Lycopene: A Monograph

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:    Frankp@chiro.org

FROM:   Alternative Medicine Review 2003 (Aug);   8 (3):   336–342 ~ FULL TEXT

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Introduction

Lycopene, a carotenoid without provitamin-A activity, is present in many fruits and vegetables. It is a red, fat-soluble pigment found in certain plants and microorganisms, where it serves as an accessory light-gathering pigment and protects these organisms against the toxic effects of oxygen and light. Tomato products, including ketchup, tomato juice, and pizza sauce, are the richest sources of lycopene in the U.S. diet, accounting for greater than 80 percent of the total lycopene intake of Americans. [1] In addition to tomatoes (Lycopersicon esculentum) and tomato-based products, lycopene is also found in watermelon, papaya, pink grapefruit, and pink guava. Lycopene from both processed and cooked tomato products is more bioavailable than from fresh tomatoes. [2]

Dietary intakes of tomatoes and tomato products containing lycopene have been shown in cell culture, animal, and epidemiological investigations to be associated with a decreased risk of chronic diseases, such as cancer and cardiovascular disease. [3-5] In addition, serum and tissue lycopene levels have been inversely correlated with risk of lung and prostate cancers. [6]

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Clinical Indications

Cardiovascular Disease

Lycopene may reduce lipids by inhibiting the enzyme macrophage 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase (an important step in cholesterol synthesis)15 and by enhancing LDL degradation.1 In addition, available evidence suggests intimal wall thickness and risk of myocardial infarction (MI) are reduced in persons with higher adipose tissue concentrations of lycopene. [1]

Recent epidemiological studies have shown an inverse relationship between tissue and serum levels of lycopene and mortality from coronary heart disease (CHD), cerebrovascular disease, and MI.16-18 The strongest population-based evidence on lycopene and MI comes from the European Community Multicenter Study on Antioxidants, Myocardial Infarction and Breast Cancer (EURAMIC) that evaluated the relationship between adipose tissue antioxidant status and acute MI. [16] The study recruited 1,379 individuals (662 patients, 717 controls) from 10 European countries. Needle aspiration biopsy samples of adipose tissue were taken shortly after the infarction, and levels of alpha- and beta-carotenes, lycopene, and alpha-tocopherol were measured. After adjusting for age, body mass index, socioeconomic status, smoking, hypertension, and maternal and paternal history of heart disease, only lycopene levels were found to be protective. The protective potential of lycopene was maximal among individuals with the highest polyunsaturated fat stores, supporting the antioxidant theory. Results also showed a dose-response relationship between each quintile of adipose tissue lycopene and the risk of MI. Similarly, lower blood lycopene levels were also found to be associated with increased risk and mortality from CHD in a concomitant cross-sectional study comparing Lithuanian and Swedish populations. [17]

In a recent clinical trial, 60 healthy individuals (30 men/30 women) were randomized to examine the change in plasma lycopene and resistance of lipoproteins to oxidative stress. Fifteen days of tomato product consumption significantly enhanced the protection of lipoproteins to oxidative stress as measured by a significant increase (p< 0.05) in the lag period (a measure of antioxidant capacity) after consumption of lycopene. [19] Increased thickness of the intima-media has been shown to predict coronary events. [20] Rissanen et al investigated the relationship between plasma concentrations of lycopene and intima- media thickness of the common carotid artery wall (CCA-IMT) in 520 males and females (age 45-69). [21] The authors conclude that low plasma lycopene concentrations are associated with early atherosclerosis in men, but not women, as manifested by increased CCA-IMT.

