This document discusses vitamin D, beginning with an overview that while vitamin D is called a vitamin, it acts more like a hormone in the body. It describes how vitamin D is synthesized in the skin and transported to tissues where its active form binds to receptors. It then summarizes several roles and physiological functions of vitamin D related to calcium homeostasis, bone and muscle health, and potential extraskeletal effects. Finally, it provides details on vitamin D production, metabolism, and biological function, showing how vitamin D is converted to its active form in the body and its role in various health processes.

1. "Vitamin D beyond bone”
Vitamin or Vitamone???
S. Abbas Raza. M.D
Consultant Endocrinologist:
Shaukat Khanum Hospital and Research Center
National Hospital

2. Vitamin D
• Although called a vitamin...
– Vitamins must be provided from the diet because they
can’t be synthesized or the rate of synthesis is not
sufficient to maintain health
– Necessary in small amounts for normal metabolic
functioning
• Vitamin D acts more like a hormone...
– Hormones are compounds produced in one part of the
body and transported to another part of the body where
they exert a specific regulatory or functional effect

3. Vitamin D
Vitamin D3 (precursor)
Calcitriol or 1,25 dihydroxyvitamin D3
(the biologically active form)
• Characteristics consistent with hormonal functions
– Synthesized in skin
– Transported in blood to distant sites to exert its action
– Activated by a tightly regulated enzyme
– Active form binds to specific receptors in target tissues
– Receptors are found in many cells throughout the body

4. Vitamin D
Role in Health Maintenance

5. Vitamin D
Physiologic functions of vitamin D
• Maintains calcium homeostasis
• Maximizes intestinal absorption of calcium
– In vitamin D-sufficient people: 30% of calcium is
absorbed from the diet
– In vitamin D-deficient people: 10-15% of calcium is
absorbed from the diet
• Maintains phosphate homeostasis
• Deficiency results in increased production and
excretion of PTH (parathyroid hormone) or
secondary hyperparathyroidism

6. Vitamin D
Musculoskeletal Effects
• Maintenance of normal musculoskeletal function
– Skeletal muscle has receptors (VDR) for 1,25(OH)2D3
– Severe vitamin D deficiency is associated with
muscle weakness, limb pain & impaired physical
function

7. Vitamin D
Extraskeletal Effects
• Regulation of cell growth and effects on immune function
• Epidemiologic studies have shown that living at lower
latitudes is associated with a decreased risk of many
chronic diseases
• Multiple sclerosis, hypertension, and cancer of the colon, breast,
and prostate
– Since the production of vitamin D is more efficient at lower
latitudes, this may explain these interesting findings
• Some studies have shown that increasing vitamin D
intake decreases the risk of certain chronic diseases
• Diabetes, rheumatoid arthritis, hypertension, and colon cancer
Additional trials are needed to definitively determine the
role of vitamin D in these conditions

8. Vitamin D Physiology

9. Vitamin D
Vitamin D
– Vitamin D2 (ergocalciferol)
• (Pharmaceutical Form derived from Ergol found in Fungus)
– Vitamin D3 (cholecalciferol)
• (Natural Form found in food and synthesized in Skin)
• metabolites and analogues of these substances
• Vitamin D
– Precursor (sometimes referred to as a “prohormone”)
– Must be metabolized to become biologically active
• Active form of vitamin D: Calcitriol
• Vitamin D is essential for healthy bone

10. Production, Metabolism, and Biological
Function of Vitamin D
Prostate
Vitamin D3 Liver 25(OH)D3
Gland,
Skin
Breast,
D D Kidney
Salmon Colon,
Supplement Lung
Milk
Orange juice Cod liver oil 1,25(OH)2D3 1,25(OH)2D3
Calcium Blood pressure regulation
Regulation of
Homeostasis Cardiovascular Health
Cell Growth
Muscle Health Immunomodulation (prevention of
(cancer prevention)
Bone Health autoimmune diseases)
25(OH)D3=25-hydroxyvitamin D3; 1,25(OH)2D3= 1,25-dihydroxyvitamin D3.
Holick MF. Am J Clin Nutr 2004;80(suppl):1678S-88S.

