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The beneficial effects of tomatoes

      Abstract

      Dietary intake of tomatoes and tomato products containing lycopene has been shown to be associated with a decreased risk of chronic diseases such as cancer and cardiovascular disease in several recent studies. Serum and tissue lycopene levels have also been inversely related to the risk of chronic disease. While the antioxidant properties of lycopene are thought to be primarily responsible for its beneficial effects, evidence is accumulating to suggest that other mechanisms, such as modulation of intercellular gap junction communication, hormonal and immune systems, and metabolic pathways, may also be involved. Lycopene inhibited the activity of an essential enzyme involved in cholesterol synthesis in an in vitro study and a small clinical study, suggesting a hypocholesterolemic effect.

      Keywords

      1. Introduction

      People who live in and around the Mediterranean present with a lowered risk of several important chronic diseases, including coronary heart disease and a number of types of cancer (breast, colon, prostate). This lowered risk appears to be related to a traditional diet consisting largely of fruits and vegetables in general, and of cooked tomatoes in particular, plus considerable amounts of olive oil. These findings have lead to public health recommendations to consume more vegetables, especially cooked tomatoes with olive oil [
      • Weisburger J.H.
      Lycopene and tomato products in health promotion.
      ].
      In a prospective study by Fawzi et al. that examined the relationship between the consumption of tomatoes and morbidity and mortality among 28,753 children aged 6–60 months, it was found that an intake of tomatoes for 2–3 days (compared with 0 days) was associated with a significant reduction in mortality (48%) and with a reduced risk of death associated with diarrhea. Intake of tomatoes was also inversely and significantly associated with respiratory infections [
      • Fawzi W.
      • Herrera M.G.
      • Nestel P.
      Tomato intake in relation to mortality and morbidity among Sudanese children.
      ].
      Lycopene, a carotenoid without provitamin-A activity, is present in many fruits and vegetables; yet, it is tomatoes and processed tomato products that constitute the major source of lycopene in the North American diet. Several recent studies have shown that a dietary intake of tomatoes and tomato products is associated with a decreased risk of chronic diseases such as cancer and cardiovascular disease [
      • Rao A.V.
      • Agarwal S.
      Role of antioxidant lycopene in cancer and heart disease.
      ]. Serum and tissue lycopene levels have also been inversely related with the risk of chronic disease [
      • Rao A.V.
      • Agarwal S.
      Role of antioxidant lycopene in cancer and heart disease.
      ]. While the antioxidant properties of lycopene are thought to be primarily responsible for its beneficial effects, evidence is accumulating to suggest that other mechanisms, such as modulation of intercellular gap junction communication, hormonal and immune systems, and metabolic pathways, may also be involved [
      • Rao A.V.
      • Agarwal S.
      Role of antioxidant lycopene in cancer and heart disease.
      ].
      Lycopene functions as a very potent antioxidant, and this is clearly an important mechanism of action of lycopene. It can trap singlet oxygen and reduce mutagenesis. In physiological concentrations, it can 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 cell apoptosis. Studies of human and animal cells have identified a gene, connexin 43, whose expression is upregulated by lycopene and that allows direct intercellular gap junctional communication (GJC). GJC is deficient in many human tumors, and its restoration or upregulation is associated with decreased proliferation [
      • Heber D.
      • Lu Q.Y.
      Overview of mechanisms of action of lycopene.
      ].

      2. Tomatoes and coronary heart disease

      Oxidative stress induced by reactive oxygen species (ROS) is also considered to play an important role in the etiology of coronary heart disease. Oxidation of the circulating low-density lipoprotein LDL is thought to play a key role in the pathogenesis of atherosclerosis and coronary heart disease. A recent study has demonstrated that healthy human subjects who ingested lycopene in the form of tomato juice or tomato sauce for 1 week had a significantly lower level of oxidized LDL than controls [
      • Rao A.V.
      Lycopene, tomatoes, and the prevention of coronary heart disease.
      ]. Four other human trials have also demonstrated the antioxidant effects of lycopene [
      • Rao A.V.
      Lycopene, tomatoes, and the prevention of coronary heart disease.
      ]. Lycopene was shown to inhibit the activity of an essential enzyme involved in cholesterol synthesis in both an in vitro study [
      • Rao A.V.
      Lycopene, tomatoes, and the prevention of coronary heart disease.
      ] and a small clinical study [
      • Rao A.V.
      Lycopene, tomatoes, and the prevention of coronary heart disease.
      ], suggesting a hypocholesterolemic effect. Other possible mechanisms include enhanced LDL degradation, LDL particle size and composition, plaque rupture, and altered endothelial functions. Recent epidemiological studies have also shown an inverse relationship between tissue and serum levels of lycopene and mortality from coronary heart disease, cerebrovascular disease, and myocardial infarction [
      • Rao A.V.
      Lycopene, tomatoes, and the prevention of coronary heart disease.
      ]. However, the most impressive population-based evidence comes from a multi-center, case-control study where subjects from ten European countries were evaluated with regard to a relationship between antioxidant status and acute myocardial infarction. After adjusting for a range of dietary variables, only lycopene levels were found to be protective [
      • Rao A.V.
      Lycopene, tomatoes, and the prevention of coronary heart disease.
      ].
      Some 725 middle-aged men, free of coronary heart disease and stroke, took part in the Kuopio Ischemic Heart Disease Risk Factor (KIHD) study. Men in the lowest quartile of serum levels of lycopene had a 3.3 fold increased risk of an acute coronary event or a stroke as compared to the other groups [
      • Rissanen T.
      • Voutilainen S.
      • Nyyssonen K.
      • Salonen J.T.
      Lycopene, atherosclerosis, and coronary heart disease.
      ].
      In a second study [
      • Rissanen T.
      • Voutilainen S.
      • Nyyssonen K.
      • Salonen J.T.
      Lycopene, atherosclerosis, and coronary heart disease.
      ], the association between plasma lycopene concentration and intima-media thickness of the common carotid artery wall (CCA-IMT) was examined. This study was part of the Antioxidant Supplementation in the Atherosclerosis Prevention (ASAP) study, in which 520 asymptomatic men and women participated. It was found that low plasma levels of lycopene were associated with an 18% increase in IMT in men compared with men whose plasma levels were higher than the median. In women, the difference did not remain significant after the adjustment [
      • Rissanen T.
      • Voutilainen S.
      • Nyyssonen K.
      • Salonen J.T.
      Lycopene, atherosclerosis, and coronary heart disease.
      ].

