Vitamin D basics

Evolving concepts & importance in overall
health status

Is there deficiency in
sunny India?
INDIA

Latitude of 22 ° 00' N

Longitude of 77 ° 00‘ W

 Can there be
chances of
deficiency in India?

1. ↓ Intake or synthesis of cholecalciferol
 ↓ sunlight: ageing, veiling, illness, immobility
 ↓ synthesis for a given UV exposure: ageing, dark skin
 As above combined with low dietary intake
1. Disorders associated with abnormal gut function and
malabsorption
 Small bowel disorders: coeliac disease, sprue, IBD, infiltrative
disorders, small bowel resection
 Pancreatic insufficiency: chronic pancreatitis, cystic fibrosis
 Biliary obstruction: 1° biliary cirrhosis, external biliary drainage

3. ↓ synthesis or enhanced degradation of 25OHD
 chronic hepatic disorders: hepatitis, cirrhosis
 drugs: rifampicin, anticonvulsants
4. AHA 2010 Conference revealed that Vitamin-D
deficiency is highly prevalent in U.S. black populations.
 Melanin in the skin blocks the UVB synthesis of vitamin D.
 Silent epidemic, often unrecognized by clinicians

 Cod liver oil – 1 TBS  1,360 IU
 Salmon 3.5 oz.  360
Fish
 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 (fortified) ¾  40
- 1 cup
 Egg 1 whole  20
 Liver, 3.5 oz.  15
 Cheese, swiss 1 oz.  12

Most Indians suffer from Vitamin D Deficiency
1. Am J Clin Nutr. 2000;72: 472-75 2. Data on file

Is there deficiency in
sunny India?
INDIA

Latitude of 22 ° 00' N

Longitude of 77 ° 00‘ W

More than 80 % of
adult Indians not
getting
enough Vitamin D

Osteomalacia & Rickets are the most common
disorders due to Vitamin D deficiency in India
Osteomalacia present in 35.3% adults with Vitamin D
deficiency1
Rickets present in 30.3 % Indian infants with
25(OH)D <10ng/ml.2
 1. Indian J Med Res. 2008;127:219-228.
 2. Indian J Med Res. 2011;133:267-273

Softening of bones due to insufficient
vitamin D, or problems with metabolism of
this vitamin.
Osteomalacia in children is known as
Rickets.
Signs & Symptoms
 Bone Weakness
 Bone Pain
 Muscle Weakness

Osteomalacia
Osteoporosis
Weakening of Bones
In osteoporosis, bones become weak, fragile and
brittle due to loss of minerals like calcium and get
fractured more easily than normal bone.
1 out of 8 males & 1 out of 3 females in India suffer
from Osteoporosis

Normal Bone Osteoporosis

Osteomalacia
Osteoporosis

↑ risk &
Muscle weakness
Rate of Fall ↑ Risk of #
Over 90% of Fractures occur after fall and fall rate
increases due to poor muscle strength and function.1
Adequate dose of Vitamin D found to be useful in ↓
of persistent non specific pain & Fractures
 Medicographia. 2010;32(4):384-390

Osteomalacia Osteoporosis

Physiology Abnormal bone building Degeneration of built bone

Occurrence Adults Elderly

Muscle Weakness Frequent fractures
Symptoms
Bone Weakness & Pain Loss on height (due to compression of spine

Bone softening
Complications Results in bone fragility & fractures
Bone bending

Can be prevented by Ca &
Prognosis Cannot be prevented. Can only be treated
Vitamin D supplements

Outcome Osteoporosis Fractures

Musculoskeletal disorders
 Low back pain, joint pain
Fatigue and Muscular Weakness
Increased susceptibility to infections
It thus adversely effects Quality of Life
[QOL].

Is it common in adults or children?

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 Vitamin D Receptor [VDR].

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.

Vitamin D3 and D2 (made in skin or ingested) are
transported to liver and metabolised to 25(OH)D
 25(OH)D is the major circulating form
Further hydroxylation occurs in kidney to form highly
biologically active 1,25(OH)2D that promotes
 Absorption of calcium and phosphate from small intestine
 Extracellular calcium homeostasis
 Mineralisation of skeleton

(DeLuca and Zierold 1998)

 Vitamin D3 is not secreted
by a classical endocrine
gland - the active form of
the hormone is released
from the kidney - and
acts at distant sites or
locally.
 Each of the forms of
vitamin D is hydrophobic,
and is transported in blood
bound to carrier proteins.
 Only remains in a free
form in the circulation and
has a serum t1/2 of about 5
hours, for a small
proportion of vitamin D.

