Dr.S. Abbas Raza

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Dr.S. Abbas Raza

  1. 1. &quot;Vitamin D beyond bone” Vitamin or Vitamone??? <ul><li>S. Abbas Raza. M.D </li></ul><ul><li>Consultant Endocrinologist: </li></ul><ul><li>Shaukat Khanum Hospital and Research Center </li></ul><ul><li>National Hospital </li></ul>
  2. 2. <ul><li>Although called a vitamin... </li></ul><ul><ul><li>Vitamins must be provided from the diet because they can’t be synthesized or the rate of synthesis is not sufficient to maintain health </li></ul></ul><ul><ul><li>Necessary in small amounts for normal metabolic functioning </li></ul></ul><ul><li>Vitamin D acts more like a hormone... </li></ul><ul><ul><li>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 </li></ul></ul>Vitamin D
  3. 3. <ul><li>Vitamin D 3 (precursor) </li></ul><ul><li>Calcitriol or 1,25 dihydroxyvitamin D 3 </li></ul><ul><li>(the biologically active form) </li></ul><ul><li>Characteristics consistent with hormonal functions </li></ul><ul><ul><li>Synthesized in skin </li></ul></ul><ul><ul><li>Transported in blood to distant sites to exert its action </li></ul></ul><ul><ul><li>Activated by a tightly regulated enzyme </li></ul></ul><ul><ul><li>Active form binds to specific receptors in target tissues </li></ul></ul><ul><ul><li>Receptors are found in many cells throughout the body </li></ul></ul>Vitamin D
  4. 4. Vitamin D Role in Health Maintenance
  5. 5. Vitamin D <ul><li>Physiologic functions of vitamin D </li></ul><ul><li>Maintains calcium homeostasis </li></ul><ul><li>Maximizes intestinal absorption of calcium </li></ul><ul><ul><li>In vitamin D-sufficient people: 30% of calcium is absorbed from the diet </li></ul></ul><ul><ul><li>In vitamin D-deficient people: 10-15% of calcium is absorbed from the diet </li></ul></ul><ul><li>Maintains phosphate homeostasis </li></ul><ul><li>Deficiency results in increased production and excretion of PTH (parathyroid hormone) or secondary hyperparathyroidism </li></ul>
  6. 6. <ul><li>Musculoskeletal Effects </li></ul><ul><li>Maintenance of normal musculoskeletal function </li></ul><ul><ul><li>Skeletal muscle has receptors (VDR) for 1,25(OH) 2 D 3 </li></ul></ul><ul><ul><li>Severe vitamin D deficiency is associated with muscle weakness, limb pain & impaired physical function </li></ul></ul>Vitamin D
  7. 7. Vitamin D <ul><li>Extraskeletal Effects </li></ul><ul><li>Regulation of cell growth and effects on immune function </li></ul><ul><li>Epidemiologic studies have shown that living at lower latitudes is associated with a decreased risk of many chronic diseases </li></ul><ul><ul><ul><li>Multiple sclerosis, hypertension, and cancer of the colon, breast, and prostate </li></ul></ul></ul><ul><ul><ul><ul><li>Since the production of vitamin D is more efficient at lower latitudes, this may explain these interesting findings </li></ul></ul></ul></ul><ul><li>Some studies have shown that increasing vitamin D intake decreases the risk of certain chronic diseases </li></ul><ul><ul><ul><li>Diabetes, rheumatoid arthritis, hypertension, and colon cancer </li></ul></ul></ul>Additional trials are needed to definitively determine the role of vitamin D in these conditions
  8. 8. Vitamin D Physiology
  9. 9. <ul><li>Vitamin D </li></ul><ul><ul><li>Vitamin D 2 (ergocalciferol) </li></ul></ul><ul><ul><ul><li>( Pharmaceutical Form derived from Ergol found in Fungus ) </li></ul></ul></ul><ul><ul><li>Vitamin D 3 (cholecalciferol) </li></ul></ul><ul><ul><ul><li>( Natural Form found in food and synthesized in Skin ) </li></ul></ul></ul><ul><ul><ul><li>metabolites and analogues of these substances </li></ul></ul></ul><ul><li>Vitamin D </li></ul><ul><ul><li>Precursor ( sometimes referred to as a “prohormone ”) </li></ul></ul><ul><ul><li>Must be metabolized to become biologically active </li></ul></ul><ul><li>Active form of vitamin D: Calcitriol </li></ul><ul><li>Vitamin D is essential for healthy bone </li></ul>Vitamin D
