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General Micronutrient Information

Vitamin Basics

A focus on the role of 13 vitamins in human health.

Linus Pauling Institute's Micronutrient Information Center

A source for scientifically accurate information regarding the roles of vitamins, minerals, other nutrients, dietary phytochemicals (plant chemicals that may affect health), and some foods and beverages in preventing disease and promoting health.

National Institute of Health's Office of Dietary Supplements

A list of fact sheets about a wide range of dietary supplements.

Nutri-Facts

In-depth coverage of recent nutrition research, including expert opinions from top names in nutrition.

Fats of Life

Cutting-edge nutrition articles about essential fats and omega-3 fatty acids. Includes summaries of the latest research articles.

100 Years of Vitamins

In 2012, the vitamins celebrate their 100th birthday! Join the party at this microsite, containing information about how the vitamins help the world meet nutritional needs.

Nutrition organizations

The Academy of Nutrition and Dietetics

Science-based food and nutrition information for consumers and nutrition professionals.

International Food Information Council

Food safety, nutrition, and healthful eating information to help consumers make good and safe food choices.

The American Society for Nutrition

A non-profit organization supporting nutrition researchers, clinical nutritionists and industry.

The Nutrition Society

An international society dedicated to promoting human and animal nutrition research.

Dietary recommendations

World Health Organization nutritional requirement resources

Publications on nutritional requirements and food-based dietary guidelines from the Food and Agriculture Organization and the World Health Organization.

US and Canadian Dietary Reference Intakes

Information about North American nutrient intake recommendations based on the Institute of Medicine.

European Food Safety Authority Dietary Reference Values and Dietary Guidelines

EU framework for scientific advice on nutrient intakes.

Australian and New Zealand Nutrient Reference Values

A set of recommendations for nutritional intake based on currently available scientific knowledge.

TalkingNutrition eNewsletter - April edition Back to homepage →

News

  • How Well Do Current Vitamin D Recommendations Supply Adequate Vitamin D? Input from a Dose-Finding Study

    Dietary Reference Intakes for vitamin D were revised recently by the Institute of Medicine to reflect more recent research supporting higher doses needed to achieve normal circulating levels (1). Studies of bone fractures in older populations show that levels of 50 nmol/L are needed to maintain bone health throughout the lifespan. The latest guidelines are that healthy adults to age 70 need 600 IU per day, and those over 71 need 800 IU per day. Exposure of the skin to sunlight also can provide sufficient vitamin D, although this can be limited by sunscreens, in the winter time, and by air pollution or also skin color.

     

    Some proponents of vitamin D supplementation (Holick, et al.) (2) have suggested that recommended levels should be increased further because vitamin D production by the skin is low and the dose response to vitamin D supplementation is not as great as has been shown previously. A recent report by Gallagher, Templin, Sai and Smith describes a dose-finding randomized trial has looked into the effect of dose on circulating vitamin D concentration (3). The study randomized 163 healthy postmenopausal women to one of seven vitamin D3 doses: 400, 800, 1600, 2400, 3200, 4000, or 4800 IU daily for one year. The women were located in Omaha, Nebraska and had vitamin D insufficiency, which was defined as below 50 nmol/L. Vitamin D levels were measured at 6 and 12 months.

     

    90% of participants completed the trial and were included in the final analyses. Mean intake of vitamin D was only 114 IU per day, far short of the 600-800 IU per day recommended for the age groups involved in this study. This means that women would be dependent on sun exposure to meet their vitamin D needs. Not surprisingly, circulating levels of vitamin D were also a concern with an average of 40 nmol/L, which is under the cut-off that indicates sufficiency. There was no significant increase in vitamin D level over the study period for the placebo group, and in the supplemented groups. An increase in serum 25-OHD levels was seen at the lowest dose level of 400 IU for six months, and the authors calculated that 97.5% of the population would reach 50 nmol/L at 600IU. A plateau in circulating vitamin D concentration was reached at 112 nmol/L with a dose of 4000 IU for six months. 97.5% of the population would reach a commonly-cited indicator of an "adequate" status with 1600 IU for 6 months. There was very little difference found between serum levels reached at 6 months and 12 months, indicating that 6 months is long enough to reach stable serum levels with a constant intake with the doses used.

     

    Of the co-variates possibly affecting 25-OH vitamin D concentration, only body mass index had a significant effect. Women in the normal weight category achieved circulating vitamin D levels 18 nmol/L higher than obese women and 12 nmol/L higher than overweight women, both significant, although the difference between overweight and obese women was not significant. This association between BMI and low vitamin D levels has been reported in other studies, such as reported on the US population by Ganji, Zhang and Tangpricha (4). No adverse events relating to dose were found: women were monitored for urinary calcium level, kidney stones, and liver enzymes specifically.

     

    Compared to other studies, the authors of the current paper found a greater serum response to 400 IU than has been found in other studies. Apparently, the low levels of vitamin D in the women in this study gave a greater dose response, that is, women who are deficient show a greater response to supplementation than women replete in vitamin D. This study is important in further work on the safety of vitamin D, and helps establish levels needed to reach certain circulating levels in a deficient population. Vitamin D supplementation studies have primarily been conducted in older populations particularly postmenopausal women, and more research is needed in younger adults and particularly infants and children regarding the safety and health effects of higher doses of vitamin D than are currently recommended.

    --Julia Bird

     

    References

    1. Institute of Medicine. (2012) "DRIs for Calcium and Vitamin D".  Accessed: April 10, 2012.  http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/DRI-Values.aspx

    2. Holick MF, et al. (2012)  J Clin Endocrinol Metab

    3. Gallagher JC, et al. (2012)  Ann Intern Med 156:6;425-37

    4. Ganji V, et al. (2012)  J Nutr 142:3;498-507

  • Integrating Health Care Interventions to Maximize Impact – Combining Vitamins and Vaccinations

    Vaccination is considered one of the great public health achievements of the twentieth century (5). In 1900, vaccines had been developed for five diseases, and 21 more in the following 100 years. This lead to a reduction by more than 95% for many diseases that caused considerable sickness and death and for smallpox and polio, a complete reduction in disease incidence in the United States and many other developed countries. In developing countries, cases of vaccine-preventable diseases are still a concern. In 1974, the World Health Organization established a program to ensure that all children had access to recommended childhood vaccinations (6). At the time, less than 5% of infants were fully immunized. The coverage of one important childhood vaccine, the diphtheria-tenanus-pertussus (DTP), vaccine reached 79% in 2005, with immunization in developing countries improved but still lacking. The World Health Organization produces annual summaries of immunization coverage for 11 vaccinations (7). This data shows that vaccine coverage per country for DTP had a median coverage of 97% for the first dose and 91% for the third dose (all three doses should be given in the first year of life). Coverage can be as low as 55% for the first dose and 33% for the third dose in countries with poor infrastructure or an unstable political situation, but overall these data show that the majority of very young children can be reached with an important healthcare intervention within their first year of life. As infants and young children are at risk of not only infectious diseases but also nutritional deficiencies, Anand, Luman and O'Connor (7a) ask whether the same infrastructure could be used to deliver vitamin A capsules to postpartum mothers and their infants as one of five interventions that is likely to yield the greatest improvement in health for this age group (the other interventions were access to safe drinking water, household ownership of bed netting to prevent malaria, HIV testing and safe sex education). Of all the interventions, vitamin A supplementation is possibly the easiest to administer to the population concurrently with immunizations.

     

    Vitamin A is an essential nutrient that is required for vision, for cell division particularly in the skin and mucous membranes, and also regulates gene expression. Deficiency results in vision loss and an increased susceptibility to infections. It is one of three micronutrients monitored by the World Health Organisation as a nutrient of concern for a large proportion of the population, particularly women of child-bearing age and young children.

     

    The authors looked at whether vitamin A capsules could be provided to children with other routine vaccinations, and to mothers when their child receives the 2 month immunization. They summarized the current coverage of vitamin A supplementation, and compared it to the percentage of the unvaccinated population not receiving vitamin A supplementation to quantify the potential for improving coverage of vitamin A supplements.

     

    In children aged 13 to 24 months, around 66% had ever received vitamin A supplementation in the 12 countries that were used for this review. This ranged from around 55% to 99%. In the population not receiving vitamin A capsules, 63% were vaccinated. The potential percentage of total population that could be reached through vaccination and current vitamin A supplementation delivery systems was 90% assuming 100% uptake of the supplements, and 89% if the uptake was set at a more realistic 95%.

     

    In total, 26 countries had data for 2 months postpartum mothers regarding vitamin A supplementation coverage. Only 33% of mothers receive vitamin A supplements, and of the women not receiving supplements, 82% are vaccinated. This would potentially increase the percentage of women who could be reached through the vaccination program to 89%, and 86% assuming a more realistic 95% uptake rate.

     

    Using existing infrastructure for childhood immunizations has the potential to improve maternal and child vitamin A supplementation in the most vulnerable countries. Given that these populations are also at risk of other micronutrient deficiencies, particularly iron deficiency anemia, the vaccination network could provide further opportunities to help lift people out of a cycle of malnutrition and disease.

    --Julia Bird

     

    References:

    5. National Immunization Program. (1999)  MMWR 48:12;243-48

    6. (2011)  Wkly Epidemiol Rec 86:46;509-13

    7. World Health Organisation. (2012) "WHO/UNICEF estimates of national immunization coverage".  Accessed: April 16, 2012.  http://www.who.int/immunization_monitoring/routine/immunization_coverage/en/index4.html

    7a. Anand A , et al. (2012)  J Infect Dis 205 Suppl 1:S28-39

  • Folic Acid Supplements Reduce Risk of Birth Defects in Women with Diabetes

    The incidence of diabetes mellitus has been increasing, according to a review of hospital births by Albrecht and co-workers. Rates of type 1 diabetes have remained fairly steady at 2-3% of deliveries, however rates of gestational and type 2 diabetes have increased over the past decade, probably due to increasing rates of overweight and older maternal age. Women with diabetes present during the first trimester are at increased risk of miscarriage and having a baby with birth defects, as summarized by Correa et al . The mechanism appears to be a teratogenic effect from higher maternal glucose concentrations when organs are being formed in the first trimester of pregnancy. In addition, higher blood glucose is associated with altered biochemical conditions that may also damage the developing embryo such as elevated triglycerides, branched chain amino acids and reactive oxygen species. Animal studies show that folic acid may help prevent birth defects in pregnant diabetic women (8, 9).

