Vitamin D deficiency is of concern now a days, it has important role in skeletal and non skeletal functions of the body. Good sunlight exposure, consumption of vitamin D rich foods, chemotherapy with vitamin D and supplements of vitamin D has shown positive effect on various non skeletal diseases like cancer, diabetes, diarrhoea, tuberculosis etc. Although Indians are blessed with ample sunlight, still 70 to 100% population is suffering from the vitamin D deficiency. Vitamin D deficiency is likely to play an important role in the very high prevalence of rickets, osteoporosis, cardiovascular diseases, diabetes, cancer and infections such as tuberculosis in India. Fortification of staple foods with vitamin D is the most viable population based strategy to achieve vitamin D sufficiency. Unfortunately, even in advanced countries like USA and Canada, food fortification strategies with vitamin D have been only partially effective and have largely failed to attain vitamin D sufficiency

1. Estuti Chandra
PhD 2nd yr
PGS14RHS6342

2. VITAMIN D: PHYSIOLOGICAL FUNCTIONS
AND ITS ROLE IN NON SKELETON DISEASES
SEMINAR - II

3. Contents
1. Introduction
2. Terminology
3. Physiological functions
4. Sources of vitamin D
5. Status of vitamin D in Indian population
6. Vitamin D and non skeletal diseases
7. Conclusion
3

4. • Vitamin D has been traditionally known as anti-ricketic factor or
sunshine vitamin. Vitamin D is unique because it is a vitamin
synthesized by the body and it functions as a hormone
• Besides its pivotal role in calcium homeostasis and bone mineral
metabolism, vitamin D endocrine system in now recognized to
subserve a wide range of fundamental biological functions
• It is a steroid that regulates complex system of genomic functions and
has a role in prevention of neo plastic transformation
• Recent evidences from genetic, nutritional and epidemiological
studies link vitamin D endocrine system with diseases
• Vitamin D modulates the transcription of cell cycle proteins, which
decrease cell proliferation and increase cell differentiation of a number
of specialized cells of the body
4
Introduction

5. TERMINOLOGY
• Cholecalciferol is the naturally occurring form of vitamin D.
Cholecalciferol is made in large quantities in skin when its exposed to
sunlight (UV – B rays 290 to 310 nm)
• Calcidiol’s main importance is that it is the storage form of vitamin D.
Serum 25-hydroxyvitamin D [25(OH)D] is the most reliable indicator of
vitamin D adequacy of an individual and also depicts the status of
vitamin D stores of an individual.
• Calcitriol (1,25- dihydroxy-vitamin D) is made from calcidiol in both the
kidneys and in other tissues and is the most potent steroid hormone
derived from cholecalciferol.
5

6. Fig 1: Synthesis of vitamin D (sources: Nair and Maseeh ., 2012)

7. PHYSIOLOGIC FUNCTIONS OF VITAMIN D
Vitamin D hormone functions to increase serum
calcium concentration through 3 separate activities
First, it is the only hormone known to
induce the proteins involved in active
intestinal calcium absorption.
Furthermore, it stimulates active intestinal
absorption of phosphate.
Second, blood calcium concentrations
remain in the normal range even when an
animal is placed on a no-calcium diet.
Therefore, an animal must possess the
ability to mobilize calcium in the absence of
calcium coming from the environment, ie.
through electrolytes
Third, the distal renal tubule is responsible
for reabsorption of the last1%of the filtered
load of calcium, and the 2 hormones
interact to stimulate the reabsorption of this
last 1% of the filtered load .
Because 7 g of calcium are filtered every
day among humans, this represents a
major contribution to the calcium pool.
Again, both parathyroid hormone and the
vitamin D hormone are required.
Deluca., 2004
7

8. Non-classic Actions of
Vitamin D
Bikle., 2009
The nonclassic actions of vitamin D can be categorized into
three general effects
Regulation of
hormone
secretion
Regulation
of immune
function
Regulation of
cellular
proliferation
and
differentiation
8

