Effect of Lycopene Supplementation on Oxidative Stress: An Exploratory Systematic Review and Meta-Analysis of Randomized Controlled Trials

February 7, 2013

Sichuan University

Jinyao Chen, Yang Song, and Lishi Zhangcorresponding author


Lycopene is a potentially useful compound for preventing and treating cardiovascular diseases and cancers. Studies on the effects of lycopene on oxidative stress offer insights into its mechanism of action and provide evidence-based rationale for its supplementation. In this analysis, randomized controlled trials of the effects of oral lycopene supplementation on any valid outcomes of oxidative stress were identified and pooled through a search of international journal databases and reference lists of relevant publications. Two reviewers extracted data from each of the identified studies. Only studies of sufficient quality were included. Twelve parallel trials and one crossover trial were included in the systematic review, and six trials provided data for quantitative meta-analysis. Our results indicate that lycopene supplementation significantly decreases the DNA tail length, as determined using comet assays, with a mean difference (MD) of −6.27 [95% confidence interval (CI) −10.74, −1.90] (P=.006) between the lycopene intervention groups and the control groups. Lycopene supplementation does not significantly prolong the lag time of low-density lipoprotein (MD 3.76 [95% CI −2.48, 10.01]; P=.24). Lycopene possibly alleviates oxidative stress; however, biomarker research for oxidative stress needs be more consistent with the outcomes in lycopene intervention trials for disease prevention.

Key Words: lycopene, meta-analysis, oxidative stress, randomized controlled trial, systematic review


Cardiovascular diseases and cancers are main contributors to human morbidity and mortality, and the pivotal role of oxidative stress in the etiology of both diseases is well known. Oxidative stress is defined as disturbances in the prooxidant–antioxidant balance that favors oxidation. Thus, oxidative stress is essentially an imbalance between the production of various reactive species and the ability of the natural protective mechanisms of organisms to cope with these reactive compounds and to prevent adverse effects.1 Oxidative status is assessed in terms of the overall oxidative/reductive potency of a given specimen (e.g., blood or urine) or the susceptibility of various oxidizable components to ex vivo peroxidation.13

Lycopene is a potentially powerful antioxidant because of its conjugated double bonds. In vitro evidence suggests that lycopene protects lipoproteins and vascular cells from oxidation, but in vivo evidence is limited.2,4 Lycopene reportedly has the strongest singlet oxygen-quenching capacity among carotenoids,5and is the most effective quencher in plasma, low-density lipoprotein (LDL), and human lymphoid cells in vitro.4,6 Epidemiologic studies have reported that the consumption of lycopene-rich foods decreases the risk of cardiovascular diseases and cancers.79 Several clinical trials have provided evidence that lycopene lowers oxidative stress, particularly by preventing LDL oxidation.4,10,11 However, in 2000, the panel on Dietary Reference Intake evaluated the potential health effects of β-carotene and other carotenoids and concluded that no convincing evidence indicates that substantially increasing the carotenoid intake above current levels significantly affects the antioxidant status; however, lycopene was not specifically addressed.12 Considering that lycopene metabolism has not been fully elucidated and antioxidative nutrients interact with each other during gastrointestinal absorption and metabolism, the function of lycopene in vivo possibly differs from thatin vitro.1316

Decades of clinical and preclinical studies have broadened our understanding of lycopene and its use in numerous chronic, oxidative stress-induced pathologies; however, the results of these studies have shown mixed results, although with promising implications on the efficacy of lycopene in vivo.13,17,18 To provide more convincing estimates, this systematic review and meta-analysis assesses the effect of lycopene supplementation on oxidative stress. A wide variety of functional assays for oxidative stress is covered, including various measures of lipid oxidation, DNA oxidation, and protein oxidation, for illustrative purposes. This article is the first systematic review on this topic.