     

    Currently, all women capable of becoming pregnant are advised to ensure an intake of 400 micrograms per day of folic acid before and during pregnancy. A mandate to increase folic acid intakes in the US food supply through fortification of cereal products has prevented 1000 cases of neural tube defects per year, according to the CDC (10), a decrease of 31%.

    The same group lead by Correa recently used data from a case-control survey conducted in 11 US states to evaluate whether folic acid supplementation could reduce the risk of birth defects in diabetic women. Data was derived from the National Birth Defects Prevention Study, an ongoing research project that compares health-related information from women who give birth to a child with birth defects to women with healthy babies. Birth defects sadly affect 1 in 33 newborns, and although many birth defects can be managed, they contribute to 20% of infant deaths. The cause of 70% of birth defects is still unknown. The birth defects studied include congenital heart defects, spina bifida, congenital cataracts, cleft palates and limb deficiencies. The researchers identified women who were taking supplements containing folic acid from their self reported supplement intake between one month before conception and the end of the first trimester.

    The current study looked at maternal factors from 14,721 cases and 5437 controls. Only 0.5% of women in the control group had pre-existing diabetes, compared to 2.4% of the control group, a significant difference that gives an odds ratio of 5.51. Vitamin use was similar in both groups. Women with a child with birth defects were more likely to be obese, were more likely to be aged over 35, and were less likely to have completed any tertiary education. Prenatal care before 10 weeks was more likely in the group with a birth defect detected, although their household income was lower. Not taking vitamins was associated with an increased risk of birth defects for the women with and without prior diagnosed diabetes, although the increase was non-significant in the non-diabetic women, and only a couple of cases of women not taking supplements were found in the group with diabetes.

    Although women taking a supplement containing folic acid were included, supplements usually contained more than just folic acid and included other micronutrients important for prenatal health. The study may also have identified not taking folic acid supplements in women with confirmed diabetes prior to pregnancy as a confounding factor indicative of poorer attention to other aspects of gravid health. Even so, taken together with the results of animal studies that indicate a mechanism, vitamin supplementation may help reduce risk of birth defects in the increasing number of pregnant women with type 2 diabetes.

     

    --Julia Bird

     

    References:

    8. Wentzel P, et al. (2005)  Diabetes 54:2;546-53

    9. Oyama K, et al. (2009)  Endocr J 56:1;29-37

    10. (2004)  MMWR Morb Mortal Wkly Rep 53:17;362-5

     

Events

  • Apr21

    Experimental Biology 2012

    Experimental Biology (EB) is a multidisciplinary, scientific meeting features plenary and award lectures, pre-meeting workshops, oral and poster sessions, on-site career services and exhibits featuring an array of equipment, supplies and publications required for research labs and experimental study. General fields of study include anatomy, physiology, biochemistry, pathology, nutrition, and pharmacology. EB 2012 is open to all members of the sponsoring and guest societies and nonmembers with interest in research and life sciences. The majority of scientists represent university and academic institutions as well as government agencies, non-profit organizations and private corporations. The meeting is comprised of nearly 14,000 scientists and exhibitors representing six sponsoring societies and over 29 guest societies. The 2012 meeting will be held in San DIego, California, USA.

  • Apr23

    Omega 3 Summit 2012 on Optimized Omega 3 Intake from Sustainable Sources

    The Global Omega 3 Summit 2012 is the follow up of the successful policy summit of 2011, where six consensus statements were signed by all participants. The Omega 3 Summit 2012 will build on these consensus statements and look at three themes. 1...How can optimized levels of omega 3s be reached and for what specific health and mental health objectives, and what are safe levels of use. 2...What is the difference of consuming short and long chain omega 3s and can all omega 3s be made beneficial in healthy food and supplement products. 3...How can the supply of long chain omega 3s such as obtained from fish and fish oil, or other new sources such as algae or vegetable sources be made more sustainable and guarantee sufficient supply as needed to obtain the targets set in the consensus positions. The Summit will be held in Ghent, Belgium. It features a presentation by DSM researcher Dr Norman Salem on omega 3 fatty acid metabolism and the requirement for preformed docosahexaenoic acid.

  • Apr27

    World Nutrition Rio2012

    The World Nutrition congress, to be held in Rio de Janeiro, Brazil, will discuss and debate the vast public health nutrition challenges and crises that now confront those in power and policy-makers in multinational bodies, civil society and public interest organisations, national governments, and industry, as well as relevant professional bodies, the academic community, field workers and community groups. It will go further, and will discuss, affirm and agree statements designed to be carried forward after the congress. Rio2012 will address the basic and underlying determinants of food systems and dietary patterns, and thus of disease, health and well-being, as well as their immediate causes. It will also take into account the social, economic, political and environmental as well as the biological determinants of nutrition and health.

  • May7

    Weight of the Nation

    Weight of the Nation (TM) is designed to provide a forum to highlight progress in the prevention and control of obesity through policy and environmental strategies, and is framed around five intervention settings: early care and education; states, tribes and communities; medical care; schools; and workplaces. Plenary and concurrent sessions will highlight impactful strategies implemented in these settings that have lead to policy and environmental supports that have improved population-level health. A key feature of the conference is a move from didactic presentations to an emphasis on interactive discussion between plenary and concurrent session panelists and the audience. The conference is hosted by the Centers for Disease Control and Prevention Division of Nutrition, Physical Activity and Obesity in Washington DC, USA.

Publications

  • Anand A, Luman ET, O’Connor PM.

    Building on success--potential to improve coverage of multiple health interventions through integrated delivery with routine childhood vaccination.

    J Infect Dis 2012;205 Suppl 1:S28-39.

    BACKGROUND: Integrating delivery of nonvaccine interventions with childhood vaccinations has been suggested as a mechanism to accelerate progress toward Millennium Development Goals. METHODS: Demographic health surveys from 28 sub-Saharan African countries were analyzed to determine potential coverage with 5 nonvaccine interventions that could be delivered to children, mothers, and families during routine infant vaccinations. Potential coverage levels were calculated among households with children aged 12-23 months, based on existing coverage of interventions and vaccinations. FINDINGS: Most (>60%) children in families that had not received nonvaccine interventions had been vaccinated. If nonvaccine interventions could be delivered with vaccinations, the median percentage of households owning a bed net could increase from 46% to 92% and those with improved or treated sources of water from 55% to 91%. The median percentage of children who had received vitamin A supplementation could increase from 66% to 90%. Mothers who have been tested for human immunodeficiency virus could increase from 16% to 86%. CONCLUSIONS: In Africa, vaccination programs could provide a platform to substantially increase coverage of nonvaccine interventions. Studies are needed to investigate programmatic approaches to optimize the selection, adoption, and long-term utilization of these interventions and to assess the impact on vaccination and other intervention coverage.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22315383

     

    Ananthakrishnan AN, Khalili H, Higuchi LM, et al.

    Higher predicted vitamin D status is associated with reduced risk of Crohn's disease.

    Gastroenterology 2012;142:482-9.

    BACKGROUND & AIMS: Vitamin D influences innate immunity, which is believed to be involved in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). However, data examining vitamin D status in relation to risk of CD and UC are lacking. METHODS: We conducted a prospective cohort study of 72,719 women (age, 40-73 y) enrolled in the Nurses' Health Study. In 1986, women completed an assessment of diet and lifestyle, from which a 25-hydroxy vitamin D [25(OH)D] prediction score was developed and validated against directly measured levels of plasma 25(OH)D. Through 2008, we confirmed reported diagnoses of incident CD or UC through medical record review. We used Cox proportional hazards modeling to examine the hazard ratio (HR) for incident CD or UC after adjusting for potential confounders. RESULTS: During 1,492,811 person-years of follow-up evaluation, we documented 122 incident cases of CD and 123 cases of UC. The median predicted 25(OH)D level was 22.3 ng/mL in the lowest and 32.2 ng/mL in the highest quartiles. Compared with the lowest quartile, the multivariate-adjusted HR associated with the highest quartile of vitamin D was 0.54 (95% confidence interval [CI], 0.30-.99) for CD (P(trend) = .02) and 0.65 (95% CI, 0.34-1.25) for UC (P(trend) = .17). Compared with women with a predicted 25(OH)D level less than 20 ng/mL, the multivariate-adjusted HR was 0.38 (95% CI, 0.15-0.97) for CD and 0.57 (95% CI, 0.19-1.70) for UC for women with a predicted 25(OH)D level greater than 30 ng/mL. There was a significant inverse association between dietary and supplemental vitamin D and UC, and a nonsignificant reduction in CD risk. CONCLUSIONS: Higher predicted plasma levels of 25(OH)D significantly reduce the risk for incident CD and nonsignificantly reduce the risk for UC in women.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22155183

     

    Arpadi SM, McMahon DJ, Abrams EJ, et al.

    Effect of supplementation with cholecalciferol and calcium on 2-y bone mass accrual in HIV-infected children and adolescents: a randomized clinical trial.

    Am J Clin Nutr 2012;95:678-85.

