A dose-response study on the effects of purified lycopene supplementation on biomarkers of oxidative stress

Abstract

Objective: While tomato product supplementation, containing antioxidant carotenoids, including lycopene, decreases oxidative stress, the role of purified lycopene as an antioxidant remains unclear. Thus, we tested the effects of different doses of purified lycopene supplementation on biomarkers of oxidative stress in healthy volunteers.

Methods: This was a double-blind, randomized, placebo-controlled trial, examining the effects of 8-week supplementation of purified lycopene, on plasma lycopene levels, biomarkers of lipid peroxidation {LDL oxidizability, malondialdehyde & hydroxynonenals (MDA & HNE), urinary F(2)-isoprostanes}, and markers of DNA damage in urine and lymphocytes. Healthy adults (n = 77, age > or = 40 years), consumed a lycopene-restricted diet for 2 weeks, and were then randomized to receive 0, 6.5, 15, or 30 mg lycopene/day for 8 weeks, while on the lycopene-restricted diet. Blood and urine samples were collected at the beginning and end of Week 2 of lycopene-restricted diet, and at end of Week 10 of the study.

Results: Independent of the dose, plasma lycopene levels significantly increased in all lycopene supplemented groups versus placebo (p < 0.05). ANOVA revealed a significant decrease in DNA damage by the comet assay (p = 0.007), and a significant decrease in urinary 8-hydroxy deoxoguanosine (8-OHdG) at 8 weeks versus baseline (p = 0.0002), with 30 mg lycopene/day. No significant inter- or intra-group differences were noted for glucose, lipid profile, or other biomarkers of lipid peroxidation at any dose/time point.

Conclusions: Thus, purified lycopene was bioavailable and was shown to decrease DNA oxidative damage and urinary 8-OHdG at the high dose.

Fig. 1

Plasma Lycopene levels in subjects before and after supplementation: Plasma lycopene levels were measured prior to lycopene restriction (Visit A), baseline (Visit B-following lycopene restricted diet) and at 8 weeks of the study (Visit C-end of supplementation) by HPLC as described in Methods. Data are given as Mean (±SD) in the 4 groups (placebo, 6.5, 15, or 30 mg/day). *p < 0.05 at Visit B vs. Visit A in all groups; #p < 0.05 at Visit C vs Visit B, and placebo.”

Fig. 2

Effect of Lycopene supplementation on Lymphocyte DNA damage: Lymphocyte DNA damage was assessed by measurement of comet tail lengths in healthy subjects supplemented with placebo, 6.5, 15, or 30 mg lycopene/day for 8 weeks as described in Methods. Data are presented as Mean (±SD) of comet tail lengths (μm). Visit A-Prior to Lycopene restricted diet; Visit B-following lycopene restricted diet and Visit C-end of supplementation *p < 0.05 at 8 weeks vs. baseline in the 30 mg lycopene/day group.”

Fig. 3

Effect of Lycopene supplementation on 8-OHdG: 8-OHdG levels were measured in urine of healthy subjects supplemented with placebo or 30 mg lycopene/day for 8 weeks as described in Methods. Data are presented as Mean (±SD) of 8-hydroxy-2′-deoxyguanosine (8-OHdG; ng/mg creatinine). *p < 0.05 at 8 weeks vs. baseline (Visit C vs Visit B).”