  10. 10. Production, Metabolism, and Biological Function of Vitamin D 1,25(OH) 2 D 3 1,25(OH) 2 D 3 Vitamin D 3 25(OH)D 3 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) Kidney 25(OH)D 3 =25-hydroxyvitamin D 3 ; 1,25(OH) 2 D 3 = 1,25-dihydroxyvitamin D 3 . Holick MF. Am J Clin Nutr 2004;80(suppl):1678S-88S. D D Milk Orange juice Supplement Cod liver oil Salmon Liver Skin
  11. 11. <ul><li>Do we need </li></ul><ul><li>Vitamin D????? </li></ul>
  12. 12. Lessons learned in 2010 - 2011
  13. 13. Studies Published in First Quarter of 2010
  14. 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 [email_address] <ul><li>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. </li></ul><ul><li>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. </li></ul>
  15. 15. Low Vitamin D levels in Northern American Adults with the Metabolic Syndrome <ul><li>S. Devaraj 1 , G. Jialal 1 , T. Cook 1 , D. Siegel 1 , 2 , I. Jialal 1 , 2 1 Department of Pathology and Laboratory Medicine, University of California, Davis, Medical Center, Sacramento, CA, USA 2 Veterans Affairs Medical Center, Mather, CA, USA </li></ul><ul><li>Abstract: </li></ul><ul><li>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. </li></ul>
  16. 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. <ul><li>Background: Accumulating evidence suggests that vitamin D is involved in the development of type 2 diabetes (T2D). </li></ul><ul><li>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. </li></ul><ul><li>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). </li></ul><ul><li>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. </li></ul>
  17. 17. Studies Published in Second Quarter of 2010
  18. 18. Vitamin D Deficiency and Coronary Artery Calcification in Subjects with Type 1 Diabetes Received May 11, 2010. Accepted October 11, 2010. <ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>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). </li></ul><ul><li>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. </li></ul>
  19. 19. Vitamin D and pregnancy: An old problem revisited <ul><li>Vitamin D has historically been considered to play a role solely in bone and calcium metabolism. </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul>
  20. 20. Studies Published in Third Quarter of 2010
  21. 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 <ul><li>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. </li></ul><ul><li>&quot;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,&quot; said Carsten Geisler of Copenhagen University's department of international health, immunology and microbiology, who led the study. </li></ul><ul><li>&quot;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.&quot; </li></ul><ul><li>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. </li></ul><ul><li>&quot;What we didn't realize is how crucial vitamin D is for actually activating the immune system -- which we know now,&quot; Geisler wrote in the study in the journal Nature Immunology. </li></ul>
  22. 22. 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 <ul><li>Most Vitamin D is made by the body as a natural by-product of the skin's exposure to sunlight. It can also be found in fish liver oil, eggs and fatty fish such as salmon, herring and mackerel, or taken as a supplement. </li></ul><ul><li>Almost half of the world's population has lower than optimal levels of vitamin D and scientists say the problem is getting worse as people spend more time indoors. </li></ul><ul><li>Geisler and his research team said the findings offered much needed information about the immune system and would be of particular use when developing new vaccines. </li></ul><ul><li>&quot;This is important not only in fighting disease but also in dealing with anti-immune reactions of the body and the rejection of transplanted organs,&quot; they wrote. </li></ul><ul><li>Active T cells multiply at an explosive rate and as well as fighting infection, can also mistakenly attack the body itself. </li></ul><ul><li>After and an organ transplant, for example, T cells can attack the new organ as a &quot;foreign invader,&quot; and in autoimmune disease, hypersensitive T cells mistake parts of the body's own cells as threats, prompting the body to attack itself. </li></ul><ul><li>Geisler said there were no definitive studies on the optimal daily vitamin D dose but experts recommend 25 to 50 micrograms. </li></ul>