11. Do we need
Vitamin D?????

12. Lessons learned in 2010 - 2011

13. Studies Published in First Quarter of 2010

14. Association between pre-diagnostic circulating vitamin D concentration and risk
of colorectal cancer in European populations: a nested case-control study
Mazda Jenab, H Bas Bueno-de-Mesquita, Pietro Ferrari, et al.
Correspondence to: M Jenab, Lifestyle and Cancer Group, International Agency for Research on Cancer, Lyon, France Jenab@iarc.fr
• Objective To examine the association between pre-diagnostic circulating vitamin D
concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in
European populations.
• Results 25-(OH)D concentration showed a strong inverse linear dose-response
association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-
defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were
associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95%
confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher
concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); 100.0
nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in
the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest
quintile (P<0.001).
Conclusions The results of this large observational study indicate a strong inverse
association between levels of pre-diagnostic 25-(OH)D concentration and risk of
colorectal cancer in western European populations. Further randomised trials are needed
to assess whether increases in circulating 25-(OH)D concentration can effectively
decrease the risk of colorectal cancer.

15. Low Vitamin D levels in Northern American Adults with
the Metabolic Syndrome
S. Devaraj1, G. Jialal1, T. Cook1, D. Siegel1,2, I. Jialal1,21 Department
of Pathology and Laboratory Medicine, University of California,
Davis, Medical Center, Sacramento, CA, USA
2
Veterans Affairs Medical Center, Mather, CA, USA
• Abstract:
Metabolic syndrome (MetS), is a constellation of cardiometabolic
disease risk factors, that affects 1 in 3 US adults and predisposes to
increased risks for both diabetes and cardiovascular disease. While
epidemiological studies show low vitamin D [(25(OH)D] levels in MetS,
there is sparse data on vitamin D status in MetS patients in North
America. Thus, the aim of our study was to examine plasma vitamin D
concentration among adults with MetS in Northern California (sunny
climate), but without diabetes or cardiovascular disease. 25(OH)D
levels were significantly decreased in MetS compared to controls. 8 %
of controls and 30% of MetS North American adult subjects were
deficient in 25(OH)D (<20 ng/ml; p=0.0236, Controls vs. MetS). There
were no significant differences between the groups with respect to
blood sampling in winter and summer months, total calcium and
phosphate, and creatinine levels. Vitamin D levels were significantly
inversely correlated with fasting glucose (r=−0.29, p=0.04) and HOMA
(r=−0.34, p=0.04). Future studies of vitamin D supplementation in
these subjects on subsequent risk of diabetes will prove instructive
with respect to potential health claims in these high risk patients with
MetS.

16. Predicted 25-hydroxyvitamin D score and incident type 2
diabetes in the Framingham Offspring Study
Enju Liu, James B Meigs, Anastassios G Pittas, Christina D Economos, Nicola M McKeown, Sarah L
Booth and Paul F Jacques 1
Received for publication July 24, 2009. Accepted for publication March 19, 2010.
• Background: Accumulating evidence suggests that vitamin D is involved in the
development of type 2 diabetes (T2D).
• Design: We used a subsample of 1972 Framingham Offspring Study
participants to develop a regression model to predict plasma 25-hydroxyvitamin
D [25(OH)D] concentrations from age, sex, body mass index, month of blood
sampling, total vitamin D intake, smoking status, and total energy intake. Using
this model, we calculated the predicted 25(OH)D score for each nondiabetic
participant at the cohort's fifth examination to assess the association between
the predicted 25(OH)D score and incidence of T2D using Cox proportional
hazards models.
• Results: A total of 133 T2D cases were identified over a 7-y average follow-up.
In comparison with individuals in the lowest tertile of the predicted 25(OH)D
score at baseline, those in the highest tertile had a 40% lower incidence of T2D
after adjustment for age, sex, waist circumference, parental history of T2D,
hypertension, low HDL cholesterol, elevated triglycerides, impaired fasting
glucose, and Dietary Guidelines for Americans Adherence Index (DGAI) score
(hazard ratio: 0.60; 95% CI: 0.37, 0.97; P for trend = 0.03).
• Conclusions: Our findings suggest that higher vitamin D status is associated
with decreased risk of T2D. Maintaining optimal 25(OH)D status may be a
strategy to prevent the development of T2D.

