Vitamin_D_ _Current_Research__Recommendations pptKH by ouJj7u


									Vitamin D: Current Research
   and Recommendations
    Across the Life Span
Seema Desai, MS, RD, LDN, CNSD
    Kerry Harwood, MSN, RN
        Vitamin D Overview
 It is a fat soluble vitamin.
 Not just a vitamin it is a prehormone

 Found in some food and made in the body
  after exposure to UV rays
 Major biological function is to maintain
  normal blood levels of Ca and Po4
 Other tissues like macrophages, prostrate
  tissue also have vit D receptor
             History of Vitamin D
   Existed over 500 million years
   Industrial revolution : rickets
   Cod liver oil: common folklore medicine
   Discovery of Vit D as the antirachitic factor in cod liver
   Discovery of conversion of 7-dehydrocholesterol in the skin
    to vit D (1937)
   Antirachitic property in food
   Fortification of food with vitamin D was patented
   Complete eradication of rickets in US
   US public service issuing warnings about sun-induced
    health risk
   Over next 30 yrs skin cancer hazard of excessive sun
    exposure became well established
Structure of Vitamin D
Endocrine, paracrine and intracrine
     functions of Vitamin D
 Vitamin D Across the Lifespan
        influencing accumulation of
 Factors
 bone minerals:
  – Heredity
  – Gender
  – Diet
  – Physical activity
  – Endocrine status
  – Maternal vitamin D status
Maternal Vitamin D Status
  Association of low intake of milk and vit D
    during pregnancy with decreased birth
  C.A. Mannion, Katherine Gray-Donald, kristine G. Koski.
     CMAJ April 25, 2006
    -Women between ages 19-45yrs
    -In Calgary
    -</= 250 ml of milk = low birth weight
    -milk or vit D independent predictor of BW
    -1 cup milk = 41 gm increase in BW
    -1 Mcg increase in dietary vit D = 11 gm increase in
          Maternal vitamin D….
Maternal vitamin D status during pregnancy
 and childhood bone mass at age 9yrs.
M.K. Javaid, SR Crozeir at al. Lancet Jan 7 2006
-198 children born in 1991-92 in South Hampton
-children were followed up at age 9yrs
-31% mother had insufficient and 18% had
  deficient serum vit D during late pregnancy
-decrease vit D in mothers = decrease bone
  mineral content in children at age 9 yrs
-mother’s exposure to UV rays and use of vit d
  predicted vit d and childhood bone mass
              Breastfed infants
Vitamin D deficiency in breastfed infants in
Ekhard E. Ziegler, Bruce w. Hollis, Steven E Nelson and Janice
  M. Jeter. Pediatrics 2006
  -84 breastfed infants
  -blood samples and dietary records were taken
  -35 infants were unsupplemented
  -49 infants were either supplemented with formula or vit D
  -10% were vit D deficient
  -Marked seasonal affect more so in the unsupplemented
  -mainly but not exclusively during winter and occurred in
  light and dark skinned infants
               Healthy adolescents
Prevalence of vitamin D deficiency among healthy
Catherine M Gordon, Kerrin C. DePeter, Henry A. Feldman, Estherann Grace,
   Jean Emans. Arch pediatr Adolesc med June 2004
   -307 healthy adolescents 11-18 yrs,
   -annual physical between july 2001-june 2003
   -Data collected on age, sex, ethnicity, Ht, wt, exercise, medical hx diet
   -Blood samples were drawn at the end of the visit