  23. 23. Vitamin D and cardiovascular disease risk: emerging evidence Swales, Heather H a ; Wang, Thomas J b Current Opinion in Cardiology: September 2010 - Volume 25 - Issue 5 - p 513–517 <ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul>
  24. 24. Maternal Vitamin D Status in Gestational Diabetes Mellitus Nutrition in Clinical Practice, 10/27/2010 Soheilykhah S et al. <ul><li>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. </li></ul>
  25. 25. Studies Published in Last Quarter of 2010
  26. 26. Vitamin D status, physical performance and body mass in patients surgically cured for primary hyperparathyroidism compared with healthy controls Clinical Endocrinology, 12/29/2010 <ul><li>Amstrup AK et al. – </li></ul><ul><li>Low plasma 25–hydroxyvitaminD (25OHD) levels, reduced muscle strength and increased body mass index (BMI) are well–known characteristics of primary hyperparathyroidism (PHPT). </li></ul><ul><li>Mechanisms for low 25OHD levels, increased BMI and potential changes after parathyroidectomy are unknown. </li></ul><ul><li>Muscle strength is reported to increase following surgical cure, but whether the improvement corresponds to healthy controls' performances remains largely unknown. </li></ul><ul><li>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. </li></ul>
  27. 27. Vitamin D for the management of multiple sclerosis <ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>Vitamin D deficiency is said to affect the general well being of patients with MS and is also associated with poorer neurologic outcomes. </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>However, the question of the safety and effectiveness of Vitamin D in people of MS remains unanswered. </li></ul><ul><li>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 </li></ul>
  28. 28. Vitamin D and the heart: Why we need large-scale clinical trials Cleveland Clinic Journal of Medicine, 12/27/2010 Manson JE et al. <ul><li>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. </li></ul><ul><li>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 </li></ul>
  29. 29. Optimal use of vitamin D when treating osteoporosis Current Osteoporosis Reports. van den Bergh JPW et al. 12/21/2010 <ul><li>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. </li></ul><ul><li>Methods </li></ul><ul><li>Discussed several aspects with regard to vitamin D status and supplementation </li></ul><ul><li>Results </li></ul><ul><li>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 </li></ul><ul><li>Additional calcium supplementation may be considered when dietary calcium intake is below 700 mg/day </li></ul><ul><li>For optimal BMD response in patients treated with antiresorptive or anabolic therapy, adequate vitamin D and calcium supplementation also necessary </li></ul><ul><li>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 </li></ul>
  30. 30. Role of Vitamin D in Blood Pressure Homeostasis American Journal of Therapeutics 11/22/2010 - Feneis JF <ul><li>Ten observational studies and nine randomized control trials concerned with the association between vitamin D and blood pressure were identified and analyzed. </li></ul><ul><li>Of these, eight observational studies and three randomized control trials supported an inverse association between vitamin D and blood pressure. </li></ul><ul><li>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. </li></ul>
  31. 31. 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 <ul><li>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 . </li></ul><ul><li>The findings may provide new insights into the understanding of the link between vitamin D deficiency and cardiovascular disease. </li></ul>
