 2000 IU Vit D3 daily
 are quite safe for almost everyone
Vitamin D Toxicity
    Signs and symptoms of toxicity
        High calcium levels in the blood and urine
        Confusion
        Severe increase in urination and thirst
        Anorexia, vomiting
        Muscle weakness
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