Indrop d references

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Indrop d references

  1. 1. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease American Journal of Clinical Nutrition. 2004 Dec;80(6 Suppl):1678S-88S. Abstract Most humans depend on sun exposure to satisfy their requirements for vitamin D. Solar ultraviolet B photons are absorbed by 7-dehydrocholesterol in the skin, leading to its transformation to previtamin D3, which is rapidly converted to vitamin D3. Season, latitude, time of day, skin pigmentation, aging, sunscreen use, and glass all influence the cutaneous production of vitamin D3. Once formed, vitamin D3 is metabolized in the liver to 25-hydroxyvitamin D3 and then in the kidney to its biologically active form, 1,25-dihydroxyvitamin D3. Vitamin D deficiency is an unrecognized epidemic among both children and adults in the United States. Vitamin D deficiency not only causes rickets among children but also precipitates and exacerbates osteoporosis among adults and causes the painful bone disease osteomalacia. Vitamin D deficiency has been associated with increased risks of deadly cancers, cardiovascular disease, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes mellitus. Maintaining blood concentrations of 25-hydroxyvitamin D above 80 nmol/L (approximately 30 ng/mL) not only is important for maximizing intestinal calcium absorption but also may be important for providing the extrarenal 1alpha-hydroxylase that is present in most tissues to produce 1,25-dihydroxyvitamin D3. Although chronic excessive exposure to sunlight increases the risk of nonmelanoma skin cancer, the avoidance of all direct sun exposure increases the risk of vitamin D deficiency, which can have serious Complied By: Asma Saleem (Product Manager)
  2. 2. consequences. Monitoring serum 25-hydroxyvitamin D concentrations yearly should help reveal vitamin D deficiencies. Sensible sun exposure (usually 5-10 min of exposure of the arms and legs or the hands, arms, and face, 2 or 3 times per week) and increased dietary and supplemental vitamin D intakes are reasonable approaches to guarantee vitamin D sufficiency. Vitamin D deficiency: a worldwide problem with health consequences American Journal of Clinical Nutrition, Vol. 87, No. 4, 1080S-1086S, April 2008 Abstract Vitamin D deficiency is now recognized as a pandemic. The major cause of vitamin D deficiency is the lack of appreciation that sun exposure in moderation is the major source of vitamin D for most humans. Very few foods naturally contain vitamin D, and foods that are fortified with vitamin D are often inadequate to satisfy either a child's or an adult's vitamin D requirement. Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia, osteoporosis, and fractures in adults. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious diseases. A circulating level of 25hydroxyvitamin D of >75 nmol/L, or 30 ng/mL, is required to maximize vitamin D's beneficial effects for health. In the absence of adequate sun exposure, at least 800-1000 IU vitamin D3/d may be needed to achieve this in children and adults. Vitamin D2 may be equally effective for maintaining circulating concentrations of 25-hydroxyvitamin D when given in physiologic concentrations. Complied By: Asma Saleem (Product Manager)
  3. 3. Sunlight, UV-radiation, vitamin D and skin cancer: how much sunlight do we need? Advances in Experimental Medicine and Biology 2008 ;624:1-15. Abstract Vtamin D is the sunshine vitamin for good reason. During exposure to sunlight, the utraviolet B photons enter the skin and photolyze 7-dehydrocholesterol to previtamin D3 which in turn is isomerized by the body's temperature to vitamin D3. Most humans have depended on sun for their vitamin D requirement. Skin pigment, sunscreen use, aging, time of day, season and latitude dramatically affect previtamin D3 synthesis. Vitamin D deficiency was thought to have been conquered, but it is now recognized that more than 50% of the world's population is at risk for vitamin D deficiency. This deficiency is in part due to the inadequate fortification of foods with vitamin D and the misconception that a healthy diet contains an adequate amount of vitamin D. Vitamin D deficiency causes growth retardation and rickets in children and will precipitate and exacerbate osteopenia, osteoporosis and increase risk of fracture in adults. The vitamin D deficiency has been associated pandemic with other serious consequences including increased risk of common cancers, autoimmune diseases, infectious diseases and cardiovascular disease. There needs to be a renewed appreciation of the beneficial effect of moderate sunlight for providing all humans with their vitamin D requirement for health. Complied By: Asma Saleem (Product Manager)
  4. 4. Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004 American Journal of Clinical Nutrition, Vol. 88, No. 6, 1519-1527, December 2008 Conclusions: Overall, mean serum 25(OH)D was lower in 2000–2004 than 1988–1994. Assay changes unrelated to changes in vitamin D status accounted for much of the difference in most population groups. In an adult subgroup, combined changes in BMI, milk intake, and sun protection appeared to contribute to a real decline in vitamin D status. Presentation and Predisposing Factors of Nutritional Rickets in Children of Hazara Division Journal of Ayub Medical College, Abbottabad : 2005;17(3) Conclusion: Rickets is common in Hazara Division presenting with variable signs and symptoms, predisposing the childhood population to different illnesses and skeletal deformities. In the presence of abundant sunshine lack of awareness of exposure to sun, malnutrition and antenatal factors may be the important predisposing factors for development of nutritional rickets.Non-infectious rickets remains an important preventable illness, which predisposes to infectious diseases like bacterial pneumonias, recurrent diarrheas and bone deformities in cases of late presentation. Nutritional rickets in sunny clime of Hazara Division presenting with multiple clinical presentation is predisposing factor for different childhood illnesses. Lack of awareness of importance of sun exposure, malnutrition and antenatal factors were found to be the predisposing factors for nutritional rickets. Complied By: Asma Saleem (Product Manager)
  5. 5. Persisting vitamin D deficiency in the Asian adolescent Archives of Disease in Childhood59 (8): 766–770. Conclusion: We conclude with other workers that until there is an improvement in the vitamin D status of the Asian population in Britain, adolescents should receive supplements. This is of particular importance to the adolescent girl who may soon be embarking on child bearing. Cholcalciferol given by the oral route in the autumn to produce a sustained rise in plasma 25-hydroxyvitamin D until the springtime would seem appropriate. It concluded that fortifying foods with vitamin D would lead to some people ingesting unacceptably high amounts of the vitamin, but recommended that health authorities should consider the provision of free vitamin D supplements to high risk Asian adolescents. Two years after publication subclinical rickets remains a problem in this group against a background of vitamin D deficiency. Vitamin D deficiency linked to asthmatic severity in kids Am J ResP and Critical Care Medicine. 23 April 2009 They study led by Dr Juan Celedon, Dr. P.H. and Dr Augusto Litonjua, of Harvard Medical School has shown that children with lower vitamin D levels were significantly more likely to have been hospitalized for asthma, tended to have airways with increased hyper reactivity and were likely to have used more inhaled corticosteroids, all signifying higher asthma severity. These children were also significantly more likely to have several markers of allergy, including dust-mite sensitivity."To our knowledge this is the first study to demonstrate an inverse association between circulating levels of vitamin D and markers of asthma severity and allergy," said researchers."While it is difficult to establish causation in a cross-sectional study such as this, the results were robust even after controlling for markers of baseline asthma severity," they added."This study suggests that there may be added health benefits to vitamin D supplementation,” said Dr. Celedon. The study showed that serum levels of vitamin D in more than 600 Costa Rican children were inversely linked to several indicators of allergy and asthma severity,Current recommendations for optimal vitamin D levels geared toward preserving bone health, such as preventing rickets in children and osteoporosis in adults."This study also provides epidemiological support for a growing body of in vitro evidence that vitamin D insufficiency may worsen asthma severity, and we suspect that giving vitamin D supplements to asthma patients who are deficient may help with their asthma control" wrote the researchers. However, whether vitamin D supplementation can prevent the development of asthma in very young children is a separate question and requires further investigation, they said. Complied By: Asma Saleem (Product Manager)
  6. 6. Vitamin D deficiency in exclusively breast-fed infants Indian Journal of Medical Research. 2008 Mar; 127(3):250-5 Conclusion With the renewed worldwide emphasis on exclusive breast-feeding of infants for the first 6 months of life, infants even in developing countries are at risk of developing vitamin D deficiency unless adequate preventive measures are taken. Predisposing factors include reduced exposure to sunlight in spite of this being available in plenty in a country like India, due to various social and cultural reasons. There is a need to consider implementation of a vitamin D Supplementation Programme in infancy at the community level. Nutritional rickets in early infancy may become a more widespread problem in the near future unless strategies to ensure optimal vitamin D status for pregnant women and newborns are developed. Vitamin-D status in a Population of healthy adults in Pakistan Pak J Med Sci 2009;25(4):545-550 ABSTRACT Objective: To determine the prevalence of hypovitaminosis D and its predictors in healthy adult Pakistanis. This study was conducted at various hospitals in Karachi from April 2007 to September 2007. Methodology: In this study 244 healthy adults 16-62 years of age, visited hospital as an attendant of the patients and fulfilled the inclusion and exclusion criteria has been enrolled. After taking written consent a questionnaire regarding age, gender, occupation, duration of sun exposure, area of skin exposed, type of residence used, clothing and dietary habits were recorded. Serum 25-OH Vitamin D3 levels were determined by electrochemiluminescence method and Vitamin D deficiency was defined as a level <20µg/ml. serum calcium. Phosphorus and Alkaline Phosphatase were also measured in all of these subjects. Results: Among 244 subjects ranging from 16-62 years, 193(79%) were female. Subjects were predominantly married (72%), mostly residing in apartments (47.5%) and most of them (41.8%) only exposed their face and hands while outdoor. Duration of sun exposure in majority was 1-2 hour /day (42%). Majority used clothes of variable colour (72%) and fabric (41%). One hundred and eighty six (76.2%) subjects had deficiency of Vitamin D and significantly correlated with duration of sunlight exposure, large area of skin exposed, vitamin D in diet consumed and colour of clothes worn. Vitamin D was Complied By: Asma Saleem (Product Manager)
  7. 7. significantly correlated negatively with serum Phosphorus and Alkaline Phosphatase whereas serum calcium correlated positively. Conclusion: Prevalence of hypovitaminosis D among healthy Pakistanis is high and duration of sun exposure is the most common predictor of hypovitaminosis D. Vitamin D and bone health in early life Proceedings of the Nutrition Society. 2003 Nov; 62(4):823-8 Abstract Prolonged vitamin D deficiency resulting in rickets is seen mainly during rapid growth. A distinct age distribution has been observed in the Copenhagen area where all registered hospital cases of rickets were either infants and toddlers or adolescents from immigrant families. Growth retardation was only present in the infant and toddler group. A state of deficiency occurs months before rickets is obvious on physical examination. Growth failure, lethargy and irritability may be early signs of vitamin D deficiency. Mothers with low vitamin D status give birth to children with low vitamin D status and increased risk of rickets. Reports showing increasing rates of rickets due to insufficient sunlight exposure and inadequate vitamin D intake are cause for serious concern. Many countries (including the USA from 2003) recommend vitamin D supplementation during infancy to avoid rickets resulting from the low vitamin D content of human milk. Without fortification only certain foods such as fatty fish contain more than low amounts of vitamin D, and many children will depend entirely on sun exposure to obtain sufficient vitamin D. The skin has a high capacity to synthesize vitamin D, but if sun exposure is low vitamin D production is insufficient, especially in dark-skinned infants. The use of serum 25-hydroxyvitamin D to evaluate vitamin D status before development of rickets would be helpful; however, there is no agreement on cut-off levels for deficiency and insufficiency. Furthermore, it is not known how marginal vitamin D insufficiency affects children's bones in the long term Complied By: Asma Saleem (Product Manager)