      3. Tomatoes and cancer

      Tomato consumption showed a consistent inverse relation with the risk of digestive tract neoplasms in an integrated series of studies conducted in Italy in the 1980s [
      • La Vecchia C.
      Tomatoes, lycopene intake, and digestive tract and female hormone-related neoplasms.
      ]. Between 1992 and 1999, a case-control study was conducted in different areas of Italy on patients below age 80 years of age with different kinds of cancers, i.e., oral cavity and pharyngeal, esophageal, colorectal, breast, and ovarian [
      • La Vecchia C.
      Tomatoes, lycopene intake, and digestive tract and female hormone-related neoplasms.
      ]. The control group consisted of 5000 patients, also below the age of 80, with acute, non-neoplastic diseases. The multivariate relative risk of oral, pharyngeal and esophageal cancer decreased with subsequent levels of lycopene intake (0.7 for oral and pharyngeal cancers and 0.7 for esophageal cancer, both with borderline statistical significance). In colorectal, breast, and ovarian cancers, tomato intake was inversely and significantly correlated with cancer risk (RR=0.8) [
      • La Vecchia C.
      Tomatoes, lycopene intake, and digestive tract and female hormone-related neoplasms.
      ].
      Thirty-two patients with localized prostate adenocarcinoma consumed tomato sauce-based pasta dishes for 3 weeks (30 mg lycopene daily) before their scheduled radical prostatectomy. Prostate tissue was obtained as a biopsy at baseline and as a resected tissue at the time of the prostatectomy. Serum and prostate lycopene, serum prostate-specific antigen (PSA) concentrations, and leukocyte DNA 8-OH deoxyguanosine/deoxyguanosine (8OhdG) were measured at baseline and at the end of the intervention. Mean serum PSA concentrations decreased by 17.5% (P<0.002) and leukocyte 8OhdG decreased by 21.3% (P<0.005) after tomato sauce consumption. Resected tissues from tomato sauce-supplemented patients had 28.3% lower prostate 8OhdG compared with the control group (P<0.03). Cancer cell 8OhdG staining in the resected prostate sections was reduced by 40.5% in mean nuclear density (P<0.005) and by 36.4% in mean area (P<0.018). The apoptotic index was higher in hyperplastic and neoplastic cells in the resected tissue after supplementation. These data indicate a significant uptake of lycopene into prostate tissue and a reduction in DNA damage in both leukocyte and prostate tissue [
      • Bowen P.
      • Chen L.
      • Stacewicz-Sapuntzakis M.
      • Duncan C.
      • Sharifi R.
      • Ghosh L.
      Tomato sauce supplementation and prostate cancer: lycopene accumulation and modulation of biomarkers of carcinogenesis.
      ].
      A clinical study investigated the biological and clinical effects of lycopene supplementation among patients with localized prostate cancer [
      • Kucuk O.
      • Sarkar F.H.
      • Djuric Z.
      • Sakr W.
      • Pollak M.N.
      • Khachik F.
      • et al.
      Effects of lycopene supplementation in patients with localized prostate cancer.
      ]. Thirty-six patients with newly diagnosed prostate cancer were randomly assigned to receive tomato extract containing 30 mg of lycopene (15 patients) or no supplementation (11 patients) for 3 weeks before radical prostatectomy. Subjects in the intervention group had smaller tumors (45% vs. 80%), less involvement of surgical margins and/or extraprostate tissues with cancer (73% vs. 18%), and less diffuse involvement of the prostate by high-grade prostatic intraepithelial neoplasia (33% vs. 0%) compared with subjects in the control group. Mean PSA levels were lower in the intervention group than in the control group [
      • Kucuk O.
      • Sarkar F.H.
      • Djuric Z.
      • Sakr W.
      • Pollak M.N.
      • Khachik F.
      • et al.
      Effects of lycopene supplementation in patients with localized prostate cancer.
      ].

      4. Conclusion

      The consumption of tomatoes has been demonstrated clinically and in in vitro studies to have beneficial, protective effects with regard to coronary artery disease and several neoplasms. Still, the mechanism of action is not totally clear. Double-blind, placebo-controlled studies should be carried out in order to clarify this interesting possible association between diet and health, especially in the prevention of chronic diseases and cancer.

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        Tomato intake in relation to mortality and morbidity among Sudanese children.
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        Role of antioxidant lycopene in cancer and heart disease.
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        Overview of mechanisms of action of lycopene.
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