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 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, 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

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 were followed, their 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

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,
24.1% of the participants were vit D deficient
Highest prevalence in african american
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.

Traditionally: regulation of calcium homeostasis and
bone metabolism

 More recently Vitamin D is known to
modulate immune function in humans and
affect a wide-range of diseases, including
autoimmune disorders, cancer, metabolic
syndrome
– suppresses (overaggressive) reactions
 Type 1 diabetes prevented by 1,25-(OH)2D in animal
models with some evidence for protective effect in
humans / only a few studies published to date.

 Vitamin D facilitates the
intestinal absorption of
calcium by stimulating the
expression of a number of
proteins involved in
transporting calcium from
the lumen of the intestine,
across the epithelial cells
and into blood.
 Calcium absorption is
transported across the
epithelial cell, greatly
enhanced by the carrier
protein calbindin, synthesis
of which is totally
dependent on vitamin D.

 The adjoining figure shows
expressed Calbindins and
how they facilitate transport
of Calcium through the
membranes.
 In the absence of vitamin D,
dietary calcium is not
absorbed efficiently.
 Vitamin D also plays an
important part in regulating
the proliferation and
differentiation of both types
of bone remodeling cells -
those responsible for bone
breakdown and those that
reform the bone anew…and
more.

 Net result is: Calcium
absorption and
remodeling….outweighs
resorption

Vitamin D deficiency
 Abnormal motor performance, ↑ body sway and
quadriceps weakness reported for 25OHD < 20-30
nmol/L (Glerup 2000, Dhesi 2002)
 An independent predictor of falls in older women in
residential care (Flicker 2003)
 Linked with falls and fractures in elderly men and
women (Pfeifer 2000, Bischoff 2003, Flicker 2005).

Aim: to determine if vitD supplementation (D2) reduced
falls in older people in residential care, not classically
vitD deficient
RCT, two years duration
 60 hostels, 89 nursing homes across Australia, 625 residents (mean
age 83.4yr),
 25OHD 25-90nmol/L
↓ falls by 27% - 37%
Estimated that 8 people need to be treated to prevent 1
fall/yr

Flicker 2005

Pivotal trial relating fracture reduction in high risk
group: 800 IU D3 for 18 mo
 41% ↓ hip fracs elderly women in residential care (Chapuy NEJM
1992)
389 people from community:
 benefit from daily Ca (500mg) + vitD (700 IU) on bone loss & frac
(Dawson-Hughes NEJM 1997)
Double-blind RCT oral 100,000 IU every 4mo for 5yr ↓
risk of first hip, wrist, forearm, vert frac in 2686 people
from community by 33% (Trivedi, BMJ 2003).

One meta-analysis concluded vitD (Papadimitopoulos
Endocr Rev 2002)
 ↓ vertebral frac risk 37% (RR 0.63; 95%CI 0.45-0.88)
 but no sig ↓ in non-vert fracs (RR 0.77; 0.57-1.04)
More recent meta-analysis showed vitD (Bischoff-Ferrari
JAMA 2005)
 ↓ hip frac (RR=0.74, 0.61-0.88) and
 ↓ non-vert frac (RR=0.77, 0.68-0.87)

Greatest benefits:
 High-risk vitamin D-deficient patients, with ↓BMD
Unlikely that supplementation effective in vitamin D
replete individuals but optimal 25OHD levels unknown:
thresholds 50-110 nmol/L reported (Parfitt 1990, Mithal
2000)
 Vitamin D examined in fracture prevention trials but
differences in baseline PTH and 25OHD make comparisons
difficult
 Adequate calcium AND vitamin D likely to be required to
reduce fracture risk

Low 25OHD

↓ Muscle strength ↓ Mineralisation ↑ PTH

↑ Falls ↑ Bone fragility

↑ Fractures

A single dose of Vit D enhances immunity to
Mycobacteria
 ( Martineau et al. Am J Respir Crit Care Med 176;208-213, 2007)
Double-blind RCT in 192 healthy adult TB contacts in
London
 Single oral dose of 2.5mg Vit D vs placebo
 Measured response to BCG-lux (measures the ability of
whole blood to restrict the growth of recombinant reporter
mycobacteria in vitro)
Single dose of Vit D significantly enhances TB pts’
antimycobacterial immunity in vitro