17. Studies Published in Second Quarter of 2010

18. Vitamin D Deficiency and Coronary Artery Calcification in Subjects with
Type 1 Diabetes
Received May 11, 2010. Accepted October 11, 2010.
Objective: To examine the relationship between serum levels of 25-
hydroxyvitamin D (25[OH]D), polymorphisms in vitamin D associated
genes, and the presence and progression of coronary artery
calcification (CAC) in adults with type 1 diabetes.
• Research Design and Methods: This prospective study included 374
non-Hispanic white (NHW) subjects with type 1 diabetes (mean age
40 ± 9 years; 46% male). CAC was measured at the baseline, three
and six-year follow-up visits by electron beam CT. Serum 25[OH]D
levels were measured by liquid chromatography tandem mass
spectrometry at the 3-year visit.
• Results: Normal (> 30 ng/ml), insufficient (20-30 ng/ml), and deficient
(< 20 ng/ml) 25-OHD levels were present in, respectively, 65%, 25%,
and 10% of the individuals with type 1 diabetes. 25[OH]D deficiency
was associated with the presence of CAC at the 3-year visit, odds
ratio (OR) = 3.3 (95% CI 1.6-7.0), adjusting for age, sex, and hours of
daylight. In subjects free of CAC at the 3-year visit, 25[OH]D
deficiency predicted development of CAC over the next 3 years in
those with the vitamin D receptor M1T CC genotype (OR=6.5 [1.1-
40.2], p=0.04), than those with the CT or TT genotype (OR=1.6 [0.3-
8.6], p=0.57).
• Conclusions: Vitamin D deficiency independently predicts prevalence
and development of coronary calcification, a marker of coronary artery
plaque burden, in individuals with type 1 diabetes.

19. Vitamin D and pregnancy: An old problem
revisited
• Vitamin D has historically been considered to play a role solely in bone
and calcium metabolism.
• Human disease associations and basic physiological studies suggest
that vitamin D deficiency is plausibly implicated in adverse health
outcomes including mortality, malignancy, cardiovascular disease,
immune functioning and glucose metabolism.
• There is considerable evidence that low maternal levels of 25
hydroxyvitamin D are associated with adverse outcomes for both
mother and fetus in pregnancy as well as the neonate and child.
• Vitamin D deficiency during pregnancy has been linked with a number
of maternal problems including infertility, preeclampsia, gestational
diabetes and an increased rate of caesarean section. Likewise, for the
child, there is an association with small size, impaired growth and
skeletal problems in infancy, neonatal hypocalcaemia and seizures,
and an increased risk of HIV transmission. Other childhood disease
associations include type 1 diabetes and effects on immune tolerance.
The optimal concentration of 25 hydroxyvitamin D is unknown and
compounded by difficulties in defining the normal range.

20. Studies Published in Third Quarter of 2010

21. Vitamin D is vital in activating human defences and low levels suffered by
around half the world's population may mean their immune systems' killer T
cells are poor at fighting infection
• The researchers found that immune systems' killer cells, known as T
cells, rely on vitamin D to become active and remain dormant and
unaware of the possibility of threat from an infection or pathogen if
vitamin D is lacking in the blood.
• "When a T cell is exposed to a foreign pathogen, it extends a signaling
device or 'antenna' known as a vitamin D receptor, with which it
searches for vitamin D," said Carsten Geisler of Copenhagen
University's department of international health, immunology and
microbiology, who led the study.
• "This means the T cell must have vitamin D or activation of the cell will
cease. If the T cells cannot find enough vitamin D in the blood, they
won't even begin to mobilize."
• Scientists have known for a long time that vitamin D is important for
calcium absorption, and that there is a link between levels of the
vitamin and diseases such as cancer and multiple sclerosis.
• "What we didn't realize is how crucial vitamin D is for actually
activating the immune system -- which we know now," Geisler wrote in

