Lycopene, obtained from fresh tomatoes, was incorporated into the chicks diet. The treatments were: (1) Control, (2) 1.5 mg T-2 toxin/kg body weight/day; (3) 25 mg lycopene/kg body weight/day, (4) 1.5 mg T-2 toxin plus 25 mg lycopene/kg body weight/day. Male broiler chicks, 7-28 days of age, were provided with feed and water ad libitum. Every 7 days, malondialdehyde (MDA) and glutathione (GSH) levels, and enzymatic activities of glutathione-S-transferase (GST), gamma-glutamyltransferase (GGT) and glutathione peroxidase (GP) were evaluated in liver homogenates. Compared to the controls after 7 days of treatment, T-2 toxin increased hepatic MDA concentration (128%). A significant consumption of endogenous antioxidant GSH (45%) was induced as well as a marked increase in hepatic enzymatic activities of GST, GGT, and GP (312, 187, and 324%, respectively). Addition of T-2 plus lycopene, at an approximate ratio of 1:17 in the diet, diminished some parameters measured (P < 0.05). Apparently lycopene participated as an antioxidant agent and also protecting the cellular level of GSH.

Brown L, Rimm EB, Seddon JM, Giovannucci EL, Chasan-Taber L, Spiegelman D, Willett WC, Hankinson SE

Departments of Epidemiology, Nutrition, and Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA. lisa.brown@channing.harvard.edu

BACKGROUND: Dietary antioxidants, including carotenoids, are hypothesized to decrease the risk of age-related cataracts by preventing oxidation of proteins or lipids within the lens. However, prospective epidemiologic data concerning this phenomenon are limited. OBJECTIVE: Our objective was to examine prospectively the association between carotenoid and vitamin A intakes and cataract extraction in men. DESIGN: US male health professionals (n = 36644) who were 45-75 y of age in 1986 were included in this prospective cohort study. Others were subsequently included as they became 45 y of age. A detailed dietary questionnaire was used to assess intake of carotenoids and other nutrients. During 8 y of follow-up, 840 cases of senile cataract extraction were documented. RESULTS: We observed a modestly lower risk of cataract extraction in men with higher intakes of lutein and zeaxanthin but not of other carotenoids (alpha-carotene, beta-carotene, lycopene, and beta-cryptoxanthin) or vitamin A after other potential risk factors, including age and smoking, were controlled for. Men in the highest fifth of lutein and zeaxanthin intake had a 19% lower risk of cataract relative to men in the lowest fifth (relative risk: 0.81; 95% CI: 0.65, 1.01; P for trend = 0.03). Among specific foods high in carotenoids, broccoli and spinach were most consistently associated with a lower risk of cataract. CONCLUSIONS: Lutein and zeaxanthin may decrease the risk of cataracts severe enough to require extraction, although this relation appears modest in magnitude. The present findings add support for recommendations to consume vegetables and fruit high in carotenoids daily.

Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst 01003, USA. LCT@schoolph.umass.edu

BACKGROUND: Oxidation of lens proteins plays a central role in the formation of age-related cataracts, suggesting that dietary antioxidants may play a role in prevention. However, the relation between specific antioxidants and risk of cataract remains uncertain. OBJECTIVE: Our objective was to examine prospectively the association between carotenoid and vitamin A intakes and cataract extraction in women. METHODS: A prospective cohort of registered female nurses aged 45-71 y and free of diagnosed cancer was followed; in 1980, 50461 were included and others were added as they became 45 y of age for a total of 77466. Information on nutrient intake was assessed by repeated administration of a food-frequency questionnaire during 12 y of follow-up. RESULTS: During 761762 person-years of follow-up, 1471 cataracts were extracted. After age, smoking, and other potential cataract risk factors were controlled for, those with the highest intake of lutein and zeaxanthin had a 22% decreased risk of cataract extraction compared with those in the lowest quintile (relative risk: 0.78; 95% CI: 0.63, 0.95; P for trend = 0.04). Other carotenoids (alpha-carotene, beta-carotene, lycopene, and beta-cryptoxanthin), vitamin A, and retinol were not associated with cataract in multivariate analysis. Increasing frequency of intakes of spinach and kale, foods rich in lutein, was associated with a moderate decrease in risk of cataract. CONCLUSIONS: Lutein and zeaxanthin and foods rich in these carotenoids may decrease the risk of cataracts severe enough to require extraction.

