Vitamin D: can the sun stop the atopic epidemic?

PURPOSE OF REVIEW: To review recent evidence on the capacity of vitamin D to prevent atopic disease, focussing on food allergy and asthma, and potential underlying mechanisms. RECENT FINDINGS: The incidence of allergic disease continues to increase worldwide. Vitamin D status is influenced by sun exposure and dietary intake. Vitamin D deficiency is linked to an increased incidence of allergic disease and asthma. These associations are generally strongest in early life. The capacity of vitamin D to enhance antimicrobial pathways, promote peripheral immunological tolerance and maintain mucosal barrier integrity may underlie these associations. Interventional studies have addressed the capacity of vitamin D supplementation in utero and early life to reduce the incidence of disease. Ancillary studies have provided insights into potential biological mechanisms linked to these effects. SUMMARY: Observational studies show an inverse association between vitamin D levels and development of food allergy and asthma. Secondary analyses of two recent interventional studies suggest that achieving vitamin D sufficiency throughout pregnancy reduces the incidence of asthma/recurrent wheeze at 3 years. Longitudinal studies of vitamin D requirements in utero and postnatally, better understanding of factors that influence bioavailability of vitamin D and mechanistic insights into vitamin D effects on neonatal-specific immune pathways are awaited.

The economic case for prevention of population vitamin D deficiency: a modelling study using data from England and Wales.

BACKGROUND: Vitamin D deficiency (VDD) affects the health and wellbeing of millions worldwide. In high latitude countries such as the United Kingdom (UK), severe complications disproportionally affect ethnic minority groups. OBJECTIVE: To develop a decision-analytic model to estimate the cost effectiveness of population strategies to prevent VDD. METHODS: An individual-level simulation model was used to compare: (I) wheat flour fortification; (II) supplementation of at-risk groups; and (III) combined flour fortification and supplementation; with (IV) a 'no additional intervention' scenario, reflecting the current Vitamin D policy in the UK. We simulated the whole population over 90 years. Data from national nutrition surveys were used to estimate the risk of deficiency under the alternative scenarios. Costs incurred by the health care sector, the government, local authorities, and the general public were considered. Results were expressed as total cost and effect of each strategy, and as the cost per 'prevented case of VDD' and the 'cost per Quality Adjusted Life Year (QALY)'. RESULTS: Wheat flour fortification was cost saving as its costs were more than offset by the cost savings from preventing VDD. The combination of supplementation and fortification was cost effective (£9.5 per QALY gained). The model estimated that wheat flour fortification alone would result in 25% fewer cases of VDD, while the combined strategy would reduce the number of cases by a further 8%. CONCLUSION: There is a strong economic case for fortifying wheat flour with Vitamin D, alone or in combination with targeted vitamin D3 supplementation.

Determinants of the magnitude of response to vitamin D supplementation in adolescent girls identified using a decision tree algorithm.

Vitamin D (VitD) supplementation is an inexpensive and effective approach for improving VitD insufficiency/deficiency. However, the response to supplementation, with respect to the increase in serum 25(OH)D level varies between individuals. In this study, we have assessed the factors associated with the response to VitD supplementation using a decision-tree algorithm. Serum VitD levels, pre- and post-VitD supplementation was used as the determinant of responsiveness. The model was validated by constructing a receiver operating characteristic curve. Serum VitD at baseline levels was at the apex of the tree in our model, followed by serum low-density lipoprotein cholesterol and triglyceride, age, waist-hip ratio, and high-density lipoprotein cholesterol. Our model suggests that these determinants of responsiveness to VitD supplementation had sensitivity, specificity, and accuracy, 59.4, 75.8 and 69.3%, respectively. The decision tree model appears to be a relatively accurate, specific, and sensitive approach for identifying the factors associated with response to VitD supplementation.

Vitamin D: too much testing and treating?