22. Vitamin D and cardiovascular disease risk: emerging evidence
Swales, Heather Ha; Wang, Thomas Jb
Current Opinion in Cardiology:
September 2010 - Volume 25 - Issue 5 - p 513–517
• Purpose of review: Vitamin D deficiency is common throughout the world, with
a particularly high prevalence in northern latitudes and colder climates.
Although the best known sequelae of vitamin D deficiency involve the
musculoskeletal system, a growing body of evidence suggests that vitamin D
status may influence cardiovascular health as well. This review focuses on
recent studies linking vitamin D and cardiovascular disease risk, emphasizing
the potential relevance to primary prevention.
• Recent findings: There is strong experimental evidence that vitamin D status
may influence cardiovascular structure and function. The number of clinical
studies has steadily grown in recent years, with the largest number comprising
observational studies showing associations between low vitamin D status, the
presence of various cardiovascular risk factors, and adverse cardiovascular
outcomes. A few small, randomized, controlled studies have been published,
but these have been largely inconclusive.
• Summary: Despite substantial clinical evidence linking vitamin D deficiency
with increased cardiovascular risk, it remains to be established whether this
represents a causal association. Further study is needed with prospective,
randomized controlled trials before vitamin D supplementation can be routinely
recommended for the primary or secondary prevention of cardiovascular
disease.

23. Maternal Vitamin D Status in Gestational Diabetes
Mellitus
Nutrition in Clinical Practice, 10/27/2010 Soheilykhah S et al.
• These results suggested that rates of vitamin D
deficiency are higher among women with
impaired glucose tolerance/gestational diabetes
mellitus, and the relationship between vitamin D
status and glucose tolerance in pregnancy
needs further study.

24. Studies Published in Last Quarter of 2010

25. Vitamin D status, physical performance and body mass in patients
surgically cured for primary hyperparathyroidism compared with healthy
controls
Clinical Endocrinology, 12/29/2010
Amstrup AK et al. –
Low plasma 25–hydroxyvitaminD (25OHD) levels, reduced muscle
strength and increased body mass index (BMI) are well–known
characteristics of primary hyperparathyroidism (PHPT).
Mechanisms for low 25OHD levels, increased BMI and potential
changes after parathyroidectomy are unknown.
Muscle strength is reported to increase following surgical cure, but
whether the improvement corresponds to healthy controls'
performances remains largely unknown.
Following cure, 25OHD levels are normalized suggesting 25OHD
insufficiency is not a constitutional characteristics in patients with
PHPT. Increased BMI seems to be sustained. Whether this is caused
by decreased muscle strength or reduced muscular performance
causes adiposity needs further investigations.

26. Vitamin D for the management of multiple sclerosis
• Multiple sclerosis is an illness in which the myelin sheaths around the nerves of the brain and
spinal cord are damaged, affecting the ability of nerve cells to communicate with each other.
• A wide range of clinical presentations and neurological symptoms can occur with the disease, and
these can progress to physical and cognitive disability often with a variable clinical course.
Although very little is known about the mechanism and causes of this disease genetic,
immunologic and environmental factors have all been implicated.
• Studies have shown a characteristic geographical pattern of disease distribution both in
occurrence and progression, which appear to be correlated with sun light exposure and lack of
vitamin D and are considered to be predisposing factors for MS.
• Vitamin D deficiency is said to affect the general well being of patients with MS
and is also associated with poorer neurologic outcomes.
• People suffering with MS are usually given regular vitamin D preparations after assessment of
their serum levels of vitamin D.This review sought to evaluate the benefits and harms of this
Vitamin D administration to people of MS.The current level of evidence from this review is based
on only one trial with potential high risk of bias, which does not at present allow confident
decision-making about the use of Vitamin D in MS.
• The review authors suggest that until further high-level evidence is available, clinicians should
continue to follow local guidelines when administering vitamin D to people with MS.
• However, the question of the safety and effectiveness of Vitamin D in people of MS remains
unanswered.
• Further research, consisting of well-designed and adequately-powered randomised controlled

27. Vitamin D and the heart: Why we need large-scale clinical
trials
Cleveland Clinic Journal of Medicine, 12/27/2010
Manson JE et al.
• Although vitamin D supplementation appears to be a
promising intervention for reducing risks of cancer,
cardiovascular disease, and other chronic diseases,
existing evidence on its benefits and risks is limited
and inconclusive.
• Recruitment is now under way for the Vitamin D and
Omega–3 Trial (VITAL), the first large–scale
randomized clinical trial of these nutritional agents for
the primary prevention of cancer and cardiovascular
disease