  32. 32. Maternal vitamin D status affects bone growth in early childhood--A prospective cohort study Osteoporosis International, 12/14/2010  Clinical Article Viljakainen HT et al. <ul><li>Postnatal vitamin D supplementation improved vitamin D status but only partly eliminated the differences in bone variables induced by maternal vitamin D status during the fetal period. Further attention should be paid to improving vitamin D status during pregnancy. </li></ul><ul><li>Methods </li></ul><ul><li>Evaluated role of prenatal and postnatal vitamin D status on bone parameters in early infancy . 87 children followed from birth to 14 months </li></ul><ul><li>Background data collected with questionnaire and 3-day food record. At 14 months bone variables measured with peripheral computed tomography (pQCT) from left tibia. Serum 25-OHD and bone turnover markers determined. Findings compared with maternal vitamin D status during pregnancy </li></ul><ul><li>Results </li></ul><ul><li>Children divided into 2 groups based on vitamin D status during pregnancy . Despite discrepant S-25-OHD at baseline (median 36.3 vs. 52.5 nmol/l, p<0.001), values at 14 months were similar (63 vs. 66 nmol/l, p=0.58) in Low D and High D. Serum 25-OHD increased more in Low D (p<0.001) despite similar total intake of vitamin D (mean 12.3 &mug/day) . In Low D, tibial bone mineral content (BMC) lower at birth but BMC gain was greater (multivariate analysis of variance [MANOVA]; p=0.032) resulting in similar BMC at 14 months in the two groups .In High D, tibial total bone cross-sectional area higher at baseline; difference persisted at 14 months (MANOVA; p=0.068) </li></ul><ul><li>BMD and &DeltaBMD were similar in 2groups </li></ul>
  33. 33. 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. <ul><li>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. </li></ul><ul><li>Future studies to evaluate the effect of vitamin D supplementation on vascular RAS activity in obesity are needed. </li></ul>
  34. 34. 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. – <ul><li>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. </li></ul><ul><li>Furthermore, ethnic differences in 25(OH)D concentrations may contribute to ethnic differences in insulin sensitivity. </li></ul>
  35. 35. Vitamin D, UV, and Skin Cancer in the Elderly: To Expose or Not to Expose Gerontology, 12/29/2010, Glossmann H et al. <ul><li>Studies with vitamin D supplements reported increased risks of prostate and esophagus cancer as well as atopy in childhood' and concluded that 'adequate levels of vitamin D are essential for the elderly', but do not suggest which level is optimal. </li></ul><ul><li>Serum 25–(OH)–vitamin D3 (25–(OH)–D) levels in the 75–100 nmol/l range. An oral cholecalciferol intake of 2,000 IU/day is recommended as a supplement throughout the year for those who cannot enjoy the sun in summer or only during 'vitamin D winter' for the others. </li></ul>
  36. 36. Is there any thing else associated with Vitamin D Deficiency ?????? <ul><li>D.M Type 2 </li></ul><ul><li>D.M Type 1 </li></ul><ul><li>Metabolic Syndrome </li></ul><ul><li>Polycystic Ovarian Disease </li></ul><ul><li>Prostate Cancer </li></ul><ul><li>Breast Cancer </li></ul><ul><li>Immune Systems </li></ul><ul><li>Myocardial Infarction </li></ul><ul><li>Arthrosclerosis </li></ul><ul><li>Etc…. </li></ul>
  37. 37. Astonishing Figures from the subcontinent
  38. 38. Astonishing Figures from the subcontinent <ul><li>Vitamin D deficiency is prevelant both in Urban and Rural areas. </li></ul><ul><li>Ranges any where from 40 – 70 % of Population </li></ul><ul><li>Equally distributed in both adults and Children. </li></ul>
  39. 39. High prevalence of vitamin D deficiency among pregnant women and their newborns in northern India <ul><li>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) </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>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). </li></ul><ul><li>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. </li></ul>
