Abstract P012: The Effect of Vitamin D Supplementation on Epigenetic Aging: A Randomized Placebo-Controlled Clinical Trial

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Li Chen ◽  
Yanbin Dong ◽  
Jigar Bhagatwala ◽  
Anas Raed ◽  
Ying Huang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Dna Methylation ◽  
Vitamin D ◽  
African Americans ◽  
Vitamin D Supplementation ◽  
Chronological Age ◽  
Controlled Clinical Trial ◽  
P Value ◽  
Epigenetic Aging ◽  
Dna Methylation Age

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.

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 ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Dna Methylation ◽  
Vitamin D ◽  
African Americans ◽  
Randomized Clinical Trial ◽  
Vitamin D3 ◽  
Vitamin D Supplementation ◽  
P Value ◽  
Epigenetic Aging ◽  
Vitamin D3 Supplementation

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.

Abstract MP20: Vitamin D Supplementation Increases Global DNA Methylation in Overweight and Obese African Americans with Vitamin D Deficiency

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Haidong Zhu ◽  
Ying Huang ◽  
Jigar Bhagatwala ◽  
Samip Parikh ◽  
Robyn Havens ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Trial ◽  
Dna Methylation ◽  
Vitamin D ◽  
African Americans ◽  
Vitamin D Deficiency ◽  
Vitamin D3 ◽  
Methylation Level ◽  
Vitamin D Supplementation ◽  
Global Dna Methylation

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.

scholarly journals Vitamin D supplementation to persistent carriers of MRSA—a randomized and placebo-controlled clinical trial

2018 ◽  
Vol 37 (9) ◽  
pp. 1735-1744 ◽  
Author(s):  
Linda Björkhem-Bergman ◽  
Catharina Missailidis ◽  
John Karlsson-Valik ◽  
Ann Tammelin ◽  
Lena Ekström ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Vitamin D ◽  
Vitamin D Supplementation ◽  
Controlled Clinical Trial

Abstract P213: Chocolate Intake is Associated With Decreased Epigenetic Aging Among African Americans

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Li Chen ◽  
Haidong Zhu ◽  
Jigar Bhagatwala ◽  
Anas Raed ◽  
Ying Huang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
African Americans ◽  
Biological Aging ◽  
Cardiometabolic Health ◽  
P Value ◽  
Peripheral Blood Mononuclear ◽  
Beneficial Effects ◽  
Epigenetic Aging ◽  
A Genome ◽  
Cardiovascular Morbidity And Mortality

Introduction: Chocolate intake has shown potential cardiometabolic health benefits in recent studies. We recently reported an association between chocolate intake and longer telomere length. Epigenetic age acceleration, an emerging marker of biological aging, predicts cardiovascular morbidity and mortality. But the relationship between chocolate intake and epigenetic aging has not been investigated. Hypothesis: We examined the association between chocolate intake and epigenetic aging among African Americans. Methods: A genome-wide methylation scan was performed among 50 overweight and obese African Americans using the Illumina Human Methylation 850K Bead Chip on peripheral blood mononuclear cell DNA. DNA methylation ages were calculated according to the Horvath and the Hannum clocks. Methylation-based age acceleration (ΔAge) was extracted from a linear regression of DNA methylation age on chronological age. Chocolate intake frequency over the past year was obtained by questionnaire, along with other major cardiovascular risk factors. Results: Fifty participants (aged 26.1 ± 9.3 years, 16% male) were included in the study. Fifteen (30%), 20 (40%), and 15 (30%) participants consumed less than 1 serving/month, 1-3 servings/month, and ≥1 serving/week of chocolate, respectively. Chocolate intake of ≥1 serving/week was associated with decreased Δage in both Horvath clock (β= -3.31, p-value = 0.046) and Hannum clock (β= -3.59, p-value = 0.096) after adjustment of age, sex, body mass index, 25(OH)D and CD4%. Conclusions: Chocolate intake may be associated with decreased epigenetic aging, with randomized controlled trials needed to establish any beneficial effects of chocolate intake on epigenetic aging processes.

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