28. Optimal use of vitamin D when treating osteoporosis
Current Osteoporosis Reports.
van den Bergh JPW et al.
12/21/2010
This paper discusses several aspects with regard to vitamin D status and supplementation when
treating patients with osteoporosis in relation to risks and prevention of falls and fractures.
• Methods
Discussed several aspects with regard to vitamin D status and supplementation
• Results
Based on evidence from literature, adequate supplementation with at least 700 IU of vitamin D,
preferably cholecalciferol, required for improving physical function and prevention of falls and
fractures
Additional calcium supplementation may be considered when dietary calcium intake is below 700
mg/day
For optimal BMD response in patients treated with antiresorptive or anabolic therapy, adequate
vitamin D and calcium supplementation also necessary
Monitoring of 25(OH)D levels during follow-up and adjustment of vitamin D supplementation
should be considered to reach and maintain adequate serum 25(OH)D levels of at least 50
nmol/L, preferably greater than 75 nmol/L in all patients

29. Role of Vitamin D in Blood Pressure Homeostasis
American Journal of Therapeutics
11/22/2010 -Feneis JF
• Ten observational studies and nine randomized control
trials concerned with the association between vitamin
D and blood pressure were identified and analyzed.
• Of these, eight observational studies and three
randomized control trials supported an inverse
association between vitamin D and blood pressure.
• Current observational studies strongly support an
inverse association between vitamin D and blood
pressure, but this association has yet to be
convincingly supported with randomized control trials.

30. Diverse associations of 25-hydroxyvitamin D and 1,25-
dihydroxy-vitamin D with dyslipidaemias
Journal of Internal Medicine,
Karhapaa P et al. – 12/13/2010 Clinical Article
• Low levels of active vitamin D are associated with low
high–density lipoprotein cholesterol (HDL–C) levels,
whereas low levels of the storage form 25–D are
associated with high levels of total–C, low–density
lipoprotein cholesterol and triglycerides.
• The findings may provide new insights into the
understanding of the link between vitamin D deficiency
and cardiovascular disease.

31. Vitamin D and the vascular sensitivity to angiotensin II in
obese Caucasians with hypertension
Journal of Human Hypertension, 12/14/2010
Vaidya A et al.
• The findings demonstrate a positive association
between 25(OH)D and the vascular sensitivity to AngII
in obese hypertensives, and further suggest that
vascular renin–angiotensin system (RAS) activity may
progressively increase when 25(OH)D deficiency
occurs in obesity.
• Future studies to evaluate the effect of vitamin D
supplementation on vascular RAS activity in obesity
are needed.

32. Serum 25-hydroxyvitamin D and parathyroid hormone are independent
determinants of whole-body insulin sensitivity in women and may
contribute to lower insulin sensitivity in African Americans
American Journal of Clinical Nutrition, 12/06/2010
Alvarez JA et al. –
• 25(OH)D and PTH concentrations were independently
associated with whole–body insulin sensitivity in a
cohort of healthy women, which suggested that these
variables may influence insulin sensitivity through
independent mechanisms.
• Furthermore, ethnic differences in 25(OH)D
concentrations may contribute to ethnic differences in
insulin sensitivity.

33. Is there any thing else associated with
Vitamin D Deficiency ??????
• D.M Type 2
• D.M Type 1
• Metabolic Syndrome
• Polycystic Ovarian Disease
• Prostate Cancer
• Breast Cancer
• Immune Systems
• Myocardial Infarction
• Arthrosclerosis
• Etc….

34. Astonishing Figures from the subcontinent

35. Astonishing Figures from the subcontinent
• Vitamin D deficiency is prevelant both in
Urban and Rural areas.
• Ranges any where from 40 – 70 % of
Population
• Equally distributed in both adults and
Children.