9. Regulation of hormone secretion
• 1,25(OH)2D inhibits the synthesis
and secretion of PTH and prevents
the proliferation of the parathyroid
gland
PTH
• 1,25(OH)2D stimulates insulin secretion,
although the mechanism is not well defined.
VDR and calbindin-D28k are found in
pancreatic cells and studies using calbindin-
D28k have suggested that calbindin-D28k, by
regulating intracellular calcium, can modulate
depolarization-stimulated insulin release
INSULIN
• FGF23 is produced primarily by bone,
particularly by osteoblasts and
osteocytes, 1,25(OH)2D3 stimulates
this process, but the mechanism is
not clear
FGF23
9

10. Fig 2: Regulation of immune function
Regulation of immune function by 1,25(OH)2D. 1,25(OH)2D suppresses adaptive immunity
(A) by inhibiting the maturation of dendritic cells
(B)the macrophage is activated
10

11. Regulation of cellular proliferation and
differentiation
 Vitamin D secosteroids alter the growth and differentiation of numerous
normal and pathological cell types.
 The antiproliferative effects of vitamin D compounds are the basis for
important therapies such as the systemic and topical treatment of
psoriasis and the suppression of parathyroid hyperplasia in chronic
renal failure.
 Vitamin D secosteroids have been demonstrated in numerous
experimental animals to inhibit the growth of many types of cancers,
and exciting studies are in progress to explore the use of vitamin D
compounds in the treatment of human malignancies.
 Differentiation of many cell types is stimulated by vitamin D through
induction of arrays of genes and stimulation of signal transduction
pathways. Antiproliferative effects of vitamin D compounds are often,
but not always, linked to promotion of cellular differentiation.
11

12. 12
Institute of medicine ., 2010

13. Sources of Vitamin D
Food sources
• oily fish – such as
salmon, sardines
and mackerel
• eggs
• fortified fat
spreads
• fortified breakfast
cereals
• Milk and some
powdered milks
• Orange juice
supplements
• capsules
• chewable tablets
• liquids
• drop
• Cod liver oil is a
good source of
vitamin D, but in
large doses there is
a risk of vitamin A
toxicity
Non food source
• sunlight
13

14. Sunlight
Supplements
Vs

15. Puri et al ., 2008 Harinarayan et al ., 2013 Venkatesh et al., 2014
Subjects
LSES=211
USES=193
Age=6-18 yrs
Biochemical assessment
Serum calcium
Serum phosphorus
Physical activity profile
 sun exposure
% of body surface area
exposed
Time spend outdoor activity
Usage of sunscreen
Sealed borosilicate glass
ampoules containing 50 μg
of 7-DHC in 1 ml of methanol
were exposed to sunlight
hourly from 8 a.m. until 4
p.m
 The percent conversion of
7-DHC to previtamin D3 and
its photoproducts and the
percent of previtamin D3
and vitamin D3 formed was
estimated and related to
solar zenith angle
 Weather reports collected
from newspaper
Data of the subjects
collected in three continuous
intervals.
 Total 160 subjects were
identified as pre diabetes
based on inclusion and
exclusion criteria.
Age between 30 to 65 years
Subjects were assigned into
two groups based on
sunlight exposure.
 All anthropometric and
metabolic parameters were
measured and interpreted.
METHODOLOGY
15

16. Kumar et al., 2011 Shah et al., 2013 Kumar et al., 2014
 Participants 2079 low birth
weight infants born at term (>37
weeks’ gestation)
 Interventions Weekly vitamin D
supplements for six months at a
dose of one recommended
nutrient intake per day (35
µg/week).
Weekly , observed
supplementation and were
brought to the clinic monthly for
clinical examination and
anthropometric measurements
Screening of serum vitamin
D of urban adults
N= 178 , age >18yrs
Subject with 25(OH)D levels
<30ng/ml enrolled and
supplemented with oral
cholecalciferol 60,000 IU
granules
follow up the estimation
25(OH)D at 60 days.
DIVIDS children
N= 446 from the vitamin D
N=466 from the placebo,
Data collected
Anthropometry
Blood pressure
 Bone structure
Strength by quantitative
ultrasound (QUS)
Blood samples for
measurement of vitamin D
status
METHODOLOGY
16

