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Table of contents
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.
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.
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.
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
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.
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.
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.
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.
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.
Ananthakrishnan AN, Khalili H, Higuchi LM, et al.
Higher predicted vitamin D status is associated with reduced risk of Crohn's disease.
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.
Barake M, Daher RT, Salti I, et al.
25-hydroxyvitamin d assay variations and impact on clinical decision making.
The decade of ideas leading to a cure for rickets.
Environmental Factors in Tiny Tim's Near-Fatal Illness.
Correa A, Gilboa SM, Botto LD, et al.
Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus-associated birth defects.
Cudmore MJ, Ramma W, Cai M, et al.
Resveratrol inhibits the release of soluble fms-like tyrosine kinase (sFlt-1) from human placenta.
Davidson ZE, Walker KZ, Truby H.
Do glucocorticosteroids alter vitamin d status? A systematic review with meta-analyses of observational studies.
Disanto G, Morahan JM, Barnett MH, Giovannoni G, Ramagopalan SV.
The evidence for a role of B cells in multiple sclerosis.
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.
Flatley JE, Garner CM, Al-Turki M, et al.
Determinants of urinary methylmalonic acid concentration in an elderly population in the United Kingdom.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
Flynn L, Zimmerman LH, McNorton K, et al.
Effects of vitamin D deficiency in critically ill surgical patients.
Gallagher JC, Sai A, Templin T, 2nd, Smith L.
Dose response to vitamin d supplementation in postmenopausal women: a randomized trial.
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.
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.
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.
Lahiri M, Morgan C, Symmons DP, Bruce IN.
Modifiable risk factors for RA: prevention, better than cure?
Leven LV, Longbottom K, Jackson AD.
Efficacy of vitamin D deficiency prevention strategies in Glasgow's maternity services.
Lin J, Kelsberg G, Safranek S.
Clinical Inquiry: Is high-dose oral B a safe and effective alternative to a B injection?
Mealy MA, Newsome S, Greenberg BM, Wingerchuk D, Calabresi P, Levy M.
Low serum vitamin d levels and recurrent inflammatory spinal cord disease.
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.
Molina-Aguilera IB, Mendoza-Rodriguez LO, Palma-Rios MA, Danovaro-Holliday MC.
Integrating health promotion and disease prevention interventions with vaccination in Honduras.
Murff HJ, Shrubsole MJ, Cai Q, et al.
Dietary intake of PUFAs and colorectal polyp risk.
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.
Selenium and human health.
Reynolds JA, Haque S, Berry JL, et al.
25-Hydroxyvitamin D deficiency is associated with increased aortic stiffness in patients with systemic lupus erythematosus.
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.
Saito K, Yokoyama T, Yoshida H, et al.
A Significant Relationship between Plasma Vitamin C Concentration and Physical Performance among Japanese Elderly Women.
Skilton MR, Ayer JG, Harmer JA, et al.
Impaired fetal growth and arterial wall thickening: a randomized trial of omega-3 supplementation.
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.
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.
Vanchinathan V, Lim HW.
A Dermatologist's Perspective on Vitamin D.
Vanstone MB, Oberfield SE, Shader L, Ardeshirpour L, Carpenter TO.
Hypercalcemia in children receiving pharmacologic doses of vitamin d.
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.
Wallace AS, Ryman TK, Dietz V.
Experiences integrating delivery of maternal and child health services with childhood immunization programs: systematic review update.
Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Kusel MM, Hart PH.
Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development.
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.
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.
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.
Zhang Y, Leung DY, Richers BN, et al.
Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1.