Future health implications of prenatal and early-life vitamin D status

Current or recent low vitamin D status (or proxy measures such as dietary intake or ambient ultraviolet radiation) is linked to several chronic diseases, including osteoporosis, cancers, and cardiovascular and autoimmune diseases. Low prenatal vitamin D status may also increase susceptibility to such diseases in later life via specific target organ effects and/or through changes to the developing immune system. Maternal vitamin D supplementation during pregnancy could be an important public health measure to decrease risk of a range of chronic diseases, but further research is required to clarify beneficial and adverse effects of high prenatal vitamin D.

Effects of vitamin D supplementation on neuroplasticity in older adults: a double-blinded, placebo-controlled randomised trial

Summary - Vitamin D can improve muscle function and reduce falls, but whether it can strengthen neural connections within the brain and nervous system is not known. This 10-week randomised controlled trial indicates that treatment with 2,000 IU/day vitamin D3 does not significantly alter neuroplasticity relative to placebo in older adults.
Introduction - The purpose of this study was to examine the effects of vitamin D supplementation on neuroplasticity, serum brain-derived neurotrophic factor (BDNF) and muscle strength and function in older adults.
Methods - This was a 10-week double-blinded, placebo-controlled randomised trial in which 26 older adults with 25-hydroxyvitamin D [25OHD] concentrations 25–60 nmol/L were randomised to 2,000 IU/day vitamin D3 or matched placebo. Single- and paired-pulse transcranial magnetic stimulation applied over the motor cortex was used to assess changes in motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI), as measures of corticospinal excitability and inhibition respectively, by recording electromyography (EMG) responses to stimulation from the wrist extensors. Changes in muscle strength, stair climbing power, gait (timed-up-and-go), dynamic balance (four square step test), serum 25(OH)D and BDNF concentrations were also measured.
Results - After 10 weeks, mean 25(OH)D levels increased from 46 to 81 nmol/L in the vitamin D group with no change in the placebo group. The vitamin D group experienced a significant 8&ndash;11 % increase in muscle strength and a reduction in cortical excitability (MEP amplitude) and SICI relative to baseline (all P < 0.05), but these changes were not significantly different from placebo. There was no effect of vitamin D on muscle power, function or BDNF.
Conclusions - Daily supplementation with 2,000 IU vitamin D3 for 10 weeks had no significant effect on neuroplasticity compared to placebo, but the finding that vitamin D treatment alone was associated with a decrease in corticospinal excitability and intracortical inhibition warrants further investigation as this suggests that it may improve the efficacy of neural transmission within the corticospinal pathway.

Effects of combined calcium and vitamin D supplementation on insulin secretion, insulin sensitivity and β-cell function in multi-ethnic vitamin D-deficient adults at risk for type 2 diabetes: A pilot randomized, placebo-controlled trial

Objectives: To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, β-cell function, inflammation and metabolic markers.

The effects of progressive resistance training combined with a whey-protein drink and vitamin D supplementation on glycaemic control, body composition and cardiometabolic risk factors in older adults with type 2 diabetes: study protocol for a randomized c

While physical activity, energy restriction and weight loss are the cornerstone of type 2 diabetes management, less emphasis is placed on optimizing skeletal muscle mass. As muscle is the largest mass of insulin-sensitive tissue and the predominant reservoir for glucose disposal, there is a need to develop safe and effective evidence-based, lifestyle management strategies that optimize muscle mass as well as improve glycaemic control and cardiometabolic risk factors in people with this disease, particularly older adults who experience accelerated muscle loss.

Communication of scientific uncertainty : international case studies on the development of folate and vitamin D Dietary Reference Values.

Transparent evidence-based decision making has been promoted worldwide to engender trust in science and policy making. Yet, little attention has been given to transparency implementation. The degree of transparency (focused on how uncertain evidence was handled) during the development of folate and vitamin D Dietary Reference Values was explored in three a priori defined areas: (i) value request; (ii) evidence evaluation; and (iii) final values.

Communication of scientific uncertainty: International case studies on the development of folate and vitamin D Dietary Reference Values

Objective Transparent evidence-based decision making has been promoted worldwide to engender trust in science and policy making. Yet, little attention has been given to transparency implementation. The degree of transparency (focused on how uncertain evidence was handled) during the development of folate and vitamin D Dietary Reference Values was explored in three a priori defined areas: (i) value request; (ii) evidence evaluation; and (iii) final values. Design Qualitative case studies (semi-structured interviews and desk research). A common protocol was used for data collection, interview thematic analysis and reporting. Results were coordinated via cross-case synthesis. Setting Australia and New Zealand, Netherlands, Nordic countries, Poland, Spain and UK. Subjects Twenty-one interviews were conducted in six case studies. Results Transparency of process was not universally observed across countries or areas of the recommendation setting process. Transparency practices were most commonly seen surrounding the request to develop reference values (e.g. access to risk manager/assessor problem formulation discussions) and evidence evaluation (e.g. disclosure of risk assessor data sourcing/evaluation protocols). Fewer transparency practices were observed to assist with handling uncertainty in the evidence base during the development of quantitative reference values. Conclusions Implementation of transparency policies may be limited by a lack of dedicated resources and best practice procedures, particularly to assist with the latter stages of reference value development. Challenges remain regarding the best practice for transparently communicating the influence of uncertain evidence on the final reference values. Resolving this issue may assist the evolution of nutrition risk assessment and better inform the recommendation setting process.