  40. 40. Vitamin D status in a sunny country: Where has the sun gone Clinical Nutrition, 12/07/2010 Unger MD et al. <ul><li>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. </li></ul><ul><li>After summer, the authors observed a decrease in the prevalence of hypovitaminosis D. </li></ul><ul><li>This unexpected finding emphasizes the need for a strong recommendation to monitor s25(OH)D, even in a sunny country such as Brazil. </li></ul>
  41. 41. Determination of vitamin D status:
  42. 42. <ul><li>Determination of vitamin D status </li></ul><ul><li>Serum 25(OH)D 3 </li></ul><ul><ul><li>Major circulating form of vitamin D </li></ul></ul><ul><ul><li>Best indicator of vitamin D status </li></ul></ul><ul><ul><li>Reflects production from sunlight exposure and dietary intake </li></ul></ul><ul><ul><li>Half-life approximately 2 weeks </li></ul></ul><ul><ul><li>Expressed as ng/mL or nmol/L </li></ul></ul><ul><ul><li>1 ng/mL 25(OH)D 3 ≈ 2.5 nmol/L 25(OH)D 3 </li></ul></ul><ul><ul><li>1,25(OH) 2 D 3 should never be used to determine vitamin D status </li></ul></ul>Vitamin D
  43. 43. Vitamin D Inadequacy = hypovitaminosis D serum 25(OH)D 3 levels < 30 ng/ml (≈ 75 nmol/L) Please note: These cutpoints are a general guideline only. Determination of vitamin D status   Vitamin D Deficiency Vitamin D Insufficiency Serum 25(OH)D 3 < 10 ng/mL (≈ 25 nmol/L) 10–30 ng/mL (≈ 25-75 nmol/L)
  44. 44. Vitamin D – Inadequacy: Caused / Etiology
  45. 45. Vitamin D - Inadequacy <ul><li>Etiology </li></ul><ul><li>– Inadequate sun exposure </li></ul><ul><li>– Inadequate dietary intake </li></ul><ul><li>– Aging </li></ul><ul><li>– Co-morbid conditions </li></ul><ul><li>– Drug interactions </li></ul>
  46. 46. <ul><li>Inadequate sun exposure </li></ul><ul><li>Sunlight –primary source of vitamin D </li></ul><ul><ul><li>Latitude </li></ul></ul><ul><ul><li>• Greater than ~ 37  -40  North or South </li></ul></ul><ul><ul><li>Season – Winter (November-February) </li></ul></ul><ul><ul><li>• More oblique zenith angle of the sun </li></ul></ul><ul><ul><li>Time of day </li></ul></ul><ul><ul><li>• 10am-3pm: maximum UVB penetration </li></ul></ul><ul><ul><li>Type of Skin </li></ul></ul><ul><ul><li>• Types I-VI </li></ul></ul>Vitamin D - Inadequacy
  47. 47. Prevalence of Vitamin D Insufficiency in Healthy Canadians Rucker, CMAJ 2002 Calgary (51° N) Subjects: 188 Female: 128 Male: 60 Mean age: 64
  48. 48. Vitamin D - Inadequacy <ul><li>Etiology </li></ul><ul><li>– Inadequate sun exposure </li></ul><ul><li>– Inadequate dietary intake </li></ul><ul><li>– Aging </li></ul><ul><li>– Co-morbid conditions </li></ul><ul><li>– Drug interactions </li></ul>
  49. 49. <ul><li>Inadequate dietary intake </li></ul><ul><li>Dietary Sources </li></ul><ul><ul><li>Fish liver oils (e.g. cod liver oil) </li></ul></ul><ul><ul><li>Fatty fish </li></ul></ul><ul><ul><li>• salmon, mackerel, sardines </li></ul></ul><ul><ul><li>Liver and fat of aquatic mammals </li></ul></ul><ul><ul><li>• seals and polar bears </li></ul></ul><ul><ul><li>Eggs (from hens fed Vitamin D) </li></ul></ul><ul><ul><li>Fortified foods </li></ul></ul><ul><ul><li>• milk, orange juice, and cereal </li></ul></ul><ul><ul><li>• infant formulas </li></ul></ul>Vitamin D - Inadequacy
  50. 50. Vitamin D - Inadequacy <ul><li>Etiology </li></ul><ul><li>– Inadequate sun exposure </li></ul><ul><li>– Inadequate dietary intake </li></ul><ul><li>– Aging </li></ul><ul><li>– Co-morbid conditions </li></ul><ul><li>– Drug interactions </li></ul>
  51. 51. Vitamin D - Inadequacy <ul><li>Aging </li></ul><ul><li>Multifactorial </li></ul><ul><li>– Decreased ability to produce vitamin D 3 </li></ul><ul><li>– Increased incidence of lactose intolerance </li></ul><ul><li>– Decreased renal function </li></ul><ul><li>•  ability to convert 25(OH)D 3 to 1,25(OH) 2 D 3 </li></ul><ul><li>May be housebound or institutionalized </li></ul><ul><li>– Minimal exposure to sunlight </li></ul>
  52. 52. Vitamin D Levels Decline With Advancing Age Baker, Age Ageing 1980 Due to: -Low dietary intake -Low sun exposure -Less effective skin production
  53. 53. Does Race Make a difference….
