The effects of high dose vitamin D supplementation as a nutritional intervention strategy on biochemical and inflammatory factors in adults with COVID-19: Study protocol for a randomized controlled trial.

Introduction: Low serum vitamin D has been shown to be a risk factor for Coronavirus 2019 (COVID-19). The aim of this study was to assess the effects of high dose vitamin D supplementation on hs-CRP, ESR and clinical outcomes, including duration of hospitalization, quality of life and New York Heart Association (NYHA) Functional Classification, in adults with COVID-19. Methods: This double-blind, randomized control trial will be conducted on patients with RT-PCR and/or chest CT scan diagnosis of COVID-19 admitted in Imam Reza Hospital, Mashhad, Iran. Participants will be randomized into control and intervention groups based on randomization sampling. The intervention group will receive soft gel containing 50,000 IU vitamin D on the first day followed by 10,000 IU/day through a supplement drop daily for 29 days. The control group will receive 1000 IU vitamin D daily through supplement drop and a placebo soft gel. All participants will undergo laboratory assessment including inflammatory markers, serum 25)OH)D, complete blood count (CBC), liver and renal profile, lipid profile and erythrocyte sedimentation rate (ESR) at baseline and at day 30. The mortality rate will be recorded in both groups. Results: Data will be presented using descriptive statistics. Comparison of changes in study parameters over the study period will be performed using analysis of covariance adjusting for possible confounders. Conclusions: The findings of this will provide evidence on the effects of high dose vitamin D supplementation on inflammatory markers in hospitalized COVID-19 patients.

A variant in CYP2R1 predicts circulating vitamin D levels after supplementation with high-dose of vitamin D in healthy adolescent girls.

AIM: The determinants of serum vitamin D seems to be the environmental factors (dietary and supplementary intake and exposure to ultraviolet light) and genetic factors. We aimed to study the relationship between a vitamin D-associated genetic polymorphism and serum 25(OH)D concentrations in healthy adolescent girls in Iran, and its effects on a high-dose supplement of vitamin D. MATERIAL AND METHOD: A total of 616 healthy adolescent girls with mean age 15 received 50,000 IU of vitamin D3 weekly over 9 weeks. Serum vitamin D levels and other metabolic factors were measured at baseline and after the intervention. The genotyping of the CYP2R1 variant (rs10741657) was performed by TaqMan genotyping assays. RESULTS: Regardless of the genetic background, at baseline, 87% of adolescent girls were vitamin D deficient (serum 25(OH)D level < 50 nmol/l). High-dose supplementation with VitD reduced the proportion of girls who were deficient substantially to about 24%. The genetic analysis revealed that although at baseline there was not a gene-vitamin D association ( p trend = 0.1), the response to supplementation appeared to be modulated by this variant ( p trend < 0.001). However, other anthropometric and biochemical measures were not affected by this intervention, over this short period. Serum 25(OH)D was increased in all participants although the carriers of the minor A allele seemed to be better responders so that the percentages of the change serum vitamin D in the holder of AA and AG genotypes were 539.4 ± 443.1 and 443.7 ± 384.6, respectively, compared with those with common GG genotype (363.3 ± 354.0). Our regression analysis revealed that the probability of an increase in serum 25(OH)D in a participant with AA genotype was 2.5-fold greater than those with a GG genotype (OR = 2.5 (1.4-4.4); p value = 0.002). CONCLUSION: Based on our findings, it appears that the rs10741657 variant of the CYP2R1 gene modulates the response to high-dose of vitamin D supplementation.

Associations of vitamin D binding protein variants with the vitamin D-induced increase in serum 25-hydroxyvitamin D.

BACKGROUND: Vitamin D deficiency is a global problem that may be improved by vitamin D supplementation; however, the individual's response to the intervention varies. We aimed to investigate possible genetic factors that may modify the impact of environmental exposure on vitamin D status. The candidate gene variant we investigated was the Gc gene-rs4588 polymorphism at the vitamin D receptor (DBP) locus. METHODS: A total of 619 healthy adolescent Iranian girls received 50000 IU of vitamin D3 weekly for 9 weeks. Serum 25(OH) D concentrations, metabolic profiles and dietary intake were measured at baseline and after 9 weeks of supplementation. The genotypes of the DBP variant (rs4588) were analyzed using the TaqMan genotyping assay. RESULTS: Our results revealed that the rs4588 polymorphism might be associated with serum 25-hydroxy vitamin D both at baseline (p value = 0.03) and after intervention (p value = 0.008). It seemed that the outcome of the intervention was gene-related so that the subjects with common AA genotype were a better responder to vitamin D supplementation (Changes (%) 469.5 (427.1) in AA carriers vs. 335.8 (530) in GG holders), and carriers of the less common GG genotype experienced a rise in fasting blood glucose after 9 weeks (Changes (%) 0 (1.5)). Our findings also showed that the statistical interaction between this variant and supplementation was statistically significant (intervention effect p-value<0.001 and p-value SNP effect = 0.03). The regression model also revealed that after adjusted for potential confounders, likelihood of affecting serum 25(OH)D in individuals who were homozygous for the uncommon allele G was less than those homozygous for the more common AA genotype (OR = 4.407 (1.82-8.89); p = 0.001). CONCLUSION: Serum vitamin 25(OH) D following vitamin 25(OH) D3 supplementation appears to be modified by genetic background. The Gc genetic variant, rs4588 encoding the vitamin D receptor seems to influence the response to vitamin D supplementation.