   -24.1% of the participants were vit D deficient
   -highest prevalence in African American
   -Most prevalent during winter
   -no difference in prevalence between girls and boys
   -+ correlation between soft drink consumption and vit D deficiency
   -inverse correlation between vit D deficiency and milk and cold cereal
    Young girls in southern US
Serum 25-hydroxy vitamin D concentration in girls
  aged 4-8 y living in the southeastern United
  States. Stein et al.. Am J clinical nutrition 2006
  -168 prepubertal girls 4-8 yrs old
  -120 non-Hispanic white
  -48 non-Hispanic black
  -Oct 1997-Oct 2000 at U of GA
  -with in 1 wk of blood draw bone scan, anthropometric
  measure dietary intake, and physical activity were assessed
o   Mean vitaminD, Calcium and multivitamin
    use was higher in white girls than in black
o   Both races had mean dietary vitamin D
    intake above adequate levels
o   Race and season strongest predictor of vit D
o   Black girls had lower mean vit D value
o   Vitamin D value were significantly higher in
    summer than in winter
o   Living at low latitude does not entirely
    prevent poor vitamin D status
        Milk Allergies and vitamin D
Milk allergy and vitamin D deficiency rickets: a common
   disorder associated with an uncommon disease. Case
Joyce w. Yu at el…
Annals of allergy, asthma and immunology…April 2006
  -Case report of Vit D deficiency rickets in 2 yr old boy with
  milk allergy
  -BF for 6-7 months
  -failed trail of cows milk formula
  -drank 500-700ml of fruit juice with no vit D and Ca
  -18 months of age started to regress
  -Lab values: Vit D of 8 mmol/l, Ca: 1.98 mmol/l, alk phos:
o   Discharged taking 4000IU of vit D, 200mg
    calcitriol, and 300mg elemental Ca
o   2 weeks later was able to stand, and his lab
    values were improved.
Vitamin D Deficiency in
 Hospitalized Patients
 Vitamin D Deficiency in
Renal Transplant Patients
Vitamin D Inadequacy in
Post-Menopausal Women
        Vitamin D and Cancer
 May  influence both incidence and
 Linked with GI cancer, prostate and
  breast cancers, lymphomas,
  endometrial and lung cancers
Something New Under the Sun?

  Apperly FL. The relation of solar
 radiation to cancer mortality in North
 Cancer Research.1941(1):191-195
            1979 - 1981
 VitaminD receptors found in
 malignant melanoma cells and
 myeloid leukemia cells

 1,25(OH)2D   inhibited melanoma cell
 proliferation and induced myeloid cell
   Northern vs. Southern U.S.

30 – 40 extra          1 – 2 extra
deaths for             skin cancer
other major            deaths
cancers (per           (per
100,000)               100,000)
 Serum   levels of 1,25(OH)2D are
  tightly controlled by the kidneys &
  don’t vary by sun exposure so how
  could vitamin D contribute to the
  north-south gradients and African-
  American excess in cancer rates?
 Non-renal cells discovered to
  hydroxylate 25(OH)D and synthesize
  1,25(OH)2D locally.
        Vitamin D & Cancer
 Environmental:     sunlight & diet
  – Calcitriol (hormonal form of vitamin D)
    controls the differentiation of many cells
    that possess vitamin D receptors (VDR)
  – Induce cell differentiation and apoptosis
    of cancer cells while inhibiting cell
    proliferation, angiogenesis, and
 Genetic:   VDR polymorphisms
 June, 2007 American Journal of
        Clinical Nutrition
 Women   who regularly took vitamin
 D3 and calcium had a 60% reduction
 in all-cancer incidence compared
 with a group taking placebo and a
 77% reduction when the analysis
 was confined to cancers diagnosed
 after the first 12 months.
            Lung cancer
 inhibits proliferation and induces
  differentiation of lung cancer cell
  lines (Higashimoto, et al., 1996,
  Guzey, et al., 1998)
 inhibits metastatic growth and
  locoregional recurrence of lung
  cancer cells in mice (Wiers, et al.,
              Lung cancer
 456   patients with early stage NSCLC
  – Median age – 69
  – 96% Caucasian
 Data   collection:
  – Season of surgery
  – Food frequency questionnaire
  – Recurrence free survival (RFS)
  – Overall survival (OS)

                          Zhou, et al., 2005
             Lung cancer
 Patients who had surgery during
  summer with the highest vitamin D
  intake had better RFS that patients
  who had surgery during winter with
  the lowest vitamin D intake.
 Similar associations were seen for
  overall survival.