    BACKGROUND: Skeletal abnormalities have been reported in HIV-infected children and adolescents. Although the etiology is not well understood, vitamin D deficiency may be involved. OBJECTIVE: The study objective was to evaluate the effect of vitamin D and calcium supplementation on bone mass accrual in HIV-infected youth. DESIGN: Perinatally HIV-infected children were randomly assigned to receive vitamin D (100,000 IU cholecalciferol given every 2 mo) and calcium (1 g/d) (supplemented group) or double placebo (placebo group) for 2 y. The total-body bone mineral content (TBBMC), total-body bone mineral density (TBBMD), spine bone mineral content (SBMC), and spine bone mineral density (SBMD) were assessed by using dual-energy X-ray absorptiometry at baseline and at 2 annual follow-up visits. RESULTS: Fifty-nine participants, aged 6-16 y, were randomly assigned to either the supplemented (n = 30) or the placebo (n = 29) group. At enrollment, supplemented and placebo groups did not differ with respect to age, sex, dietary intakes of vitamin D and calcium, mean baseline serum 25-hydroxyvitamin D [25(OH)D] concentration, TBBMC, TBBMD, SBMC, or SBMD. Significant increases in serum 25(OH)D were observed in the supplemented group but not in the placebo group. TBBMC, TBBMD, SBMC, and SBMD increased significantly at 1 and 2 y in both groups. No between-group differences were observed at any time before or after adjustment for stage of sexual maturation by mixed linear model analysis. CONCLUSION: One gram of calcium per day and oral cholecalciferol at a dosage of 100,000 IU every 2 mo administered to HIV-infected children and adolescents did not affect bone mass accrual despite significant increases in serum 25(OH)D concentrations. This trial was registered at clinicaltrials.gov as NCT00724178.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22258265

     

    Barake M, Daher RT, Salti I, et al.

    25-hydroxyvitamin d assay variations and impact on clinical decision making.

    J Clin Endocrinol Metab 2012;97:835-43.

    Context: Laboratories are increasingly shifting to new automated 25-hydroxyvitamin D (25-OHD) assays, with subsequent variability in results. Objective/Setting: We describe the experience at our center with such a shift and illustrate its clinical implications. Methods: 25-OHD levels were measured in 494 patients using Immunodiagnostic Systems RIA (IDS-RIA) and DiaSorin Liaison assays. Sources of variability between the assays were investigated in a subset of 83 samples, retested in the reference laboratory in the United States, and by reviewing the performance reports issued by the International Vitamin D External Quality Assessment Scheme, DEQAS. 25-OHD cut-points for target levels were used to compare the two assays. Results: 25-OHD concentrations were significantly lower when measured with Liaison as compared to IDS-RIA: mean bias was -5 ng/ml, range was -38.1 to 18.7 ng/ml, P < 0.001; the absolute bias was independent of 25-OHD value. Interassay variability was also detected in values obtained in the reference laboratory and in DEQAS reports. Using 20 ng/ml as the target 25-OHD level, 52% of patients required treatment when tested by Liaison, as opposed to 36% by IDS-RIA (P < 0.001). Using 30 ng/ml as the desirable level, the proportions were 79 and 64%, respectively (P < 0.001). The two assays agreed in only 41-68% of subjects, proportions that depended on criteria used to define agreement. Conclusion: A change in 25-OHD assays has a significant impact on results, patient classification, and treatment recommendations. Such variability cannot be ignored when deriving and applying vitamin D guidelines. It also renders universal assay standardization a pressing call.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22238386

     

    Chesney RW.

    The decade of ideas leading to a cure for rickets.

    J Pediatr 2012;160:508-10.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22137665

     

    Chesney RW.

    Environmental Factors in Tiny Tim's Near-Fatal Illness.

    Arch Pediatr Adolesc Med 2012;166:271-5.

    Physicians, Dickens scholars, and historians have tried to diagnose the condition that affected Tiny Tim in A Christmas Carol. Leading entities include tuberculosis (TB), rickets, malnutrition, cerebral palsy, spinal dysraphism, and renal tubular acidosis. This article posits that an examination of the environment of London of 1820 to 1843 (when the novella was written) can provide important clues as to his condition. The blackened skies from burning coal, the crowding of people in tenements, the limited diet of the underclass, and the filth of London resulted in a haven for infectious diseases and rickets in children. Sixty percent of children in London had rickets, and nearly 50% had signs of TB. Tiny Tim likely had a combination of both diseases. After Ebenezer Scrooge's transformation, Scrooge could have ensured an improved diet, sunshine exposure, and possibly cod liver oil for Tiny Tim, which could have led to a "cure." Dickens was familiar with both rickets and TB and wrote about cod liver oil as a possible cure for rickets and scrofula. Improved vitamin D status can result in enhanced macrophage synthesis of 1,25-dihydroxyvitamin D, which increases the synthesis of the antimicrobial peptide cathelicidin (LL-37). This component of the innate immune system has strong killing properties for Mycobacterium tuberculosis. The combination of rickets and TB represent a crippling condition that could be reversed by improved vitamin D status.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22393183

     

    Correa A, Gilboa SM, Botto LD, et al.

    Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus-associated birth defects.

    Am J Obstet Gynecol 2012;206:218 e1-13.

    OBJECTIVE: The purpose of this study was to examine the risk of birth defects in relation to diabetes mellitus and the lack of use of periconceptional vitamins or supplements that contain folic acid. STUDY DESIGN: The National Birth Defects Prevention Study (1997-2004) is a multicenter, population-based case-control study of birth defects (14,721 cases and 5437 control infants). Cases were categorized into 18 types of heart defects and 26 noncardiac birth defects. We estimated odds ratios for independent and joint effects of preexisting diabetes mellitus and a lack of periconceptional use of vitamins or supplements that contain folic acid. RESULTS: The pattern of odds ratios suggested an increased risk of defects that are associated with diabetes mellitus in the absence vs the presence of the periconceptional use of vitamins or supplements that contain folic acid. CONCLUSION: The lack of periconceptional use of vitamins or supplements that contain folic acid may be associated with an excess risk for birth defects due to diabetes mellitus.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22284962

     

    Cudmore MJ, Ramma W, Cai M, et al.

    Resveratrol inhibits the release of soluble fms-like tyrosine kinase (sFlt-1) from human placenta.

    Am J Obstet Gynecol 2012;206:253 e10-5.

    OBJECTIVE: Soluble vascular endothelial growth factor receptor-1 (also know as soluble fms-like tyrosine kinase [sFlt]-1) is a key causative factor of preeclampsia. Resveratrol, a plant phytoalexin, has antiinflammatory and cardioprotective properties. We sought to determine the effect of resveratrol on sFlt-1 release. STUDY DESIGN: Human umbilical vein endothelial cells, transformed human trophoblast-8 (HTR/SVneo)-8/SVneo trophoblast cells, or placental explants were incubated with cytokines and/or resveratrol. Conditioned media were assayed for sFlt-1 by enzyme-linked immunosorbent assay and cell proteins used for Western blotting. RESULTS: Resveratrol inhibited cytokine-induced release of sFlt-1 from normal placental explants and from preeclamptic placental explants. Preincubation of human umbilical vein endothelial cells or HTR-8/SVneo cells with resveratrol abrogated sFlt-1 release. Resveratrol prevented the up-regulation of early growth response protein-1 (Egr-1), a transcription factor necessary for induction of the vascular endothelial growth factor receptor-1 gene and caused up-regulation of heme oxygenase-1, a cytoprotective enzyme found to be dysfunctional in preeclampsia. CONCLUSION: In summary, resveratrol can inhibit sFlt-1 release and up-regulate heme oxygenase-1; thus, may offer therapeutic potential in preeclampsia.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22197494

     

    Davidson ZE, Walker KZ, Truby H.

    Do glucocorticosteroids alter vitamin d status? A systematic review with meta-analyses of observational studies.

    J Clin Endocrinol Metab 2012;97:738-44.

    Context: Vitamin D supplementation is an important adjunct therapy for the prevention and management of glucocorticoid-induced osteoporosis. There has been little exploration of the relationship between glucocorticosteroid (GCS) use and serum 25-hydroxyvitamin D [25(OH)D]. Objective: The aim of this study was to systematically explore how serum 25(OH)D is altered in adult patients receiving GCS. Data Sources: We reviewed Medline and Cinahl databases between January 1970 and August 2011. Study Selection: Experimental studies were included where 25(OH)D was measured in patients more than 18 yr of age receiving GCS therapy. Studies were excluded if patients received at least 400 IU/d (10 mug/d) vitamin D, if GCS treatment was less than 2-wk duration, if more than 50% of the study population received GCS for renal or hepatic disease or after transplant, or if the study population included patients with Cushing's syndrome. A consensus method was used to classify studies. Of identified studies, 3% met the selection criteria. Data Extraction: Data were extracted by a single author. Study quality was assessed using criteria developed by the American Dietetic Association. Data Synthesis: The weighted mean 25(OH)D (by sample size or sd) was 22.4 [95% confidence interval (CI), 19.4, 25.3] ng/ml and 21.0 (95% CI, 13.5, 28.5) ng/ml, respectively. Random effects meta-analysis was used to compare serum 25(OH)D in patients treated with GCS compared to steroid-naive controls (either healthy or with active disease) and in patients before and after GCS administration. Serum 25(OH)D in GCS users was on average -0.5 (95% CI, -1.0, -0.1) ng/ml lower than in healthy controls (P = 0.03; I(2) = 56.4%). Serum 25(OH)D did not differ between GCS users and disease controls [standardized mean difference = 0.0 (95% CI, -0.2, 0.3) ng/ml; P = 0.793; I(2) = 16.2%]. Conclusion: The suboptimal concentrations of serum 25(OH)D found in adults receiving GCS are inadequate for prevention and management of glucocorticoid-induced osteoporosis. Recommendations for vitamin D supplementation should be adjusted accordingly.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22188740

     

    Disanto G, Morahan JM, Barnett MH, Giovannoni G, Ramagopalan SV.

    The evidence for a role of B cells in multiple sclerosis.

    Neurology 2012;78:823-32.

    Understanding the pathogenesis of complex immunologic disorders such as multiple sclerosis (MS) is challenging. Abnormalities in many different cell types are observed in the immune system and CNS of patients with MS and the identification of the primary and secondary events is difficult. Recent studies suggest that the model of MS as a disorder mediated only by T cells is overly simplistic and propose an important role for B cells in the propagation of the disease. B-cell activation in the form of oligoclonal bands (OCB) production is the most consistent immunologic finding in patients with MS. Notably, markers of B-cell activation within the CSF of patients with MS predict conversion from clinically isolated syndrome to clinically definite MS and correlate with MRI activity, onset of relapses, and disability progression. In addition, the main genetic risk factor in MS is associated with OCB production, and environmental agents associated with MS susceptibility (vitamin D and the Epstein-Barr virus) influence B-cell proliferation and function. Finally, the only cell-specific treatments that are effective in patients with MS are monoclonal antibodies targeting the B-cell antigen CD20, suggesting a potentially causative role for B cells. Based on current evidence there is no longer doubt that B cells are relevant to the etiology and pathogenesis of MS. Elucidating the role of B cells in MS will be a fruitful strategy for disease prevention and treatment.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22411958

     

    Fernandes TF, Figueiroa JN, Grande de Arruda IK, Diniz Ada S.