Indonesian study in 2006
 Double-blind RCT, Vit D vs placebo (in addition to RIPE)
in 67 pts with active pulmonary TB
 Rate of sputum conversion as follows
Vit D 100%
Placebo 76% (p=0.002)
 More subjects with radiologic improvement in Vit D group

In 1986-1987, Rook and Crowle infected human
monocytes and macrophages with M. Tb. and added
1,25D3, which triggered significant antimicrobial activity
 Subsequently, Toll-like receptors were discovered.
 TLRs are pattern-recognition receptors whose activation induces
expression of antimicrobial peptides
 11 subtypes of TLRs are expressed on various types of immune and
non-immune cells
 TLRs trigger direct antimicrobial activity against intracellular bacteria
as well as apoptosis, cytokine secretion, and so on

 Upregulation of macrophage 1α,25(OH)2D synthesis following administration of pharmacologic doses of vitamin D in active
Mycobacterium tuberculosis infection.
 In the granuloma both IFNγ and ligation of macrophage TLR2/1 by M. tuberculosis induces macrophage expression of 25(OH)D-1α-
hydroxylase.
 Administration of pharmacologic doses of vitamin D results in increased circulating concentrations of free 25(OH)D, which is metabolised
by upregulated 1α-hydroxylase to 1α,25(OH)2D.
 DEFENSINs are antimicrobial peptides produced by activation of TLR.

 TLR2–TLR1 stimulation results in the upregulation of the expression of Cyp27B1 and of VDR. Cyp27B1 converts inactive vitamin D
(25D3) into its active form (1,25D3).
 The intracellular pool of 25D3 is shuttled into the cell via the vitamin D binding protein (DBP). Once activated, 1,25D3 can then bind to
and activate the VDR, and induce transcription of antimicrobial factors, including the antimicrobial peptide cathelicidin (Cath.). The
cathelicidin peptide can then traffic into intracellular compartments harboring mycobacteria.
 The cathelicidin peptide has been demonstrated to kill Mycobacterium tuberculosis directly. Therefore, cathelicidin probably has an
important role in the TLR2–TLR1-mediated antimicrobial activity, but is probably not the only effector. The induction of host-defense
mechanisms by TLR2–TLR1 depends on the amount of 25D3 present in the serum.

 1,25-D3 and the VDR then together induce
the expression of the gene encoding the
human antimicrobial peptide LL-37.
 Vitamin D3 enters the systemic circulation
and is converted to 25-D3 by the liver.
 Circulating monocytes are activated by
TLR2/1 agonists present on specific
microbes.
 The genes encoding VDR and CYP 27B1
are induced. CYP27B1 converts 25-D3 from
the circulation to 1,25-D3, joins with the
VDR and activates the gene encoding LL-
37, leading to an increase in cellular LL-37
and enhanced microbicidal activity of the
phagocyte.
 Nature Medicine - 12, 388 - 390 (2006)

May influence both incidence and mortality
 Linked with GI cancer, prostate and breast cancers,
lymphomas, endometrial and lung cancers
Vitamin D receptors[VDR] found in malignant
melanoma cells and myeloid leukemia cells
 1,25(OH)2D inhibited melanoma cell proliferation and
induced myeloid cell differentiation

Altered vitamin D &calcium homeostasis may play a role
in development of type 2 diabetes
Low serum levels of 25(OH)D = impaired pancreatic β
cell function & insulin resistance
High calcium intake is inversely associated with body
weight
Daily intake of >1,200 mg calcium & >800IU vitamin D -
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

• 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

• 50 COPD >70 year patients with a history of
exacerbations were assigned to receive a monthly dose of
vitamin D [100,000 IUs (international units) of vitamin
D] or placebo.
• All patients participated in a pulmonary rehabilitation
program for 3 months.
• At the beginning and again at the completion of the
rehabilitation program, peripheral and respiratory muscle
strength, exercise capacity and vitamin D levels were
measured.
• Patients were also asked to complete a quality of life survey
both before and after rehabilitation.