Polymorphisms affecting vitamin D-binding protein modify the relationship between serum vitamin D (25[OH]D3) and food allergy

BACKGROUND: There is evolving evidence that vitamin D insufficiency may contribute to food allergy, but findings vary between populations. Lower vitamin D-binding protein (DBP) levels increase the biological availability of serum vitamin D. Genetic polymorphisms explain almost 80% of the variation in binding protein levels. OBJECTIVE: We sought to investigate whether polymorphisms that lower the DBP could compensate for adverse effects of low serum vitamin D on food allergy risk. METHODS: From a population-based cohort study (n = 5276) we investigated the association between serum 25-hydroxyvitamin D3 (25[OH]D3) levels and food allergy at age 1 year (338 challenge-proven food-allergic and 269 control participants) and age 2 years (55 participants with persistent and 50 participants with resolved food allergy). 25(OH)D3 levels were measured using liquid chromatography-tandem mass spectrometry and adjusted for season of blood draw. Analyses were stratified by genotype at rs7041 as a proxy marker of DBP levels (low, the GT/TT genotype; high, the GG genotype). RESULTS: Low serum 25(OH)D3 level (≤50 nM/L) at age 1 years was associated with food allergy, particularly among infants with the GG genotype (odds ratio [OR], 6.0; 95% CI, 0.9-38.9) but not in those with GT/TT genotypes (OR, 0.7; 95% CI, 0.2-2.0; P interaction = .014). Maternal antenatal vitamin D supplementation was associated with less food allergy, particularly in infants with the GT/TT genotype (OR, 0.10; 95% CI, 0.03-0.41). Persistent vitamin D insufficiency increased the likelihood of persistent food allergy (OR, 12.6; 95% CI, 1.5-106.6), particularly in those with the GG genotype. CONCLUSIONS: Polymorphisms associated with lower DBP level attenuated the association between low serum 25(OH)D3 level and food allergy, consistent with greater vitamin D bioavailability in those with a lower DBP level. This increases the biological plausibility of a role for vitamin D in the development of food allergy.

Weekday sunlight exposure, but not vitamin D intake, influences the association between vitamin D receptor genotype and circulating concentration 25-hydroxyvitamin D in a pan-European population: the Food4Me study

SCOPE: Little is known about diet- and environment-gene interactions on 25-hydroxyvitamin D (25(OH)D concentration. This cross-sectional study aimed to investigate (i) predictors of 25(OH)D concentration and relationships with vitamin D genotypes and (ii) whether dietary vitamin D intake and sunlight exposure modified these relationships.

METHODS AND RESULTS: Participants from the Food4Me study (n = 1312; age 18-79) were genotyped for vitamin D receptor (VDR) and vitamin D binding protein at baseline and a genetic risk score was calculated. Dried blood spot samples were assayed for 25(OH)D concentration and dietary and lifestyle information collected. Circulating 25(OH)D concentration was lower with increasing genetic risk score, lower in females than males, higher in supplement users than non-users and higher in summer than winter. Carriage of the minor VDR allele was associated with lower 25(OH)D concentration in participants with the least sunlight exposure. Vitamin D genotype did not influence the relationship between vitamin D intake and 25(OH)D concentration.

CONCLUSION: Age, sex, dietary vitamin D intake, country, sunlight exposure, season, and vitamin D genetic risk score were associated with circulating 25(OH)D concentration in a pan-European population. The relationship between VDR genotype and 25(OH)D concentration may be influenced by weekday sunlight exposure but not dietary vitamin D intake.

Calcium supplementation: the bare bones

An adequate calcium intake is an essential part of the prevention and treatment of osteoporosis. Two to threeserves of calcium-rich foods each day provides sufficient calcium for most non-pregnant adults. If this target is not achievable, calcium supplementation is generally effective, cheap and safe for most people. Calciumcarbonate(without vitamin and mineral additives) is the preferred supplement in most cases. Problems with calcium absorption arise due to factors including high&middot;fibre vegetarian diets, achlorhydria, long&middot;term glucocorticoid therapy and vitamin D deficiency. Vitamin D deficiency is extremely common in some ethnic groups and the elderly who are housebound or in residential care. These at risk groups generally require vitamin D supplementation to achieve adequate intestinal absorption of calcium.