There is clinical uncertainty as to the testing of serum 25--Hydroxy vitamin D (25[OH]D) concentrations and when to use high-dose supplementation. Data show that there has been a rapid increase in the number of tests performed within the Northumbria Healthcare NHS Foundation Trust over the past 8 years and an increase in high-dose supplementation over the past 5 years. We performed a retrospective analysis of the 25(OH)D test requests over the period from January to -October 2017. A total of 17,405 tests were performed in this time period. The overall average concentration was 57.5 nmol/L and this figure was similar across age groups, although a larger proportion of patients aged over 75 had a concentration <25 nmol/L. Test requests were classified into 'appropriate', 'inappropriate' and 'uncertain' categories based on current expert opinion. We found that between 70.4% and 77.5% of tests could be inappropriate, depending on whether the 'uncertain' categories of falls and osteoporosis are considered to be justified. Tiredness, fatigue or exhaustion was the reason for testing in 22.4% of requests. We suggest that a more rational approach to testing, and subsequent treating, could lead to reductions in costs to the healthcare system and patients.

Assessment of 3-epi-25-hydroxyvitamin D levels during cholecalciferol supplementation in adults with chronic liver diseases.

Recently, hepatic immaturity was cited as a possible reason for high levels of the C-3 epimer of 25-hydroxyvitamin (25(OH)D) in premature infants: however what role, if any, the liver plays in controlling epimer concentrations is unknown. This study assesses 3-epi-25-hydroxyvitamin D (3-epi-25(OH)D) levels during the course of cholecalciferol supplementation in adults with chronic liver diseases (CLD). Vitamin D metabolites were analyzed in 65 CLD patients with 25(OH)D <30 ng/mL who received 20 000 IU cholecalciferol/week for 6 months. The primary outcome assessed serum 25(OH)D and 3-epi-25(OH)D in response to supplementation. Corresponding values from 16 CLD patients with sufficient vitamin D levels receiving no supplementation were compared. The epimer was detected in all samples and at lower relative concentrations with lower vitamin D baseline status, i.e., severe vitamin D deficiency (<10 ng/mL) as compared with deficient (10-19.9 ng/mL), insufficient (20-29.9 ng/mL), or sufficient (≥30 ng/mL) vitamin D levels (2.4% vs. 4.8%, 5.2%, 5.8%, respectively; P < 0.001). Similar relative concentrations for 3-epi-25(OH)D, ranging from 4.3%-7.1% (absolute concentrations: 1.1-4.0 ng/mL; all P < 0.001), were obtained in response to cholecalciferol in all supplemented patients, regardless of inadequacy threshold. Epimer levels significantly decreased (P = 0.007) in unsupplemented patients, coinciding with decreasing serum 25(OH)D concentrations over time. No epimer differences between patients with (n = 17) or without (n = 48) cirrhosis were demonstrated. The 3-epi-25(OH)D was present in serum of all patients at comparable levels to those reported by others. Epimer levels increased linearly with increasing 25(OH)D levels after supplementation. However, no effect of cirrhosis on epimer concentrations was observed.

Differences in homeostatic model assessment (HOMA) values and insulin levels after vitamin D supplementation in healthy men: a double-blind randomized controlled trial.

Vitamin D is thought to play a role in glucose metabolism. The aim of the present study was to determine the effect of vitamin D supplementation on markers of insulin sensitivity and inflammation in men without diabetes with vitamin D deficiency/insufficiency. In this 1-year double-blind randomized controlled trial, 130 men aged 20-65 years (mean age 47.52 ± 11.84 years) with serum 25-hydroxyvitamin D levels <50 nmol/l (mean 38.89 ± 8.64 nmol/l) were randomized to treatment (100 000 IU vitamin D bimonthly) or placebo. Anthropometric measurements, demographic questionnaires, and blood indices (fasting glucose, insulin, high-sensitivity C-reactive protein, lipids) were collected and repeated after 6 and 12 months. The compliance rate was 98.5%. Multivariate models, adjusted for baseline levels, age, body mass index, sun exposure, physical activity and LDL, showed significant differences in insulin and homeostatic model assessment of insulin resistance (HOMA-IR) values between groups. Levels of insulin and HOMA-IR values remained steady during the study period in the treatment group but increased by 16% in the control group (p = 0.038 and p = 0.048, respectively). Vitamin D supplementation administered for 12 months in healthy men maintained insulin levels and HOMA-IR values relative to the increase in the control group. Further studies are needed to establish the long-term effect of vitamin D supplementation on the risk of diabetes.

Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review.

PURPOSE: To review the current literature regarding the role of vitamin D status in pregnancy outcomes in women undergoing assisted reproductive technology (ART) and to assess cost-effectiveness of routine vitamin D deficiency screening and repletion prior to initiation of ART. METHODS: A systematic literature review was conducted using PubMed. Relevant study outcomes were compared among the selected studies. A cost-benefit analysis was performed using a decision tree mathematical model with sensitivity analyses from the perspective of direct societal cost. Published data were used to estimate probabilities and costs in 2014 US dollars. RESULTS: Thirty-four articles were retrieved, of which eight met inclusion criteria. One study demonstrated a negative relationship between vitamin D status and ART outcomes, while two studies showed no association. The remaining five studies concluded that ART outcomes improved after vitamin D repletion. CONCLUSION: The majority of reviewed studies reported a decrement in ART outcomes in patients with vitamin D deficiency. Cost-benefit analyses suggested that screening and supplementing vitamin D prior to ART might be cost effective, but further evidence is needed. Given the absence of Level I evidence regarding vitamin D status and ART outcomes, full endorsement of routine vitamin D screening and supplementation prior to ART is premature.

Impact of vitamin D supplementation on health-care use in a 25-hydroxyvitamin D-tested population in France: a population-based descriptive cohort study.

OBJECTIVE: Chronic vitamin D deficiency has been associated in some patients with diffuse musculoskeletal pain. These unspecific symptoms may partly explain why vitamin D deficiency is often diagnosed late. Our aim was to analyse health-care claims after vitamin D supplementation in patients likely to have vitamin D deficiency. DESIGN: Ambulatory health-care claims were compared before and after a vitamin D supplementation prescribed following a 25-hydroxyvitamin D assay. SETTING: Health Insurance Fund (FHIF) database of the Rhône-Alpes area, France. SUBJECTS: Among patients reimbursed for a 25-hydroxyvitamin D assay between 1 December 2008 and 31 January 2009, those supplemented with vitamin D after the assay were matched on the date of assay to patients who did not receive vitamin D. RESULTS: Among the 3023 patients who had a 25-hydroxyvitamin D assay, 935 were consequently supplemented and matched to 935 patients not supplemented. Their median age was 50·0 and 49·5 years, respectively. Patients supplemented decreased their muscle relaxant consumption whereas no change was observed in the reference group, the difference between the two groups was significant (P=0·03). Second and third Pain Relief Ladder prescriptions decreased in both groups but not significantly differently between groups (P=0·58). There was a decrease in prescriptions of biological examination in both groups with no significant difference. CONCLUSIONS: Besides a decrease in muscle relaxant prescriptions in the supplemented group, it was difficult to assess the impact of vitamin D supplementation in patients likely to have vitamin D deficiency. Prospective cohort studies and randomized trials are needed to assess the efficiency of screening and supplementing vitamin D deficiency.

Vitamin D in multiple sclerosis: implications for assessment and treatment.

Epidemiological and experimental evidence suggest that a poor vitamin D status is associated with an increased risk of developing multiple sclerosis (MS), and also an unfavorable disease course. Vitamin D may exert relevant effects both on the immune system and on resident cells within the CNS. The data from clinical trials is, however, restricted, and does not allow any conclusion on the effect of high-dose vitamin D supplementation on disease course. The results from sufficiently powered studies will not be available for at least 2 years. MS patients are, however, prone to develop osteoporosis and have increased risk of fractures. Therefore, the authors advise that the serum concentration of 25-hydroxyvitamin D is monitored in order to prevent bone deficit, and that a serum level of 75-125 nmol/l is targeted. This level is sufficient for maintenance of bone health, is not known to be associated with adverse events, and is in the range that has been associated with low risk of developing MS and low disease activity.