    Effect on Infant Illness of Maternal Supplementation With 400 000 IU Vs 200 000 IU of Vitamin A.

    Pediatrics 2012;129:e960-6.

    BACKGROUND AND OBJECTIVE: Postpartum vitamin A supplementation is a strategy used to combat vitamin A deficiency and seems to reduce maternal/infant morbidity and mortality. However, studies have shown that a dose of 200 000 IU (World Health Organization [WHO] protocol) does not seem to provide adequate retinol levels in maternal breast milk, infant serum, and infant tissue. The objective of this study was to compare the effect of postpartum maternal supplementation with 400 000 IU (International Vitamin A Consultative Group protocol) compared with 200 000 IU of vitamin A on infant morbidity. METHODS: This was a randomized controlled, triple-blinded clinical trial conducted at 2 public maternity hospitals in Recife in northeastern Brazil. There were 276 mother-child pairs that were allocated to 2 treatment groups: 400 000 IU or 200 000 IU of vitamin A. They were followed up for >6 months to evaluate infant morbidity. RESULTS: Fever (rate ratio [RR]: 0.92 [95% confidence interval (CI): 0.75-1.14]), diarrhea (RR: 0.96 [95% CI: 0.72-1.28]), otitis (RR: 0.94 [95% CI: 0.48-1.85]), acute respiratory infection (RR: 1.03 [95% CI: 0.88-1.21]), the need for intravenous rehydration (RR: 2.08 [95% CI: 0.64-2.07]), and the use of antibiotic treatment (RR: 0.80 [95% CI: 0.43-1.47]) did not differ significantly between the 2 treatment groups. CONCLUSIONS: Our findings suggest that postpartum maternal supplementation with 400 000 IU of vitamin A does not provide any additional benefits in the reduction of illness in children aged <6 months; therefore, we do not support the proposal to increase the standard vitamin A dose in the existing WHO protocol.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22412025

     

    Flatley JE, Garner CM, Al-Turki M, et al.

    Determinants of urinary methylmalonic acid concentration in an elderly population in the United Kingdom.

    Am J Clin Nutr 2012;95:686-93.

    BACKGROUND: An age-related deterioration of vitamin B-12 status has been well documented. The early detection of deficiency may prevent the development of serious clinical symptoms, but plasma vitamin B-12 concentration is known to be an imperfect measure of vitamin B-12 status. Urinary methylmalonic acid (MMA) may be a more informative biomarker of vitamin B-12 status; however, biochemical, dietary, and other lifestyle determinants are not known. OBJECTIVE: We identified determinants of urinary MMA concentrations in free-living men and women aged >/=65 y in the United Kingdom. DESIGN: A cross-sectional study in 591 men and women aged 65-85 y, with no clinical evidence of vitamin B-12 deficiency, was conducted to determine the demographic, clinical, and lifestyle determinants of urinary MMA concentration expressed as the ratio of micromoles of MMA to millimoles of creatinine (uMMA ratio). RESULTS: Twenty percent of subjects had plasma vitamin B-12 concentrations <200 pmol/L. Seventeen percent of the variation in the uMMA ratio could be explained by plasma holotranscobalamin and sex; total vitamin B-12 intake and measures of renal function and gastric function made only a small contribution to the model. The uMMA ratio was lower in people with moderately impaired renal function. CONCLUSIONS: Plasma holotranscobalamin and sex were the most important determinants of uMMA ratio in elderly people with no clinical diagnosis of renal impairment. This biomarker might underestimate vitamin B-12 deficiency in a population in which renal impairment is prevalent. This trial was registered at

    www.controlled-trials.com

    as ISRCJN83921062.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22301932

     

    Flynn L, Zimmerman LH, McNorton K, et al.

    Effects of vitamin D deficiency in critically ill surgical patients.

    Am J Surg 2012;203:379-82; discussion 382.

    BACKGROUND: The incidence of vitamin D deficiency in critically ill patients is reported to be up to 50%, with a 3-fold increase in predicted mortality, but limited data exist concerning vitamin D deficiency in critically ill surgical patients. METHODS: Sixty-six adult surgical intensive care unit patients who had 25-hydroxyvitamin D serum levels evaluated from January 2010 to February 2011 were prospectively identified. Patients were divided into groups according to vitamin D level (<20 vs >/=20 ng/mL). RESULTS: Of the 66 patients evaluated, 49 (74%) had vitamin D levels < 20 ng/mL, and 17 (26%) had vitamin D levels >/= 20 ng/mL. Patients with vitamin D levels < 20 versus >/= 20 ng/mL had longer lengths of hospital stay. Lengths of intensive care unit stay were clinically longer, although not significant. Infection rates tended to be higher (P = .09), and a higher incidence of sepsis was seen in the patients with vitamin D levels < 20 ng/mL. CONCLUSIONS: Vitamin D levels < 20 ng/mL have a significant impact on length of stay, organ dysfunction, and infection rates. More data are needed on the value of supplementation to improve these outcomes.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22206852

     

    Gallagher JC, Sai A, Templin T, 2nd, Smith L.

    Dose response to vitamin d supplementation in postmenopausal women: a randomized trial.

    Ann Intern Med 2012;156:425-37.

    Background: Serum 25-hydroxyvitamin D (25-[OH]D) is considered the best biomarker of clinical vitamin D status. Objective: To determine the effect of increasing oral doses of vitamin D(3) on serum 25-(OH)D and serum parathyroid hormone (PTH) levels in postmenopausal white women with vitamin D insufficiency (defined as a 25-[OH]D level </=50 nmol/L) in the presence of adequate calcium intake. These results can be used as a guide to estimate the Recommended Dietary Allowance (RDA) (defined as meeting the needs of 97.5% of the population) for vitamin D(3). Design: Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00472823) Setting: Creighton University Medical Center, Omaha, Nebraska. Participants: 163 healthy postmenopausal white women with vitamin D insufficiency enrolled in the winter or spring of 2007 to 2008 and followed for 1 year. Intervention: Participants were randomly assigned to receive placebo or vitamin D(3), 400, 800, 1600, 2400, 3200, 4000, or 4800 IU once daily. Daily calcium supplements were provided to increase the total daily calcium intake to 1200 to 1400 mg. Measurements: The primary outcomes were 25-(OH)D and PTH levels at 6 and 12 months. Results: The mean baseline 25-(OH)D level was 39 nmol/L. The dose response was curvilinear and tended to plateau at approximately 112 nmol/L in patients receiving more than 3200 IU/d of vitamin D(3). The RDA of vitamin D(3) to achieve a 25-(OH)D level greater than 50 nmol/L was 800 IU/d. A mixed-effects model predicted that 600 IU of vitamin D(3) daily could also meet this goal. Compared with participants with a normal body mass index (<25 kg/m(2)), obese women (>/=30 kg/m(2)) had a 25-(OH)D level that was 17.8 nmol/L lower. Parathyroid hormone levels at 12 months decreased with an increasing dose of vitamin D(3) (P = 0.012). Depending on the criteria used, hypercalcemia occurred in 2.8% to 9.0% and hypercalciuria in 12.0% to 33.0% of participants; events were unrelated to dose. Limitation: Findings may not be generalizable to other age groups or persons with substantial comorbid conditions. Conclusion: A vitamin D(3) dosage of 800 IU/d increased serum 25-(OH)D levels to greater than 50 nmol/L in 97.5% of women; however, a model predicted the same response with a vitamin D(3) dosage of 600 IU/d. These results can be used as a guide for the RDA of vitamin D(3), but prospective trials are needed to confirm the clinical significance of these results. Primary Funding Source: National Institute on Aging.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22431675

     

    Hawkins TL, Roberts JM, Mangos GJ, Davis GK, Roberts LM, Brown MA.

    Plasma uric acid remains a marker of poor outcome in hypertensive pregnancy: a retrospective cohort study.

    BJOG 2012;119:484-92.

    OBJECTIVE: To examine the relationship between hyperuricaemia, haemoconcentration and maternal and fetal outcomes in hypertensive pregnancies. DESIGN: Retrospective analysis of a database of hypertensive pregnancies. SETTING: St George Hospital, a major obstetric unit in Australia. POPULATION: A cohort of 1880 pregnant women without underlying hypertension or renal disease, referred for management of pre-eclampsia or gestational hypertension. METHODS: Demographic, clinical and biochemical data at time of referral and delivery were collected for each pregnancy. Women were grouped according to diagnosis (pre-eclampsia or gestational hypertension) and logistic regression analysis was used to determine the relationship between uric acid, haemoglobin, haematocrit and adverse outcomes; an alpha level of P < 0.01 was used for statistical significance. MAIN OUTCOME MEASURES: Composites of adverse maternal and fetal outcomes. RESULTS: In women with 'benign' GH (without proteinuria or any other maternal clinical feature of pre-eclampsia) gestation-corrected hyperuricaemia was associated with increased risk of a small-for-gestational-age infant (OR 2.5; 95% CI 1.3-4.8) and prematurity (OR 3.2; 95% CI 1.4-7.2), but not with adverse maternal outcome. In the whole cohort of hypertensive pregnant women (those with pre-eclampsia or gestational hypertension) the risk of adverse maternal outcome (OR 2.0; 95% CI 1.6-2.4) and adverse fetal outcome (OR 1.8; 95% CI 1.5-2.1) increased with increasing concentration of uric acid. Hyperuricaemia corrected for gestation provided additional strength to these associations. Haemoglobin and haematocrit were not associated with adverse pregnancy outcome. CONCLUSIONS: Hyperuricaemia in hypertensive pregnancy remains an important finding because it identifies women at increased risk of adverse maternal and particularly fetal outcome; the latter, even in women with gestational hypertension without any other feature of pre-eclampsia.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22251368

     

    Hong SN, Kim JH, Choe WH, et al.