36. High prevalence of vitamin D deficiency among
pregnant women and their newborns in northern India
• Alok Sachan, Renu Gupta, Vinita Das, Anjoo Agarwal, Pradeep K Awasthi and Vijayalakshmi
Bhatia 1 From the Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical
Sciences, Lucknow, India (AS, PKA, and VB), and Queen Mary’s Hospital, King George’s Medical
University, Lucknow, India (RG, VD, and AA)
• Background: Vitamin D deficiency is prevalent in India, a finding that is unexpected in a tropical country
with abundant sunshine. Vitamin D deficiency during pregnancy has important implications for the
newborn and infant. There are few data from India about the prevalence of hypovitaminosis D in
pregnancy and in the newborn.
• Objective: Our aim was to determine the prevalence of osteomalacia and hypovitaminosis D in
pregnancy and in cord blood and to correlate maternal 25-hydroxyvitamin D [25(OH)D] status with sun
exposure, daily calcium intake (dietary plus supplemental), and intact parathyroid hormone (PTH)
concentrations.
• Design: Serum calcium, inorganic phosphorus, 25(OH)D, heat-labile alkaline phosphatase, and PTH
were studied in 207 urban and rural pregnant subjects at term. Alkaline phosphatase and 25(OH)D were
measured in the cord blood of 117 newborns.
• Results: Mean maternal serum 25(OH)D was 14 ± 9.3 ng/mL, and cord blood 25(OH)D was 8.4 ± 5.7
ng/mL. PTH rose above the normal range when 25(OH)D was <22.5 ng/mL. Eighty-four percent of
women (84.3% of urban and 83.6% of rural women) had 25(OH)D values below that cutoff. Fourteen
percent of the subjects had elevated alkaline phosphatase (17% of urban and 7% of rural subjects).
Calcium intake was uniformly low, although higher in urban (842 ± 459 mg/d) than in rural (549 ± 404
mg/d) subjects (P < 0.001). Maternal serum 25(OH)D correlated positively with cord blood 25(OH)D (r =
0.79, P < 0.001) and negatively with PTH (r = –0.35, P < 0.001).
• Conclusion: We observed a high prevalence of physiologically significant hypovitaminosis D among
pregnant women and their newborns, the magnitude of which warrants public health intervention.

37. Vitamin D status in a sunny country:
Where has the sun gone
Clinical Nutrition, 12/07/2010 Unger MD et al.
• In Sao Paulo, at the end of winter, the authors
observed a high prevalence of hypovitaminosis D and
secondary hyperparathyroidism in healthy adults.
s25(OH)D was dependent on age and skin color.
• After summer, the authors observed a decrease in the
prevalence of hypovitaminosis D.
• This unexpected finding emphasizes the need for a
strong recommendation to monitor s25(OH)D, even in
a sunny country such as Brazil.

38. Determination of vitamin D status:

39. Vitamin D
Determination of vitamin D status
• Serum 25(OH)D3
– Major circulating form of vitamin D
– Best indicator of vitamin D status
– Reflects production from sunlight exposure and dietary
intake
– Half-life approximately 2 weeks
– Expressed as ng/mL or nmol/L
– 1 ng/mL 25(OH)D3 ≈ 2.5 nmol/L 25(OH)D3
– 1,25(OH)2D3 should never be used to determine
vitamin D status

40. Vitamin D
Determination of vitamin D status
Inadequacy = hypovitaminosis D
serum 25(OH)D3 levels < 30 ng/ml (≈ 75 nmol/L)
Vitamin D Vitamin D
Deficiency Insufficiency
Serum < 10 ng/mL 10–30 ng/mL
25(OH)D3 (≈ 25 nmol/L) (≈ 25-75 nmol/L)
Please note: These cutpoints are a general guideline only.

41. Vitamin D – Inadequacy:
Caused / Etiology

42. Vitamin D - Inadequacy
• Etiology
– Inadequate sun exposure
– Inadequate dietary intake
– Aging
– Co-morbid conditions
– Drug interactions

43. Vitamin D - Inadequacy
Inadequate sun exposure
• Sunlight –primary source of vitamin D
– Latitude
• Greater than ~ 37°-40°North or South
– Season – Winter (November-February)
• More oblique zenith angle of the sun
– Time of day
• 10am-3pm: maximum UVB penetration
– Type of Skin
• Types I-VI

44. Prevalence of Vitamin D Insufficiency in Healthy Canadians
Calgary (51° N)
Subjects: 188
Female: 128
Male: 60
Mean age: 64
Rucker, CMAJ 2002

45. Vitamin D - Inadequacy
• Etiology
– Inadequate sun exposure
– Inadequate dietary intake
– Aging
– Co-morbid conditions
– Drug interactions

