Effects of lycopene supplementation on oxidative stress and markers of endothelial function in healthy men

doi:10.1016/j.atherosclerosis.2010.11.036

Atherosclerosis

Volume 215, Issue 1, March 2011, Pages 189-195

https://doi.org/10.1016/j.atherosclerosis.2010.11.036 Get rights and content

Abstract

Objective

The objective was to determine the effects of lycopene supplementation on endothelial function assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) and oxidative stress.

Methods

Healthy men (n = 126) were randomized to receive placebo (n = 38), 6 mg (n = 41), or 15 mg (n = 37) lycopene daily for 8-week.

Results

Serum lycopene increased in a dose-dependent manner after 8-week supplementation (P < 0.001). The 15 mg/day group had greater increase in plasma SOD activity (P = 0.014) and reduction in lymphocyte DNA comet tail length (P = 0.042) than the placebo group. Intragroup comparison revealed a 23% increase in RH-PAT index from baseline (1.45 ± 0.09 vs. 1.79 ± 0.12; P = 0.032) in the 15 mg/day group after 8-week. hs-CRP, systolic blood pressure, sICAM-1 and sVCAM-1 significantly decreased, and β-carotene and LDL-particle size significantly increased only in the 15 mg/day group. Interestingly, the beneficial effect of lycopene supplementation on endothelial function (i.e., RH-PAT and sVCAM-1) were remarkable in subjects with relatively impaired endothelial cell function at initial level. Changes in RH-PAT index correlated with SOD activity (r = 0.234, P = 0.017) especially in the 15 mg lycopene/day group (r = 0.485, P = 0.003), lymphocyte DNA comet tail moment (r = −0.318, P = 0.001), and hs-CRP (r = −0.238, P = 0.011). In addition, changes in lycopene correlated with hs-CRP (r = −0.230, P = 0.016) and SOD activity (r = 0.205, P = 0.037).

Conclusion

An increase in serum lycopene after supplementation can reduce oxidative stress which may play a role in endothelial function.

Introduction

Lycopene is the most powerful antioxidant among the major carotenoids and has received attention for its potential role in preventing cardiovascular disease in humans [1]. Low serum and adipose tissue lycopene concentrations are associated with excess incidence of acute coronary events and stroke [2]. Further, plasma lycopene is inversely associated with early atherosclerosis, as measured by intima-media thickness [3], and an independent inverse relationship between circulating lycopene and arterial stiffness was reported in healthy subjects [4], [5]. Recently, lycopene was reported to attenuate atherogenesis in rabbits fed on a high-fat diet and this effect was comparable to fluvastatin [6].

Oxidative stress can inactivate nitric oxide, impairing endothelium-dependent vasodilation [7]. However, the studies of the relationship between lycopene and early atherosclerosis are inconsistent [8]. Dietary intervention studies involving either lycopene-containing foods or lycopene supplementation have shown potential short-term improvement in LDL oxidation [9], oxidative damage of lymphocyte DNA [10], and blood pressure [11]. However, studies that measure effects on a robust marker of cardiovascular health, such as endothelial function using precise amounts of lycopene supplements, are sparse.

Endothelial function is considered one of the best indicators of vascular health, and its dysfunction is viewed as the common pathway between coronary risk factors and the development of atherosclerosis [12]. Measurement of flow-mediated dilatation of the brachial artery has been the standard method of assessing endothelial function, but in recent years, reactive hyperemia peripheral arterial tonometry (RH-PAT) [6], [13], an equally reliable, less operator-dependent, non-invasive test for endothelial function has been developed for use in clinical research.

Our hypothesis was that an increase in serum lycopene levels following supplementation with capsules containing natural lycopene rich tomato extract would reduce oxidative stress and improve endothelial function in healthy men with frequently smoke cigarettes or consume alcohol and low intake of fruits and vegetables. A randomized double-blind, placebo-controlled study was designed to assess the changes in serum lycopene levels, oxidative stress and endothelial function in response to an 8-week treatment with lycopene supplementation.