17. Table 1. Characteristics, lifestyle and biochemical parameters of the
cohort (Mean values and standard deviations)
Parameters LSES (N=193) SD USES (N=211) SD
Serum calcium(mmol/l) 2.22 0.2 2.30 0.1
Serum phosphorus
(mmol/l)
1.48 0.25 1.35 0.22
25(OH)D (nmol/l) 34.61 ** 17.43 29.38 12.69
Daily sun exposure(%) 45 25
Body surface area
exposed (%)
28 15
Suns screen
application(%)
0 28
LSES, lower socioeconomic strata
USES, upper socioeconomic strata
Results of
Puri et al ., 2008
17

18. Table 2. Intake of food vitamin D of the LSES and USES
(Mean values and standard deviations)
18
DIET
VARIABLE
LSES(n193) USES(n211)
RDA Mean SD Mean SD
Vitamin D
(µg)
NA 1.5 1.3 2.8 1.4

19. 19
Solar zenith angle
The zenith angle is the
angle between the sun
and the vertical. The
zenith angle is similar
to the elevation angle
but it is measured
from the vertical
rather than from the
horizontal, thus
making the zenith
angle = 90° - elevation

20. Fig3: Showing the mean ± SD of the zenith angles, percent conversion of 7-
Dehydrocholesterol (7-DHC) to previtamin D3 and photoproducts, and the percentage of
previtamin D3 and vitamin D3 against time (for the study duration).
20
Results of
Harinarayana et al., 2013

21. 21
Figure 4: Graph showing the inverse correlation between the 25 (OH ) D levels
and latitude (r = -0.48; p < 0.0001) from various studies conducted in the
country .

22. 22
Fig 5: The 25 (OH ) D levels of various studies from India along with latitude and
location from various studies conducted in the country

23. pre diabetic group sunlight exposure per diabetic group
Male(43) Female (37 ) Male(49) Female (31) P Value
Hypertension
Primary 22(55.1%) 9(24%) 14(28%) 7(22%) p<0.05
Secondary 14(32.5%) 20(54%) 8(16.3%) 13(41.9%)
T2DM 34(79%) 28(75%) 24(48%) 17(54.8%) P<0.01
Dyslipidemia 14(32.5%) 18(48.6%) 15(30%) 13(41.9%) P>0.5(NS)
Table 3.Change in risk factors at the end of the visits between groups
Results of
Venkatesh et
al., 2014
23

24. Kumar et al., 2011 Shah et al., 2013 Kumar et al., 2015
 Participants 2079 low birth
weight infants born at term (>37
weeks’ gestation)
 Interventions Weekly vitamin D
supplements for six months at a
dose of one recommended
nutrient intake per day (35
µg/week).
Weekly , observed
supplementation and were
brought to the clinic monthly for
clinical examination and
anthropometric measurements
Screening of serum vitamin
D of urban adults
N= 178 , age >18yrs
Subject with 25(OH)D levels
<30ng/ml enrolled and
supplemented with oral
cholecalciferol 60,000 IU
granules
follow up the estimation
25(OH)D at 60 days.
DIVIDS children
N= 446 from the vitamin D
N=466 from the placebo,
Data collected
Anthropometry
Blood pressure
 Bone structure
Strength by quantitative
ultrasound (QUS)
Blood samples for
measurement of vitamin D
status
METHODOLOGY
24

25. Variables
Vitamin D group
(n=216)
Placebo group
(n=237) P value
Mean (SD) calcidiol
level (nmol/L)
55.0 (22.5%) 36.0 (25.5%) <0.001
Type of deficiency:
Severe (<25
nmol/L)
18 (8%) 92 (39%) <0.001
Mild (10-20
nmol/L)
76 (35%) 82 (35%)
Adequate (>50
nmol/L)
122 (57%) 63 (2%)
Table 4. Effect of vitamin D supplementation on plasma calcidiol*
levels at six months. Values are numbers (percentages) unless stated
otherwise
*25-hydroxyvitamin D
Results of Kumar
et al.,2011
25

26. Fig. 6. Kaplan-Meier plot of time to admission to hospital or death of infants receiving
vitamin D supplementation or placebo
26

