The etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate are primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) accelerates bone turnover, bone loss, and osteoporotic fractures. These risks can be reduced by 800 IU of vitamin D together with an appropriate calcium intake, given to institutionalized or vitamin D-deficient elderly subjects. VDR and vitamin D metabolic enzymes are widely expressed. Numerous genetic, molecular, cellular, and animal studies strongly suggest that vitamin D signaling has many extraskeletal effects. These include regulation of cell proliferation, immune and muscle function, skin differentiation, and reproduction, as well as vascular and metabolic properties. From observational studies in human subjects, poor vitamin D status is associated with nearly all diseases predicted by these extraskeletal actions. Results of randomized controlled trials and Mendelian randomization studies are supportive of vitamin D supplementation in reducing the incidence of some diseases, but, globally, conclusions are mixed. These findings point to a need for continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health. Vitamin D deficiency enhances the risk of osteoporotic fractures and is associated with many diseases. We review what is established and what is plausible regarding the health effects of vitamin D.

/pdf/skeletal-and-extraskeletal-actions-of-vitamin-d-current-16dotycegb.pdf

Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions.

Vitamin D is an essential nutrient for bone health and may influence the risks of respiratory illness, adverse pregnancy outcomes, and chronic diseases of adulthood. Because many countries have a relatively low supply of foods rich in vitamin D and inadequate exposure to natural ultraviolet B (UVB) radiation from sunlight, an important proportion of the global population is at risk of vitamin D deficiency. There is general agreement that the minimum serum/plasma 25-hydroxyvitamin D concentration (25(OH)D) that protects against vitamin D deficiency-related bone disease is approximately 30 nmol/L; therefore, this threshold is suitable to define vitamin D deficiency in population surveys. However, efforts to assess the vitamin D status of populations in low- and middle-income countries have been hampered by limited availability of population-representative 25(OH)D data, particularly among population subgroups most vulnerable to the skeletal and potential extraskeletal consequences of low vitamin D status, namely exclusively breastfed infants, children, adolescents, pregnant and lactating women, and the elderly. In the absence of 25(OH)D data, identification of communities that would benefit from public health interventions to improve vitamin D status may require proxy indicators of the population risk of vitamin D deficiency, such as the prevalence of rickets or metrics of usual UVB exposure. If a high prevalence of vitamin D deficiency is identified (>20% prevalence of 25(OH)D 1%), food fortification and/or targeted vitamin D supplementation policies can be implemented to reduce the burden of vitamin D deficiency-related conditions in vulnerable populations.

/pdf/global-prevalence-and-disease-burden-of-vitamin-d-deficiency-4i2ikaq0yp.pdf

Global prevalence and disease burden of vitamin D deficiency: a roadmap for action in low- and middle-income countries.

Objectives To estimate the effects of vitamin D supplementation during pregnancy on 11 maternal and 27 neonatal/infant outcomes; to determine frequencies at which trial outcome data were missing, unreported, or inconsistently reported; and to project the potential contributions of registered ongoing or planned trials.Design Systematic review and meta-analysis of randomised controlled trials; systematic review of registered but unpublished trials.Data sources Medline, Embase, PubMed, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception to September 2017; manual searches of reference lists of systematic reviews identified in the electronic search; and online trial registries for unpublished, ongoing, or planned trials.Eligibility criteria for study selection Trials of prenatal vitamin D supplementation with randomised allocation and control groups administered placebo, no vitamin D, or vitamin D ≤600 IU/day (or its equivalent), and published in a peer reviewed journal.Results 43 trials (8406 participants) were eligible for meta-analyses. Median sample size was 133 participants. Vitamin D increased maternal/cord serum concentration of 25-hydroxyvitamin D, but the dose-response effect was weak. Maternal clinical outcomes were rarely ascertained or reported, but available data did not provide evidence of benefits. Overall, vitamin D increased mean birth weight of 58.33 g (95% confidence interval 18.88 g to 97.78 g; 37 comparisons) and reduced the risk of small for gestational age births (risk ratio 0.60, 95% confidence interval 0.40 to 0.90; seven comparisons), but findings were not robust in sensitivity and subgroup analyses. There was no effect on preterm birth (1.0, 0.77 to 1.30; 15 comparisons). There was strong evidence that prenatal vitamin D reduced the risk of offspring wheeze by age 3 years (0.81, 0.67 to 0.98; two comparisons). For most outcomes, meta-analyses included data from a minority of trials. Only eight of 43 trials (19%) had an overall low risk of bias. Thirty five planned/ongoing randomised controlled trials could contribute 12 530 additional participants to future reviews.Conclusions Most trials on prenatal vitamin D published by September 2017 were small and of low quality. The evidence to date seems insufficient to guide clinical or policy recommendations. Future trials should be designed and powered to examine clinical endpoints, including maternal conditions related to pregnancy (such as pre-eclampsia), infant growth, and respiratory outcomes.Systematic review registration PROSPERO CRD42016051292.