46. Vitamin D - Inadequacy
Inadequate dietary intake
• Dietary Sources
– Fish liver oils (e.g. cod liver oil)
– Fatty fish
• salmon, mackerel, sardines
– Liver and fat of aquatic mammals
• seals and polar bears
– Eggs (from hens fed Vitamin D)
– Fortified foods
• milk, orange juice, and cereal
• infant formulas

47. Vitamin D - Inadequacy
• Etiology
– Inadequate sun exposure
– Inadequate dietary intake
– Aging
– Co-morbid conditions
– Drug interactions

48. Vitamin D - Inadequacy
Aging
• Multifactorial
– Decreased ability to produce vitamin D3
– Increased incidence of lactose intolerance
– Decreased renal function
• ↓ ability to convert 25(OH)D3 to 1,25(OH)2D3
• May be housebound or institutionalized
– Minimal exposure to sunlight

49. Vitamin D Levels Decline With Advancing Age
60
50
J
P sm 2 H (ng l)
la a 5O D /m
Due to: 40
J
-Low dietary intake J J
30
-Low sun exposure J J
-Less effective 20
J
skin production 10
0
20 30 40 50 60 70 80 90
A e (years)
g
Baker, Age Ageing 1980

50. Does Race Make a difference….

51. Effect of Season and Skin Color on Vitamin D Insufficiency
(NHANES III)
.
African American White
% with 25OHD below 15 ng/ml
50
African American : 40
1546
And 30
White Women:
1426 20
10
Age: 15-49
0
Spring Fall Spring Fall
Summer Winter Summer Winter
Nesby-O’Dell, AJCN 2002

52. Vitamin D - Inadequacy
• Etiology
– Inadequate sun exposure
– Inadequate dietary intake
– Aging
– Co-morbid conditions
– Drug interactions

53. Vitamin D - Inadequacy
Co-morbid conditions
• Diseases affecting intestinal absorption of
vitamin D
– Crohn’s disease
– Whipple’s disease
– Sprue
• Severe liver failure
• Obesity

54. Vitamin D - Inadequacy
• Etiology
– Inadequate sun exposure
– Inadequate dietary intake
– Aging
– Co-morbid conditions
– Drug interactions

55. Vitamin D - Inadequacy
Drug interactions
• Drugs that impair vitamin D absorption
– Mineral oil laxatives
– Obesity management medication – Orlistat
– Bile acid sequestrants – Cholestyramine and Colestipol
• Drugs that may increase vitamin D catabolism
– Anticonvulsants, cimetidine, thiazides
• Fat substitutes may also decrease vitamin D
absorption
– Olestra

56. How Can We Correct Vitamin D
Insufficiency ?

57. Vitamin D
• 25(OH)D3 levels ≥ 30 ng/ml are required to
maintain maximum bone and cellular health
– 25(OH)D3 levels < 30 ng/ml
• Suboptimal calcium absorption
• Increase in PTH secretion

58. Vitamin D
• Institute of Medicine (IOM)
– Adequate Intake (AI) of vitamin D for males & females
• Infants – 50 years is 200 IU/day (5 mcg/day)
• ages 51-70 years is 400 IU/day (10 mcg/day)
• ≥ 71 years is 600 IU/day (15 mcg/day)
– Patients taking glucocorticoids may require additional
vitamin D

59. How Can We Correct Vitamin D Insufficiency?
40
B Placeb o H
J 5000 IU /D H 34 Subjects from Buenos
H 10,000 IU/D Aires were randomized
J into 3 groups.
30 H
J J 50% of the 5,000 IU
group
75% of the 10,000 IU
20
B B achieved vitamin D
B B values > 34 ng/ml after 3
J
H months of
supplementation.
10
B ase 1 M onth 2 M onths 3 M onths
Mastaglia, ASBMR 2003

60. Vitamin D is Food:

61. So, We Don’t Get Enough Vitamin D, is Cod
Liver Oil an Answer??
One tablespoon of cod liver oil contains:
~1400 IU vitamin D
~13,500 IU vitamin A