                     Zhou, et al., 2005
           Lung cancer

Insert survival graph from Zhou article
            Breast cancer
 inhibits cell proliferation, induces
  differentiation & apoptosis, and inhibits
  angiogenesis in normal and breast cancer
  cells (Colston, et al, 1989, Saez, et al,
  1993, Mantell, et al., 2000)
 suppresses high-fat diet-induced
  mammary tumorigenesis in rats
  (Jacobson, et al., 1989, Xue, 1999)
            Breast cancer
 Inverse association between vitamin D &
  calcium intake and breast density
 Inconclusive results in studies looking at
  VDR genetic polymorphisms and breast
 Inverse association between high sunlight
  exposure and breast cancer risk
 Association may be stronger for
  premenopausal than postmenopausal
  women due to interactions between
  vitamin D, the VDR, estrogen and insulin-
  like growth factor-I (IGF-I)
                            Cui & Rohan, 2006
           Breast cancer
 Case-control   study – 972 women
  with newly-diagnosed breast cancer
  & 1,135 healthy controls
 Interviews regarding vitamin D-
  related exposures, e.g. outdoor
  activities, use of sunscreen, dietary

                           Knight, 2007
           Breast cancer
 More   frequent sun exposure during
  adolescence was associated with a
  35% reduction in breast cancer risk
  later in life
 Lower risk also linked to cod liver oil
  and milk intake > 10 glasses / week
 Milder protection seen for people age
  20 – 29
 No protection for people over age 45
             Breast cancer
 Epidemiologic study of different regions of
  Norway, each with a different annual UV
 Prognosis 15 – 25% better for women
  diagnosed / treated in the summer vs.

    <get this article: Breast Cancer Research
          and Treatment, May>Knight , 2007
      Endometrial cancer

Is ultraviolet B irradiance inversely
  associated with incidence rates of
 endometrial cancer: an ecological
        study of 107 countries.
                     Mohr, et al, 2007
       Endometrial cancer
 Objective:  perform an ecological
 analysis of the relationship between
 low levels of ultraviolet B irradiance
 and age-standardized incidence rates
 of endometrial cancer by country,
 controlling for known confounders
             Endometrial cancer
   107 countries:
    –   UVB irradiance
    –   cloud cover
    –   intake of energy from animal sources
    –   proportion overweight
    –   skin pigmentation
    –   cigarette consumption
    –   health expenditure
    –   total fertility rates
   vs. age-standardized incidence of
    endometrial cancer
        Endometrial cancer
            found between
 Association
 endometrial cancer incidence rates
  – Low UVB irradiance
  – High intake of energy from animal
    sources ( IGF-I?)
  – Per capital health expenditure
  – Proportion of population overweight
            Pancreatic cancer
   Prospectively collected diet and lifestyle
    – Nurses’ Health Study – 75,427 women
    – Health Professionals Follow-up Study – 46,771
   Pancreatic cancer risk 41% lower among
    those who consumed > 600 IU of vitamin
    D / day vs. those who consumed < 150 IU
    / day
                           Skinner, et al., 2006
       Cancer Survival
 Summer  / Fall (vs. Winter /
 Spring) diagnosis associated with
 improved survival in:
 – Colorectal cancer
 – Hodgkin’s lymphoma
 – Breast cancer
          Cancer Survival
 Intermittentsun exposure
 associated with increased survival
 following a diagnosis of melanoma
                Berwick, et al., 2005
            Type 2 Diabetes
 Altered  vitamin D and calcium
  homeostasis may play a role in
  development of type 2 diabetes
 Low serum levels of 25(OH)D are
  associated with impaired pancreatic
  β cell function and insulin resistance
 High calcium intake is inversely
  associated with body weight
          Type 2 Diabetes
       Health Study – 83,779
 Nurses’
 women (98% Caucasian)