Section snippets

Study subjects

This was a randomized double-blind, placebo-controlled intervention trial conducted by the Laboratory of Clinical Nutrigenetics/Nutrigenomics (project#: 2010-0015017 and M10642120002-06N4212-00210) at Yonsei University. The study design was approved by the Institutional Review Board of Yonsei University. One hundred twenty-six healthy men aged 22–57 years, who frequently smoked cigarettes or consumed alcohol, were enrolled in this study. Subjects were excluded if they consumed more than 3

Results

Among enrolled subjects (n = 126), 10 dropped out for personal reasons and 116 subjects completed the study. Among the drop-outs, 4 were in the placebo group, 1 was in the 6-mg lycopene supplement/day group, and 5 were in the 15-mg lycopene supplement/day group. Thus, compliance was high (92.1%) and no serious adverse reactions due to lycopene supplementation were noted. Participants were supplied with 30 capsules of placebo pills, low-dose or high-dose lycopene pills at 0-week and at 4-week

Discussion

In this randomized, double-blind, placebo-controlled study, lycopene supplementation had beneficial effects on biomarkers of oxidative stress, as evidenced by decreased oxidative DNA damage and increased plasma SOD activity. In addition, changes in RH-PAT index, a measure of peripheral microvascular endothelial function [13], correlated with the increase in SOD activity and negatively with changes in oxidative DNA damage and hs-CRP levels. This result suggests that the antioxidant effects of

Conflict of interest

There is no potential conflict of interest.

Acknowledgements

We thank the research volunteers who participated in the studies described in this report. All the authors were involved in the development of the study protocol and the experimental design. Sample collection and experiments were performed by JYK, JKP, HWP, JHL and YJ. Data were analyzed by JYK, JKP, and OYK. JHL provided the research funding and wrote the manuscript. All the authors read, commented on, and contributed to the submitted manuscript. None of the authors have any conflicts of

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Citation Excerpt :
It has been shown that lycopene supplementation particularly high-dose supplementation might play a positive role in endothelial function, which is greater in subjects who had relatively impaired endothelial cell function at the initial level (Kim et al., 2011). Alike, SBP and hs-CRP declined only in subjects consuming 15-mg lycopene daily for 8-week (Kim et al., 2011). The study also showed that lycopene might play a certain role in lowering SBP especially among prehypertensive or hypertensive populations (Li and Xu, 2013).
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A systematic search was carried out in PubMed, SCOPUS, EMBASE and ISI Web of Science, without any restrictions on date and language publication to February 2020. Data were pooled using random-effects method and were expressed as weighted mean difference (WMD) and 95% confidence intervals (CI).
The elementary search consisted of 2564 records. Finally, 10 RCTs were included in the study. The pooled results of 10 studies with 16 effect size sizes including 688 participants (case=438 and control=250) showed that lycopene supplementation significantly decreased systolic blood pressure (SBP) (weighted mean differences (WMD): − 2.63 mmHg; 95% CI: − 5.17, − 0.09; P = 0.042). Greater effects on SBP were observed in subjects with a baseline SBP≥ 130 mmHg, at the lycopene dosages of ≥ 15 mg, duration≥ 8 weeks, and in hypertensive subjects. The changes observed in diastolic blood pressure (DBP) (WMD: −1.02 mmHg; 95% CI: −2.51, 0.46; P = 0.179) were not statistically significant. However, subgroup analysis showed that DBP decreased significantly in studies that enrolled hypertensive subjects or with elevated DBP (>80 mmHg). Lycopene supplementation reduced SBP in non-linear fashion based on dosage (P-nonlinearity = 0.04, Coef = −9.68).
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^☆: Financial support: National Research Foundation, Ministry of Education, Science and Technology (2010-0015017, M10642120002-06N4212-00210, and 2008-359-C00050) and Korea Health 21 R&D Projects, Ministry of Health & Welfare (A080348), Seoul, Korea.

¹: These authors contributed equally to this work.

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Effects of lycopene supplementation on oxidative stress and markers of endothelial function in healthy men☆

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Study subjects

Results

Discussion

Conflict of interest

Acknowledgements

Atherosclerosis

Nutrition

J Nutr

Mutat Res

Am J Clin Nutr

Am J Clin Nutr

J Am Coll Cardiol

Tomato lycopene and its role in human health and chronic diseases

Can Med Assoc J

Low serum lycopene concentration is associated with an excess incidence of acute coronary events and stroke: the Kuopio ischaemic heart disease risk factor study

Br J Nutr

Low plasma lycopene concentration is associated with increased intima-media thickness of the carotid artery wall

Arterioscler Thromb Vasc Biol

Association of serum lycopene and brachial-ankle pulse wave velocity with metabolic syndrome

Metabolism