• At the end of the study, researchers found that patients
treated with vitamin D had a significant
• improvement in exercise capacity and respiratory muscle
strength compared to those in the placebo group.
• The genetic association of VDR with COPD may be
mediated by effects on macrophage activation, since VDR
relates to FEV1, and affects macrophage activation.
• Thorax 2011;66:205-210 , Vitamin D-binding protein contributes
to COPD by activation of alveolar macrophages by A M Wood et
al.

• Respiratory epithelial cells constitutively activate vitamin
D and are capable of creating a microenvironment that
has high levels of active form of the vitamin.
• Activation has effects that include up-regulation of the
cathelicidin antimicrobial peptide gene and the toll-like
receptor, co-receptor.
• Viral infection leads to increased activation of vitamin D
and further increases in cathelicidin mRNA.
• Local vitamin D activation might be an important
component of host defense.
• J Immunol. 2008 November 15; 181(10): 7090–7099.

Recent association studies demonstrating a significant inverse
correlation between the serum 25D level and an increase in components
of the human metabolic syndrome
Mortality causes First author Year Ref.
All causes Melamed 2008 Arch Intern Med
168:1629
Dobnig 2008 Arch Intern Med
168:1340
Cardiovascular Kim 2008 Am J Cardiol
disease 102:1540 (34)

Wang 2008 Circulation 117:503

Kendrick 2009 Atherosclerosis
205:255
Hypertension Judd 2008 Am J Clin Nutr
87:136
BMI Looker 2008 Am J Clin Nutr
88:1519 (14)

Insulin resistance Liu 2009 J Nutr 139:329

Wu 2009 J Nutr 139:547

Supplementation dosage and safety

Vitamin D insufficiency, 25(OH)D levels <30ng/ml is prevalent,
worldwide, especially in Middle East and South Asia. 2

J Am Coll Cardiol. 2008;52:1949–1956.
Osteoporos Int. 2010 Jul;21(7):1151-4.

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

Age Children Men Women Pregnancy lactation
Birth-13 5mcgs
yrs =200IU
14-18yrs 5mcgs 5mcgs 5mcgs 5mcgs
=200IU =200IU =200IU =200IU
19-50 5mcgs 5mcgs 5mcgs 5mcgs
Yrs =200IU =200IU =200IU =200IU
51-70 10 mcg 10 mcg
Yrs =400 IU =400 IU
71+ 15 mcg 15 mcg
=600 IU =600 IU

100 I.U./day of Vitamin D(3) increases circulating
25(OH)D by 1 ng/ml when taken for 2 months
 If the typical serum 25 (OH)D level in Indians is 10 ng/ml…
 And if the target serum 25 (OH)D level is 30 ng/ml…
Patients would require about 2000 IU/Day or 60000 IU per month
50-60% fractures can be reduced at ~30 ng/ml serum Vitamin D.1
 1. Alt Med Rev. 2008;13(1):21-33.

To raise Serum 25-
(OH)D by 1 ng./ml. [2.5
nmol / L] one needs
100 additional i.u. / day
of vitamin D3
 Hence, to raise a
patient’s Vitamin D level
from 15 to 30 ng. / ml.;
there will be an
additional requirement
of 1500 i.u./ day.
 Great inter-patient
variability in Cmax
levels, too.

With oral vitamin D supplements, serum levels can be
expected to plateau after 3-4 months.
Among patients with osteoporosis, check 25-OH-D levels
at baseline and 3 months after initiation of vitamin D
supplementation.
Vitamin D3 is the preferred supplement for adults.
Calcitriol (1,25-dihydroxyvitamin D) has a narrow safety
index and should not be used for routine
supplementation.

Vitamin D deficient ( < 10 ng /ml) population:
 Prevention of Osteoporosis:
60,000 IU (1gm Sachet /Month)

In Osteomalacia, treatment of osteoporosis
 60,000 IU (1 gm sachet )/week* 8 weeks
Followed by 60,000 IU (1 gm Sachet ) /month

Dose safe to be used, upto:
 Pediatrics 0 – 12 months – 1000 IU / Day
 All others – 2000 IU / Day

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

Routine screening / Annual testing of 25(OH)D
Rectify deficiency / insufficiency
Maintain levels through a patient-specific combination
of diet, supplementation, and sun exposure
25(OH)D closely reflects total amount of vit D produced
in the skin and from diet