  8. 8. Vitamin D deficiency: a worldwide problem with health consequences. American Journal of Clinical Nutrition. 2008 Apr; 87(4):1080S-6S. Abstract Vitamin D deficiency is now recognized as a pandemic. The major cause of vitamin D deficiency is the lack of appreciation that sun exposure in moderation is the major source of vitamin D for most humans. Very few foods naturally contain vitamin D, and foods that are fortified with vitamin D are often inadequate to satisfy either a child's or an adult's vitamin D requirement. Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia, osteoporosis, and fractures in adults. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious diseases. A circulating level of 25hydroxyvitamin D of >75 nmol/L, or 30 ng/mL, is required to maximize vitamin D's beneficial effects for health. In the absence of adequate sun exposure, at least 800-1000 IU vitamin D3/d may be needed to achieve this in children and adults. Vitamin D2 may be equally effective for maintaining circulating concentrations of 25-hydroxyvitamin D when given in physiologic concentrations. Complied By: Asma Saleem (Product Manager)
  9. 9. Low vitamin D during pregnancy linked to pre-eclampsia Journal of Clinical Endocrinology and Metabolism. September 7, 2007 “Vitamin D deficiency early in pregnancy is associated with a five-fold increased risk of preeclampsia”. “Our results showed that maternal vitamin D deficiency early in pregnancy is a strong, independent risk factor for preeclampsia,” said Lisa M. Bodnar, Ph.D., M.P.H., R.D., assistant professor of epidemiology at the University of Pittsburgh Graduate School of Public Health (GSPH) and lead author of the study. “Women who developed preeclampsia had vitamin D concentrations that were significantly lower early in pregnancy compared to women whose pregnancies were normal. And even though vitamin D deficiency was common in both groups, the deficiency was more prevalent among those who went on to develop preeclampsia.” “Even a small decline in vitamin D concentration more than doubled the risk of preeclampsia,” noted James M. Roberts, M.D., senior author of the study and MWRI founding director. “And since newborn’s vitamin D stores are completely reliant on vitamin D from the mother, low vitamin levels also were observed in the umbilical cord blood of newborns from mothers with preeclampsia.” Low vitamin D during pregnancy linked to pre-eclampsia American Journal of Obstetrics & Gynecology Volume 203, Issue 4 , Pages 366.e1-366.e6, October 2010 Objective: Vitamin D deficiency has been linked to adverse pregnancy outcomes. The purpose of this investigation was to assess total 25-hydroxyvitamin D (25-OH-D) levels at diagnosis of early-onset severe preeclampsia (EOSPE). Study Design: After institutional review board approval, we enrolled subjects with EOSPE (<34 weeks' gestation with severe preeclampsia) in this case-control investigation in a 1:2 ratio with gestation-matched, contemporaneous control subjects. Demographic and outcome information was collected for each subject. Plasma total 25OH-D levels were determined by radioimmunoassay and reported in nanograms per milliliter. Results were analyzed by Mann-Whitney U and multivariable regression. Complied By: Asma Saleem (Product Manager)
  10. 10. Results: Subjects with EOSPE (n = 50) were noted to have decreased total 25-OH-D levels relative to healthy control subjects (n = 100; P < .001). This difference in total 25OH-D remained significant after control for potential confounders. Conclusion: Total 25-OH-D is decreased at diagnosis of EOSPE. Further study is needed to understand the impact of vitamin D deficiency on pregnancy outcomes. Maternal vitamin-D deficiency in Pakistan. Scandinavian Association of Obstetricians and Gynecologists 1998 Nov;77(10):970-3. Abstract OBJECTIVE OF THE STUDY: This study was performed to assess the vitamin D status of healthy Pakistani nursing mothers and their breastfed infants. METHODS: Seventy-one nursing mothers and their breastfed infants belonging to upper and lower socio-economic class were examined 6 weeks to 11 months after delivery. Serum 25-hydroxy vitamin D [25(OH)D], serum calcium, phosphorus and alkaline phosphatase were measured. RESULTS: The mean serum 25(OH)D in mothers was 36.7+/-32.4 nmol/L and 41.25+/-35.4 nmol/ L in infants. Thirty-four (48%) mothers and 37 (52%) infants had levels less than 25 nmol/ L. Significantly higher levels were found in uneducated mothers (p=0.01), mothers of lower socio-economic class (p<0.001) and in those living in mud houses (p<0.001). A significant correlation was found between serum 25(OH)D levels of infants under three months of age and their mothers (p<0.01). CONCLUSIONS: High prevalence of vitamin D deficiency was found in nursing mothers and their infants predominantly in the upper socioeconomic class. Complied By: Asma Saleem (Product Manager)
  11. 11. Vitamin D and cardiovascular disease risk Current Opinion in Clinical Nutrition & Metabolic Care: January 2008 - Volume 11 - Issue 1 - p 7-12 Abstract Purpose of review: Despite our understanding of how to prevent and treat traditional cardiovascular risk factors, cardiovascular disease remains the leading cause of death of both men and women in the US. Thus, there is widespread interest in a number of emerging nontraditional risk factors for the detection of early cardiovascular disease in order to implement aggressive preventive therapies. 25-Hydroxyvitamin D deficiency has been identified as a potential novel cardiovascular disease risk factor. This review outlines what is known about the association of 25-hydroxyvitamin D levels and cardiovascular disease risk. Recent findings: Low 25-hydroxyvitamin D levels have been associated with the cardiovascular disease risk factors of hypertension, obesity, diabetes mellitus and the metabolic syndrome, as well as cardiovascular disease events including stroke and congestive heart failure. Studies suggest vitamin D deficiency may be a contributor to the development of cardiovascular disease potentially through associations with diabetes or hypertension. Summary: Vitamin D deficiency is easy to screen for and easy to treat with supplementation. Further larger observational studies and randomized clinical trials are, however, needed to determine whether vitamin D supplementation could have any potential benefit in reducing future cardiovascular disease events and mortality risk. Vitamin D for the Prevention of Preeclampsia? Nutrition Reviews Volume 63, Issue 7, pages 225–232, July 2005 Abstract:Preeclampsia has been suggested to result from a partial breakdown of tolerance to the developing fetus after maternal immune maladaptation. Several of the proposed immunomodulatory properties of the hormonal vitamin D system could potentially have beneficial effects for successful maintenance of pregnancy. Preeclampsia is characterized by marked changes in vitamin D metabolism. This paper reviews the evidence suggesting that the immunomodulatory properties of 1,25(OH)2D may play a key role in maintaining immunological tolerance in pregnancy, and proposes that ensuring adequate vitamin D status/intake may help in the prevention and management of preeclampsia Complied By: Asma Saleem (Product Manager)
  12. 12. Vitamin D supplementation and reduced risk of preeclampsia in nulliparous women. Epidemiology. 2009 Sep;20(5):720-6. Abstract Background: A recent study showed that nulliparous women who develop preeclampsia had low concentrations of vitamin D in serum sampled in midpregnancy. The aim of the present study was to estimate the association between intake of vitamin D during pregnancy and the risk of preeclampsia in 23,423 nulliparous pregnant women taking part in the Norwegian Mother and Child Cohort Study. Methods: Participating women answered questionnaires at gestational week 15 (general health questionnaire), at week 22 (food frequency questionnaire), and at week 30 (general health questionnaire). Pregnancy outcomes were obtained from the Medical Birth Registry. Nutrient intake was calculated from foods and dietary supplements. We estimated relative risks as odds ratios, and controlled for confounding with multiple logistic regression. Results: The odds ratio of preeclampsia for women with a total vitamin D intake of 1520 microg/d compared with less than 5 microg/d was 0.76 (95% confidence interval = 0.60-0.95). Considering only the intake of vitamin D from supplements, we found a 27% reduction in risk of preeclampsia (OR = 0.73 [0.58-0.92]) for women taking 10-15 microg/d as compared with no supplements. No association was found between intake of vitamin D from the diet alone and the occurrence of preeclampsia. Conclusions: These findings are consistent with other reports of a protective effect of vitamin D on preeclampsia development. However, because vitamin D intake is highly correlated with the intake of long chain n-3 fatty acids in the Norwegian diet, further research is needed to disentangle the separate effects of these nutrients. Complied By: Asma Saleem (Product Manager)
  13. 13. Vitamin D deficiency widespread across India Pakistan News.Net Tuesday 14th December, 2010 (ANI) The results of various studies show severe Vitamin D deficiency across India and Pakistan in all age groups,as well as insufficiency in populations of South-East and East Asia.Bone health experts attending the 1st Asia-Pacific Osteoporosis Meeting in Singapore this week have flagged vitamin D deficiency as a major concern in the region, particularly in South Asia. Nikhil Tandon, Professor of Endocrinology and Metabolism at the All India Institute of Medical Sciences of New Delhi, said, "A lack of exposure to sunshine, genetic traits and dietary habits are all factors which influence vitamin D levels. In certain regions, vitamin D deficiency can also be attributed to skin pigmentation and traditional clothing, as well as air pollution and limited outdoor activity in urban populations."Vitamin D is primarily made in the skin when it is exposed to sunlight, with limited amounts obtained from food sources.At a Vitamin D Roundtable held in conjunction with the meeting, nutrition and bone health experts discussed the importance of encouraging further studies on vitamin D status and risk factors in countries where data are scarce. The group is developing interactive vitamin D maps based on published data of 25(OH)D serum levels, the biomarker used to measure vitamin D status in the blood. Chair of the Roundtable, Professor Robert Josse, Professor in the Departments of Medicine and Nutritional Sciences at the University of Toronto, Canada commented, "The maps will track vitamin D levels by region and different population groups, giving a valuable overview of the prevalence of vitamin D deficiency around the world." "The global maps are innovative tools that will help identify problem areas, encourage awareness and stimulate research studies. By facilitating global comparisons, the maps should provide an incentive for health authorities to implement strategies to improve vitamin D status in the population," he concluded. Low vitamin D levels tied to pregnancy complication By Amy Norton NEW YORK | Wed Aug 18, 2010 12:20pm EDT (Reuters Health) - A new study finds that women who develop a severe form of pregnancy-related high blood pressure tend to have lower blood levels of vitamin D than healthy pregnant women -- raising the possibility that the vitamin plays a role in the complication.The condition is known as early-onset severe preeclampsia, and while it arises in about 2 to 3 percent of pregnancies, it contributes to about 15 percent of Complied By: Asma Saleem (Product Manager)
