We studied the plasma chain-breaking antioxidants alpha carotene, beta carotene, lycopene, Vitamin A, Vitamin C, Vitamin E and a measure of total antioxidant capacity, TAC, in 79 patients with Alzheimer's disease (AD), 37 patients with vascular dementia (VaD), 18 patients with Parkinson's disease and dementia (PDem), and 58 matching controls, together with 41 patients with Parkinson's disease (PD) and 41 matching controls. Significant reductions in individual antioxidants were observed in all dementia groups. When compared to controls, the following were reduced: Vitamin A in AD (p < 0.01) and VaD (p < 0.001); Vitamin C in AD (p < 0.001), VaD (p < 0.001) and PDem (p < 0.01); Vitamin E in AD (p < 0.01) and VaD (p < 0.001); beta carotene in VaD (p = 0.01); lycopene in PDem (p < 0.001). Lycopene was also reduced in PDem compared to AD (p < 0.001) and VaD (p < 0.001). Antioxidant levels in PD were not depleted. No significant change in TAC was seen in any group. The reduction in plasma chain-breaking antioxidants in patients with dementia may reflect an increased free-radical activity, and a common role in cognitive impairment in these conditions. Increased free-radical activity in VaD and PDem could be associated with concomitant AD pathology. Individual antioxidant changes are not reflected in TAC.

Higher plasma lycopene concentrations have been associated with a reduced risk of several chronic diseases. Determinants of lycopene concentrations in humans have received limited attention. We had blood lycopene concentrations and lycopene consumption data available from 111 participants in a two-center cancer prevention trial involving beta-carotene and examined determinants of plasma lycopene levels cross-sectionally. The median plasma lycopene level was 0.59 micromol/L (range 0.07-1.79). Low plasma concentrations of lycopene were associated with the following variables in univariate analyses: study site (Florida lower than Connecticut, P = 0.001), being nonmarried (P = 0.02), having lower income (P = 0.003), being nonwhite race/ethnicity (P = 0.03), having lower dietary lycopene intake (r = 0.29, P = 0.002), having lower plasma cholesterol (r = 0. 43, P = 0.0001) and triglyceride levels (r = 0.26, P = 0.005), and consuming less vitamin C (r = 0.20, P = 0.03). Women had slightly higher plasma lycopene levels than men (0.65 vs. 0.58 micromol/L; P = 0.31), despite lower dietary intake of lycopene (1,040 vs. 1,320 microg/d; P = 0.50). Plasma lycopene levels did not differ in smokers and nonsmokers. In stepwise regression analyses, the determinants of plasma lycopene were plasma cholesterol, dietary lycopene, and marital status; these three variables explained 26% of the variance in plasma lycopene. Relatively few lifestyle and demographic factors were important determinants of plasma lycopene levels, with plasma cholesterol, marital status, and lycopene intake being of greatest importance.

The effects of dietary ingestion of tomato were studied in mice that had been made hypercholesterolemic by feeding atherogenic diets. Mice which had been fed on the atherogenic diet without tomato for 4 months had significantly increased plasma lipid peroxide, and the vaso-relaxing activity in the aorta induced by acetylcholine (ACh) was harmed when compared with mice fed on a common commercial diet. On the other hand, mice which had been fed on the atherogenic diet containing 20% (w/w) lyophilized powder of tomato showed less increase in the plasma lipid peroxide level, and ACh-induced vaso-relaxation was maintained at the same level as that in normal mice. These results indicate that tomato has a preventive effect on atherosclerosis by protecting plasma lipids from oxidation