27. Table 5. Demographic profileResults of Shah
et al., 2013
Gender (n=178) No %
Male 58 32.58
Female 120 67.42
Age (yr) Mean =32.52 SD=7.5 Min. =19 Max =62
Table 6. Vitamin D 3 25(OH)D status at baseline (n=178)
Mean SD
Plasma 25(OH)D (ng/ml) 9.36 5.19
Range 2.90-28.73
Plasma vitamin D3 status No . %
Deficiency (<20 ng/ml) 169 99.94
Insufficiency (20-30ng/ml) 9 5.06
Sufficiency (>30-40 ng/ml) 0 0.00 27

28. Fig 7. Change in 25(OH)D levels at the
end of eight weeks with 60,000 IU
vitamin D (n = 178).
Fig 8. Subjects reaching 25(OH)D level
>20 ng/ml at the end of eight weeks.
28

29. 29
Result : Kumar et al., 2014
Body mass index were lower (adjusted P = 0.003) in the vitamin D Group
[1.18 (SD 0.92)] when compared with the placebo [1.02 (SD 0.91)] group
as a result of slightly lower weight and greater height.
The vitamin D group also had lower thigh circumference, arm muscle
area and slightly lower midupper arm circumference.
There were no group differences in body fat percentage, bone QUS or
blood pressure and few differences in motor development measures.
Vitamin D supplementation to lowbirth weight infants in infancy resulted
in children being thinner at age 36 years but no differences in functional
outcomes.

30. 30
Status of vitamin D in India Ritu and Gupta .,2014

31. Table 7. Status of vitamin D in Indian
Infants
31

32. Table 8: Vitamin D status of expecting and
lactating mothers in India
32

33. Table 9.Vitamin D status of professionals in
India
33

34. Vitamin D and non
skeletal diseases
34

35. 35
LIST OF NON SKELETAL DISEASES
Cancers
Diabetes
 Autism
Cardiovascular Diseases
Chronic Kidney Diseases
Pulmonary Diseases: Asthma, COPD ,
Infections
Tuberculosis

36. Vitamin D and Diabetes
36

37. Mechanism of action vitamin D in diabetes
Other potential mechanisms associated with vitamin D and diabetes include improving
insulin action by stimulating expression of the insulin receptor, enhancing insulin
responsiveness for glucose transport, having an indirect effect on insulin action potentially
via a calcium effect on insulin secretion, and improving systemic inflammation by a direct
effect on cytokines.
β-cell in the pancreas that secretes insulin has been shown to contain VDRs as well as the 1
alpha hydroxylase enzyme.
Vitamin D deficiency leads to reduced insulin secretion. Supplementation with vitamin
D has been shown to restore insulin secretion in animals.
An indirect effect on insulin secretion, potentially by a calcium effect on insulin secretion.
Vitamin D contributes to normalization of extracellular calcium, ensuring normal calcium flux
through cell membranes; therefore, low vitamin D may diminish calcium’s ability to affect
insulin secretion.
37

38. Athanassiou et al ., 2013 Venkatesh et al., 2014 Laway et al., 2014
Glycosylated haemoglobin
(HbA1c) and 25(OH)D3 levels
were measured in a group of
120 diabetes mellitus type 2
patients.
The same measurements
were performed in a group of
120 control subjects of the
same age and sex.
25(OH)D3 was measured by
radioimmunoassay and
glycosylated haemoglobin
(HbA1c) was measured by
high-performance liquid
chromatography.
Data of the subjects collected
in three continuous intervals.
 Total 160 subjects were
identified as pre diabetes
based on inclusion and
exclusion criteria.
Age between 30 to 65 years
Subjects were assigned into
two groups based on sunlight
exposure.
 All anthropometric and
metabolic parameters were
measured and interpreted
N=102
 newly detected T2D patients
similar number of age, body
mass index (BMI) and Gender
matched healthy controls
without diabetes.
Basic information
metabolic parameters and
serum 25 hydroxy vitamin D
(25HD)
Methodology
38

39. Table 10 . 25(OH)D3 (ng/ml) (mean ± SEM), HbA1c (%) (mean ±
SEM) in the diabetes mellitus type 2 patients and controls and
statistical significance (Student’s t-test)
Subjects HbA1c (%) mean ±
SEM
25(OH)D3 (ng/ml) mean
± SEM
25(OH)D3
≤ 10 ng/ml < 20 ng/ml
Patients (n = 120)
7.2±0.18 19.26±0.94 21 (17.5%) 76 (63.3%)
Controls (n = 120)
5.1±0.05 25.48±1.02 7 (5.8%) 28 (23.3%)
Statistical
significance p < 0.001 p < 0.001 p = 0.0089 p < 0.0001
Results of
Athanassiou et
al ., 2013
number and percentage of subjects with 25(OH)D3 deficiency and insufficiency [25(OH)D3
≤ 10 ng/ml and < 20 ng/ml] in the patient and control groups and statistical significance
(chi-squared test).
39