    Circulating vitamin D and colorectal adenoma in asymptomatic average-risk individuals who underwent first screening colonoscopy: a case-control study.

    Dig Dis Sci 2012;57:753-63.

    BACKGROUND: A higher circulating vitamin D level is inversely associated with the risk of colorectal cancer, but the association with adenoma risk is less clear. AIMS: We examined the association between the circulating 25-hydroxyvitamin D(3) [25(OH)D(3)] concentration and colorectal adenoma in asymptomatic average-risk participants undergoing initial screening colonoscopy. METHODS: The study subjects were comprised of 143 cases of colorectal adenomas and 143 age- and gender-matched controls with normal colonoscopy among the 586 asymptomatic average-risk subjects (median age, 58 years; range, 50-73 years) who underwent first screening colonoscopy and measurement of the serum 25(OH)D(3) between December 2009 and April 2010, consistent with winter months of the region. RESULTS: The mean concentration of serum 25(OH)D(3) in the adenoma and control groups was 20.0 +/- 11.0 ng/ml and 25.0 +/- 20.0 ng/ml, respectively (P = 0.009). Using multivariate analysis, higher levels of 25(OH)D(3) were associated with a statistically significant decreased risk of colorectal adenoma after multivariable adjustment (highest vs. lowest quartile OR 0.38, 95% CI 0.18-0.80, P (trend) = 0.012). The inverse association of circulating 25(OH)D(3) with colorectal adenoma was stronger among the patients with proximal adenoma than that among the patients without proximal adenoma (highest vs. lowest quartile OR 0.29, 95% CI 0.13-0.66, P (trend) = 0.001). CONCLUSIONS: The present study suggests that high levels of circulating vitamin D are associated with a decreased risk of colorectal adenoma, and especially adenoma located in the proximal colon.

    http://www.ncbi.nlm.nih.gov/sites/entrez/21984438

     

    Kayira D, Bentley ME, Wiener J, et al.

    A lipid-based nutrient supplement mitigates weight loss among HIV-infected women in a factorial randomized trial to prevent mother-to-child transmission during exclusive breastfeeding.

    Am J Clin Nutr 2012;95:759-65.

    BACKGROUND: Breastfeeding increases metabolic demands on the mother, and excessive postnatal weight loss increases maternal mortality. OBJECTIVE: We evaluated the efficacy of a lipid-based nutrient supplement (LNS) for prevention of excess weight loss in breastfeeding, HIV-infected women. DESIGN: The BAN (Breastfeeding, Antiretrovirals, and Nutrition) Study was a randomized controlled trial in Lilongwe, Malawi. At delivery, HIV-infected mothers and their infants were randomly assigned according to a 2-arm (with and without LNS) by 3-arm (maternal triple-antiretroviral prophylaxis, infant-nevirapine prophylaxis, or neither) factorial design. The 28-wk LNS intervention provided daily energy (700 kcal), protein (20 g), and micronutrients (except for vitamin A) to meet lactation needs. Women were counseled to breastfeed exclusively for 24 wk and to wean by 28 wk. Weight change (0-28 wk) was tested in an intent-to-treat analysis by using 2-factor ANOVA and with longitudinal mixed-effects models. RESULTS: At delivery, the LNS (n = 1184) and control (n = 1185) groups had similar mean weights and BMIs. Women receiving the LNS had less 0-28-wk weight loss (-1.97 compared with -2.56 kg, P = 0.003). This difference remained significant after adjustment for maternal antiretroviral drug therapy and baseline BMI. Women receiving antiretroviral drugs had more weight loss than did those not receiving antiretroviral drugs (-2.93 compared with -1.90 kg, P < 0.001). The benefit of the LNS for reducing weight loss was observed both in those receiving antiretroviral drugs (-2.56 compared with -3.32 kg, P = 0.019) and in those not receiving antiretroviral drugs (-1.63 compared with -2.16 kg, P = 0.034). CONCLUSIONS: The LNS reduced weight loss among HIV-infected, breastfeeding women, both in those taking maternal antiretroviral prophylaxis to prevent postnatal HIV transmission and in those not receiving antiretroviral prophylaxis. Provision of an LNS may benefit HIV-infected, breastfeeding women in resource-limited settings. This trial was registered at clinicaltrials.gov as NCT00164762.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22258269

     

    Lahiri M, Morgan C, Symmons DP, Bruce IN.

    Modifiable risk factors for RA: prevention, better than cure?

    Rheumatology (Oxford) 2012;51:499-512.

    OBJECTIVE: To perform a meta-synthesis of the evidence for modifiable lifestyle risk factors for inflammatory polyarthritis (IP) and RA. METHODS: We performed a MEDLINE literature search. Case-control and cohort studies and systematic reviews published from 1948 through February 2011 and studying modifiable risk factors for RA were retrieved. The main outcome measure was diagnosis of RA according to the standard criteria. RESULTS: Smoking contributes up to 25% of the population burden of RA. The risk is dose related, stronger in males and especially strong for anti-citrullinated peptide antibody positive (ACPA(+)) RA through an interaction with the shared epitope. After smoking cessation, there is, however, a latency of up to 20 years to return to baseline risk. Other associations are less definitive; however, prospective studies suggest that dietary antioxidants and breastfeeding may be protective and that high coffee consumption may increase RA risk. An inverse association with alcohol intake (especially in smokers) and with education/social class (especially seropositive RA) and an increased risk with obesity (seronegative RA) is also noted. CONCLUSION: There is a need for further large-scale prospective studies with a consistent definition of RA phenotype (undifferentiated IP through to ACPA(+)/RF(+) disease). This will ultimately afford the opportunity to evaluate preventative population strategies for RA akin to the well-established programmes for cardiovascular disease and cancer, targeting common risk factors.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22120459

     

    Leven LV, Longbottom K, Jackson AD.

    Efficacy of vitamin D deficiency prevention strategies in Glasgow's maternity services.

    Arch Dis Child 2012;97:299.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22172586

     

    Lin J, Kelsberg G, Safranek S.

    Clinical Inquiry: Is high-dose oral B a safe and effective alternative to a B injection?

    J Fam Pract 2012;61:162-3.

    Yes. Both high-dose oral B and injected B raised low vitamin B levels and improved hematologic parameters and neurologic symptoms in short-term studies (3-4 months) predominantly involving patients with conditions associated with intestinal malabsorption.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22393558

     

    Mealy MA, Newsome S, Greenberg BM, Wingerchuk D, Calabresi P, Levy M.

    Low serum vitamin d levels and recurrent inflammatory spinal cord disease.

    Arch Neurol 2012;69:352-6.

    BACKGROUND: Low 25-hydroxyvitamin D levels have been associated with a higher risk of developing multiple sclerosis and increased relapse rates in patients with multiple sclerosis. As a sterol hormone involved in multiple immunologic pathways, vitamin D may play a role in preventing monophasic immune-mediated central nervous system attacks from developing into recurrent disease. OBJECTIVE: To investigate the association between low serum vitamin D levels and recurrent spinal cord disease. Design, Setting, and Patients We performed a retrospective analysis at Johns Hopkins Transverse Myelitis Center, Baltimore, Maryland, evaluating 25-hydroxyvitamin D levels in 77 patients with monophasic and recurrent inflammatory diseases of the spinal cord. Main Outcome Measure Levels of 25-hydroxyvitamin D. RESULTS: Vitamin D levels are significantly lower in patients who developed recurrent spinal cord disease, adjusting for season, age, sex, and race. CONCLUSIONS: This study provides a basis for a prospective trial of measuring 25-hydroxyvitamin D levels in these patient populations and assessing the influence of vitamin D supplementation on the frequency of relapses in those with recurrent inflammatory spinal cord disease.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22083799

     

    Mok CC, Wong SN, Ma KM.

    Childhood-onset disease carries a higher risk of low bone mineral density in an adult population of systemic lupus erythematosus.

    Rheumatology (Oxford) 2012;51:468-75.

    OBJECTIVE: To study the BMD of patients with SLE according to the age of disease onset. METHODS: Consecutive SLE patients were screened for BMD at the hip, lumbar spine and whole body by the dual-energy X-ray absorptiometry (DXA). Comparison was made between patients who had disease onset in childhood (<18 years) and adulthood (>/=18 years). Factors associated with low BMD were studied by linear regression. RESULTS: A total of 395 SLE patients were studied (94% women; 11% childhood-onset disease). Osteoporosis of the lumbar spine and the hip/femoral neck was present in 20 and 10% of the patients, respectively. Childhood-onset SLE patients were less likely to be post-menopausal, but had significantly lower BMI, longer SLE duration and a higher frequency of ever use of high-dose CSs, CYC and AZA. Despite a significantly younger age, the BMD of the hip, femoral neck and lumbar spine was significantly lower in childhood- than adult-onset SLE patients. In linear regression models, childhood-onset disease was an independent factor for lower BMD at the lumbar spine (beta = -0.18; P = 0.002), hip (beta = -0.20; P = 0.001) and femoral neck (beta = -0.16; P = 0.01) after adjustment for age, sex, BMI, smoking, menopause, SLE duration and damage index, duration and current dose of prednisolone treatment and the ever use of high-dose glucocorticoids, other immunosuppressive agents, calcium, vitamin D and the bisphosphonates. CONCLUSIONS: In adult SLE patients, childhood-onset disease carries a higher risk of osteoporosis, which may possibly be related to a higher cumulative dose of glucocorticoids used for more active disease and failure to achieve a normal peak bone mass during puberty.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22096013

     

    Molina-Aguilera IB, Mendoza-Rodriguez LO, Palma-Rios MA, Danovaro-Holliday MC.

    Integrating health promotion and disease prevention interventions with vaccination in Honduras.

    J Infect Dis 2012;205 Suppl 1:S77-81.

