scholarly journals Effects of Vitamin D3 Supplementation on Epigenetic Aging in Overweight and Obese African Americans With Suboptimal Vitamin D Status: A Randomized Clinical Trial

2018 ◽  
Vol 74 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Li Chen ◽  
Yanbin Dong ◽  
Jigar Bhagatwala ◽  
Anas Raed ◽  
Ying Huang ◽  
...  

Abstract Background We have previously shown that vitamin D supplementation increases telomerase activity, suggesting an anti-aging effect. In this study, we aim to test the hypothesis that vitamin D supplementation would slow down epigenetic aging, a new marker of biological aging. Methods A randomized clinical trial was previously conducted among 70 overweight/obese African Americans with serum 25-hydroxyvitamin D [25(OH)D] < 50 nmol/L, who were randomly assigned into four groups of 600 IU/d, 2,000 IU/d, 4,000 IU/d of vitamin D3 supplements or placebo followed by 16-week interventions. Whole genome-wide DNA methylation analysis was conducted in 51 participants. DNA methylation ages were calculated according to the Horvath and the Hannum methods. Methylation-based age acceleration index (∆Age) is defined as the difference between DNA methylation age and chronological age in years. Mixed-effects models were used to evaluate the treatment effects. Results Fifty-one participants (aged 26.1 ± 9.3 years, 16% are male) were included in the study. After the adjustment of multi-covariates, vitamin D3 supplementation of 4,000 IU/d was associated with 1.85 years decrease in Horvath epigenetic aging compared with placebo (p value = .046), and 2,000 IU/d was associated with 1.90 years decrease in Hannum epigenetic aging (p value = .044). Serum 25(OH)D concentrations were significantly associated with decreased Horvath ∆Age only (p values = .002), regardless of treatments. Conclusions Our results suggest that vitamin D supplementation may slow down Horvath epigenetic aging. But the effect on Hannum epigenetic aging is not conclusive. Large-scale and longer duration clinical trials are needed to replicate the findings.

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Li Chen ◽  
Yanbin Dong ◽  
Jigar Bhagatwala ◽  
Anas Raed ◽  
Ying Huang ◽  
...  

Background: Vitamin D deficiency is associated with age-related diseases, such as cardiovascular disease, diabetes and cancer. We have previously shown that vitamin D plays a role in regulating human epigenome. Moreover, we have demonstrated that vitamin D supplementation increases telomerase activity, suggesting an anti-aging property. Epigenetic age acceleration, an emerging marker of biological aging, predicts cardiovascular mortality, morbidity and cancer. In this study, we tested the hypothesis that vitamin D supplementation would decelerate epigenetic aging. Methods: We have previously completed a 16 week randomized placebo-controlled clinical trial of vitamin D3 supplementation in overweight/obese African-Americans (NCT01583621). The participants were randomly assigned into four groups of placebo, 600 IU/day, 2000 IU/day, and 4000 IU/day of vitamin D supplements. A genome-wide methylation scan was performed using the Illumina Human Methylation 480K Bead Chip on peripheral blood mononuclear cell DNA. DNA methylation age of 52 participants was determined based on 353 CpG sites using the statistical pipeline developed by Horvath. Epigenetic aging, methylation-based age acceleration index (Δage) was defined as the difference between DNA methylation age and chronological age in years. Mixed-effects models were used to evaluate the treatment effects. Results: DNAm age was significantly correlated with chronological age (r=0.9082, p-value < 0.001). The correlation was higher at baseline (r=0.9281, p-value < 0.001) than at 16 weeks (r=0.8887, p-value < 0.001), which implies that the 16 week treatment may drive the DNAm age deviated from the chronological age. Compared with placebo, vitamin D supplementation was also associated with decreased Δage after adjustment for sex, BMI, lymphocyte percentage, month and baseline 25(OH)D concentration (600 IU/day: β = 0.90, p-value = 0.325; 2000 IU/day: β= -1.21, p-value = 0.118; 4000 IU/day: β= -1.70, p-value = 0.035), but only the treatment effect of 4000 IU/day supplementation was significant. Conclusion: Our results suggest that vitamin D supplementation might decelerate epigenetic aging, further supporting the anti-aging effect of vitamin D supplementation in overweight/obese African Americans. Larger studies are needed to replicate the findings.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Haidong Zhu ◽  
Ying Huang ◽  
Jigar Bhagatwala ◽  
Samip Parikh ◽  
Robyn Havens ◽  
...  