In the elderly, to maintain recommended levels, if not
getting enough sun exposure to maintain vitamin D
levels :
 1000 - 2000 IU / day or
 60,000 IU monthly OR MORE

‘…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

“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

Depends on:
 Age
 Amount of vitamin D obtained from diet
 Skin darkness
 Sunshine intensity

 Q. 1 What is Vitamin D?
(a) Fat Soluble vitamin
(b) Hormone necessary for the body
(c) Water Soluble vitamin
(d) Both (a) & (b)

 Q. 2 Conversion of Vitamin D3 to 25(OH) vitamin
D3 takes place in the
(a) Liver
(b) Heart
(c) Kidney
(d) All of the above

 Q. 3 The active form of Vitamin D is
(a) Cholecalciferol
(b) 25(OH) vitamin D3
(c) Ergocalciferol
(d) Calcitriol

 Q. 4 What is the optimum level of Vitamin D in the body?
(a) 10 ng/ml
(b) 20 ng/ml
(c) > 30 ng/ml
(d) None of the above

 Q. 5 What is vitamin D Deficiency
(a) High level of Vitamin D in the Body
(b) Low level of Vitamin D in the Body
(c) Optimum level of Vitamin D in the Body
(d) None of the above

 Q. 6 How many Indians have Vitamin Deficiency?
(a) 20%
(b) 30%
(c)50%
(d) More than 80%

 Q. 7 Vitamin D has the following actions on the body?
a) Increases bone mineralization
b) Inhibits PTH secretion
c) Increase calcium absorption from intestine
d) All of the above

 Q. 8 What are Osteoblasts?
a) Cells which help bone formation
b) Cells which help bone resorption
c) Both (a) &(b)
d) None of the above

 Q. 9 Vitamin D Deficiency is associated with ?
a) Osteomalacia
b) Musculoskeletal Disorders
c) Osteoporosis & Fractures
d) All of the above

 Q. 10 What is Osteomalacia?
a) Softening of bones due to Vitamin D Deficiency
b) Breaking of bones
c) Indigestion

 Q. 11 Rickets occur commonly in?
a) Pregnant Women
b) Children
c) Adults
d) All of the above

 Q. 12 What is Osteoporosis?
a) Disease caused due to iron deficiency
b) Disease caused by bacterial infection
c) Disease in which bones become fragile resulting in fractures

 Q. 13 What is the correct statement?
a) Vitamin D Deficiency also affects Musculoskeletal health
b) Ca & Vitamin D Deficiency can cause fractures
c) Vitamin D supplements can cause fractures
d) Both (a) & (b)

 Q. 14 What are the advantages of Vitamin D oral supplement
Vs. injection?
a) Higher absorption of Vitamin D with oral supplement
b) Better safety profile with oral supplement
c) Both (a) & (b)

Osteomalacia
Muscloskeletal disorders
Osteoporosis
Fracture

Dosage:
1 sachet/week for 8-12 weeks, followed by 1 sachet every month

Low back pain
Joint pain
Osteomalacia
Perimenopausal osteoporosis

Dosage:

Rickets

Dosage:

Most currently available supplements contain
Calcium (500 mg)+ Vitamin D (500-800IU)
But in Indians ....... High prevalence of Vitamin
Deficiency (25 (OH)D ~10 ng/ml)

 To achieve Sufficiency (target 25 (OH)D level =
30 ng/ml)… patients would require 2000
IU/Day (60,000 IU/month)
 Existing products would increase vitamin D by
only 5-8 ng/ml

If you want to convey more info

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

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.

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)

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

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

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)

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
insulin-like growth factor-I (IGF-I)
Cui & Rohan, 2006

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
contributions

Knight, 2007

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

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

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

Is ultraviolet B irradiance inversely associated with
incidence rates of endometrial cancer: an ecological
study of 107 countries.
Mohr, et al, 2007

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

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

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

Prospectively collected diet and lifestyle data
 Nurses’ Health Study – 75,427 women
 Health Professionals Follow-up Study – 46,771 men
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

Summer / Fall (vs. Winter / Spring) diagnosis
associated with improved survival in:
 Colorectal cancer
 Hodgkin’s lymphoma
 NSCLC
 Breast cancer

Intermittent sun exposure associated with
increased survival following a diagnosis of
melanoma
Berwick, et al., 2005

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Editor's Notes