To study the relationship between lycopene intake and plasma concentration, ten healthy female subjects were given one or more portions of tomato puree or fresh raw tomato containing 16.5 mg total lycopene (all-trans + cis forms). In Expt 1 subjects (n 9) were randomly assigned the single portions of the two tomato products and blood samples were collected to follow the change in plasma carotenoid concentrations within the first 12 h and on each of the following 5 d (104 h). In Expt 2 subjects (n 10) were divided into two groups of five each receiving daily dietary portions of tomato puree or fresh raw tomato containing 16.5 mg total lycopene for 7 d. Fasting blood samples were collected daily. In Expt 1 the plasma total lycopene (all-trans + cis forms) concentration, after the single portions of tomato puree and raw tomato, varied significantly over time, with a first peak reached after 6 h, a further increase after 12 h and a slow decrease until 104 h. In Expt 2, when the tomato products were given daily, there was a day-by-day increase in the plasma total lycopene concentration, and through the following week of a diet without tomato there was a gradual decrease. However, values did not return to basal concentrations. Plasma total lycopene concentration was higher after the tomato puree intake than after the raw tomato in both the first (F(1,8) 7.597; P < 0.025) and the second experiments (F(1,8) 12.193; P < 0.01) demonstrating a significant effect of food matrix on absorption.

The antioxidant properties of the carotenoid lycopene were compared in three different model oxidative systems. In egg yolk liposomes, in the presence of 2.5 mM FeSO4 and 200 mM ascorbate, lycopene, alpha-tocopherol, and beta-carotene inhibited the accumulation of lipid peroxidation products reacting with 2-thiobarbituric acid (TBARS) in a dose-dependent mode, with the concentration of half-inhibition being 80, 30 and 130 mM, respectively. In the liposomes subjected to illumination with a He-Ne laser (632.8 nm) at a dose of 10.5 J/cm2, in the presence of 32.5 micrograms/ml hematoporphyrin derivatives (Fotogem, NIOPIC, Russia) TBARS accumulated, and this effect was inhibited by lycopene, alpha-tocopherol, and dihydroquercetin with approximately equal efficiencies (the half-inhibition concentrations were 10(-5) mM). In both systems studied, sodium azide at a concentration of 10 mM inhibited the TBARS accumulation by no more than 20%. Apparently, the inhibitory action of not only alpha-tocopherol, but also beta-carotene and lycopene was the result of their antiradical action, rather than quenching of the singlet oxygen in an aqueous medium. The introduction of lycopene, as well as beta-carotene in liposomes subjected to Fe(2+)-induced lipid peroxidation decreased the chemiluminescence (CL) intensity at the stage of CL slow flash, with no essential influence on the lag period. These data suggest that the effect of lycopene on lipid peroxidation was the result of its interaction with free radicals rather than chelating ferrous ions. The antiradical activity of lycopene was also confirmed by the method of luminol photochemiluminescence (PCL). Lycopene increased the PCL lag period (L) and decreased the PCL amplitude (A), which implies its antiradical and SOD-like activity in this system

The bioavailability of lycopene from tomato juice and 2 dietary supplements, each containing 70-75 mg lycopene, was studied in 15 healthy volunteers in a randomized, crossover design. Subjects ingested lycopene-rich tomato juice, tomato oleoresin, lycopene beadlets, and a placebo for 4 wk each while consuming self-selected diets. Treatment periods were separated by 6-wk washout periods. Plasma lycopene concentrations, assessed at baseline and weekly throughout the treatment periods, were significantly higher during tomato juice, oleoresin, and lycopene beadlet ingestion than during placebo ingestion. Mean (+/-SEM) increases in plasma lycopene at week 4 of tomato juice, oleoresin, and lycopene beadlet ingestion were not significantly different: 0.24 +/- 0.07, 0.23 +/- 0.05, and 0.24 +/- 0.06 micromol/L, respectively. Plasma concentrations of phytofluene and phytoene, which were present in small amounts in tomato juice, oleoresin, and lycopene beadlets, increased significantly with ingestion of these 3 products. Beta-carotene, zeta-carotene, and 2,6-cyclolycopene-1,5-diol (a metabolite of lycopene)--also present in tomato juice and supplements--were significantly increased with consumption of the tomato juice and lycopene beadlets, but not with oleoresin consumption. A marked increase in plasma concentrations of an unknown compound was observed; it was detected in trace amounts in tomato juice, oleoresin, and lycopene beadlets, and had a maximum absorbance at 448 nm and a molecular weight of 556. Concentrations of plasma lycopene and other carotenoids with potential for enhancing human health can be increased by ingestion of realistic amounts of tomato juice. Lycopene appears to be equally bioavailable from tomato juice and the supplements used in this study.

