Dr.S. Abbas Raza

"Vitamin D beyond bone”

Vitamin or Vitamone???

S. Abbas Raza. M.DConsultant Endocrinologist:

Shaukat Khanum Hospital and Research CenterNational Hospital

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

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

Vitamin D

Vitamin DVitamin DRole in Health MaintenanceRole in Health Maintenance

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

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

Vitamin D

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

Vitamin D Physiology

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

Vitamin D

Production, Metabolism, and Biological Function of Vitamin D

1,25(OH)2D3 1,25(OH)2D3

Vitamin D3 25(OH)D3

Prostate

Gland,

Breast,

Colon,

Lung

Calcium

Homeostasis

Muscle Health

Bone Health

Blood pressure regulation

Cardiovascular Health

Immunomodulation (prevention of

autoimmune diseases)

Regulation of

Cell Growth

(cancer prevention)

Liver

Kidney

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.

Skin

D D

Milk Orange juice

SupplementCod liver oil

Salmon

Do we need

Vitamin D?????

Lessons learned in 2010 - 2011

Studies Published in First Quarter of 2010

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 [email protected]

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.

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, USA2 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.

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.

Studies Published in Second Quarter of 2010

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.

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.

Studies Published in Third Quarter of 2010

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 the study in the journal Nature Immunology.

Vitamin D and cardiovascular disease risk: emerging evidenceSwales, 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.

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.

Studies Published in Last Quarter of 2010

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.

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 trials, should aim to provide reliable evidence for people to make informed decisions as to whether this treatment can be effective in the management of MS

Vitamin D and the heart: Why we need large-scale clinical trials

Cleveland Clinic Journal of Medicine, 12/27/2010Manson 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

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

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.

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.

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.

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.

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….

Astonishing Figures from the subcontinent

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.

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.

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.

Determination of vitamin D status:

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

Vitamin D

Inadequacy = hypovitaminosis D serum 25(OH)D3 levels < 30 ng/ml (≈ 75 nmol/L)

Please note: These cutpoints are a general guideline only.

Vitamin D

Determination of vitamin D status

Vitamin D Deficiency

Vitamin D Insufficiency

Serum 25(OH)D3

< 10 ng/mL(≈ 25 nmol/L)

10–30 ng/mL(≈ 25-75 nmol/L)

Vitamin D – Inadequacy:Caused / Etiology

Vitamin D - Inadequacy

Etiology

– Inadequate sun exposure

– Inadequate dietary intake

– Aging

– Co-morbid conditions

– Drug interactions

Inadequate sun exposure

Sunlight –primary source of vitamin D– Latitude

• Greater than ~ 37-40North 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


Prevalence of Vitamin D Insufficiency in Healthy Canadians

Rucker, CMAJ 2002

Calgary (51° N)Subjects: 188Female: 128

Male: 60Mean age: 64


Etiology



– Aging



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



Etiology



– Aging




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

Vitamin D Levels Decline With Advancing Age

.

20 30 40 50 60 70 80 900

10

20

30

40

50

60

Age (years)

Pla

sma

25O

HD

(ng/

ml) J

JJ J

J J

J

Baker, Age Ageing 1980

Due to:-Low dietary intake-Low sun exposure-Less effective skin production

Does Race Make a difference….

Effect of Season and Skin Color on Vitamin D Insufficiency (NHANES III)

Nesby-O’Dell, AJCN 2002

.

0

10

20

30

40

50

% w

ith 2

5O

HD

belo

w 1

5 n

g/m

l White

SpringSummer Winter

Fall SpringSummer Winter

Fall

African American

African American : 1546 And

White Women: 1426

Age: 15-49


Etiology



– Aging




Co-morbid conditions

Diseases affecting intestinal absorption of vitamin D – Crohn’s disease – Whipple’s disease – Sprue

Severe liver failure

Obesity


Etiology



– Aging




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

How Can We Correct Vitamin D Insufficiency ?

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

Vitamin D

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

How Can We Correct Vitamin D Insufficiency?

Mastaglia, ASBMR 2003

B BB B

J

J J

J

H

H

H

H

Base 1 Month 2 Months 3 Months10

20

30

40B Placebo

J 5000 IU/D

H 10,000 IU/D34 Subjects from Buenos Aires were randomized

into 3 groups.

50% of the 5,000 IU group

75% of the 10,000 IU

achieved vitamin D values > 34 ng/ml after 3

months of supplementation.

Vitamin D is Food:

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

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

Vitamin D is Rare in FoodsVitamin D is Rare in Foods

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

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.

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 receive enough sun to equal even 400 IU of vitamin D.

All That Glitters is not GOLD…

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?”

Vitamin D - Conclusions

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

The Planet is Vitamin D Deficient

The Planet is Vitamin D Deficient

I Thank You for your Attention

Dr.S. Abbas Raza

Education

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