    OBJECTIVE: We sought to review and describe health interventions integrated with immunization delivery, both routine and during national vaccination weeks, in Honduras between 1991 and 2009. METHODS: We compiled and examined all annual evaluation reports from the national Expanded Program on Immunization and reports from the national vaccination weeks (NVWs) between 1988 and 2009. We held discussions with the persons responsible for immunization and other programs in the Health Secretary of Honduras for the same time period. RESULTS: Since 1991, several health promotion and disease prevention interventions have been integrated with immunization delivery, including vitamin A supplementation (since 1994), folic acid supplementation (2003), early detection of retinoblastoma (since 2003), breastfeeding promotion (2007-2008), and disease control activities during public health emergencies, such as cholera control (1991-1992) and dengue control activities (since 1991, when a dengue emergency coincides with the NVW). Success factors included sufficient funds and supplies to ensure sustainability and joint planning, delivery, and monitoring. CONCLUSIONS: Several health interventions have been integrated with vaccination delivery in Honduras for nearly 20 years. The immunization program in Honduras has sufficient structure, organization, acceptance, coverage, and experience to achieve successful integration with health interventions if carefully planned and suitably implemented.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22315390

     

    Murff HJ, Shrubsole MJ, Cai Q, et al.

    Dietary intake of PUFAs and colorectal polyp risk.

    Am J Clin Nutr 2012;95:703-12.

    BACKGROUND: Marine-derived n-3 (omega-3) PUFAs may reduce risk of developing colorectal cancer; however, few studies have investigated the association of n-3 PUFA intakes on colorectal polyp risk. OBJECTIVE: The objective of this study was to examine the associations of dietary PUFA intake on risk of colorectal adenomatous and hyperplastic polyps. DESIGN: This was a colonoscopy-based case-control study that included 3166 polyp-free control subjects, 1597 adenomatous polyp cases, and 544 hyperplastic polyp cases. Dietary PUFA intake was calculated from food-frequency questionnaires and tested for association by using unconditional logistic regression. The urinary prostaglandin E(2) metabolite, which is a biomarker of prostaglandin E(2) production, was measured in 896 participants by using liquid chromatography and tandem mass spectrometry. RESULTS: n-6 PUFAs were not associated with adenomatous or hyperplastic polyps in either men or women. Marine-derived n-3 PUFAs were associated with reduced risk of colorectal adenomas in women only, with an adjusted OR of 0.67 (95% CI: 0.47, 0.97) for the highest quintile of intake compared with the lowest quintile of intake (P-trend = 0.01). Dietary intake of alpha-linolenic acid was associated with an increased risk of hyperplastic polyps in men (P-trend = 0.03), which was not seen in women. In women, but not in men, dietary intake of marine-derived n-3 PUFAs was negatively correlated with urinary prostaglandin E(2) production (r = -0.18; P = 0.002). CONCLUSION: Higher intakes of marine-derived n-3 PUFAs are associated with lower risk of adenomatous polyps in women, and the association may be mediated in part through a reduction in the production of prostaglandin E(2). This trial was registered at clinicaltrials.gov as NCT00625066.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22277551

     

    Papillard-Marechal S, Sznajder M, Hurtado-Nedelec M, et al.

    Iron metabolism in patients with anorexia nervosa: elevated serum hepcidin concentrations in the absence of inflammation.

    Am J Clin Nutr 2012;95:548-54.

    BACKGROUND: Only a few studies based on small cohorts have been carried out on iron status in anorexia nervosa (AN) patients. OBJECTIVE: The aim of this study was to evaluate the role of hepcidin in hyperferritinemia in AN adolescents. DESIGN: Twenty-seven adolescents hospitalized for AN in the pediatric inpatient unit of Ambroise Pare Academic Hospital were enrolled in the study. The control group comprised 11 patients. Hematologic variables and markers of iron status, including serum hepcidin, were measured before and after nutritional rehabilitation. RESULTS: The mean age of patients was 14.4 y. Except for 2 AN patients and 1 control patient, all patients presented normal hemoglobin, vitamin B-12, and folate concentrations. Markers of inflammation and cytokines were normal throughout the study. None of the muscular lysis markers were elevated. Most AN patients had normal serum iron concentrations on admission. Serum ferritin concentrations were significantly higher in patients than in control subjects (198 compared with 49 mug/L, respectively; P < 0.001). The median hepcidin concentration was significantly higher in AN patients than in the control group (186.5 compared with 39.5 mug/L, respectively; P = 0.002). There was a highly significant correlation between ferritinemia and serum hepcidin concentrations (P < 0.0001). After nutritional rehabilitation, a significant reduction was observed (P = 0.004) in serum ferritin. Serum hepcidin analyzed in a smaller number of patients also returned to within the normal range. CONCLUSIONS: Hepcidin and ferritin concentrations were higher in the serum of AN patients, without any evidence of iron overload or inflammation. These concentrations returned to normal after nutritional rehabilitation. These results suggest that nutritional stress induced by malnourishment in the hepatocyte could be yet another mechanism that regulates hepcidin.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22301927

     

    Rayman MP.

    Selenium and human health.

    Lancet 2012;379:1256-68.

    Selenium is incorporated into selenoproteins that have a wide range of pleiotropic effects, ranging from antioxidant and anti-inflammatory effects to the production of active thyroid hormone. In the past 10 years, the discovery of disease-associated polymorphisms in selenoprotein genes has drawn attention to the relevance of selenoproteins to health. Low selenium status has been associated with increased risk of mortality, poor immune function, and cognitive decline. Higher selenium status or selenium supplementation has antiviral effects, is essential for successful male and female reproduction, and reduces the risk of autoimmune thyroid disease. Prospective studies have generally shown some benefit of higher selenium status on the risk of prostate, lung, colorectal, and bladder cancers, but findings from trials have been mixed, which probably emphasises the fact that supplementation will confer benefit only if intake of a nutrient is inadequate. Supplementation of people who already have adequate intake with additional selenium might increase their risk of type-2 diabetes. The crucial factor that needs to be emphasised with regard to the health effects of selenium is the inextricable U-shaped link with status; whereas additional selenium intake may benefit people with low status, those with adequate-to-high status might be affected adversely and should not take selenium supplements.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22381456

     

    Reynolds JA, Haque S, Berry JL, et al.

    25-Hydroxyvitamin D deficiency is associated with increased aortic stiffness in patients with systemic lupus erythematosus.

    Rheumatology (Oxford) 2012;51:544-51.

    OBJECTIVE: To determine the relationship between serum vitamin D and markers of subclinical cardiovascular disease (CVD) in patients with SLE. METHODS: We recruited SLE patients (>/= 4 ACR 1997 criteria) from outpatient clinics between January 2007 and January 2009. Vitamin D deficiency was defined as serum 25(OH)D <20 ng/ml measured by ELISA. Disease activity was measured using the SLEDAI-2K score. Aortic pulse wave velocity (aPWV) was measured using PulseTrace 3600 (Micromedical) and carotid plaque (CP) and intima-media thickness (IMT) assessed using B-mode Doppler US. RESULTS: Seventy-five women with SLE were recruited with a median (interquartile range) disease duration of 16 (8-27) years. Patients with vitamin D deficiency had higher BMI (P = 0.014) and insulin resistance (P = 0.023) than those with 25(OH)D >20 ng/ml. Subjects with SLEDAI-2K >/= 4 had lower 25(OH)D than those with SLEDAI-2K <4 (median 12.9 vs 20.3 ng/ml, P = 0.031). Aortic stiffness was significantly associated with serum 25(OH)D [log(aPWV) beta (95% CI) -0.0217 (-0.038, -0.005), P = 0.010] independently of BMI, CVD risk factors and serum insulin. Adjustment for disease activity reduced the strength of the association. There was no association between 25(OH)D and CP or IMT. CONCLUSIONS: Vitamin D deficiency is associated with increased aortic stiffness in SLE, independent of CVD risk factors and insulin. Increased inflammatory disease activity may be the mechanism by which vitamin D deficiency mediates vascular stiffness in this patient group.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22120462

     

    Ropero-Alvarez AM, Kurtis HJ, Danovaro-Holliday MC, Ruiz-Matus C, Tambini G.

    Vaccination Week in the Americas: an opportunity to integrate other health services with immunization.

    J Infect Dis 2012;205 Suppl 1:S120-5.

    Vaccination Week in the Americas (VWA) is an initiative of the countries and territories of the Americas that works to advance equity and access to vaccination. The initiative focuses on reaching populations with limited access to regular health services and promotes solidarity among countries. As the Expanded Program on Immunization is one of the world's best-established health programs, integrating other interventions with immunization services has been highly promoted. Using data available from the Pan American Health Organization, we explored the extent of integration of other interventions with immunization in Latin American and Caribbean (LAC) countries as part of VWA. At least 14 countries or territories have integrated other interventions with immunization during VWA. The most common integrated intervention is vitamin A supplementation, followed by deworming. However, a variety of other interventions have been integrated, such as educational activities, supplementation with vitamins and minerals, and provision of health services. Data on coverage of integrated interventions are limited. Integration of other interventions with immunization in LAC countries is widespread, and its impact and lessons learned merit further examination.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22315379

     

    Saito K, Yokoyama T, Yoshida H, et al.

    A Significant Relationship between Plasma Vitamin C Concentration and Physical Performance among Japanese Elderly Women.

    J Gerontol A Biol Sci Med Sci 2012;67:295-301.

    BACKGROUND: Maintenance of physical performance could improve the quality of life in old age. Recent studies suggested a beneficial relationship between antioxidant vitamin (eg, vitamin C) intake and physical performance in elderly people. The purpose of this study was to examine the relationship between plasma vitamin C concentration and physical performance among Japanese community-dwelling elderly women. METHODS: This is a cross-sectional study involving elderly females residing in an urban area in Tokyo, Japan, in October 2006. We examined anthropometric measurements, physical performance, lifestyles, and plasma vitamin C concentration of participants. RESULTS: A total of 655 subjects who did not take supplements were analyzed. The mean age (+/-standard deviation) of participants was 75.7 +/- 4.1 years in this study. The geometric mean (geometric standard deviation) of plasma vitamin C concentration was 8.9 (1.5) mug/mL. The plasma vitamin C concentration was positively correlated with handgrip strength, length of time standing on one leg with eyes open and walking speed, and inversely correlated with body mass index. After adjusting for the confounding factors, the quartile plasma vitamin C level was significantly correlated with the subject's handgrip strength (p for trend = .0004) and ability to stand on one leg with eyes open (p for trend = .049). CONCLUSIONS: In community-dwelling elderly women, the concentration of plasma vitamin C related well to their muscle strength and physical performance.

    http://www.ncbi.nlm.nih.gov/sites/entrez/21934124

     

    Skilton MR, Ayer JG, Harmer JA, et al.