Introduction: Vitamin D deficiency is associated with cardiovascular disease, diabetes and cancer. Individuals with obesity or darker skin are at risk for vitamin D deficiency. Our genome-wide methylation study has shown that African Americans with vitamin D deficiency have reduced levels of methylation compared with controls. Global decrease in DNA methylation, a common feature of cancer, is associated with genomic and chromosomal instability. Therefore, we aimed to test our hypothesis that vitamin D supplementation will increase global DNA methylation level in overweight and obese African Americans with vitamin D deficiency. Methods: We recently conducted a 16 weeks randomized, placebo controlled clinical trial of vitamin D3 supplementation (NCT01583621). A total of 65 young overweight and obese African Americans (13-45 years, 83% females) with vitamin D deficiency (25-hydroxyvitamin D3 [25(OH)D] < 20 ng/ml) were randomly assigned to receive a supervised monthly oral vitamin D3 dose of placebo (n=16), 18,000 IU (~600 IU/day, the current RDA; n=15), 60,000 IU (~2,000 IU/day; n=17), or 120,000 IU (~4,000 IU/day, the deemed tolerable upper intake level; n=17). Global DNA methylation level (percentage of 5-methylcytosine, %5-mC) was quantified using leukocyte DNA with the MethylFlash Methylated DNA Quantification kit (Epigentek) in a total of 58 participants. Results: At baseline, serum 25(OH)D levels were positively correlated with %5-mC (r=0.26, p=0.04) in the entire cohort. A significant increase was observed in the changes of serum 25(OH)D from baseline to 16 weeks (0.9 ± 2.0, placebo; 8.6 ± 2.1, 600 IU/day; 20.1 ± 2.0, 2,000 IU/day; and 21.2 ± 2.0 ng/ml, 4,000 IU/day; p<0.01). In addition, a significant dose-responsive increase was observed in the changes of %5-mC from baseline to 16 weeks (0.00 ± 0.18, placebo; 0.02 ± 0.20, 600 IU/day; 0.29 ± 0.17, 2,000 IU/day; and 0.66 ± 0.18%, 4,000 IU/day group; p<0.01). This response remained significant even after adjusting for age, sex and BMI. Moreover, the changes in %5-mC were significantly correlated with the changes in serum 25(OH)D (r=0.60, p=0.02) in the 4,000 IU group. Conclusions: Vitamin D supplementation increases global DNA methylation level in a dose-responsive manner. Increased global DNA methylation, subsequently increased genomic and chromosomal stability may be one of the underlying mechanisms by which vitamin D exerts its beneficial effects on cardiovascular disease, diabetes and cancer. Large scale vitamin D supplementation clinical trial is warranted to verify our findings.


Author(s):  
Cora M Best ◽  
Leila R Zelnick ◽  
Kenneth E Thummel ◽  
Simon Hsu ◽  
Christine Limonte ◽  
...  

Abstract Context The effect of daily vitamin D supplementation on the serum concentration of vitamin D (the parent compound) may offer insight into vitamin D disposition. Objective To assess the total serum vitamin D response to vitamin D3 supplementation and whether it varies according to participant characteristics. To compare results with corresponding results for total serum 25-hydroxyvitamin D (25(OH)D), which is used clinically and measured in supplementation trials. Design Exploratory study within a randomized trial. Intervention 2,000 International Units of vitamin D3 per day (or matching placebo). Setting Community-based. Participants 161 adults (mean ± SD age 70 ± 6 years; 66% males) with type 2 diabetes. Main Outcome Measures Changes in total serum vitamin D and total serum 25(OH)D concentrations from baseline to year 2. Results At baseline, there was a positive, nonlinear relation between total serum vitamin D and total serum 25(OH)D concentrations. Adjusted effects of supplementation were a 29.2 (95% CI: 24.3, 34.1) nmol/L increase in serum vitamin D and a 33.4 (95% CI: 27.7, 39.2) nmol/L increase in serum 25(OH)D. Among those with baseline 25(OH)D &lt; 50 compared with ≥ 50 nmol/L, the serum vitamin D response to supplementation was attenuated (15.7 vs 31.2 nmol/L; interaction p-value = 0.02), whereas the serum 25(OH)D response was augmented (47.9 vs 30.7 nmol/L; interaction p-value = 0.05). Conclusions Vitamin D3 supplementation increases total serum vitamin D and 25(OH)D concentrations with variation according to baseline 25(OH)D, which suggests that 25-hydroxylation of vitamin D3 is more efficient when serum 25(OH)D concentration is low.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2170
Author(s):  
Shaun Sabico ◽  
Mushira A. Enani ◽  
Eman Sheshah ◽  
Naji J. Aljohani ◽  
Dara A. Aldisi ◽  
...  

Objective: Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. Study Design and Setting: A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males; 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males; 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. Results: Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values < 0.05) but was not clinically significant in between-group comparisons. Kaplan–Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8; p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7; p = 0.035). Conclusion: A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.


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