Preventive strategies in depression : gathering evidence for risk factors and potential interventions

This editorial critiques the recent literature concerning both vitamin D deficiency in major depression and supplementation as a treatment strategy, and contextualises it within a broader approach to the prevention of depression, based on the recent evidence for lifestyle as a risk factor for depression and anxiety.

Food fortification : the evidence, ethics and politics of adding nutrients to food

This research book presents a critical analysis of mandatory food fortification as a technology for protecting and promoting public health. Increasing numbers of foods fortified with novel amounts and combinations of nutrients are being introduced into the food supplies of countries around the world to raise populations’ nutrient intakes. Three topical food fortification case studies representing the different public health rationales for adding nutrients to food were assessed for their public health benefits, risks and ethical considerations: Universal salt iodisation (USI) to help prevent iodine deficiency disorders; mandatory flour fortification with folic acid (MFFFA) to help prevent neural tube defects; and mandatory milk fortification with vitamin D (MMFVD) to help prevent vitamin D deficiency. These assessments found that whereas USI performs strongly as a public health intervention, MFFFA and MMFVD are associated with more risks and less ethical justification than an alternative policy option. Food fortification can be a blunt policy response to complex policy problems. The findings highlight that the primary predictor of a mandatory food fortification policy’s benefits, risks and ethics is its ability to address the underlying cause of the policy problem. The analysis of the policy-making processes for each case study found that certain powerful actors use their influence to determine what counts as evidence in policy processes to privilege food fortification activities over alternative policy options. Policy-making frequently was notable for the low prominence it afforded ethical considerations and its lack of public engagement. Priority activities to help strengthen policy processes and outcomes are suggested.

Shining the light on sunshine: a systematic review of the influence of sun exposure on type 2 diabetes mellitus-related outcomes

Prospective observational studies uniformly link vitamin D deficiency with the incidence of type 2 diabetes mellitus (T2DM), yet trials supplementing participants at risk of T2DM with vitamin D to reduce progression to T2DM have yielded inconsistent results. Inconsistencies between supplementation trials may be due to insufficient dosing or small sample sizes. Observational studies may also have reported spurious associations due to uncontrolled confounding by lifestyle or genetic factors. Alternatively, observational and intervention studies may not be entirely comparable. Observational studies show an association between higher vitamin D status, which is predominantly derived from sun exposure, and decreased incidence of T2DM. Trials intervene with vitamin D supplementation, and therefore may be missing alternate causes of the effect of sun exposure, as seen in observational studies. We propose that sun exposure may be the driving force behind the associations seen in observational studies; sun exposure may have additional benefits beyond increasing serum 25-hydroxyvitamin D (25OHD) levels. We performed an electronic literature search to identify articles that examined associations between sun exposure and T2DM and/or glucose metabolism. A best evidence synthesis was then conducted using outcomes from analyses deemed to have high methodological quality. Ten eligible full-text articles were identified, yielding 19 T2DM-related outcomes. The best evidence analysis considered 11 outcomes which were grouped into six outcome types: T2DM, fasting glucose, glucose tolerance, fasting insulin, insulin secretion and insulin sensitivity. There was moderate evidence to support a role of recreational sun exposure in reducing odds of T2DM incidence. High-level evidence was lacking; evidence presented for other outcomes was of low or insufficient level. This review highlights significant gaps in research pertaining to sun exposure and T2DM-related outcomes. Further research is encouraged as we aim to identify novel preventative strategies for T2DM.

Fibromyalgia and bipolar disorder: emerging epidemiological associations and shared pathophysiology

Fibromyalgia (FM) is a prevalent disorder defined by the presence of chronic widespread pain in association with fatigue, sleep disturbances and cognitive dysfunction. Recent studies indicate that bipolar spectrum disorders frequently co-occur in individuals with FM. Furthermore, shared pathophysiological mechanisms anticipate remarkable phenomenological similarities between FM and BD. A comprehensive search of the English literature was carried out in the Pubmed/MEDLINE database through May 10th, 2015 to identify unique references pertaining to the epidemiology and shared pathophysiology between FM and bipolar disorder (BD). Overlapping neural circuits may underpin parallel clinical manifestations of both disorders. Fibromyalgia and BD are both characterized by functional abnormalities in the hypothalamic-pituitary-adrenal axis, higher levels of inflammatory mediators, oxidative and nitrosative stress as well as mitochondrial dysfunction. An over-activation of the kynurenine pathway in both illnesses drives tryptophan away from the production of serotonin and melatonin, leading to affective symptoms, circadian rhythm disturbances and abnormalities in pain processing. In addition, both disorders are associated with impaired neuroplasticity (e.g., altered brain-derived neurotrophic factor signaling). The recognition of the symptomatic and pathophysiological overlapping between FM and bipolar spectrum disorders has relevant etiological, clinical and therapeutic implications that deserve future research consideration.