    Impaired fetal growth and arterial wall thickening: a randomized trial of omega-3 supplementation.

    Pediatrics 2012;129:e698-703.

    OBJECTIVES: Impaired fetal growth is an independent cardiovascular risk factor and is associated with arterial wall thickening in children. No preventive strategy has been identified. We sought to determine whether dietary omega-3 fatty acid supplementation during early childhood prevents the association between impaired fetal growth and carotid arterial wall thickening. METHODS: The Childhood Asthma Prevention Study was a randomized, controlled single-blind trial in 616 children born at term, recruited antenatally from maternity hospitals in Sydney. Participants were randomized to either a 500-mg-daily fish oil supplement and canola-based margarines and cooking oil (omega-3 group), or a 500-mg-daily sunflower oil supplement and omega-6 fatty acid-rich margarines and cooking oil (control group), from the start of bottle-feeding or 6 months of age until 5 years of age. Carotid intima-media thickness (IMT), a noninvasive measure of subclinical atherosclerosis, was the primary endpoint of a cardiovascular substudy (CardioCAPS) at age 8 years. We examined the association of fetal growth with carotid IMT in children with birth weight <90th percentile (omega-3 group [n = 187], control group [n = 176]). RESULTS: In the control group, fetal growth was inversely associated with carotid IMT, but this was prevented in the omega-3 group (difference between groups of 0.041 mm [95% confidence interval 0.006, 0.075] per kg birth weight, adjusted for gestational age and gender, P(heterogeneity) = .02). CONCLUSIONS: The inverse association of fetal growth with arterial wall thickness in childhood can be prevented by dietary omega-3 fatty acid supplementation over the first 5 years of life.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22351892

     

    Sultan J, Griffin SM, Di Franco F, et al.

    Randomized clinical trial of omega-3 fatty acid-supplemented enteral nutrition versus standard enteral nutrition in patients undergoing oesophagogastric cancer surgery.

    Br J Surg 2012;99:346-55.

    BACKGROUND: Oesophagogastric cancer surgery is immunosuppressive. This may be modulated by omega-3 fatty acids (O-3FAs). The aim of this study was to assess the effect of perioperative O-3FAs on clinical outcome and immune function after oesophagogastric cancer surgery. METHODS: Patients undergoing subtotal oesophagectomy and total gastrectomy were recruited and allocated randomly to an O-3FA enteral immunoenhancing diet (IED) or standard enteral nutrition (SEN) for 7 days before and after surgery, or to postoperative supplementation alone (control group). Clinical outcome, fatty acid concentrations, and HLA-DR expression on monocytes and activated T lymphocytes were determined before and after operation. RESULTS: Of 221 patients recruited, 26 were excluded. Groups (IED, 66; SEN, 63; control, 66) were matched for age, malnutrition and co-morbidity. There were no differences in morbidity (P = 0.646), mortality (P = 1.000) or hospital stay (P = 0.701) between the groups. O-3FA concentrations were higher in the IED group after supplementation (P < 0.001). The ratio of omega-6 fatty acid to O-3FA was 1.9:1, 4.1:1 and 4.8:1 on the day before surgery in the IED, SEN and control groups (P < 0.001). There were no differences between the groups in HLA-DR expression in either monocytes (P = 0.538) or activated T lymphocytes (P = 0.204). CONCLUSION: Despite a significant increase in plasma concentrations of O-3FA, immunonutrition with O-3FA did not affect overall HLA-DR expression on leucocytes or clinical outcome following oesophagogastric cancer surgery. Registration number: ISRCTN43730758 (http://www.controlled-trials.com).

    http://www.ncbi.nlm.nih.gov/sites/entrez/22237467

     

    Tee SI, Yosipovitch G, Chan YC, et al.

    Prevention of Glucocorticoid-Induced Osteoporosis in Immunobullous Diseases With Alendronate: A Randomized, Double-blind, Placebo-Controlled Study.

    Arch Dermatol 2012;148:307-14.

    OBJECTIVE: To evaluate the efficacy and safety of oral alendronate sodium therapy once daily in preventing glucocorticoid-induced bone loss in patients with immunobullous skin diseases treated with long-term glucocorticoid therapy. DESIGN: A 12-month randomized, double-blind, placebo-controlled trial. SETTING: A tertiary referral dermatology center in Singapore. PARTICIPANTS: Patients newly diagnosed as having an immunobullous disease and deemed to require at least 6 months of systemic glucocorticoid therapy. Interventions The patients were randomized to receive either oral alendronate sodium (10 mg/d) or a matching placebo for 12 months. All patients also received concurrent calcium with vitamin D, 2 tablets daily. MAIN OUTCOME MEASURES: Percent change in bone mineral density (BMD) at the lumbar spine and the femoral neck at 12 months. RESULTS: A total of 29 patients (alendronate [n = 15], placebo [n = 14]) were evaluated. The percent change in BMD in the alendronate group was +3.7% and +3.5% at the lumbar spine and the femoral neck, respectively, whereas in the placebo group, it was -1.4% and -0.7% at the lumbar spine and the femoral neck, respectively. The increase in BMD observed in the alendronate group compared with the placebo group was statistically significant at both the lumbar spine (P = .01) and the femoral neck (P = .01). There was also a statistically significant decrease in serum heat-labile alkaline phosphatase levels after 12 months (-32.6%, P < .01) in the alendronate group but not in the placebo group. Adverse events were generally minor, and the frequency of occurrence did not differ significantly between both treatment groups (P = .59). CONCLUSIONS: There were statistically significant increases in BMD at both the lumbar spine (P = .01) and the femoral neck (P = .01) with alendronate therapy. It is imperative to use bisphophonate therapy in patients with immunobullous disorders who are receiving oral corticosteroids because it largely prevents the morbidity associated with low BMD.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22105813

     

    Vanchinathan V, Lim HW.

    A Dermatologist's Perspective on Vitamin D.

    Mayo Clin Proc 2012;87:372-80.

    Vitamin D is a fat-soluble steroid hormone that is crucial for human health and has recently generated controversy regarding its role in human health and disease. In this Special Article, we discuss our dermatologic perspective on vitamin D in a question-and-answer format. We discuss methods of obtaining vitamin D, including cutaneous photobiosynthesis, diet, and supplements and include the recent US Institute of Medicine recommendations. Other reviewed topics include the associations among skin pigmentation, climate, photoprotection, and vitamin D levels. We also elaborate on the popular interest in sun exposure as a method of normalizing vitamin D levels in the context of the risks of solar and artificial radiation. We also discuss groups at risk for vitamin D inadequacy, the need for testing serum vitamin D levels, and the role of phototherapy in patients with malabsorption conditions and hypervitaminosis D, with a focus on patients with sarcoidosis. Finally, we summarize our recommendations on vitamin D.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22425213

     

    Vanstone MB, Oberfield SE, Shader L, Ardeshirpour L, Carpenter TO.

    Hypercalcemia in children receiving pharmacologic doses of vitamin d.

    Pediatrics 2012;129:e1060-3.

    Vitamin D deficiency causes rickets, requiring vitamin D at doses greater than daily dietary intake. Several treatment regimens are found in the literature, with wide dosing ranges, inconsistent monitoring schedules, and lack of age-specific guidelines. We describe 3 children, ages 2 weeks to 2 and 9/12 years, who recently presented to our institution with hypercalcemia and hypervitaminosis D (25-hydroxyvitamin D levels >75 ng/mL), associated with treatment of documented or suspected vitamin D-deficient rickets. The doses of vitamin D used were within accepted guidelines and believed to be safe. The patients required between 6 weeks and 6 months to correct the elevated serum calcium, with time to resolution of hypercalcemia related to age and peak serum calcium, but not to peak 25-hydroxyvitamin D level. With recent widespread use of vitamin D in larger dosages in the general population, we provide evidence that care must be taken when using pharmacologic dosing in small children. With limited dosing guidelines available on a per weight basis, the administration of dosages to infants that are often used in older children and adults has toxic potential, requiring a cautious approach in dose selection and careful follow-up. Dosage recommendations may need to be reassessed, in particular, where follow-up and monitoring may be compromised.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22412034

     

    Wallace A, Ryman T, Mihigo R, et al.

    Strengthening evidence-based planning of integrated health service delivery through local measures of health intervention delivery times.

    J Infect Dis 2012;205 Suppl 1:S40-8.

    BACKGROUND: Immunization services in developing countries are increasingly used as platforms for delivery of other health interventions. A challenge for scaling up interventions on existing platforms is insufficient resources allocated to the integrated platform with the risk of overburdening a health worker. Determining the length of time to deliver priority interventions can be useful information in planning integrated services and mitigating this risk. We designed and tested a methodology for collecting the time needed to deliver selected interventions. METHODOLOGY: At 18 health facilities in Mali, Ethiopia, and Cameroon, we observed delivery of 11 maternal and child health interventions to determine delivery times. We interviewed health workers to estimate self-reported delivery times. RESULTS: Based on observations, vitamin A supplementation (median, 2:00 minutes per child) and vaccinations (median, 2:22 minutes) took the least amount of time to deliver, whereas human immunodeficiency virus counseling and testing and sick infant treatment interventions were among the longest to deliver. Health worker-reported times to deliver interventions were consistently higher than observed times. CONCLUSIONS: Using locally-obtained data can be useful to step for planners to determine how best to use existing platforms for delivering new interventions, particularly since these interventions may require substantially more time to deliver compared to immunizations.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22315385

     

    Wallace AS, Ryman TK, Dietz V.

    Experiences integrating delivery of maternal and child health services with childhood immunization programs: systematic review update.

    J Infect Dis 2012;205 Suppl 1:S6-19.