62. Vitamin D is Rare in Foods
Food IU
Cod Liver Oil, 1 Tbs 1360
Salmon, 3.5 oz 360
Mackerel, 3.5 oz 345
Milk, 1 cup 100
Fortified cereal, 3/4 cup 50
Liver, 3.5 oz 30
Egg, one whole 25

63. Vitamin D
Ensuring adequate vitamin D
• Sunlight is the best & most reliable source of
vitamin D
– Recommendations:
• Exposure of hands, face, arms, & legs
• ~ 5-15 minutes between 10 a.m.–3 p.m. for
people with skin types II-III
• ~ 25% of the time required to produce a MED
(i.e., mild sunburn) 2-3 X/week
• After this exposure, apply sunscreen with an SPF
≥ 15 to prevent damaging effects of excessive
exposure to sun

64. How Much Sunlight Is Equivalent to Vitamin D
Supplementation?
• Vitamin D is essential for bone mineralization and may have other health
benefits. Experts disagree on the serum vitamin D level necessary to maintain
health.
• Some recommend concentrations above 30 ng/mL and consider the range
between 20 and 30 ng/mL insufficient and concentrations lower than 20 ng/mL
deficient.
• By this reckoning, many Americans are vitamin D insufficient or deficient.
Because it is difficult to obtain enough vitamin D from food intake, oral
supplements and sunlight have been recommended for individuals with low
serum D levels.
• The suggested dose for supplements is 400 to 1000 IU/day. It has been
suggested that a few minutes of sunlight each day to the face, neck, hands,
and arms are all that is necessary to restore vitamin D sufficiency, but the
amount of sunlight required for photoconversion of 7-dehydrocholesterol to
pre–vitamin D varies considerably depending on a person's age, Fitzpatrick
sun-reactive skin type, geographic location, and season. (The six Fitzpatrick
skin types classify sensitivity to ultraviolet light; skin type I is fair skin that
always burns, never tans; type III is darker white skin that burns and tans; type
V is brown skin that rarely burns, tans easily.) Investigators employed the
FastRT computational tool to predict the length of daily exposure required to
obtain the sunlight equivalent of 400 and 1000 IU oral vitamin D
supplementation.

65. How Much Sunlight Is Equivalent to Vitamin D
Supplementation?
• At noon in Miami, someone with Fitzpatrick skin type
III would require 6 minutes to synthesize 1000 IU of
vitamin D in the summer and 15 minutes in the
winter.
• Someone with skin type V would need 15 and 29
minutes, respectively.
• At noon in the summer in Boston, necessary
exposure times approximate those in Miami, but in
winter, it would take about 1 hour for type III skin
and 2 hours for type V skin to synthesize 1000 IU of
D.
• After 2 PM in the winter in Boston, it is impossible
for even someone with Fitzpatrick type I skin to

66. All That Glitters is not GOLD…

67. Skepticism grows regarding widespread vitamin D
supplementation
• Serious questions exist about the safety and efficacy of the
popular practice of high-dose vitamin D supplementation across a
broad swathe of the population
• One of these concerns is that not all of the extra calcium
absorption promoted by boosting vitamin D is going into bone to
prevent fractures
• Serum 25-hydroxyvitamin D levels were positively associated with
increased calcified atherosclerotic plaque in the aorta and carotid
arteries (J.Clin.Endo.Metab. Jan. 8, 2010; Epub ahead of print
PMID:20061416).
• A large prospective randomized trial assessed the effects of using
calcium supplements on vascular event rates The NNT for 5 years
of supplemental calcium in order to cause one additional MI than
with placebo was 44. The NNT for one stroke was 56. And the
NNT to cause one additional cardiovascular event was 29. In
contrast, the NNT to prevent one symptomatic fracture was 50.
• “The question we have to ask is: What does that low serum
vitamin D level mean? Is it the thing that predisposes, or is it
somehow a byproduct of illness?”

68. Vitamin D - Conclusions

69. Vitamin D Summary
– Hypovitaminosis D is endemic
– Due to lack of sun exposure and low dietary intake
– Leads to rickets, osteomalacia, osteoporosis and fractures
– Perhaps associated with a multitude of other diseases
– Need better assays and consensus definition of “optimal”
25OHD status
– 400/600 IU per day is too low

70. The Planet is Vitamin D
Deficient

71. I Thank You for your Attention