  54. 54. Effect of Season and Skin Color on Vitamin D Insufficiency (NHANES III) Nesby-O’Dell, AJCN 2002 African American : 1546 And White Women: 1426 Age: 15-49
  55. 55. Vitamin D - Inadequacy <ul><li>Etiology </li></ul><ul><li>– Inadequate sun exposure </li></ul><ul><li>– Inadequate dietary intake </li></ul><ul><li>– Aging </li></ul><ul><li>– Co-morbid conditions </li></ul><ul><li>– Drug interactions </li></ul>
  56. 56. Vitamin D - Inadequacy <ul><li>Co-morbid conditions </li></ul><ul><li>Diseases affecting intestinal absorption of </li></ul><ul><li>vitamin D </li></ul><ul><li>– Crohn’s disease </li></ul><ul><li>– Whipple’s disease </li></ul><ul><li>– Sprue </li></ul><ul><li>Severe liver failure </li></ul><ul><li>Obesity </li></ul>
  57. 57. Vitamin D - Inadequacy <ul><li>Etiology </li></ul><ul><li>– Inadequate sun exposure </li></ul><ul><li>– Inadequate dietary intake </li></ul><ul><li>– Aging </li></ul><ul><li>– Co-morbid conditions </li></ul><ul><li>– Drug interactions </li></ul>
  58. 58. Vitamin D - Inadequacy <ul><li>Drug interactions </li></ul><ul><li>Drugs that impair vitamin D absorption </li></ul><ul><ul><li>Mineral oil laxatives </li></ul></ul><ul><ul><li>Obesity management medication – Orlistat </li></ul></ul><ul><ul><li>Bile acid sequestrants – Cholestyramine and Colestipol </li></ul></ul><ul><li>Drugs that may increase vitamin D catabolism </li></ul><ul><ul><li>Anticonvulsants, cimetidine, thiazides </li></ul></ul><ul><li>Fat substitutes may also decrease vitamin D absorption </li></ul><ul><ul><li>Olestra </li></ul></ul>
  59. 59. <ul><li>How Can We Correct Vitamin D Insufficiency ? </li></ul>
  60. 60. <ul><li>25(OH)D 3 levels ≥ 30 ng/ml are required to maintain maximum bone and cellular health </li></ul><ul><ul><li>25(OH)D 3 levels < 30 ng/ml </li></ul></ul><ul><ul><ul><li>Suboptimal calcium absorption </li></ul></ul></ul><ul><ul><ul><li>Increase in PTH secretion </li></ul></ul></ul>Vitamin D
  61. 61. Vitamin D <ul><li>Institute of Medicine (IOM) </li></ul><ul><ul><li>Adequate Intake (AI) of vitamin D for males & females </li></ul></ul><ul><ul><ul><li>Infants – 50 years is 200 IU/day (5 mcg/day) </li></ul></ul></ul><ul><ul><ul><li>ages 51-70 years is 400 IU/day (10 mcg/day) </li></ul></ul></ul><ul><ul><ul><li>≥ 71 years is 600 IU/day (15 mcg/day) </li></ul></ul></ul><ul><ul><li>Patients taking glucocorticoids may require additional vitamin D </li></ul></ul>
  62. 62. How Can We Correct Vitamin D Insufficiency? Mastaglia, ASBMR 2003 34 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.
  63. 63. Vitamin D is Food:
  64. 64. 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
  65. 65. Vitamin D is Rare in Foods
  66. 66. Vitamin D <ul><li>Ensuring adequate vitamin D </li></ul><ul><li>Sunlight is the best & most reliable source of vitamin D </li></ul><ul><ul><li>Recommendations: </li></ul></ul><ul><ul><ul><li>Exposure of hands, face, arms, & legs </li></ul></ul></ul><ul><ul><ul><li>~ 5-15 minutes between 10 a.m.–3 p.m. for people with skin types II-III </li></ul></ul></ul><ul><ul><ul><li>~ 25% of the time required to produce a MED (i.e., mild sunburn) 2-3 X/week </li></ul></ul></ul><ul><ul><ul><li>After this exposure, apply sunscreen with an SPF ≥ 15 to prevent damaging effects of excessive exposure to sun </li></ul></ul></ul>
  67. 67. How Much Sunlight Is Equivalent to Vitamin D Supplementation? <ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul>
  68. 68. How Much Sunlight Is Equivalent to Vitamin D Supplementation? <ul><li>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. </li></ul><ul><li>Someone with skin type V would need 15 and 29 minutes, respectively. </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul>
  69. 69. All That Glitters is not GOLD…
  70. 70. Skepticism grows regarding widespread vitamin D supplementation <ul><li>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 </li></ul><ul><li>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 </li></ul><ul><li>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). </li></ul><ul><li>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. </li></ul><ul><li>“ 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?” </li></ul>
  71. 71. Vitamin D - Conclusions
  72. 72. Vitamin D Summary <ul><ul><li>Hypovitaminosis D is endemic </li></ul></ul><ul><ul><li>Due to lack of sun exposure and low dietary intake </li></ul></ul><ul><ul><li>Leads to rickets, osteomalacia, osteoporosis and fractures </li></ul></ul><ul><ul><li>Perhaps associated with a multitude of other diseases </li></ul></ul><ul><ul><li>Need better assays and consensus definition of “optimal” 25OHD status </li></ul></ul><ul><ul><li>400/600 IU per day is too low </li></ul></ul>
  73. 73. The Planet is Vitamin D Deficient
  74. 74. I Thank You for your Attention

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