40. Fig 9. Inverse association between 25(OH)D3 (ng/ml) and HbA1c (%) in diabetes
mellitus type 2 patients, (p = 0.008, r2 = 0.058, linear regression analysis).
25(OH)D3, 25-hydroxy vitamin D3; HbA1c, glycosylated haemoglobin
40

41. Table11. Comparative analysis between the prediabetic and sun light
exposed group
Results of
Venkatesh et
al., 2014
COMPARISION SCORE (%) P VALUE
BMI 2.95 0.0309
Blood Glucose 10.54 p<0.0001
HbA1c 11.10 P<0.0001
Systolic BP 4.81 0.0042
Diastolic BP 1.09 0.2893(NS)
Cholesterol 4.41 0.0002
HDL 1.42 0.131(NS)
LDL 0.68 0.4735(NS)
TG 4.27 0.0019
Note : data represented as percentage(%). NS- not significant at p<0.05
41

42. Results of Laway
et al ., 2014
Table 12.Clinical and biochemical parameters of cases and healthy
controls
PARAMETER CASES CONTROLS P VALUE
Age(year) 45.95±7.56 45.79±6.17 0.871
BMI(Kg/m²) 24.35±3.72 24.31±3.02 0.925
Calcium
intake(mg/day)
972.62±299.43 1452.13±390.72 0.00
Sunlight exposer(%) 13.45±5.49 13.44±5.55 0.99
FPG(mgs/dl) 190.9±36 82.86±0.5 0.000
HbA 1c(%) 8.87±1.87 5.30±0.42 0.000
Vitamin D(ng/ml) 18.81±15.18 28.46±18.89 0.000
VD sufficiency(%) 18.6 33.3 0.002
VD insufficiency(%) 14.7 28.4 0.002
VD deficiency(%) 66.7 38.2 0.002
Mild VDD(%) 38.2 27.5 0.030
Moderate VDD(%) 45.6 70.0 0.525
Severe VDD(%) 16.2 2.5 0.525
42

43. Table 13. Comparison of clinical and biochemical parameters as per severity of vitamin D
deficiency
Deficiency
PARAMETER MILD(26) MODERATE(31) SEVERE(11) P VALUE
Age 47.00±8.96 47.10±6.56 46.36±7.58 0.96
Sex(M/F) 15/11 12/19 5/6 0.36
BMI(kg/m²) 24.49±3.53 23.92±4.14 23.12±3.61 0.57
HbA 1c(%) 8.60±2.01 9.29±1.94 8.90±2.45 0.46
Calcium (mgs/dl) 9.56±0.48 9.72±0.52 9.52±0.72 0.49
Phosphorus
(mg/dl)
3.86±0.40 3.37±0.55 3.25±0.58 0.10
ALP(U/L) 246.03±79.34 278.92±100.74 257.27±42.58 0.34
VitaminD (ng/ml) 14.95±3.06 7.66±1.39 3.56±1.04 0.00
43
Values are in mean―SD unless indicated. BMI: Body mass index; ALP:
Alkaline phosphatase. M/F: Male/Female

44. Cancer, also called malignancy, is an abnormal growth of
cells. There are more than 100 types of cancer, including
breast cancer, skin cancer, lung cancer, colon cancer, prostate
cancer, and lymphoma. Symptoms vary depending on the
type. Cancer treatment may include chemotherapy,
radiation, and/or surgery.
Cancer
44