Cancer

Oxidative stress is recognized as one of the major contributors to increased risk of cancer, and in chemical assays lycopene is the most potent antioxidant among various common carotenoids. [22] Lycopene has been found to inhibit proliferation of several types of human cancer cells, including endometrial, breast, and lung. [23-25] In addition, in vivo studies have shown lycopene has tumor-suppressive activity. [26] Other studies support the hypothesis that carotenoid-containing plant products, such as lycopene, exert a cancer protective effect via a decrease in oxidative and other damage to DNA in humans. [27] Lycopene has also recently been shown to elevate levels of hepatic reduced glutathione and biotransformation enzymes, potentially playing a key role in preventing cancer development at extrahepatic sites. [28] In one epidemiological review regarding intake of tomatoes, tomato-based products, and blood lycopene levels in relation to the risk of various cancers, 72 studies were identified. [29] Of those, 57 reported inverse associations between tomato intake or blood lycopene level and the risk of cancer at a defined anatomic site; [35] of these inverse associations were statistically significant. The evidence for a benefit was strongest for cancers of the prostate, lung, and stomach. Data were also suggestive of a benefit for cancers of the pancreas, colon and rectum, esophagus, oral cavity, breast, and cervix.

Prostate Cancer

Cancer of the prostate is the most commonly diagnosed solid malignancy and the second- leading cause of cancer-related death in men in developed countries. [30] A study published by members of the Department of Epidemiology at the Harvard School of Public Health stated, “The strongest known dietary risk factor for prostate cancer is a lycopene deficit.” [31] A number of studies, examining tomato products, lycopene intake, or circulating lycopene levels in relation to prostate cancer risk, suggest high consumption or high circulating concentrations are associated with a reduction in risk of prostate cancer. [32-35] In addition, studies have demonstrated an inverse correlation between dietary lycopene intake and both serum insulin-like growth factor-1 (IGF-1) levels and risk of prostate cancer. 31 IGF-1 has been shown to play a role in the pathogenesis of prostate cancer; [36] therefore, if as proposed, increased serum IGF-1 levels do raise the risk of prostate cancer, lycopene may exert protection against the disease, particularly in its early stages, by decreasing serum IGF-1 levels. [37]

In a study of lycopene supplementation in males with prostate cancer before radical prostatectomy, Kucuk et al randomized 26 patients to lycopene supplementation (15 mg twice daily) or no supplementation for three weeks prior to surgery. [38] In the intervention group 73 percent, compared to 18 percent of the controls, had negative margins (p=0.02), and diffuse prostatic intraepithelial neoplasia was seen in 67 percent of the intervention group, compared to 100 percent in the control group. Prostatic-specific antigen (PSA) levels decreased 18 percent in the lycopene group; whereas, they increased 14 percent in the controls. Although the sample size in this randomized study was small, it suggests even a short course of lycopene prior to surgery has the potential to decrease the growth of prostate cancer. Lycopene at physiological concentrations has also been shown to inhibit human cancer cell growth by interfering with growth factor receptor signaling and cell cycle progression, specifically in prostate cancer cells, without evidence of toxic effects or apoptosis of cells. Studies using human and animal cells have identified a gene, connexin [43], whose expression is up-regulated by lycopene, allowing direct intercellular gap junction communication (GJC). GJC is deficient in many human tumors and its restoration or up-regulation is associated with decreased proliferation. [6]

Breast Cancer

Some studies have found a significant inverse association between lycopene in breast tissue and breast cancer risk.39 In cell cultures, lycopene has been found to inhibit breast cancer tumors more efficiently when compared to alphaand beta-carotene. [23] In a case-control study conducted between 1993 and 1999, examining the relationship between 17 micronutrients and breast cancer risk in 289 women with confirmed breast cancer and 442 controls, lycopene was significantly inversely associated with breast cancer risk. [40] Median intake of lycopene in the “high intake” group was 6.2 mg/day.

In a 1998 study, samples taken from the Breast Cancer Serum Bank in Columbia, Missouri, were analyzed to evaluate the relationship of levels of carotenoids (including lycopene), selenium, and retinol with breast cancer. [41] Only lycopene was found to be associated with a reduced risk for developing breast cancer.

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