Vitamin D

Vitamin D is a fat-soluble vitamin, normally produced in skin after exposure to sunlight. When a derivative of cholesterol (7-dehydrocholesterol) is absorbs UV light, it is converted into previtamin D3., which is then isomerised within a few hours to vitamin D3.

Exposure of skin to sunshine is the main source of vitamin D for people as the active form of this vitamin is not present in most foods, except fatty fish livers.

Vitamin D plays a key role in the bone formation but also in several other physiological processes. It prevents some degenerative diseases and cancers.

The Most Relevant Recent Scientific Reviews

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Role of Vitamin D Beyond the Skeletal Function: A Review of the Molecular and Clinical Studies.

The classical function of Vitamin D, which involves mineral balance and skeletal maintenance, has been known for many years. With the discovery of vitamin D receptors in various tissues, several other biological functions of vitamin D are increasingly recognized and its role in many human diseases like cancer, diabetes, hypertension, cardiovascular, and autoimmune and dermatological diseases is being extensively explored. The non-classical function of vitamin D involves regulation of cellular proliferation, differentiation, apoptosis, and innate and adaptive immunity. In this review, we discuss and summarize the latest findings on the non-classical functions of vitamin D at the cellular/molecular level and its role in complex human diseases.

Role of nutritional vitamin D in osteoporosis treatment.

Osteoporosis is a systemic skeletal disorder characterized by a decrease in bone mass and microarchitectural deterioration of bone tissue. The World Health Organization has defined osteoporosis as a decrease in bone mass (50%) and bony quality (50%). Vitamin D, a steroid hormone, is crucial for skeletal health and in mineral metabolism. Its direct action on osteoblasts and osteoclasts and interaction with nonskeletal tissues help in maintaining a balance between bone turnover and bone growth. Vitamin D affects the activity of osteoblasts, osteoclasts, and osteocytes, suggesting that it affects bone formation, bone resorption, and bone quality. At physiological concentrations, active vitamin D maintains a normal rate of bone resorption and formation through the RANKL/OPG signal. However, active vitamin D at pharmacological concentration inhibits bone resorption at a higher rate than that of bone formation, which influences the bone quality and quantity. Nutritional vitamin D rather than active vitamin D activates osteoblasts and maintains serum 25(OH)D3 concentration. Despite many unanswered questions, much data support nutritional vitamin D use in osteoporosis patients. This article emphasizes the role of nutritional vitamin D replacement in different turnover status (high or low bone turnover disorders) of osteoporosis together with either anti-resorptive (Bisphosphonate, Denosumab et.) or anabolic (Teriparatide) agents when osteoporosis persists.

Effect of vitamin D supplementation on blood pressure parameters in patients with vitamin Ddeficiency: a systematic review and meta-analysis.

Evidence suggests that supplementation of vitamin D cannot decrease blood pressure in normal populations. However, in randomized controlled trials (RCTs) with vitamin D deficient participants (defined as baseline serum 25[OH]D levels <30 ng/mL or 50 nmol/L), this effect is inconsistent and under debate. Thus, we performed this systematic review and meta-analysis to evaluate whether vitamin D supplementation could affect blood pressure parameters in vitamin D-deficient subjects. The PubMed, Web of Science, ScienceDirect, and Cochrane library databases were searched. Extracted data were pooled as weighted mean differences with 95% confidence intervals to evaluate the effects. Subgroup analysis was further conducted according to the characteristics of included studies. Seven RCTs that contained 560 participants were included in our meta-analysis. The pooled weighted mean difference of peripheral diastolic blood pressure was -1.65 mm Hg (95% confidence interval: -3.05 to -0.25, I2 = 30.3%). No significant effect of vitamin D supplementation was found on other parameters. Subgroup analysis showed a significant decrease in peripheral systolic blood pressure and diastolic blood pressure in Asia, 8 weeks of intervention, and more than 5000 IU of daily vitamin D supplementation subgroups. For vitamin D-deficient patients, there is a small but significant fall in peripheral blood pressure but no significant fall in other blood pressure parameters with vitamin D supplementation. Further RCTs with large numbers of participants is still warranted to confirm these effects.

Lower Vitamin D Status Is Associated with an Increased Risk of Ischemic Stroke: A Systematic Review and Meta-Analysis.

