Transcript Vitamin D Overview

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
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History of Vitamin D
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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
oil(1920)
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
 Factors
influencing accumulation of
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
weight.
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
BW
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
UK
-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
Iowa.
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
group
-mainly but not exclusively during winter and occurred in
light and dark skinned infants
Healthy adolescents
Prevalence of vitamin D deficiency among healthy
adolescents.
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
consumption
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
https://docme.mc.duke.edu/ada/index.asp
-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
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Mean vitaminD, Calcium and multivitamin
use was higher in white girls than in black
Both races had mean dietary vitamin D
intake above adequate levels
Race and season strongest predictor of vit D
status
Black girls had lower mean vit D value
Vitamin D value were significantly higher in
summer than in winter
Living at low latitude does not entirely
prevent poor vitamin D status
Milk Allergies and vitamin D
deficiency
Milk allergy and vitamin D deficiency rickets: a common
disorder associated with an uncommon disease. Case
Report
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
supplementation
-18 months of age started to regress
-Lab values: Vit D of 8 mmol/l, Ca: 1.98 mmol/l, alk phos:
-2,822u/l
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Discharged taking 4000IU of vit D, 200mg
calcitriol, and 300mg elemental Ca
2 weeks later was able to stand, and his lab
values were improved.
Adults
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
mortality
 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
America.
Cancer Research.1941(1):191-195
1979 - 1981
 Vitamin
D receptors found in
malignant melanoma cells and
myeloid leukemia cells
 1,25(OH)2D
inhibited melanoma cell
proliferation and induced myeloid cell
differentiation
Northern vs. Southern U.S.
30 – 40 extra
deaths for
other major
cancers (per
100,000)
1 – 2 extra
skin cancer
deaths
(per
100,000)
1998
 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 AfricanAmerican 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
metastasis
 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
1,25(OH)2D:
 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.,
2000)
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
here
Breast cancer
1,25(OH)2D:
 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
cancer
 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 insulinlike growth factor-I (IGF-I)
Cui & Rohan, 2006
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Breast cancer
 Case-control
study – 972 women
with newly-diagnosed breast cancer
& 1,135 healthy controls
 Interviews regarding vitamin Drelated exposures, e.g. outdoor
activities, use of sunscreen, dietary
contributions
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
exposure
 Prognosis 15 – 25% better for women
diagnosed / treated in the summer vs.
winter
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<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
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107 countries:
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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
 Association
found between
endometrial cancer incidence rates
and:
– Low UVB irradiance
– High intake of energy from animal
sources ( IGF-I?)
– Per capital health expenditure
– Proportion of population overweight
Pancreatic cancer
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Prospectively collected diet and lifestyle
data
– Nurses’ Health Study – 75,427 women
– Health Professionals Follow-up Study – 46,771
men
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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
– NSCLC
– Breast cancer
Cancer Survival
 Intermittent
sun 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
 Nurses’
Health Study – 83,779
women (98% Caucasian)
 Daily
intake 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
diabetes
 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
suspected.
Hopponen, et al., 2001
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Metabolic Syndrome
 Third
National Health & Nutrition
Examination Survey (NHANES III)
– 8,421 men and non-pregnant women >
20 years of age and had fasted > 8 hrs
 Unadjusted
prevalence 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:
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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
Hypertension
 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
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Stroke
Chronic Kidney Disease
Multiple Sclerosis
Osteo- & Rheumatoid Arthritis
Where do we go from here?
 Routine
 Rectify
screening
deficiency / insufficiency
 Maintain
levels through a patientspecific combination of diet,
supplementation, and sun exposure
Recommendations
 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
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Goals in Maintaining
Vitamin D Levels
1.
2.
3.
Prevent disease of deficiency –
rickets, osteomalacia
Prevent complications of
insufficiency – impaired calcium
absorption and increased bone
resorption
Minimize risks of future disease –
cancer, cardiopulmonary diseases,
diabetes, other immune-related
diseases
25(OH)D concentration
 To
prevent deficiency disease –
> 25 nmol / L
 To
prevent complications of
insufficiency –
> 50 nmol/L
 For
maximum bone health and
prevention of chronic disease –
75 – 100 nmol/L
Who is at greatest risk?
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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
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
Birth13 yrs
Children Men
Women
Pregnancy lactation
5mcgs
=200IU
1418yrs
5
200IU
5
200 IU
5
200IU
5
200IU
19-50
Yrs
5
200
IU
5
200 IU
5
200 IU
5
200 IU
51-70
Yrs
10
10
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
 Special
groups – 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
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Cod liver oil – 1 TBS
Salmon 3.5 oz.
Mackerel 3.5 oz.
Tuna, canned, in oil, 3 oz.
Sardines 3.5 oz.
Milk (fortified) 8 oz.
Ready to eat cereal
(fortified) ¾ - 1 cup
Egg 1 whole
Liver, 3.5 oz.
Cheese, swiss 1 oz.
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1,360 IU
360
345
200
250
98
40
20
15
12