Increase in low density lipoprotein (LDL) oxidation is hypothesized to be causally associated with increasing risk of atherosclerosis and coronary heart disease. In recent epidemiological studies, tissue and serum levels of lycopene, a carotenoid available from tomatoes, have been found to be inversely related to risk of coronary heart disease. A study was undertaken to investigate the effect of dietary supplementation of lycopene on LDL oxidation in 19 healthy human subjects. Dietary lycopene was provided using tomato juice, spaghetti sauce, and tomato oleoresin for a period of 1 wk each. Blood samples were collected at the end of each treatment. Serum lycopene was extracted and measured by high-performance liquid chromatography using an absorbance detector. Serum LDL was isolated by precipitation with buffered heparin, and thiobarbituric acid-reactive substances (TBARS) and conjugated dienes (CD) were measured to estimate LDL oxidation. Both methods, to measure LDL oxidation LDL-TBARS and LDL-CD, were in good agreement with each other. Dietary supplementation of lycopene significantly increased serum lycopene levels by at least twofold. Although there was no change in serum cholesterol levels (total, LDL, or high-density lipoprotein), serum lipid peroxidation and LDL oxidation were significantly decreased. These results may have relevance for decreasing the risk for coronary heart disease.

Epidemiological studies continue to identify an association of dietary antioxidant micronutrients in cancer prevention. A number of case-control and cohort studies have demonstrated a relationship between high intake of foods rich in carotenoids, tocopherols, and vitamin C with a reduced risk of certain human malignancies. The purpose of this study was to investigate the comparative plasma levels of a profile of known dietary antioxidants, namely, beta-carotene, lycopene, canthaxanthin, retinol, alpha-tocopherol, and tau-tocopherol. The target population was women with a histopathological diagnosis of cervical intraepithelial neoplasia (CIN) or cervical cancer and a control group. All women resided in the same catchment area (Bronx Borough, New York City) and were of similar inner-city socioeconomic backgrounds representing a fairly homogenous population group. A cross-sectional sample of 235 women was recruited with informed consent. Plasma nutrient levels were measured by reverse-phase high pressure liquid chromatography under study codes. The mean plasma levels of carotenoids (beta-carotene, lycopene, and canthaxanthin), as well as alpha-tocopherol, were significantly lower in women with CIN and cervical cancer. In contrast, the mean plasma level of tau-tocopherol was higher among patients with CIN, while the mean plasma level of retinol was comparable among the groups. There were significant linear trends for all three carotenoids and quadratic trends for alpha- and tau-tocopherol with the degree of cervical histopathology. Plasma beta-carotene concentrations in cigarette smokers were significantly lower regardless of cervical pathology, whereas plasma lycopene and canthaxanthin levels were significantly lower in smokers with CIN. The findings of a decrease in all plasma antioxidant nutrient levels except tau-tocopherol in women with CIN and cancer suggest a potential role for antioxidant deficiency in the pathogenesis of CIN and carcinoma of the cervix, which requires further investigation.

Studies employing time-resolved techniques have shown that beta-carotene, astaxanthin, and lycopene behave quite distinctly with respect to radical quenching and stability, lycopene being the least stable. These results are compatible with the relative effects of the various carotenoids on ultraviolet (UV)-mediated carcinogenesis in mice in which a statistically significant exacerbation by beta-carotene and astaxanthin, but not by lycopene, was observed. Interactions between these carotenoids and vitamin C and E radicals not only provide a chemical basis to explain the failure of beta-carotene to provide benefit in recent clinical trials but suggest that future carotenoid supplementation studies should proceed with caution until carotenoid interactions and radical repair mechanism(s) are elucidated.