https://www.bmj.com/content/bmj/359/bmj.j5237.full.pdf

Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials

Severe vitamin D deficiency may cause rickets in infants or children and osteomalacia in adults, though it is now uncommon in developed countries. However, subclinical vitamin D deficiency is more prevalent, and it is associated with osteoporosis and higher incidence of falls or fractures. It was reported that 96% children with rickets were breastfed, since breast milk contains inadequate vitamin D. The American Academy of Pediatrics 2008 recommended infants who were exclusively or partially breastfed required 400 international units vitamin D daily from the first few days of life. Furthermore, since vitamin D receptors are present all over the body, insufficient vitamin D status may correlate with several extra-skeletal effects, such as pregnancy-related complications and immune dysfunction. This paper discusses the researches regarding system-based vitamin D effects, the possible risk factors leading to vitamin D deficiency, and the recommendations of vitamin D requirements. It is well-known that vitamin D can be obtained by sun exposure or limited natural dietary sources. The American Academy of Dermatology declared ultraviolet radiation to be a known skin carcinogen, so it may not be safe or efficient to obtain vitamin D via sun exposure or other artificial sources. Therefore, many pediatricians and physicians recommend appropriate vitamin D supplementation to achieve optimal plasma concentration. Trials assessing the effects of vitamin D repletion and establishing its optimum serum level are ongoing. Medical advice for vitamin D supplementation should be individualized accordingly.

Vitamin D and health - The missing vitamin in humans.

Pollution is known to cause and exacerbate a number of chronic respiratory diseases. The World Health Organisation has placed air pollution as the world’s largest environmental health risk factor. There has been recent publicity about the role for diet and anti-oxidants in mitigating the effects of pollution, and this review assesses the evidence for alterations in diet, including vitamin supplementation in abrogating the effects of pollution on asthma and other chronic respiratory diseases. We found evidence to suggest that carotenoids, vitamin D and vitamin E help protect against pollution damage which can trigger asthma, COPD and lung cancer initiation. Vitamin C, curcumin, choline and omega-3 fatty acids may also play a role. The Mediterranean diet appears to be of benefit in patients with airways disease and there appears to be a beneficial effect in smokers however there is no direct evidence regarding protecting against air pollution. More studies investigating the effects of nutrition on rapidly rising air pollution are urgently required. However it is very difficult to design such studies due to the confounding factors of diet, obesity, co-morbid illness, medication and environmental exposure.

/pdf/pollution-and-respiratory-disease-can-diet-or-supplements-4f3fs7rghj.pdf

Pollution and respiratory disease: can diet or supplements help? A review

Despite the authors' caution that further data are needed to clarify the role of vitamin D in care, this Cochrane review found that its use reduces the average number of asthma exacerbations requiring corticosteroid treatment from 0.44 to 0.28 per person per year.

Juan Qiu

Papers

Vitamin D for the Management of Asthma.

Cognitive behavior therapy for depression in people with epilepsy: A systematic review and meta-analysis