  14. 14. preterm births in the U.S. each year.Preeclampsia is a syndrome marked by a sudden increase in blood pressure and a buildup of protein in the urine due to stress on the kidneys. Early-onset severe preeclampsia is a particularly serious form that arises before the 34th week of pregnancy. In the current study, researchers found that vitamin D levels were generally lower among 50 women with early severe preeclampsia compared with those of 100 healthy pregnant women. The average vitamin D level in the former group was 18 nanograms per milliliter (ng/mL), versus 32 ng/mL in the latter group.There is debate over what constitutes an adequate level of vitamin D in the blood. But many experts say that at least 32 ng/mL is needed for overall health.The findings, reported in the American Journal of Obstetrics & Gynecology, do not prove that lower vitamin D levels contribute to early-onset severe preeclampsia.They do, however, add to a spate of recent research finding connections between vitamin D levels in the blood, or vitamin D intake, and the risks of a host of health problems.Studies have, for example, linked relatively low vitamin D levels to higher risks of type 1 diabetes and severe asthma attacks in children and, in adults, heart disease, certain cancers and depression.But whether vitamin D is the reason for the excess risks -- and whether taking supplements can curb those risks -- has yet to be shown.A few past studies have found an association between vitamin D and preeclampsia in general. Now more work is needed to see whether pregnant women's vitamin D levels predict the odds of preeclampsia developing -- and whether raising those levels with vitamin D supplements lowers women's risk of the complication, according to Dr. Christopher J. Robinson, of the Medical University of South Carolina in Charleston.If vitamin D is involved in preeclampsia risk, Robinson told Reuters Health, then it might help explain why African American women are at greater risk of the complication than other racial groups -- even when factors like income and healthcare access are taken into account. Vitamin D is naturally synthesized in the skin when it is exposed to sunlight. This process is less efficient in people with darker skin, and studies have found that African Americans commonly have low levels of vitamin D in their blood; a recent study of U.S. teenagers, for example, found that while 14 percent overall had vitamin D deficiency -defined as less than 20 ng/mL -- the same was true of half of black teens.The current findings are based on 50 pregnant women with early-onset preeclampsia seen at the Medical University of South Carolina, along with 100 women with healthy pregnancies.Of the preeclampsia group, 54 percent were deemed to have vitamin D deficiency (less than 20 ng/mL), versus 27 percent of the healthy group. Only 24 percent of women with preeclampsia had vitamin D levels greater than 32 ng/mL, compared with 47 percent of their healthy counterparts.When Robinson and his colleagues accounted for a number of factors in preeclampsia risk -- including older age, heavier body weight and African American race -- vitamin D levels were independently related to the odds of early preeclampsia. Complied By: Asma Saleem (Product Manager)
  15. 15. Severe proximal myopathy with remarkable recovery after vitamin D treatment. The Canadian Journal Neurological Sciences. 2009 May;36(3):336-9. CONCLUSIONS: Vitamin D deficiency is an important treatable cause of osteomalacic myopathy in Saudi Arabia. The diagnosis is frequently delayed or missed. Screening for Vitamin D deficiency in patients with acquired myopathy is needed to identify this treatable disorder. A phase 2 trial exploring the effects of high-dose (10,000 IU/day) vitamin D(3) in breast cancer patients with bone metastases. Cancer. 2010 Jan 15;116(2):284-91. Conclusions: Daily doses of 10,000 IU vitamin D(3) for 4 months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Treatment reduced inappropriately elevated parathyroid hormone levels, presumably caused by long-term bisphosphonate use. There did not appear to be a significant palliative benefit nor any significant change in bone resorption. Vitamin D and chronic widespread pain in a white middleaged British population: evidence from a cross-sectional population survey. Annals of the rheumatic diseases2009 Jun;68(6):817-22. Epub 2008 Aug 12. CONCLUSION: Current vitamin D status was associated with CWP in women but not in men. Follow-up studies are needed to evaluate whether higher vitamin D intake might have beneficial effects on the risk of CWP. Complied By: Asma Saleem (Product Manager)
  16. 16. Post herpetic neuralgia, schwann cell activation and vitamin D. The Medical Hypotheses. 2009 Dec;73(6):927-9. Epub 2009 Jul 26. Abstract While the underlying pathophysiology of herpes zoster infection has been well characterised, many of the mechanisms relating to the subsequent development of post herpetic neuralgia (PHN) remain uncertain. The dorsal horn atrophy and reduction in skin innervation seen in PHN patients does not adequately explain many clinical features or the efficacy of a number of topical treatments. In the central nervous system the glia, their receptors and their secreted signalling factors are now known to have a major influence on neural function. In the peripheral nervous system, schwann cell activation in response to infection and trauma releases a number of neuroexcitatory substances. Activation of the nervi nervorum in the peripheral nervous system also leads to the release of calcitonin gene related peptide, substance P and nitric oxide. Schwann cell and/or nervi nervorum activation could be an additional mechanism of pain generation in PHN. Such a paradigm shift would mean that drugs useful in the treatment of glial cell activation such as naloxone, naltrexone, minocycline, pentoxifyllline, propentofylline, AV411 (ibudilast) and interleukin 10 could be useful in PHN. These drugs could be used systemically or even topically. High dose topical vitamin D would appear to offer particular promise because vitamin D has the ability to both reduce glial inflammation and reduce nitric oxide production. Vitamin D status and its associations with disease activity and severity in African Americans with recent-onset rheumatoid arthritis The Journal of Rheumatology. 2010 Feb;37(2):275-81. Epub 2009 Dec 23 Conclusion: Vitamin D insufficiency is common in African Americans with recent-onset RA. Unadjusted associations of circulating vitamin D with baseline pain, swollen joints, and DAS28 were explained by differences in season, age, and gender and were not significant in multivariate analyses. In contrast to reports of Northern Europeans with Complied By: Asma Saleem (Product Manager)
  17. 17. early inflammatory arthritis, there are not strong associations of 25(OH)-D concentration with symptoms or disease severity in African Americans with RA. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Archives of Internal Medicines. 2009 Mar 23;169(6):626-32. Conclusions: National data demonstrate a marked decrease in serum 25(OH)D levels from the 1988-1994 to the 2001-2004 NHANES data collections. Racial/ethnic differences have persisted and may have important implications for known health disparities. Current recommendations for vitamin D supplementation are inadequate to address the growing epidemic of vitamin D insufficiency. Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer. Breast Cancer Research Treatment. 2010 Jan;119(1):111-8. Epub 2009 Aug 5. Abstract Vitamin D deficiency and insufficiency may contribute to musculoskeletal symptoms and bone loss observed in women taking aromatase inhibitors (AIs). This study was conducted to determine the prevalence of suboptimal vitamin D levels in women initiating adjuvant letrozole for breast cancer and to determine whether supplementation with 50,000 IU of vitamin D3 weekly could reduce musculoskeletal symptoms and fatigue in women who have suboptimal vitamin D levels. Sixty women about to begin an adjuvant AI were enrolled. Baseline 25OHD levels were obtained, and women completed symptom questionnaires. They were then started on letrozole, along with standard dose calcium and vitamin D. Four weeks later, women with baseline 25OHD levels </=40 ng/ml started additional vitamin D3 supplementation at 50,000 IU per week for 12 weeks. 25OHD levels were re-assessed at 4, 10, and 16 weeks; the questionnaires were repeated at weeks 4 and 16. At baseline, 63% of women exhibited vitamin D deficiency (<20 ng/ml) or insufficiency (20- Complied By: Asma Saleem (Product Manager)
  18. 18. 31 ng/ml). 25OHD levels >40 ng/ml were achieved in all 42 subjects who received 12 weeks of supplementation with 50,000 IU vitamin D3 weekly, with no adverse effects. After 16 weeks of letrozole, more women with 25OHD levels >66 ng/ml (median level) reported no disability from joint pain than did women with levels <66 ng/ml (52 vs. 19%; P = 0.026). Vitamin D deficiency and insufficiency are prevalent in post-menopausal women initiating adjuvant AI. Vitamin D3 supplementation with 50,000 IU per week is safe, significantly increases 25OHD levels, and may reduce disability from AI-induced arthralgias. The same annual dose of 292000 IU of vitamin D (cholecalciferol) on either daily or four monthly basis for elderly women Clinical Endocrinology (Oxf). 2010 Apr;72(4):455-61. Epub 2009 May 25. Conclusions: In terms of serum 25(OH)D(3) concentrations, 800 IU daily was more efficient than a 97333 IU every 4 months. However, to increase adherence, the latter is still worth developing. Both treatments increased urinary excretion of calcium, but did not worsen renal function. Vitamin D: Bone and Beyond, Rationale and Recommendations for Supplementation The American Journal of Medicine Volume 122, Issue 9 Pages 793-802 (September 2009) Conclusions:Vitamin D deficiency remains an evolving, worldwide health concern contributing to a multitude of disease entities, whereas vitamin D sufficiency is proving to be essential for overall health and well-being. Although ultraviolet radiation serves as an option to assist in increasing serum vitamin D levels, less harmful and more reliable alternatives exist. Because ultraviolet radiation-induced skin cancer and photoaging are an increasing problem, we recommend vitamin D supplementation over deliberate sun Complied By: Asma Saleem (Product Manager)
  19. 19. exposure to ensure adequate vitamin D levels, especially in fair-skinned individuals. Mounting evidence has shown that it remains vital for physicians and health professionals to counsel their patients and ensure adequate intake to avoid the harmful effects of vitamin D deficiency. Vitamin d and chronic pain in immigrant and ethnic minority patients-investigation of the relationship and comparison with native Western populations. International Journal of Endocrinology. 2010; 2010:753075. Epub 2009 Oct 19. Abstract Vitamin D deficiency has been implicated in chronic pain. Immigrant and ethnic minority populations have been shown to have lower vitamin D levels than native Western populations and often to be vitamin D deficient. This systematic review investigates the relationship between vitamin D and chronic pain in immigrant and ethnic minority populations. Included were studies reporting on 25-OH vitamin D levels in immigrant/ethnic minority populations affected by chronic pain, and/or reporting on the treatment of chronic pain with vitamin D preparations in such populations. We found that 25-OH vitamin D levels were low and often deficient in immigrant/ethnic minority populations. Vitamin D levels depended on the latitude of the study location and hence sunlight exposure. There was insufficient evidence to reach a verdict on the value of treating chronic pain in immigrant/ethnic minority patients with vitamin D preparations because the studies were few, small, and of low quality. Vitamin D insufficiency and musculoskeletal symptoms in breast cancer survivors on aromatase inhibitor therapy Cancer Nursing. 2009 Mar-Apr;32(2):143-50. Abstract:Breast cancer survivors (BCSs) on aromatase inhibitor (AI) therapy often experience musculoskeletal symptoms (joint pain and stiffness, bone and muscle pain, and muscle weakness), and these musculoskeletal symptoms may be related to low serum levels of vitamin D. The primary purpose of this pilot exploratory study was to determine whether serum levels of 25hydroxyvitamin D (25[OH]D) concentration were below normal (<30 ng/mL) in 29 BCSs on AI therapy and if musculoskeletal symptoms were related to these low vitamin D levels. The mean (SD) serum 25(OH)D level was 25.62 (4.93) ng/mL; 86% (n = 25) had levels below 30 ng/mL. Patients reported muscle pain in the neck and back, and there was a significant inverse correlation between Complied By: Asma Saleem (Product Manager)
