Protective Effect of Folic Acid on Oxidative DNA Damage

Abstract

Although previous reports have linked DNA damage with both transmissions across generations as well as our own survival, it is unknown how to reverse the lesion. Based on the data from a Randomized, Double-blind, Placebo Controlled Clinical Trial, this study aimed to assess the efficacy of folic acid supplementation (FAS) on DNA oxidative damage reversal.In this randomized clinical trial (RCT), a total of 450 participants were enrolled and randomly assigned to 3 groups to receive folic acid (FA) 0.4 mg/day (low-FA), 0.8 mg/day (high-FA), or placebo (control) for 8 weeks. The urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) and creatinine (Cr) concentration at pre- and post-FAS were measured with modified enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. A multivariate general linear model was applied to assess the individual effects of FAS and the joint effects between FAS and hypercholesterolemia on oxidative DNA damage improvement. This clinical trial was registered with ClinicalTrials.gov, number NCT02235948.Of the 438 subjects that received FA fortification or placebo, the median (first quartile, third quartile) of urinary 8-OHdG/Cr for placebo, low-FA, and high-FA groups were 58.19 (43.90, 82.26), 53.51 (38.97, 72.74), 54.73 (39.58, 76.63) ng/mg at baseline and 57.77 (44.35, 81.33), 51.73 (38.20, 71.30), and 50.65 (37.64, 76.17) ng/mg at the 56th day, respectively. A significant decrease of urinary 8-OHdG was observed after 56 days FA fortification (P < 0.001). Compared with the placebo, after adjusting for some potential confounding factors, including the baseline urinary 8-OHdG/Cr, the urinary 8-OHdG/Cr concentration significantly decreased after 56 days FAS [β (95% confidence interval) = −0.88 (−1.62, −0.14) and P = 0.020 for low-FA; and β (95% confidence interval) = −2.68 (−3.42, −1.94) and P < 0.001 for high-FA] in a dose-response fashion (Ptrend < 0.001). Test of interaction between hypercholesterolemia and FA supplementation on urinary 8-OHdG reduction was significant (P = 0.001).The present study demonstrates that FA fortification is independently linked to the reduction of urinary 8-OHdG/Cr in a dose-related pattern, which suggests that FA is beneficial to protect against oxidative damage to DNA. This effect is apparently stronger in those with hypercholesterolemia. The authors provide a new insight into the prevention and reversal of oxidative DNA damage.

A moderate increase in dietary zinc reduces DNA strand breaks in leukocytes and alters plasma proteins without changing plasma zinc concentrations

“…However, this DNA damage is not specific for low zinc intake. DNA strand breaks also increase with low intakes of folate and vitamin B-6 ( 48 , 49 ).…”

Folic acid supplementation reduces multigenerational sperm miRNA perturbation induced by in utero environmental contaminant exposure

“…The protective role of FA supplementation in the F1 sperm may be partly explained by its antioxidant activity if the miRNA changes are caused by oxidative stress induced by POPs exposure (i.e. F1 POPs males) [39–41]. If, however, the miRNA changes in POPs exposed sperm are due to an altered methylation capacity or dysregulated nucleotide synthesis or mutations, then the increased availability of methyl groups provided by FA supplementation may mitigate the POPs effect by supporting DNA repair through nucleotide synthesis.…”

Folic Acid Supplementation and the Association between Maternal Airborne Particulate Matter Exposure and Preterm Delivery: A National Birth Cohort Study in China

“…Studies of maternal PM exposure and PTD have suggested that oxidative stress could be a potential biological pathway (Moore et al 2018;Li et al 2017;Pereira et al 2014). A randomized clinical trial of 438 healthy adults compared urine 8-hydroxy-2 0deoxyguanosine (8-OHdG/Cr), a marker of oxidative damage to DNA, before and after intervention among three groups-a) FA at 0:4 mg=d for 8 wk; b) FA at 0:8 mg=d for 8 wk; and c) placebo for 8 wk-and found that urinary 8-OHdG/Cr levels were decreased in a dose-related pattern for participants who had FA supplementation (Guo et al 2015). These findings suggest that FA might have a protective effect on PM-related PTD by regulating the imbalance of oxidants and antioxidants as an antioxidant.…”

“…2014 ). A randomized clinical trial of 438 healthy adults compared urine 8-hydroxy-2′-deoxyguanosine (8-OHdG/Cr), a marker of oxidative damage to DNA, before and after intervention among three groups— a ) FA at for 8 wk; b ) FA at for 8 wk; and c ) placebo for 8 wk—and found that urinary 8-OHdG/Cr levels were decreased in a dose-related pattern for participants who had FA supplementation ( Guo et al. 2015 ).…”