45. Process of carcinogenesis
Initiation Promotion Progression
Neoplasia initiation is essentially
irreversible changes in appropriate
target somatic cells. In the simplest
terms, initiation involves one or
more stable cellular changes arising
spontaneously or induced by
exposure to a carcinogen. This is
considered to be the first step in
carcinogenesis, where the cellular
genome undergoes mutations,
creating the potential for
neoplastic development
The transformed (initiated)
cell can remain harmless,
unless and until it is
stimulated to undergo
further proliferation,
upsetting the cellular
balance. The subsequent
changes of an initiated cell
leading to neoplastic
transformation may involve
more than one step and
requires repeated and
prolonged exposures to
promoting stimuli
the process through which
successive changes in the
neoplasm give rise to
increasingly malignant sub-
populations. Molecular
mechanisms of tumor
progression are not fully
understood, but mutations
and chromosomal
aberrations are thought to
be involved.
45

46. Mechanism of action of vitamin D in cancer
Vitamin D via VDR directly alert patterns of gene expression and
can influence the outcome between proliferation, differentiation
or apoptosis, these genomic effects can be distinguish into
classical mechanism of VDR recruitment of co-activators on
VDREs and the non classical interaction with the activated beta
catenins on the other promoters.
VDR – Vitamin D Response/Receptors
VDREs – Vitamin D Response Elements
46

47. Figure 10: The renal endocrine pathway and the extrarenal autocrine or paracrine pathway
of calcitriol synthesis.
47
The role of vitamin D in reducing cancer risk and progression, Feldman et al., 2014

48. Figure 11: Calcitriol regulation of specific signalling pathways that drive breast,
colon and prostate cancer growth.
48

49. 49
METHODOLOGY
Skinner et al., 2006 Lappe et al., 2007 Garland et al.,2007
 data pooled from two
cohort study
1). Nurses’ Health Study(F)
2). Health Professionals
Follow-up Study(M)
N= 121,701(F) & 51,529(M)
Questionnaires : dietary
assessment , smoking history ,
Pancreatic Cancer Case and
Death Ascertainment and
other information(in period of
two years )
 Statistical Methods
Study period -4 yr
N = 1,179
Mean age - 66 yr
87.5% finished trial
 Baseline serum 25(OH)D:
29 ± 8 ng/ml
 Three treatment groups:
1). Vitamin D3 (1,100 IU/day)
and calcium (1450 mg/day)
2). Calcium (1,450 mg/day)
3). Placebo
 Outcome: progression
towards all cancers (mainly
breast, lung and colon)
A literature search for all
studies that reported risk by of
breast cancer by quantiles of
25(OH)D identified two
studies with 1760 individuals.
Data were pooled to assess
the dose–response association
between serum 25(OH)D and
risk of breast cancer.

50. 50
Table 14. Age-standardized characteristics of men in the HPFS in 1986 and
women in the NHS in 1984 by total daily energy adjusted vitamin D intake
Variable Total daily vitamin D intake (IU)
<150 150-299 300-449 450-599 ≥600
HPFS (1986)
HPFS - Health Professionals Follow-up Study
MET- metabolic equivalent task.
No .men 10,783 15,321 7,528 5,062 8,077
Age (y) 52 54 54 55 56
Daily vitamin D(IU) 100 214 368 521 893
Body mass index(kg/m²) 25 25 25 25 25
Height (m) 1.8 1.8 1.8 1.8 1.8
Multivitamin supplement use 11% 22% 43% 79% 95%
Physical activity(METs/wk) 19 21 21 22 24
Smoking history
Current 12% 9% 9% 9% 8%
Former 45% 41% 39% 41% 42%
Never 40% 46% 48% 46% 46%
Result skinner
et al., 2006

51. 51
Table 15. Age-standardized characteristics women in the NHS in 1984 by total daily energy
adjusted vitamin D intake
Variable Total daily vitamin D intake (IU)
<150 150-299 300-449 450-599 ≥600NHS(1984)
NHS - Nurses’ Health Study , MET- metabolic equivalent task.
No .men 22,494 24,566 10,922 8,104 9,341
Age (y) 49 50 51 51 52
Daily vitamin D(IU) 95 212 368 522 829
Body mass index(kg/m²) 24 24 24 24 24
Height (m) 1.6 1.6 1.6 1.6 1.6
Multivitamin supplement
use(%)
8 17 56 88 94
Physical activity(METs/wk) 12 14 15 16 17
Smoking history
Current(%) 30 22 22 21 20
Former(%) 30 31 32 34 36
Never (%) 40 46 46 45 44