    BACKGROUND: The World Health Organization and the United Nations Children's Fund promote integration of maternal and child health (MCH) and immunization services as a strategy to strengthen immunization programs. We updated our previous review of integrated programs and reviewed reports of integration of MCH services with immunization programs at the service delivery level. METHODS: Published and unpublished reports of interventions integrating MCH and immunization service delivery were reviewed by searching journal databases and Web sites and by contacting organizations. RESULTS: Among 27 integrated activities, interventions included hearing screening, human immunodeficiency virus services, vitamin A supplementation, deworming tablet administration, malaria treatment, bednet distribution, family planning, growth monitoring, and health education. When reported, linked intervention coverage increased, though not to the level of the corresponding immunization coverage in all cases. Logistical difficulties, time-intensive interventions ill suited for campaign delivery, concern for harming existing services, inadequate overlap of target age groups, and low immunization coverage were identified as challenges. CONCLUSIONS: Results of this review reinforce our 2005 review findings, including importance of intervention compatibility and focus on immunization program strength. Ensuring proper planning and awareness of compatibility of service delivery requirements were found to be important. The review revealed gaps in information about costs, comparison to vertical delivery, and impact on all integrated interventions that future studies should aim to address.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22315388

     

    Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Kusel MM, Hart PH.

    Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development.

    Pediatrics 2012;129:485-93.

    OBJECTIVES: To determine the association between maternal serum 25(OH)-vitamin D concentrations during a critical window of fetal neurodevelopment and behavioral, emotional, and language outcomes of offspring. METHODS: Serum 25(OH)-vitamin D concentrations of 743 Caucasian women in Perth, Western Australia (32 degrees S) were measured at 18 weeks pregnancy and grouped into quartiles. Offspring behavior was measured with the Child Behavior Checklist at 2, 5, 8, 10, 14, and 17 years of age (n range = 412-652). Receptive language was assessed with the Peabody Picture Vocabulary Test-Revised at ages 5 (n = 534) and 10 (n = 474) years. Raw scores were converted to standardized scores, incorporating cutoffs for clinically significant levels of difficulty. RESULTS: chi(2) analyses revealed no significant associations between maternal 25(OH)-vitamin D serum quartiles and offspring behavioral/emotional problems at any age. In contrast, there were significant linear trends between quartiles of maternal vitamin D levels and language impairment at 5 and 10 years of age. Multivariate regression analyses, incorporating a range of confounding variables, found that the risk of women with vitamin D insufficiency (</=46 nmol/L) during pregnancy having a child with clinically significant language difficulties was increased close to twofold compared with women with vitamin D levels >70 nmol/L. CONCLUSIONS: Maternal vitamin D insufficiency during pregnancy is significantly associated with offspring language impairment. Maternal vitamin D supplementation during pregnancy may reduce the risk of developmental language difficulties among their children.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22331333

     

    Wilson CP, Ward M, McNulty H, et al.

    Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up.

    Am J Clin Nutr 2012;95:766-72.

    BACKGROUND: We recently reported that the elevated blood pressure (BP) observed in patients with cardiovascular disease who are homozygous for the 677C-->T polymorphism (TT genotype) in the gene encoding methylenetetrahydrofolate reductase (MTHFR) was responsive to supplementation with riboflavin-the cofactor for MTHFR. OBJECTIVE: The objective was to investigate the effect of riboflavin on BP targeted at patients with the TT genotype 4 y after initial investigation, during which time major changes in the clinical guidelines for antihypertensive therapy were introduced. DESIGN: A total of 83 patients (representing all 3 genotypes) who participated in a placebo-controlled riboflavin intervention for 16 wk in 2004 agreed to take part. Nested within this follow-up, those with the TT genotype (n = 31) proceeded to intervention with riboflavin (1.6 mg/d for 16 wk) or placebo, conducted in a crossover style whereby the 2004 treatment groups were reversed. RESULTS: At follow-up in 2008, as in 2004, patients with the TT genotype had higher systolic BP (P < 0.01), with a nonsignificant trend noted for higher diastolic BP (P = 0.051). Despite the marked changes in antihypertensive therapy that had occurred, BP remained unchanged in patients with the TT genotype at the time of follow-up. Riboflavin supplementation (administered in 2004 and 2008) produced an overall decrease in systolic (-9.2 +/- 12.8 mm Hg; P = 0.001) and diastolic (-6.0 +/- 9.9 mm Hg; P = 0.003) BP. CONCLUSIONS: Optimizing riboflavin status offers a low-cost targeted strategy for managing elevated BP in this genetically at-risk group. These findings, if confirmed in the general population, could have important implications for the prevention of hypertension.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22277556

     

    Wu JH, Lemaitre RN, King IB, et al.

    Association of plasma phospholipid long-chain omega-3 Fatty acids with incident atrial fibrillation in older adults: the cardiovascular health study.

    Circulation 2012;125:1084-93.

    BACKGROUND: Experimental studies suggest that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) may reduce the risk of atrial fibrillation (AF). Prior studies evaluating fish or n-3 PUFA consumption from dietary questionnaires and incident AF have been conflicting. Circulating levels of n-3 PUFAs provide an objective measurement of exposure. METHODS AND RESULTS: Among 3326 US men and women >/=65 years of age and free of AF or heart failure at baseline, plasma phospholipid levels of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were measured at baseline by use of standardized methods. Incident AF (789 cases) was identified prospectively from hospital discharge records and study visit ECGs during 31 169 person-years of follow-up (1992-2006). In multivariable Cox models adjusted for other risk factors, the relative risk in the top versus lowest quartile of total n-3 PUFAs (eicosapentaenoic acid+docosapentaenoic acid+docosahexaenoic acid) levels was 0.71 (95% confidence interval, 0.57-0.89; P for trend=0.004) and of DHA levels was 0.77 (95% confidence interval, 0.62-0.96; P for trend=0.01). Eicosapentaenoic acid and docosapentaenoic acid levels were not significantly associated with incident AF. Evaluated nonparametrically, both total n-3 PUFAs and docosahexaenoic acid showed graded and linear inverse associations with incidence of AF. Adjustment for intervening events such as heart failure or myocardial infarction during follow-up did not appreciably alter results. CONCLUSIONS: In older adults, higher circulating total long-chain n-3 PUFA and docosahexaenoic acid levels were associated with lower risk of incident AF. These results highlight the need to evaluate whether increased dietary intake of these fatty acids could be effective for the primary prevention of AF.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22282329

     

    Zhang X, Spiegelman D, Baglietto L, et al.

    Carotenoid intakes and risk of breast cancer defined by estrogen receptor and progesterone receptor status: a pooled analysis of 18 prospective cohort studies.

    Am J Clin Nutr 2012;95:713-25.

    BACKGROUND: Epidemiologic studies examining associations between carotenoid intakes and risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status are limited. OBJECTIVE: We investigated these associations in a pooled analysis of 18 cohort studies. DESIGN: Of 1,028,438 participants followed for a maximum follow-up of 26 y across studies, 33,380 incident invasive breast cancers were identified. Study-specific RRs and 95% CIs were estimated by using Cox proportional hazards regression and then pooled by using a random-effects model. RESULTS: alpha-Carotene, beta-carotene, and lutein/zeaxanthin intakes were inversely associated with the risk of ER-negative (ER-) breast cancer (pooled multivariable RRs of the comparison between the highest and lowest quintiles): alpha-carotene (0.87; 95% CI: 0.78, 0.97), beta-carotene (0.84; 95% CI: 0.77, 0.93), and lutein/zeaxanthin (0.87; 95% CI: 0.79, 0.95). These variables were not inversely associated with the risk of ER-positive (ER+) breast cancer (pooled multivariable RRs for the same comparison): alpha-carotene (1.04; 95% CI: 0.99, 1.09), beta-carotene (1.04; 95% CI: 0.98, 1.10), and lutein/zeaxanthin (1.00; 95% CI: 0.93, 1.07). Although the pooled RRs for quintile 5 for beta-cryptoxanthin were not significant, inverse trends were observed for ER- and ER+ breast cancer (P-trend </= 0.05). Nonsignificant associations were observed for lycopene intake. The associations were largely not appreciably modified by several breast cancer risk factors. Nonsignificant associations were observed for PR-positive and PR-negative breast cancer. CONCLUSIONS: Intakes of alpha-carotene, beta-carotene, and lutein/zeaxanthin were inversely associated with risk of ER-, but not ER+, breast cancer. However, the results need to be interpreted with caution because it is unclear whether the observed association is real or due to other constituents in the same food sources.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22277553

     

    Zhang Y, Leung DY, Richers BN, et al.

    Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1.

    J Immunol 2012;188:2127-35.

    It is estimated that 1 billion people around the world are vitamin D deficient. Vitamin D deficiency has been linked to various inflammatory diseases. However, the mechanism by which vitamin D reduces inflammation remains poorly understood. In this study, we investigated the inhibitory effects of physiologic levels of vitamin D on LPS-stimulated inflammatory response in human blood monocytes and explored potential mechanisms of vitamin D action. We observed that two forms of the vitamin D, 1,25(OH)(2)D(3), and 25(OH)D(3), dose dependently inhibited LPS-induced p38 phosphorylation at physiologic concentrations, IL-6 and TNF-alpha production by human monocytes. Upon vitamin D treatment, the expression of MAPK phosphatase-1 (MKP-1) was significantly upregulated in human monocytes and murine bone marrow-derived macrophages (BMM). Increased binding of the vitamin D receptor and increased histone H4 acetylation at the identified vitamin D response element of the murine and human MKP-1 promoters were demonstrated. Moreover, in BMM from MKP1(-/-) mice, the inhibition of LPS-induced p38 phosphorylation by vitamin D was completely abolished. Vitamin D inhibition of LPS-induced IL-6 and TNF-alpha production by BMM from MKP-1(-/-) mice was significantly reduced as compared with wild-type mice. In conclusion, this study identified the upregulation of MKP-1 by vitamin D as a novel pathway by which vitamin D inhibits LPS-induced p38 activation and cytokine production in monocytes/macrophages.

    http://www.ncbi.nlm.nih.gov/sites/entrez/22301548

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