  20. 20. pain intensity and serum 25(OH)D levels (r = -0.422; P < .05 [2 tailed]). This sample of BCSs taking AIs had below normal levels of serum 25(OH)D despite vitamin D supplements. This is one of the few studies to document a significant relationship between vitamin D levels and muscle pain in BCSs on AI therapy. Findings from this pilot study can be used to inform future studies examining musculoskeletal symptoms in BCSs on AI therapy and relationships with low serum levels of vitamin D. Vitamin D and Bone Health Current Sports Medicine Reports July/August 2010 - Volume 9 - Issue 4 - pp 220-226 Abstract While it is well recognized that vitamin D is necessary for optimal bone health, emerging evidence is finding that adequate vitamin D intake reduces risk for conditions such as stress fracture, total body inflammation, infectious illness, and impaired muscle function. Studies in athletes have found that vitamin D status is variable and is dependent on outdoor training time (during peak sunlight), skin color, and geographic location. Although research has found that athletes generally do not meet the U.S. dietary reference intake for vitamin D, inadequate endogenous synthesis is the most probable reason for insufficient/deficient status. Given the recent findings, it is imperative that sports dietitians and physicians routinely assess vitamin D status and make recommendations to help athletes achieve a serum 25(OH)D concentration of ≥32 and preferably ≥40 ng·mL−1. Further research is needed to determine the effect of vitamin D status on injury, training, and performance in athletes. Athletic Performance and Vitamin D. Medicine and Science in Sports and Exercise 2009 May;41(5):1102-10 ABSTRACT PURPOSE: Activated vitamin D (calcitriol) is a pluripotent pleiotropic secosteroid hormone. As a steroid hormone, which regulates more than 1000 vitamin D-responsive human genes, calcitriol may influence athletic performance. Recent research indicates that intracellular calcitriol levels in numerous human tissues, including nerve and muscle tissue, are increased when inputs of its substrate, the prehormone vitamin D, are increased. METHODS: We reviewed the world's literature for evidence that vitamin D affects physical and athletic performance. RESULTS: Numerous studies, particularly in the German literature in the 1950s, show vitamin D-producing ultraviolet light improves athletic performance. Furthermore, a consistent literature indicates physical and athletic performance is seasonal; it peaks when Complied By: Asma Saleem (Product Manager)
  21. 21. 25-hydroxy-vitamin D [25(OH)D] levels peak, declines as they decline, and reaches its nadir when 25(OH)D levels are at their lowest. Vitamin D also increases the size and number of Type II (fast twitch) muscle fibers. Most cross-sectional studies show that 25(OH)D levels are directly associated with musculoskeletal performance in older individuals. Most randomized controlled trials, again mostly in older individuals, show that vitamin D improves physical performance. CONCLUSIONS: Vitamin D may improve athletic performance in vitamin D-deficient athletes. Peak athletic performance may occur when 25(OH)D levels approach those obtained by natural, full-body, summer sun exposure, which is at least 50 ng x mL(-1). Such 25(OH)D levels may also protect the athlete from several acute and chronic medical conditions. Vitamin D and Human Skeletal Muscle Scandinavian Journal of Medicine & Science in Sports 2010 Apr;20(2):182-90. Epub 2009 Oct Abstract Vitamin D deficiency is an increasingly described phenomenon worldwide, with wellknown impacts on calcium metabolism and bone health. Vitamin D has also been associated with chronic health problems such as bowel and colonic cancer, arthritis, diabetes and cardiovascular disease. In recent decades, there has been increased awareness of the impact of vitamin D on muscle morphology and function, but this is not well recognized in the Sports Medicine literature. In the early 20th century, athletes and coaches felt that ultraviolet rays had a positive impact on athletic performance, and increasingly, evidence is accumulating to support this view. Both cross-sectional and longitudinal studies allude to a functional role for vitamin D in muscle and more recently the discovery of the vitamin D receptor in muscle tissue provides a mechanistic understanding of the function of vitamin D within muscle. The identification of broad genomic and non-genomic roles for vitamin D within skeletal muscle has highlighted the potential impact vitamin D deficiency may have on both under-performance and the risk of injury in athletes. This review describes the current understanding of the role vitamin D plays within skeletal muscle tissue. Vitamin D - Muscle Function and Exercise Performance Pediatric clinics of North America 2010 Jun;57(3):849-61 Abstract Vitamin D has an important role in skeletal muscles. Previously recognized for its effects on bone, it is now known that vitamin D has a much wider spectrum of usefulness for muscle. Complied By: Asma Saleem (Product Manager)
  22. 22. Studies indicate that vitamin D deficiency is pandemic. Those affected include the young and otherwise healthy members of the population, including athletes. Controversy exists regarding the amount of supplementation required to reverse deficiency and the relative effect of such a reversal on overall health. This article reviews current data on the role of vitamin D on muscle function, and explores the potential implications of its deficiency and supplementation on physical fitness and athletic performance. Vitamin D Status and Muscle Function in Post-Menarchal Adolescent Girls The Journal of Clinical Endocrinology and Metabolism 2009 Feb;94(2):559-63. Epub 2008 Nov 25 ABSTRACT Context: There has been a resurgence of vitamin D deficiency among infants, toddlers, and adolescents in the United Kingdom. Myopathy is an important clinical symptom of vitamin D deficiency, yet it has not been widely studied. Objective: Our objective was to investigate the relationship of baseline serum 25 hydroxyvitamin D [25(OH)D] concentration and PTH with muscle power and force. Design: This was a cross-sectional study. Setting: The study was community based in a secondary school. Participants: A total of 99 post-menarchal 12- to 14-yr-old females was included in the study. Main Outcome Measures: Jumping mechanography to measure muscle power, velocity, jump height, and Esslinger Fitness Index from a two-legged counter movement jump and force from multiple one-legged hops was performed. Body height, weight, and serum concentrations of 25(OH)D, PTH, and calcium were measured. Results: Median serum 25(OH)D concentration was 21.3 nmol/liter (range 2.5-88.5) and PTH 3.7 pmol/liter (range 0.47-26.2). After correction for weight using a quadratic function, there was a positive relationship between 25(OH)D and jump velocity (P = 0.002), jump height (P = 0.005), power (P = 0.003), Esslinger Fitness Index (P = 0.003), and force (P = 0.05). There was a negative effect of PTH upon jump velocity (P = 0.04). Conclusion: From these data we conclude that vitamin D was significantly associated with muscle power and force in adolescent girls. Vitamin D and Calcium Supplementation Reduces Cancer Risk American Journal of Clinical Nutrition 2007; 85(6):1586–1591. Complied By: Asma Saleem (Product Manager)
  23. 23. Randomized clinical trials designed to investigate the effects of vitamin D intake on bone health have suggested that higher vitamin D intakes may reduce the risk of cancer. One study involved nearly 1,200 healthy postmenopausal women who took daily supplements of calcium (1,400 mg or 1,500 mg) and vitamin D (25 μg vitamin D, or 1,100 IU-a relatively large dose) or a placebo for 4 years. The women who took the supplements had a 60 percent lower overall incidence of cancer. Vitamin D and Colorectal Cancer American Journal of Clinical Nutrition 1999; 69(6):1330S–1338S. A number of observational studies have investigated whether people with higher vitamin D levels or intake have lower risks of specific cancers, particularly colorectal cancer and breast cancer. Associations of vitamin D with risks of prostate, pancreatic, and other, rarer cancers have also been examined. These studies have yielded inconsistent results, most likely because of the challenges of conducting observational studies of diet. Prospective Study of Serum Vitamin D and Cancer Mortality in the United States Journal of the National Cancer Institute 2007; 99(21):1594–1602. At least one epidemiologic study has reported an association between vitamin D and reduced mortality from colorectal cancer. Among the 16,818 participants in the Third National Health and Nutrition Examination Survey, those with higher vitamin D blood levels (≥80 nmol/L) had a 72 percent lower risk of colorectal cancer death than those with lower vitamin D blood levels (< 50 nmol/L). Vitamin D and Neoplasia Journal of the American Medical Association 2003; 290(22):2959–2967 The vitamin D intakes of 3,000 people from several Veterans Affairs medical centers were examined to determine whether there was an association between intake and advanced colorectal neoplasia (an outcome that included high-risk adenomas as well as colon cancer). Individuals with the highest vitamin D intakes (more than 16 μg, or 645 IU, per day) had a lower risk of developing advanced neoplasia than those with lower intakes. Vitamin D and Colorectal Adenoma Cancer Epidemiology, Biomarkers, and Prevention 2008; 17(11):2958–2969 A pooled analysis of data from these and a number of other observational studies found that higher circulating levels of vitamin D and higher vitamin D intakes were associated with lower risks of colorectal adenoma. Vitamin D and Breast Cancer Journal of Steroid Biochemistry and Molecular Biology 2008; 111(3–5):195–199 Most women in these studies had relatively low vitamin D intakes, and, when the analysis was Complied By: Asma Saleem (Product Manager)
  24. 24. restricted to women with the highest vitamin D intakes (>10 μg, or 400 IU, per day), their breast cancer risks were lower than those of women with the lowest intakes (typically <1.25 μg, or 50 IU, per day). Vitamin D and Pancreatic Cancer Cancer Epidemiology, Biomarkers, and Prevention 2006; 15(9):1688–1695 There is conflicting evidence about vitamin D’s relationship to risk of pancreatic cancer. A study of more than 120,000 men and women from the Health Professionals Follow-Up Study and the Nurses’ Health Study showed that participants with higher dietary intake of vitamin D had progressively lower risk of pancreatic cancer, compared with those who had the lowest intake. Vitamin D deficiency with cognitive impairment in older women Neurology. 2010. 74(1), 27-32. Low vitamin D levels are associated with cognitive impairment, specifically in individuals over age 75. A 2010 study of 752 women found that women with vitamin D deficiency had increased rates of significant cognitive impairment. Low levels of vitamin D have previously been associated with neurological concerns and disorders, but this new research indicates the importance of ample vitamin D for optimal brain health. Cancer Prevention Clinical Cancer Research. 2011. 17(4), 817-26. Vitamin D has been linked with fighting numerous cancers including lung, breast, colon, and prostate. In the case of lung cancer, supplementing with Vitamin D may help offset elevated levels of an enzyme that is associated with the development of aggressive lung cancer tumors. In a 2011 study, lung cancer patients with high vitamin D levels had an 81 percent survival rate after five years compared to those with low levels (41percent survival rate). Scientists are investigating other anti-cancer benefits of taking vitamin D supplementation. Complied By: Asma Saleem (Product Manager)