 Dailyintake of >1,200 mg calcium
 & >800IU vitamin D was
 associated with a 33% lower risk
 of type 2 diabetes compared with
 an intake of <600 mg calcium &
 <400 IU vitamin D
                  Pittas, et al., 2006
           Type 1 Diabetes
 Birth-cohort study in Finland – all women
  due to give birth in 1966 enrolled
 10,366 children born alive and followed to
  one year; 81 diagnosed with Type 1
 Children who regularly took recommended
  dose of vitamin D (2000 IU) had a RR of
  0.22 compared with those who did not.
 Children suspected of having rickets had a
  RR of 3.0 compared with those not
                       Hopponen, et al., 2001
          Metabolic Syndrome
     National Health & Nutrition
 Third
 Examination Survey (NHANES III)
  – 8,421 men and non-pregnant women >
    20 years of age and had fasted > 8 hrs
 Unadjustedprevalence of metabolic
 syndrome - 21.9%
            Metabolic Syndrome
 After adjustments for known risk factors,
  odd of metabolic syndrome decreased
  progressively across increasing
  concentrations of 25(OH)D
 Relative risk compared with bottom
  quintile of vitamin D level:
    –   2nd quintile – 0.85
    –   3rd quintile – 0.75
    –   4th quintile – 0.62
    –   5th quintile – 0.46
                              Ford, et al., 2005
        Pulmonary / COPD
• Third National Health & Nutrition
  Examination Survey (NHANES III)
  • 14,000 subjects
  • Dose-response correlation between
    percent predicted FEV1 and FVC values
    and circulating 25(OH)D
  • Plausibility: vitamin D shown to prevent
    experimental inflammatory diseases in
    mice including allergic asthma

                  Black, et al., Chest, 2005
    Congestive Heart Failure
 RCT of vitamin D + calcium vs.
 placebo + calcium x 9 months in
 subjects with CHF
 – 93 subjects completed study
 – Anti-inflammatory cytokine interleukin
   10 significantly higher
 – Suppressed release of TNF-α
 – No difference in survival but blood levels
   not optimized
                     Schleithoff, et al., 2006
 Prospectively   followed two cohorts:
  – Nurses’ Health Study – 1198 women
  – Health Professionals Follow-up Study –
    613 men
 Relative   risk of hypertension:
  – < 15 ng/mL vs > 30 ng/mL 25(OH)D
     Men: RR = 6.13
     Women: RR = 2.67
Chronic Kidney Disease
Multiple Sclerosis
Osteo- & Rheumatoid Arthritis
  Where do we go from here?
 Routine   screening
 Rectify   deficiency / insufficiency
 Maintain levels through a patient-
 specific combination of diet,
 supplementation, and sun exposure

 Annual testing of 25(OH)D
 Consider time of year in testing
  – Lowest levels generally towards
    end of winter, early spring
      Vitamin D Assessment
 Lab assays are available to measure both
  25(OH)D and 1,25-D.
 25(OH)D closely reflects total amount of
  vit D produced in the skin and from diet
 D2 and D3: have similar biological activity

 Both D2 and D3 should be measured

 DO NOT USE - 1,25-D. This can often be
  normal with vit D deficiency
          Goals in Maintaining
           Vitamin D Levels
1.   Prevent disease of deficiency –
     rickets, osteomalacia
2.   Prevent complications of
     insufficiency – impaired calcium
     absorption and increased bone
3.   Minimize risks of future disease –
     cancer, cardiopulmonary diseases,
     diabetes, other immune-related
        25(OH)D concentration

