title: Protective Effect of Folic Acid on Oxidative DNA Damage: A Randomized, Double-Blind, and Placebo Controlled Clinical Trial.
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.
authors.affiliation: From the School of Environmental Science & Public Health, Wenzhou Medical University, Wenzhou (XG, HZ, XG, CJ, HY, WQ, CZ, GM); School of Public Health, Inner Mongolia Medical University, Inner Mongolia (XG, ZZ); University Hospital of Wenzhou Medical University (HC); School of Laboratory Medicine & Life Science, Wenzhou Medical University, Wenzhou (JW); Center for Disease Control and Prevention of Wuyuan County, Inner Mongolia, China (ZY); Center on the Early Life Origins of Disease, the Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (ZC, GM); and Center on Clinical & Epidemiological Eye Disease, the Affiliated Eye Hospital of Wenzhou Medical University, Wenzhou, China (GM).
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Guo
authors.forename: Huan
authors.initials: H
authors.lastname: Cui
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Guan
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Chaonan
authors.initials: C
authors.lastname: Jia
authors.forename: Jia
authors.initials: J
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Wenting
authors.initials: W
authors.lastname: Qiu
authors.forename: Chuanwu
authors.initials: C
authors.lastname: Zhang
authors.forename: Zuopeng
authors.initials: Z
authors.lastname: Yang
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.forename: Guangyun
authors.initials: G
authors.lastname: Mao
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000368:Aged; D003404:Creatinine / Q000652:urine; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D014803:Vitamin B Complex / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D014803:Vitamin B Complex; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005492:Folic Acid; D003404:Creatinine; D003849:Deoxyguanosine