  25. 25. Vitamin D and the postmenopausal population Menopause Int 2011 17: 102-107 Abstract Vitamin D, a hormone critical to the body's maintenance of serum calcium and phosphorus concentrations, is currently the subject of much scientific interest. Low levels of vitamin D have been observed in many populations and epidemiological studies have suggested a link between this biochemical state and a range of diseases, such as cancer, diabetes and multiple sclerosis. While the consequence of vitamin D deficiency is well documented for bone (rickets and osteomalacia), with mixed findings relating to falls and fractures, a causal link between vitamin D deficiency and these wider health outcomes has not been established. If these relationships were found to be causal, the morbidity and mortality resulting from low levels of vitamin D could be substantial; the current evidence base, however, most robustly supports the assessment of serum 25(OH)-vitamin D in the context of specific symptoms, low bone mineral density or biochemical abnormalities, rather than as an entity to treat in its own right or as the basis for a population-wide screening programme. Prevalence of Vitamin D Deficiency in Healthy Adults in Scotland, and Supplementation Reduces the Proportion That Are Severely Deficient J. Nutr. 2011 141: 1535-1542 Abstract Vitamin D deficiency has recently been implicated as a possible risk factor in the etiology of numerous diseases, including nonskeletal conditions. In humans, skin synthesis following exposure to UVB is a potent source of vitamin D, but in regions with low UVB, individuals are at risk of vitamin D deficiency. Our objectives were to describe the prevalence of vitamin D deficiency and to investigate determinants of plasma 25-hydroxyvitamin D (25-OHD) concentrations in a high northern latitude country. Detailed dietary, lifestyle, and demographic data were collected for 2235 healthy adults (21–82 y) from Scotland. Plasma 25-OHD was measured by liquid chromatography-tandem MS. Among study participants, 34.5% were severely deficient (25-OHD <25 nmol/L) and 28.9% were at high risk of deficiency (25–40 nmol/L). Only 36.6% of participants were at low risk of vitamin D deficiency or had adequate levels Complied By: Asma Saleem (Product Manager)
  26. 26. (>40 nmol/L). Among participants who were taking supplements, 21.3% had a Maystandardized 25-OHD concentration >50 nmol/L, 54.2% had 25–50 nmol/L, and 24.5% had <25 nmol/L, whereas this was 15.6, 43.3, and 41%, respectively, among those who did not take supplements (P < 0.0001). The most important sources of vitamin D were supplements and fish consumption. Vitamin D deficiency in Scotland is highly prevalent due to a combination of insufficient exposure to UVB and insufficient dietary intake. Higher dietary vitamin D intake modestly improved the plasma 25-OHD concentration (P = 0.02) and reduced the proportion of severely deficient individuals (P < 0.0001). In regions with low UVB exposure, dietary and supplement intake may be much more important than previously thought and consideration should be given to increasing the current recommended dietary allowance of 0–10 μg/d for adults in Scotland. A cross-sectional study of vitamin D and insulin resistance in children Arch. Dis. Child. 2011 96: 447-452 Abstract Objective Vitamin D deficiency is common and has been associated with several nonbone/calcium related outcomes. The objective was to determine the association between serum 25-hydroxyvitamin D (25-OH-D) and fasting glucose, insulin and insulin sensitivity in obese and non-obese children. Patients/setting/design Cross-sectional study of 85 children aged 4–18 years recruited from the local Philadelphia community and Sleep Center. Main outcomes measures Fasting blood glucose, insulin and 25-OH-D were measured. Insulin resistance was calculated using homeostasis model assessment (HOMA). Body mass index standard deviation scores (BMI-Z) and pubertal stage were determined. Multivariable linear regression was used to determine factors associated with decreased 25-OH-D and to determine the association of vitamin D with HOMA. Results Median 25-OH-D was 52 nmol/l (IQR 34–76). 26% of subjects were vitamin D sufficient (25-OH-D ≥75 nmol/l), 27% had intermediate values (50–75 nmol/l) and 47% were insufficient (25–50 nmol/l) or frankly deficient (<25 nmol/l). In the multivariable model, older age, higher BMI-Z and African–American race were all negatively associated with 25-OH-D; summer was positively associated with 25-OH-D. Lower 25OH-D was associated with higher fasting blood glucose, insulin and HOMA after adjustment for puberty and BMI-Z. Conclusion Low 25-OH-D, common in the paediatric population at risk for diabetes (older children, African–Americans, children with increasing BMI-Z) is associated with worse insulin resistance. Complied By: Asma Saleem (Product Manager)
  27. 27. Vitamin D Insufficiency in Korea—A Greater Threat to Younger Generation J. Clin. Endocrinol. Metab. 2011 96: 643-651 Abstract Context:Vitamin D status in the Korean population has not been adequately determined. Objective:To investigate the vitamin D status and the prevalence of vitamin D insufficiency in the Korean population, and also identify the predictors for vitamin D insufficiency in Korea. Design and Setting:The Fourth Korea National Health and Nutrition Examination Surveys (KNHANES IV) in the Korean population conducted in 2008. Participants:3,047 males and 3,878 females aged 10 years and older selected in all the 16 administrative districts of South Korea. Main Outcome Measures:Serum 25-hydroxyvitamin D [25(OH)D] levels and the prevalence of vitamin D insufficiency defined as serum 25(OH)D level of less than 20 ng/ml. Results:Vitamin D insufficiency was found in 47.3% of males and 64.5% of females, whereas only 13.2% of male and 6.7% of female population had a serum 25(OH)D level of greater than 30 ng/ml. Vitamin D insufficiency was most prevalent in the age of 20– 29, with a rate of 65.0% in males and 79.9% in females, and least prevalent in the age of 60–69 in males and 50–59 in females. Those who work usually indoors were more predisposed to vitamin D insufficiency. In the adult population, predictors for vitamin D insufficiency included young age groups, spring and winter seasons, living in an urban area, and indoor occupations. Conclusions:Vitamin D insufficiency is very common, and it is now a greater threat to the younger generation in Korea. Current recommendations for vitamin D intakes for Koreans are inadequate, especially for the youth. Complied By: Asma Saleem (Product Manager)
  28. 28. Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia Blood 2011 117: 1492-1498 Abstract Vitamin D insufficiency is common globally and low levels are linked to higher cancer incidence. Although vitamin D insufficiency is related to inferior prognosis in some cancers, no data exist for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We evaluated the relationship of 25(OH)D serum levels with time-totreatment (TTT) and overall survival (OS) in newly diagnosed CLL patients participating in a prospective cohort study (discovery cohort) and a separate cohort of previously untreated patients participating in an observational study (confirmation cohort). Of 390 CLL patients in the discovery cohort, 119 (30.5%) were 25(OH)D insufficient. After a median follow-up of 3 years, TTT (hazard ratio[HR] = 1.66; P = .005) and OS (HR = 2.39; P = .01) were shorter for 25(OH)D-insufficient patients. In the validation cohort, 61 of 153 patients (39.9%) were 25(OH)D insufficient. After a median follow-up of 9.9 years, TTT (HR = 1.59; P = .05) and OS (HR 1.63; P = .06) were again shorter for 25(OH)D-insufficient patients. On pooled multivariable analysis of patients in both cohorts adjusting for age, sex, Rai stage, CD38 status, ZAP-70 status, immunoglobulin heavy chain variable (IGHV) gene mutation status, CD49d status, and cytogenetic abnormalities assessed by interphase fluorescent in situ hybridization testing, 25(OH)D insufficiency remained an independent predictor of TTT (HR = 1.47; P = .008), although the association with OS was not significant (HR = 1.47; P = .07). Vitamin D insufficiency is associated with inferior TTT and OS in CLL patients. Whether normalizing vitamin D levels in deficient CLL patients would improve outcome merits clinical testing. Clinical Response in Patients with Dengue Fever to Oral Calcium plus Vitamin D Administration Proc. West. Pharmacol. Soc. 52: 14-17 (2009) Abstract A dengue epidemic is one of the most important public health problems in the tropical and subtropical areas of the World. In 2005, 7,062 dengue cases were reported in Tamaulipas on Mexico's eastern coast, including 1,832 (26%) cases classified as Dengue Complied By: Asma Saleem (Product Manager)
  29. 29. Hemorrhagic Fever (DHF). Dengue fever (DF) is characterized by fever, intense headache, myalgias, arthralgias, rash, nausea and vomiting. A proportion of infected persons may develop DHF characterized by prominent hemorrhagic manifestations associated with thrombocytopenia. An immune mechanism of thrombocytopenia due to increased platelet destruction appears to be operative in patients with DHF. Excessive capillary permeability may lead to Dengue Shock Syndrome (DSS). Patients with DHF/DSS who also have prolonged fever (> 5 days) are at high risk for concurrent bacteremia. Standard treatment is limited to electrolytic solutions, rest, measurements of body temperature, blood pressure, hematocrit, platelet count, and administration of antipyretics like paracetamol when fever is too high. Extracellular calcium plays a key role in platelet aggregation and for the regulation of the immune response in persons infected with Dengue Virus (DV), and dihydroxy-vitamin D has recently been found to alter IL-12 expression and dendritic cell maturation. We report the cases of five patients who received oral calcium carbonate plus Vitamin D3, who improved overall clinical condition and reduced the duration of signs and symptoms of DF. Vitamin D and the anti-viral state Journal of clinical Virology vol 150 issue 3, March 2011 Vitamin D has long been recognized as essential to the skeletal system. Newer evidence suggests that it also plays a major role regulating the immune system, perhaps including immune responses to viral infec- tion. Interventional and observational epidemiological studies provide evidence that vitamin deficiency may confer increased risk of influenza and respiratory tract infection. Vitamin D deficiency is also preva- lent among patients with HIV infection. Cell culture experiments support the thesis that vitamin D has direct anti-viral effects particularly against enveloped viruses. Though vitamin D’s anti-viral mechanism has not been fully established, it may be linked to vitamin D’s ability to up-regulate the anti-microbial peptides LL-37 and human beta defensin 2. Additional studies are necessary to fully elucidate the efficacy and mechanism of vitamin D as an anti-viral agent. Genetic Influences on Dengue Virus Infections J.F.P. Wagenaar#, A.T.A. Mairuhu and E.C.M. van Gorp Department of Internal Medicine, Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam,The Netherlands Abstract Dengue virus infections are an important cause of morbidity and mortality in the tropics, with 100 million people infected annually and an estimated 2.5 billion people at risk. Human infections can be asymptomatic or can manifest as the self-limited febrile dengue fever, or the more severe and lifethreatening dengue haemorrhagic fever (DHF). There are several possible reasons why some infected individuals might develop a more Complied By: Asma Saleem (Product Manager)
  30. 30. severe form of the disease than others. Antibody enhancement and viral virulence have been implicated in the pathogenesis of DHF but host genetic factors may also be relevant and predispose some individuals to DHF. This review discusses the possible involvement of a variety of genetic polymorphisms on the course of dengue virus infections. It has been shown that several common genetic polymorphisms can influence the susceptibility to dengue hemorrhagic fever. Gene polymorphisms concerning human leucocyte antigens, antibody receptors, inflammatory mediators and other factors with immunoregulatory effects are described. The study of genetic polymorphisms might provide important insights into the pathogenesis of a more severe disease and could have an impact on the design of future vaccines. Reducing fracture risk with calcium and vitamin D Clinical Endocrinology. 2010. 73( 3), 277–285. Low levels of vitamin D contribute to osteopenia, osteoporosis, and bone fractures. It is not news that low calcium intake and poor vitamin D status are key determinants of osteoporosis and fracture risk, but a 2010 study suggests that calcium and vitamin D supplementation is an essential component in maintaining bone health. Together these minerals can improve bone mineralization, and correct secondary hyperparathyroidism , thereby preventing falls. The role of vitamin D in skeletal muscle function Endocrine Reviews. 1986. 7(4), 434-448 New England Journal of Medicine. 2007. 357(3), 266-281 