52. 52
Table16.: Total daily vitamin D intake and the risk for pancreatic cancer in the HPFS
and NHS cohorts
•All RRs are adjusted for age (1-year intervals) and total energy intake (kcal)
•Multivariate RRs additionally adjusted for cigarette smoking (current, former,
never),BMI
•Multivariate + multivitamin RRs are additionally adjusted for the use of multivitamin
supplements

53. 53
Table 17. vitamin D intake from food sources alone and the risk of pancreatic cancer in the
HPFS and NHS cohorts
All RRs were adjusted for age (1-year intervals) and total energy intake (kcal).
Multivariate RRs additionally adjusted for cigarette smoking (current, former,
never), body mass index.

54. 54
Year 1-4 year 2-4
Site Placebo
(n=288)
Calcium
only
(n=445)
Vit D &
calcium
(n=446)
Placebo
(n=266)
Calcium
only
(n=416)
Vitamin D
and
calcium
(403)
Breast(n) 8 6 5 7 6 4
Colon(n) 2 0 1 2 0 0
Lungs(n) 3 3 1 3 2 1
Lymph(n) 4 4 2 4 4 2
uterus 0 2 1 0 1 0
Other 3 2 3 2 2 1
Total(%) 20(6.9) 17(3.8) 13(2.9) 18(6.8) 15(3.6) 8(2.0)
Results of Lappe et al.,2007
Table 18. Cancers by primary site and by treatment assignment
n; percentage of total randomly assignment in each group who developed cancer
in parentheses

55. Fig .12 . Kaplan-Meier survival curves (ie, free of cancer), The survival at the end of study
for the Ca+D group is significantly higher than that for placebo, by logistic regression.
Sample sizes –
•placebo group-288
•calcium-only (Ca-
only) group- 445
•calcium plus
vitamin D (CaD)
group 446
55

56. Sample sizes –
• placebo group-
266
•calcium-only (Ca-
only) group -416
• calcium plus
vitamin D(CaD)
group- 403
logistic regression.
Fig 13. Kaplan-Meier survival curves (ie, free of cancer) for the 3
treatment groups randomly assigned in the cohort of women who
were free of cancer at 1 y of intervention (n 1085).
56

57. Fig 14. Dose–response gradient of risk of breast cancer according to prediagnostic
serum 25-hydroxyvitamin D concentration, Harvard Nurses’ Health
57
Results of Garland et al.,2007

58. Fig. 15. Dose–response gradient of risk of breast cancer according to serum
25-hydroxyvitamin D concentration, St. George’s Hospital, London, study
58

59. Fig 16. Dose–response gradient of risk of breast cancer according to serum
25-hydroxyvitamin D concentration, pooled analysis
59

60. Gaps in understanding !!!
60
 No standard in India to define vitamin D deficiency. Lack of standards can lead to
overestimation of the prevalence of the deficiency and irrational use of vitamin D
supplements
 No study to estimate how much vitamin D is adequate for Indians, who receive ample
sunlight
 No understanding on why there is enough vitamin D produced in some and not in others
even though their exposure to sunlight is the same
 No study in India to gauge how much vitamin D-producing UVB rays reach the ground
and whether air pollution blocks it.
 No study on how toxins affect the production or absorption of vitamin D in the body
 No study showing if sunscreen and skin-lightening products impair vitamin D
production

61. Conclusion
Vitamin D deficiency is of concern now a days, it has important role in skeletal
and non skeletal functions of the body. Good sunlight exposure, consumption
of vitamin D rich foods, chemotherapy with vitamin D and supplements of
vitamin D has shown positive effect on various non skeletal diseases like
cancer, diabetes, diarrhoea, tuberculosis etc. Although Indians are blessed with
ample sunlight, still 70 to 100% population is suffering from the vitamin D
deficiency. Vitamin D deficiency is likely to play an important role in the very
high prevalence of rickets, osteoporosis, cardiovascular diseases, diabetes,
cancer and infections such as tuberculosis in India. Fortification of staple foods
with vitamin D is the most viable population based strategy to achieve vitamin
D sufficiency. Unfortunately, even in advanced countries like USA and Canada,
food fortification strategies with vitamin D have been only partially effective
and have largely failed to attain vitamin D sufficiency
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