 To   prevent deficiency disease –
  > 25 nmol / L
 Toprevent complications of
 insufficiency –
  > 50 nmol/L
 Formaximum bone health and
 prevention of chronic disease –
  75 – 100 nmol/L
         Who is at greatest risk?
   Low dietary intake: BF infants, children who do not drink
    fortified milk
   Malabsorption syndrome
   Severe liver disease
   Kidney disease
   Drugs
   Higher latitudes
   People who spend little time outside
   Older adults
   Decreased sun exposure due to cultural reasons
   Races with high skin melanin levels
  Supplementation (adults)

To correct deficiency: 50,000 IU
vitamin D weekly x 8 weeks,
reassess and repeat if necessary
       Supplementation (peds)
 To   correct deficiency
        IOM Recommendations (AI)
Age      Children Men     Women    Pregnancy lactation

13 yrs   5mcgs
14-               5       5        5          5
18yrs             200IU   200 IU   200IU      200IU
19-50             5       5        5          5
Yrs               200     200 IU   200 IU     200 IU
51-70             10     10
Yrs               400 IU 400 IU
71+               15     15
                  600 IU 600 IU
  Do recommendations reflect the
       state of the science?
„Our studies in children (3 – 16 years
 of age) in Edmonton, Alberta, show
 that 200 IU daily is not even
 adequate for maintaining levels now
 considered mildly to moderately
 deficient (40 nmol/L), let alone
 optimum (80 nmol/L).‟

    A.B. Jones, Canadian Family Physician, 2006
   Do recommendations reflect the
        state of the science?
„Oral doses currently consumed in the US
 (an estimated mean of 320 IU / day) are
 far too low, and the designation of the
 2000 IU/day dosage as safe by NAS
 provides latitude to the community to
 increase intakes to levels required to
 reduce risk of cancer, with essentially no
 likelihood of adverse effects.‟

  Grant and Gorham, International J of Epidemiology, 2006
   Do recommendations reflect the
        state of the science?

„…the present recommended
 allowance for vitamin D – 400 IU –
 for individuals aged 50 – 70 years is
 inadequate even to maintain skeletal
 health and is probably too low for
 meaningful anticancer effects.‟

Schwartz & Blot, J National Cancer Institute, 2006
 National Academy of Science
 Tolerable Upper Intake Levels

Pediatrics 0 – 12 months –
  1000 IU / Day

All others –
  2000 IU / Day
USDHHS Dietary Guidelines for
     America - 2005

 Specialgroups – elderly and
 individuals with dark skin –
  1,000 IU / day
       Maintenance (adults)
 To maintain recommended levels:
 800 - 1000 IU / day if not getting
 enough sun exposure to maintain
 vitamin D levels or 50,000 IU 1-2
 times monthly
  North American Conference
         on Vitamin D
“to minimize the health risks
associated with UVB radiation
exposure while maximizing the
potential benefits of optimum
vitamin D status, {dietary}
supplementation and small amounts
of sun exposure are the preferred
methods of obtaining vitamin D.”

        Consensus statement, 2006
         How much sun?
 Depends   on:
 – Age
 – Amount of vitamin D obtained from diet
 – Skin darkness
 – Sunshine intensity
          How much sun?
 Significant   skin exposure
  – Face, neck, arms, hands
  – Arms, legs
 Adequate   sun strength
 Time
  – 25% of the time it would take to cause
    pinkness of the skin (Caucasians)
  – People with dark skin require
    significantly more sun exposure
                                Holick, 2004
Food Sources of Vitamin D
   Cod liver oil – 1 TBS            1,360 IU
   Salmon 3.5 oz.                   360
   Mackerel 3.5 oz.                 345
   Tuna, canned, in oil, 3 oz.      200
   Sardines 3.5 oz.                 250
   Milk (fortified) 8 oz.           98
   Ready to eat cereal              40
    (fortified) ¾ - 1 cup
   Egg 1 whole                      20
   Liver, 3.5 oz.                   15
   Cheese, swiss 1 oz.              12

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