 Researchers have known for years that skeletal muscle is a target organ for vitamin D and that deficiencies lead to muscle weakness. Specifically, a lack of vitamin D leads to abnormalities in muscle contraction and relaxation, affecting muscle force production. There is also evidence that adequate levels of vitamin D reduce the degradation of protein in muscle. Vitamin D status and muscle function in post-menarchal adolescent girls The Journal of Clinical Endocrinology and Metabolism. 2009. 94(2), 559-563 Optimal levels of vitamin D have been shown to improve muscle power development and jump height. Researchers found that the ability of the muscles to contract and produce force is affected by vitamin D status. Participants in a 2008 study with low Complied By: Asma Saleem (Product Manager)
  31. 31. concentrations of vitamin D generated less power than those with higher concentrations, leading to the conclusion that vitamin D is significantly associated with power and force Further, researchers suggest that sub-optimal force development has negative implications for long-term bone development. Vitamin D status and its relation to muscle mass and muscle fat in young women Journal of Clinical Endocrinology and Metabolism. 2010. (95)4. 1595-1601. Vitamin D is essential for the maintenance of muscle, lean body mass, and for avoiding the development of fat in muscle. A vitamin D deficiency can cause both muscle weakness and an increase in fat mass. A 2010 study found that vitamin D shortage is associated with increased fat infiltration in muscle. Vitamin D deficiency was identified as a serum concentration less than 29 ng/ml, a level that 59 percent of the subjects were below. The vitamin D-insufficient subjects had approximately 24 percent greater muscle fat infiltration than those with vitamin D levels above 29 ng/ml, leading researchers to conclude that vitamin D levels are significantly associated with the degree of fat in skeletal muscle. Vitamin D importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis American Journal of Clinical Nutrition. 2004. 29 (3), 362-371 Skin disorders such as psoriasis can be responsive to treatment with vitamin D because it lessens inflammation. Recent studies have shown that patients suffering from a variety of inflammatory conditions including psoriasis, dermatitis, dandruff, eczema, rosacea, and severe acne were often vitamin D-deficient. Vitamin D may actually help retard the abnormal growth and shedding rate of skin cells in conditions like psoriasis. Complied By: Asma Saleem (Product Manager)
  32. 32. Blood sugar regulation and insulin resistance British Journal of Nutrition. 2009. 4(103), 549 – 555. Journal of Clinical Endocrinology and Metabolism. 2007. 92, 2017-2029. New England Journal of Medicine. 2007. 357(3), 266-81. Supplementing with vitamin D has been shown to increase insulin sensitivity and decrease insulin resistance, indicating that it may be an effective way to offset the symptoms of diabetes. A 2010 study of South Asian women with insulin sensitivity (in a pre-diabetes state) found that taking 4,000 IUs of vitamin D a day resulted in significant decreases in insulin sensitivity, adding to data from a 2009 study that found that higher vitamin D levels lowered diabetes risk. 

 Vitamin D intake and incidence of multiple sclerosis Neurology. 2004. 62(1), 60-65. Neurology. 2011. (76)21, 1824-1830. Vitamin D deficiency is known to contribute to bone mineral loss and osteoporosis, but the good news is that adequate vitamin D levels have a protective effect on the risk of multiple sclerosis (MS). Researchers studied over 190,000 women in two studies called the Nurses’ Study I and II and found that women who used supplemental vitamin D, largely from multivitamins, had a 40 percent lower risk of MS than women who did not supplement. Findings from a second study of African Americans with MS published in 2011 supported the link between vitamin D deficiency and MS. Researchers reported that low vitamin D is a major risk factor for MS susceptibility and severity. Interestingly, in national surveys, African Americans have a lower vitamin D status than non-Hispanic whites and Mexican Americans. The most likely explanation for this disparity is that melanin, the primary determinant of skin pigmentation, functions as an optical filter of ultraviolet (UV) light, limiting vitamin D synthesis. Darker pigmented individuals require longer UV exposure times than lighter pigmented individuals to synthesize equivalent amounts of vitamin D. Complied By: Asma Saleem (Product Manager)
  33. 33. Vitamin D levels, lung function, and steroid response in adult asthma American Journal of Respiratory Critical Care Medicine. 2010. 181(7), 699-704. Journal of Clinical Endocrinology and Metabolism. 2003. 88(1), 157-161 Journal of Clinical Endocrinology and Metabolism. 2010. 89(3), 1196-9. A study at the University of Colorado-Denver found that higher vitamin D levels are associated with improved lung function, reduced airway hyper-responsiveness, and improved in vitro glucocorticoids. The findings suggest that supplementation of vitamin D in patients with asthma may result in decreasing asthma severity and improved treatment response. This study also found that participants with lower vitamin D levels had more inflammation. Also, there was an inverse relationship between the participants’ Body Mass Index and their vitamin D levels, meaning that the fattest participants had the lowest vitamin D levels—more data to support what we already know about vitamin D supporting weight loss and an ideal lean body mass. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa European Journal of Human Reproduction and Embryology. 2011. 26(6), 1307-1317. New research from the University of Copenhagen found that vitamin D is associated with male reproductive health, specifically in regards to normal sperm count and sperm motility. Men with vitamin D deficiency had a lower proportion of mobile and morphologically normal sperm compared with men with high vitamin D levels. For maximal reproductive health and optimal sperm function, vitamin D supplementation is crucial in light of studies indicating that 51percent of men have low D levels. Vitamin D deficiency and risk of cardiovascular disease Journal of the American Heart Association. 2008. 117, 503-511. Vitamin D deficiency is linked with cardiovascular disease and high levels of vitamin D are associated with heart health. The Framingham Heart Study followed 1739 Caucasian individuals with a mean age of 59 years without prior cardiovascular disease. Participants’ vitamin D levels and cardiovascular health was assessed at the beginning of the study and 5 years later. The follow up study identified 120 individuals who had developed a first cardiovascular event. Additionally, for individuals with high blood pressure and low vitamin D levels there was a two-fold risk of cardiovascular Complied By: Asma Saleem (Product Manager)
  34. 34. incidence. The study indicates that maintaining optimal vitamin D levels is crucial in avoiding cardiovascular disease and that vitamin D supplementation could contribute to the prevention of cardiovascular disease. Maternal vitamin D depletion alters neurogenesis in the developing rat brain International Journal of Developmental Neuroscience. 2007. 25, 227–232. Federation of American Societies of Experimental Biology Journal. 2008. 22, 982–1001. Journal of Tropical Pediatrics. 2004. 50, 364–368. In light of the role of vitamin D on brain health, it is not surprising that it plays a role in fetal brain development. Scientists have concluded that pregnant mothers who are deficient in vitamin D have fetuses with developmental impairment in brain cells. Additionally, there is evidence that the offspring of vitamin D-deficient mothers are more susceptible to schizophrenia, bone disorders such as rickets, and the development of diabetes. Vitamin D inadequacy in pregnancy Fertility and Sterility. E-Pub: July 8, 2009. Journal of Clinical Endocrinology and Metabolism. 2009. 94(3), 940–945. Nutrition Reviews. 2010. 68(8), 465-477. Vitamin D plays a role in female fertility and rates of fetal implantation in the uterus. Additionally, vitamin D-deficient women are at risk for pre-eclampsia and gestational diabetes. Interestingly, due to the effect of vitamin D on muscle strength and function, women with low vitamin D levels appear to have a higher rate of cesarean sections due to sub-optimal muscle performance and strength during pregnancy. Serum vitamin D concentrations are related to depression in young adult US population International Archives of Medicine. 3(1), 29. Likelihood of having depression and other brain disorders is significantly higher in vitamin D-deficient persons compared to those with adequate levels. Scientists are not entirely clear how vitamin D plays a role in mental health but they do know that vitamin D enhances the metabolic processes in brain neurons, promoting antioxidant activities that protect from oxidative degenerative processes. Additionally, vitamin D promotes nerve growth, and is an essential enzyme involved in the production of Complied By: Asma Saleem (Product Manager)
  35. 35. neurotransmitters that play a paramount role in mood regulation. Low levels are also linked to incidences of bipolar and schizophrenia. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nature Immunology. 2010. 11, 344–349. New England Journal of Medicine. 2007. 357(3), 266-281. Vitamin D is crucial to activating immune defenses and low serum levels inhibit the body’s T-cells ability to fight off serious infections. Specifically, inactive T-cells rely on vitamin D to activate them so that they can effectively fight off harmful pathogens that enter the body. Along with helping immune cells fight viruses such as the H1N1 flu, vitamin D helps increase the immune response by limiting inflammation, a major obstacle to healing and health. Vitamin D and Chronic Kidney Disease Ethnicity and Disease. 2009. 19(4 Suppl 5), 8-11. Vitamin D is vital for kidney health. Vitamin D is a key compound in treating chronic kidney disease and decreasing subsequent death rates. Understandably, individuals who are vitamin D deficient are at risk to develop kidney disease. The association of serum vitamin D level with presence of metabolic syndrome and hypertension in middle-aged Clinical Endocrinology. 73(3), 330–338. Vitamin D deficiency is strongly associated with high blood pressure and associated metabolic diseases such as diabetes and obesity. Vitamin D supplementation is most effective at significantly reducing blood pressure when it is paired with taking calcium. Complied By: Asma Saleem (Product Manager)
  36. 36. Relationship of vitamin D and parathyroid hormone with obesity and body composition in African Americans Clinical Endocrinology. 72(5), 595–603. Low vitamin D levels may make you fat. Research shows that body fat mass is higher in individuals with vitamin D deficiency and that this shortage correlates with elevated levels of parathyroid hormone and intracellular calcium, considered to be major factors in determining obesity. The increased calcium levels trigger metabolic pathways that promote the accumulation of fat tissue and suppress fat burning. Previously it was thought that low vitamin D levels were consequences of obesity but a 2010 study suggests that reduced levels actually play a role in the development of obesity. High prevalence of hypovitaminosis D status in patients with early Parkinson Disease Archives of Neurology. 2011. 68, 314-319. Researchers have found a relationship between low Vitamin D levels and the early onset of Parkinson’s disease. Parkinson’s disease is an incurable disorder of the nervous system, with symptoms that include trembling hands, stiff muscles, digestive and urinary problems, and a decrease in dexterity and coordination. The average age of onset of the disease is 60, and when the disease appears before the age of 40 it is referred to as early-onset Parkinson’s disease. It is estimated that Parkinson’s affects approximately 5 million people worldwide, with 50,000 new Americans being diagnosed each year. Muhammad Ali, Michael J. Fox, and the Reverend Billy Graham are among the most famous people who have this disease.
 Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents Pediatrics. 2008. 122(5), 1142-1152. The development of rickets and osteomalacia is directly related to vitamin D deficiency. Rickets is a childhood disease that is characterized by the softening of bone, leading to bone fractures and skeletal deformities. For adults, osteomalacia is associated with osteoporosis but is a separate disease that starts with aches in the lumbar region and spreads to the arms and ribs. Bones become deformed, often fracturing, and sufferers typically complain of chronic fatigue. Complied By: Asma Saleem (Product Manager)
  37. 37. Chronic Obstructive Pulmonary Disease Prevention and Treatment American Journal of Respiratory Critical Care Medicine. 183, A2533. Chronic Obstructive Pulmonary Disease, also known as COPD, is characterized by respiratory weakness and the obstruction of the air pathways in the lungs. It typically manifests as emphysema and chronic bronchitis and can be treated by vitamin D supplementation. Considering the effect of vitamin D on increasing muscle strength and diminishing the symptoms of asthma, it is logical that it has positive effects on COPD. A 2011 study found that individuals supplementing with a monthly dose of 100,000 IU of vitamin D had significant improvements in all measures of COPD including oxygen consumption. Vitamin D and clinical disease progression in HIV infection Official Journal of the International AIDS Society. 2010 Vitamin D deficiency affects immune function and is associated with an increased risk of AIDS progression and death from the disease. Conversely, in recent studies individuals with the highest levels of vitamin D have been seen to have a significantly lower risk of death than those with low levels. Vitamin D deficiency is seen as an important co-factor in HIV progression and supplementing with the vitamin may be an effective anti-viral therapy. Low vitamin D levels linked to anemia in children. Annual Meeting of the Pediatric Academic Societies 2011. Low vitamin D levels in children can cause anemia, a severe condition that leads to the damage of vital organs by depriving them of oxygen. Anemia occurs when the body has too few oxygen-carrying red blood cells and is diagnosed by measuring hemoglobin levels. Symptoms of mild anemia include fatigue, lightheadedness, and low energy. Complied By: Asma Saleem (Product Manager)
  38. 38. A review of the critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D deficiency. Molecular Nutrition and Food Research. 2011 55(1), 96–108. Adequate vitamin D plays a role in the prevention of infections and it may be used as a primary treatment for viral, bacterial, and fungal infections. In a recent review of the benefits of vitamin D on immune health and avoiding infections, researchers found that treatments of all of the following conditions benefit from optimal vitamin D levels: tuberculosis, psoriasis, eczema, Crohn's disease, chest infections, wound infections, influenza, urinary tract infections, eye infections, and wound healing. Relationship between Serum Vitamin D, Disease Severity and Airway Remodeling in Children with Asthma Am. J. Respir. Crit. Care Med..2011 Abstract Objective:Rationale little is known about vitamin D status and its effect on asthma pathophysiology in children with severe, therapy resistant asthma (STRA). Relationships between serum vitamin D, lung function, and pathology were investigated in pediatric STRA. Methods: Serum 25-hydroxyvitamin D (25[OH]D3) was measured in 86 children (mean age 11.7 years), 36 STRA, 26 moderate asthmatics (MA) and 24 non-asthmatic controls. Relationships between 25[OH]D3, the asthma control test (ACT), spirometry, corticosteroid usage, and exacerbations were assessed. 22/36 children with STRA underwent fibreoptic bronchoscopy, bronchoalveolar lavage and endobronchial biopsy with assessment of airway inflammation and remodeling. Results 25[OH]D3 levels (median [IQR]) were significantly lower in STRA (28[22-38])nmol/L than MA (42.5[2963])nmol/L and controls (56.5[45-67])nmol/L (p<0.001). There was a positive relationship between 25[OH]D3 levels and %predicted forced expired volume (FEV1) (r=0.4, p<0.001) and forced vital capacity (FVC) (r=0.3, p=0.002) in all subjects. 25[OH]D3 levels were positively associated with ACT (r=0.6, p<0.001), and inversely associated with exacerbations (r=-0.6, p<0.001) and inhaled steroid dose (r=-0.39, p=0.001) in MA & STRA. Airway smooth muscle (ASM) mass, but not epithelial shedding or reticular basement membrane thickness, was inversely related to 25[OH]D3 Complied By: Asma Saleem (Product Manager)
  39. 39. levels (r=-0.6, p=0.008). There was a positive correlation between ASM mass and bronchodilator reversibility (r=0.6, p=0.009) and an inverse correlation between ASM mass and ACT (r=-0.7, p<0.001) Conclusions: Lower vitamin D levels in children with STRA were associated with increased ASM mass, worse asthma control and lung function. The link between vitamin D, airway structure and function suggests vitamin D supplementation may be useful in pediatric STRA. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 2011 Dec; 26(12):3001. Abstract The need, safety, and effectiveness of vitamin D supplementation during pregnancy remain controversial. In this randomized, controlled trial, women with a singleton pregnancy at 12 to 16 weeks' gestation received 400, 2000, or 4000 IU of vitamin D(3) per day until delivery. The primary outcome was maternal/neonatal circulating 25hydroxyvitamin D [25(OH)D] concentration at delivery, with secondary outcomes of a 25(OH)D concentration of 80 nmol/L or greater achieved and the 25(OH)D concentration required to achieve maximal 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] production. Of the 494 women enrolled, 350 women continued until delivery: Mean 25(OH)D concentrations by group at delivery and 1 month before delivery were significantly different (p < 0.0001), and the percent who achieved sufficiency was significantly different by group, greatest in 4000-IU group (p < 0.0001). The relative risk (RR) for achieving a concentration of 80 nmol/L or greater within 1 month of delivery was significantly different between the 2000- and the 400-IU groups (RR = 1.52, 95% CI 1.24-1.86), the 4000- and the 400-IU groups (RR = 1.60, 95% CI 1.321.95) but not between the 4000- and. 2000-IU groups (RR = 1.06, 95% CI 0.93-1.19). Circulating 25(OH)D had a direct influence on circulating 1,25(OH)(2)D(3) concentrations throughout pregnancy (p < 0.0001), with maximal production of 1,25(OH)(2)D(3) in all strata in the 4000-IU group. There were no differences between groups on any safety measure. Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels. It is concluded that vitamin D supplementation of 4000 IU/d for pregnant women is safe and most effective in achieving sufficiency in all women and their neonates regardless of race, whereas the current estimated average requirement is comparatively ineffective at achieving adequate circulating 25(OH)D concentrations, especially in African Americans. Complied By: Asma Saleem (Product Manager)
  40. 40. Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial Am J ClinNutr 2007;85:1586–91. ABSTRACT Background: Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers. However, interventional studies to test this effect are lacking. Objective: The purpose of this analysis was to determine the efficacyof calcium alone and calcium plus vitamin D in reducing incidentcancer risk of all types. Design: This was a 4-y, population-based, double-blind, randomized placebocontrolled trial. The primary outcome was fracture incidence, and the principal secondary outcome was cancer incidence. The subjects were 1179 community-dwelling women randomly selected from the population of healthy postmenopausal women aged_55 y in a 9-county rural area of Nebraska centered at latitude 41.4°N. Subjects were randomly assigned to receive 1400– 1500 mg supplemental calcium/d alone (Ca-only), supplemental calcium plus 1100 IU vitamin D3/d (Ca _ D), or placebo. Results: When analyzed by intention to treat, cancer incidence was lower in the Ca_Dwomen than in the placebo control subjects (P_ 0.03). With the use of logistic regression, the unadjusted relative risks (RR) of incident cancer in the Ca_Dand Ca-only groups were 0.402 (P_0.01) and 0.532 (P_0.06), respectively. When analysis was confined to cancers diagnosed after the first 12 mo, RR for the Ca _ D group fell to 0.232 (CI: 0.09, 0.60; P _ 0.005) but did not change significantly for the Ca-only group. In multiple logistic regression models, both treatment and serum 25-hydroxyvitamin D concentrations were significant, independent predictors of cancer risk. Conclusions: Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women. This trial Complied By: Asma Saleem (Product Manager)
  41. 41. Vitamin D supplementation to improve treatment outcomes among children diagnosed with respiratory infections Biological, behavioral and contextual rationale April 2011 Acute lower respiratory infections, predominantly pneumonia, kill more children under the age of five in every region of the world1 than any other cause. In 2007, of the estimated nine million child deaths that occurred globally, close to 20% or 1.8 million were attributable to pneumonia. Under nutrition has been shown to both increase the severity and overall prevalence of acute lower respiratory infections and is an important factor in determining the mortality rates from severe forms of respiratory infections1–4. Poor nutritional status is a well-recognized cause of early childhood susceptibility to acute lower respiratory infections, along with lower socioeconomic status, ethnicity, suboptimal immunization, tobacco exposure, air pollution and other underlying chronic diseases or infant prematurity5–7. Several micro nutrient interventions have been proposed to both protect and prevent children from developing acute lower respiratory infections. Vitamin D deficiency in children has been strongly associated with risk of acute lower respiratory infections in a number of settings8–13. In Ethiopia, for example, researchers found that 42% of children in hospital with pneumonia had rickets, or severe vitamin D deficiency14. Vitamin D is a group of fat-soluble molecules that are important micro nutrients for health. Both vitamin D2 and vitamin D3 can be obtained from the diet15, 16 but in relatively low quantity. Only fatty fish such as salmon, tuna, sardines or cod liver oil contain significant amounts of vitamin D3. Most vitamin D3 is synthesized in the skin after exposure to UVB light from the sun. For children, fortified foods such as cereals, cheese and milk represent an important source of vitamin D in some countries, although these items contain low and often fluctuating amounts of vitamin D15, 16, 17. Diet contributes to only 10–20% of vitamin D stores in adults, with this percentage most likely even smaller in children 18. During the winter months, when vitamin D synthesis is naturally diminished because of the decreasing hours of sunlight, angle of solar radiation and skin exposed, acute lower respiratory infections are more frequent in adults and children19, 20. Vitamin D is thought to play an important role in immune system regulation, and can potentially protect against infections21, 22, in addition to cancer, cardiovascular disease and autoimmune disorders such as type 1 diabetes23–26. Vitamin D supplementation appears to reduce the incidence of and adverse outcomes from these conditions and others such as acute lower respiratory infections, as well as reducing all-cause mortality27, 28. Complied By: Asma Saleem (Product Manager)