In recent years, accumulating evidence has supported the hypothesis that lower vitamin D status is associated with several known risk factors of stroke. However, the relationship between vitamin D and stroke is still uncertain. To explore if there was an association between vitamin D status and the risk of stroke, a systematic review and a meta-analysis were conducted by searching three databases: Pubmed, Embase, and the Cochrane Library. Following the application of inclusion and exclusion criteria, the relative risk estimates of all the included studies were pooled together to compare the risk of stroke between the lowest and the highest category of vitamin D. The Newcastle-Ottawa Scale (NOS) and the Cochrane Risk of Bias Tool were used to assess the risk of bias, and the publication bias was detected by using a funnel plot and Egger’s test. Nineteen studies were included and the pooled relative risk was 1.62 (95% CI: 1.34-1.96). Further analysis found that vitamin D status was associated with ischemic stroke (relative risk = 2.45, 95% CI: 1.56-3.86), but not with hemorrhagic stroke (relative risk = 2.50, 95% CI: 0.87-7.15). In conclusion, our meta-analysis supported the hypothesis that lower vitamin D status was associated with an increased risk of ischemic stroke. Further studies are required to confirm this association and to explore the association among different subtypes.

Vitamin D and gastrointestinal cancer.

Vitamin D serves as a precursor to the potent steroid hormone calcitriol, which has widespread actions throughout the body. Calcitriol regulates numerous cellular pathways that could have a role in determining cancer risk and prognosis. Low Vitamin D levels have been implicated in numerous disease processes including fracture risk, falls, cardiovascular disease, hypertension, diabetes mellitus, and cancers. Metabolite of 1, 25-dihydroxyvitamin D3 (1,25[OH]2D3) regulates numerous genes that control gut physiology and homeostasis. 1,25(OH)2D3 serves various functions such as maintaining the integrity of epithelial barrier and absorption of calcium and phosphate, and the host’s defense against pathogens, and the inflammatory response by several types of secretory and immune cells. Although epidemiological data remain inconsistent, and randomized control trials in humans do not yet exist to conclusively support a beneficial role for Vitamin D, results from some correlating studies strongly suggest that Vitamin D deficiency increases the risk of developing cancer and that avoiding deficiency and adding Vitamin D supplements might be an economical and safe way to reduce cancer incidence and improve cancer prognosis and outcome. The present review highlights the role of Vitamin D in cancer of the gastrointestinal tract including esophagus, gastric (stomach), liver, pancreas, and colon.

Vitamin D: Current Guidelines and Future Outlook.

Vitamin D is of public health interest because its deficiency is common and is associated with musculoskeletal diseases, as well as extraskeletal diseases, such as cancer, cardiovascular diseases, and infections. Several health authorities have reviewed the existing literature and published nutritional vitamin D guidelines for the general population. There was a wide consensus that serum 25-hydroxyvitamin D [25(OH)D] concentration should be used to assess vitamin D status and intake, and that musculoskeletal, and not extraskeletal, effects of vitamin D should be the basis for nutritional vitamin D guidelines. Recommended target levels for 25(OH)D range from 25 to 50 nmol/l (10 to 20 ng/ml), corresponding to a vitamin D intake of 400 to 800 International Units (10 to 20 μg) per day. It is of concern that significant sections of the general population do not meet these recommended vitamin D levels. This definitely requires action from a public health perspective.

Vitamin D and Multiple Sclerosis: A Comprehensive Review.

Numerous observational studies have suggested that there is a correlation between the level of serum vitamin D and MS risk and disease activity. To explore this hypothesis, a literature search of large, prospective, observation studies, epidemiological studies, and studies using new approaches such as Mendelian randomization was conducted. Available data and ongoing research included in this review suggest that the level of serum vitamin D affects the risk of developing MS and also modifies disease activity in MS patients. Newer Mendelian randomization analyses suggest there is a causal relationship between low vitamin D level and the risk of MS. Post-hoc evaluations from two phase 3 studies, BENEFIT and BEYOND, support the findings of observational trials. Study limitations identified in this review recognize the need for larger controlled clinical trials to establish vitamin D supplementation as the standard of care for MS patients. Though there is increasing evidence indicating that lower vitamin D levels are associated with increased risk of MS and with greater clinical and brain MRI activity in established MS, the impact of vitamin D supplementation on MS activity remains inadequately investigated.

Vitamin D and Neurological Diseases: An Endocrine View.

Vitamin D system comprises hormone precursors, active metabolites, carriers, enzymes, and receptors involved in genomic and non-genomic effects. In addition to classical bone-related effects, this system has also been shown to activate multiple molecular mediators and elicit many physiological functions. In vitro and in vivo studies have, in fact, increasingly focused on the “non-calcemic” actions of vitamin D, which are associated with the maintenance of glucose homeostasis, cardiovascular morbidity, autoimmunity, inflammation, and cancer. In parallel, growing evidence has recognized that a multimodal association links vitamin D system to brain development, functions and diseases. With vitamin D deficiency reaching epidemic proportions worldwide, there is now concern that optimal levels of vitamin D in the bloodstream are also necessary to preserve the neurological development and protect the adult brain. The aim of this review is to highlight the relationship between vitamin D and neurological diseases.