  42. 42. Nutritional interventions aimed at the treatment or prevention of forms of acute lower respiratory infections have thus far been very few in the published literature. A randomized control trial in Afghanistan showed that one high dose of vitamin D3, combined with antibiotic treatment, given to children aged 1–36 months who were hospitalized for pneumonia, did reduce the re-occurrence of pneumonia among children living in an area of high vitamin D deficiency28. Future studies, however, need to be undertaken in different settings to confirm these results, especially among populations of children who are not classified as vitamin D deficient living in high-resource settings. Children in more northern latitudes lacking sun exposure, and darkskinned children, are most at risk of vitamin D deficiency and of developing more severe forms of acute lower respiratory infections29, 30. However, cut-off values for vitamin D sufficiency and recommended daily intake in children are still under debate13, 31, 32. The American Academy of Pediatrics currently recommends supplementation with 400 IU (international units) daily of vitamin D from shortly after birth and continued throughout childhood and adolescence22. Recommendations for increased sun exposure to increase vitamin D3 synthesis in areas where supplementation does not occur must be balanced with concerns over excess exposure to UV radiation33. More data on the role of vitamin D in pediatric infection and immune function are required34. References 1 . Geneva, World Health Organization, 2009. 2 Bulletin of the World Health Organization, 2008, 86:356–364. 3 Turkish Journal of Pediatrics, 2009, 51(2):110–115. 4 Pediatric Pulmonology, 2009, 44(12):1207–1215. 5 Journal of Pediatrics, 2003, 143:S112–S117. 6 Pediatric Pulmonology, 2009, 44(10):981–988. 7 The Lancet, 2010, 375(9725):1545–1555. 8 Acta Paediatrica, 2010, 99(3):389–393. 9 European Journal of Clinical Nutrition, 2004, 58(4):563–567. 10Journal of Tropical Pediatrics, 1994, 40:58. 11 Journal of Infectious Diseases, 2008, 197(5):676–680. 12 . European Journal of Clinical Nutrition, 2009, 63(4):473–477. Complied By: Asma Saleem (Product Manager)
  43. 43. 13 Tropical Medicine and International Health, 2010, 15:1148–1155. 14 The Lancet, 1997, 349:1801–1804. 15 Pediatric Research, 2009, 65:106R–113R. 16 Institute of Medicine. Dietary reference intakes for calcium and vitamin D. 2011. 17 Journal of Pediatrics, 2010, 156(5):698–703. 18 Journal of Nutrition, 2006, 136:1329–1333. 19 Annals of Otology, Rhinology and Laryngology, 2010, 119(1):64–70. 20 Journal of Nutrition, 2005, 135(11):2602–2608. 21 Maternal and Child Nutrition, 2008, 4(2):83–85. 22 Breastfeed Medicine, 2008, 3(4):239–250. 23 American Journal of Clinical Nutrition, 2003, 78(6):1128–34. 24 Nutrition and Clinical Practice, 2007, 22(3):305–22. 25 Journal of Allergy and Clinical Immunology, 2008, 121(2):533–534. 26 American Journal of Clinical Nutrition, 2010, 91(5):1255–1260. 27 Archives of Internal Medicine, 2007, 167:1730–1737. 28 Tropical Medicines and International Health, 2010, 15(10):1148–1155. 29 Journals of Pediatrics and Child Health, 2010. 30 Pediatric Infectious Diseases Journal, 2008, 27(9):853. 31 Journal of Human Nutrition and Dietetics, 2006, 19(3):203–8. 32 Archives of Internal Medicine, 2009, 169(4):384–390. 33 I Geneva, World Health Organization, 2003. 34 Cochrane Database of Systematic Reviews, 2010, Issue 11. Art no: CD008824. Complied By: Asma Saleem (Product Manager)
  44. 44. Vitamin D (New Literature) Jan 2013 Vitamin D Deficiency J Am Coll Cardiol 2008;52:1949–56) Vitamin D deficiency is a highly prevalent condition; present in approximately 30% to 50% of the general population.A growing body of data suggests that low 25-hydroxyvitamin D levels may adversely affect cardiovascular health. Vitamin D deficiency activates the reninangiotensin-aldosterone system and can predispose to hypertension and left ventricular hypertrophy. Additionally, vitamin D deficiency causes an increase in parathyroid hormone, which increases insulin resistance and is associated with diabetes, hypertension, inflammation, and increased Cardio vascular risk. Epidemiologic studies have associated low 25hydroxyvitamin D levels with coronary risk factors and adverse cardiovascular outcomes. Vitamin D supplementation is simple, safe, and inexpensive .Large randomized controlled trials are needed to firmly establish the relevance of vitamin D status to cardiovascular health. In the meanwhile, monitoring serum 25-hydroxyvitamin D levels and correction of vitamin D deficiency is indicated for optimization of musculoskeletal and general health. Complied By: Asma Saleem (Product Manager)
  45. 45. Longitudinal vitamin D status in pregnancy and the risk of pre-eclampsia BJOG 2012;119:832–839. Objective Whether vitamin D deficiency in pregnancy is a cause of preeclampsia remains controversial. Most previous studies to date have assessed exposure at only one time-point in pregnancy. We assessed longitudinal vitamin D status during pregnancy and the risk of preeclampsia. Design: Prospective cohort study. Setting: Seventeen urban obstetric hospitals, Canada. Population :Pregnant women who were participants in a trial of vitamin C and E supplementation for the prevention of preeclampsia.Canadian participants who consented to participate in a biobank with plasma specimens available at the baseline visit were included (n = 697). Methods Maternal plasma 25-hydroxyvitamin D (25(OH)D) concentrations were measured at 12–18 and 24–26 weeks of gestation using chemiluminescence immunoassay. Main outcome measures Pre-eclampsia. Results: Of the women, 39% were vitamin D deficient (25(OH)D <50 nmol/l). A strong positive correlation was observed in maternal 25(OH)D concentrations between the two gestational age windows (r = 0.69, P < 0.0001). Mean maternal 25(OH)D concentrations at 24–26 weeks of gestation were significantly lower in women who subsequently developed pre-eclampsia compared with those who did not (mean ± SD: 48.9 ± 16.8 versus 57.0 ± 19.1 nmol/l, P = 0.03). Women with 25(OH)D < 50 nmol/l at 24–26 weeks gestation experienced an increased risk of pre-eclampsia (adjusted odds ratio 3.24, 95% confidence interval 1.37–7.69), whereas the association was not statistically significant for maternal 25(OH)D level at 12–18 weeks of gestation. Conclusions: Lower maternal 25(OH)D levels at late mid-trimester were associated with an increased risk of pre-eclampsia. Complied By: Asma Saleem (Product Manager)
  46. 46. The relationship between vitamin D and cancer. Clin J Oncol Nurs. 2011 Oct;15(5):557-60. Abstract Vitamin D, a fat-soluble vitamin naturally present in very few foods, is synthesized when ultraviolet rays from sunlight contact the skin. Research suggests that vitamin D insufficiency may result from lack of exposure to sunlight and ultraviolet-B radiation. Individuals from geographic areas of high latitude and low sunlight exposure may be at increased risk for vitamin D deficiency. Emerging evidence supports the protective role of vitamin D in the prevention of several cancers, including breast, colon, and prostate.. Complied By: Asma Saleem (Product Manager)
  47. 47. Vitamin D deficiency and supplementation and relation to cardiovascular health Am J Cardiol. 2012 Feb 1;109(3):359-63 Abstract Recent evidence supports an association between vitamin D deficiency and hypertension, peripheral vascular disease, diabetes mellitus, metabolic syndrome, coronary artery disease, and heart failure. The effect of vitamin D supplementation, however, has not been well studied. We examined the associations between vitamin D deficiency, vitamin D supplementation, and patient outcomes in a large cohort. Serum vitamin D measurements for 5 years and 8 months from a large academic institution were matched to patient demographic, physiologic, and disease variables. The vitamin D levels were analyzed as a continuous variable and as normal (≥30 ng/ml) or deficient (<30 ng/ml). Descriptive statistics, univariate analysis, multivariate analysis, survival analysis, and Cox proportional hazard modeling were performed. Of 10,899 patients, the mean age was 58 ± 15 years, 71% were women (n = 7,758), and the average body mass index was 30 ± 8 kg/m(2). The mean serum vitamin D level was 24.1 ± 13.6 ng/ml. Of the 10,899 patients, 3,294 (29.7%) were in the normal vitamin D range and 7,665 (70.3%) were deficient. Vitamin D deficiency was associated with several cardiovascular-related diseases, including hypertension, coronary artery disease, cardiomyopathy, and diabetes (all p <0.05). Vitamin D deficiency was a strong independent predictor of all-cause death (odds ratios 2.64, 95% confidence interval 1.901 to 3.662, p <0.0001) after adjusting for multiple clinical variables. Vitamin D supplementation conferred substantial survival benefit (odds ratio for death 0.39, 95% confidence interval 0.277 to 0.534, p <0.0001). In conclusion, vitamin D deficiency was associated with a significant risk of cardiovascular disease and reduced survival. Vitamin D supplementation was significantly associated with better survival, specifically in patients with documented deficiency. Complied By: Asma Saleem (Product Manager)
  48. 48. Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents Pediatrics 2008;122:1142–1152 ABSTRACT Rickets in infants attributable to inadequate vitamin D intake and decreased exposure to sunlight continues to be reported in the United States. There are also concerns for vitamin D deficiency in older children and adolescents. Because there are limited natural dietary sources of vitamin D and adequate sunshine exposure for the cutaneous synthesis of vitamin D is not easily determined for a given individual and may increase the risk of skin cancer, the recommendations to ensure adequate vitamin D status have been revised to include all infants, including those who are exclusively breastfed and older children and adolescents. It is now recommended that all infants and children, including adolescents, have a minimum daily intake of 400 IU of vitamin D beginning soon after birth. The current recommendation replaces the previous recommendation of a minimum daily intake of 200 IU/day of vitamin D supplementation beginning in the first 2 months after birth and continuing through adolescence. These revised guidelines for vitamin D intake for healthy infants, children, and adolescents are based on evidence from new clinical trials and the historical precedence of safely giving 400 IU of vitamin D per day in the pediatric and adolescent population. New evidence supports a potential role for vitamin D in maintaining innate immunity and preventing diseases such as diabetes and cancer. The new data may eventually refine what constitutes vitamin D sufficiency or deficiency. Complied By: Asma Saleem (Product Manager)

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