BACKGROUND: Lycopene has been identified as a phytochemical with potentially protective health benefits. OBJECTIVE: Our objective was to monitor lycopene changes in buccal mucosa cells (BMCs) in response to 3 vehicles for oral delivery of lycopene. DESIGN: Fifteen healthy subjects ingested lycopene-rich tomato juice, tomato oleoresin, lycopene beadlets (each containing 70-75 mg lycopene) and a placebo for 4 wk each in a randomized crossover design while consuming self-selected diets. A 6-wk washout period separated the treatment periods. BMCs were collected at baseline and after 4 wk of supplementation. RESULTS: Lycopene in BMCs increased significantly ( approximately 2-fold) after 4 wk of ingestion of oleoresin and of beadlets to 4.95 (P < 0.001) and 3.75 &mgr;g/g protein (P = 0.053), respectively, but was not significantly affected by tomato juice treatment. The placebo treatment produced a significant decrease in BMC lycopene concentrations (P = 0.018). We observed significant treatment differences between oleoresin and tomato juice, oleoresin and placebo, and beadlets and placebo. BMC concentrations of phytofluene and beta-carotene, which were present in small amounts in the lycopene-containing treatments, increased significantly with ingestion of these products. Strong correlations were found between plasma and BMC concentrations of lutein, beta-cryptoxanthin, alpha-carotene, and beta-carotene. In contrast, correlations between lycopene concentrations in plasma and in BMCs were weak and not significant for any treatment. CONCLUSIONS: The cellular content of lycopene and other tomato-related carotenoids with proposed beneficial health effects can be increased through prolonged supplementation.

Among the many carotenoids present in nature, lycopene has been of special interest and has received attention in recent times due to its suggestive association in reducing risk for cancer at many sites including breast, prostate and pancreas. Several studies have attempted to determine the bioactive levels of this carotenoid in human tissues and the influence of plant food and cancer on carotenoid levels. Experimental studies have also implicated the protective role of lycopene during carcinogenesis. These observations should justify further exploration and evaluation of the biological function of lycopene alone or in combination with other chemical compounds present in tomato fruit for their use in cancer prevention.

Morris-Stiff GJ, Bowrey DJ, Oleesky D, Davies M, Clark GW, Puntis MC

Department of Surgery, University Hospital of Wales, Health Park, Cardiff, United Kingdom.

OBJECTIVE: It has been suggested that patients with chronic pancreatitis have antioxidant deficiencies. It is unclear whether these antioxidant deficiencies also occur in patients with recurrent acute pancreatitis and whether this condition represents an intermediate state between normality and chronic pancreatitis. The aim of this study was to determine the antioxidant profiles of patients with pancreatitis (recurrent acute and chronic) and to compare their profiles with a control population. METHODS: The antioxidant profiles of patients with chronic pancreatitis (n = 27) and recurrent acute pancreatitis (n = 11) were determined and compared with the antioxidant profiles of control subjects (n = 19). The following parameters were measured in blood: trace elements (selenium, copper, zinc), vitamins A and E, and carotenoids (alpha-carotene, beta-carotene, xanthine, beta-cryptoxanthine, lycopene). RESULTS: Patients with chronic pancreatitis had significantly lower plasma concentrations of selenium, vitamin A, vitamin E, beta-carotene, xanthine, beta-cryptoxanthine, and lycopene compared with both control subjects and patients with recurrent acute pancreatitis (p < 0.05). There were no significant differences between the antioxidant profiles of patients with chronic pancreatitis due to alcohol excess and patients with idiopathic chronic pancreatitis, or between the antioxidant profiles of patients with recurrent acute pancreatitis and control subjects. CONCLUSIONS: Patients with chronic pancreatitis had evidence of multiple antioxidant deficiencies. The antioxidant profiles of patients with recurrent acute pancreatitis did not differ from those of control subjects, discounting the hypothesis that recurrent acute pancreatitis represents an intermediate state between normality and chronic pancreatitis.

BACKGROUND: The etiology of prostate cancer has not been fully resolved in the scientific and medical literature, although the non-fat portion of milk and calcium are emerging as leading dietary risk factors, with lycopene (found in tomatoes) and vitamin D apparently being risk reduction factors. METHODS: The ecologic (multi-country statistical) approach is used to study dietary links to prostate cancer. Mortality data from 1986 for various age groups in 41 countries are compared with national consumer macronutrient supply values for 1983 and tomato supply values for 1985. RESULTS: For 28 countries with more than five Kcal/day of tomatoes in the consumer supply, a linear combination of non-fat milk (risk factor) and tomatoes (risk reduction factor) was found to have the highest statistical association with prostate cancer mortality rates for men over the age of 35, with the Pearson regression coefficient (R2) for those aged 65-74 years = 0.67 and p < 0.001. For the 13 countries with fewer than six Kcal/day of tomatoes, non-fat milk had the highest association (R2 = 0.92, p < 0.001 for men aged 65-74 years). For 41 countries combined, the non-fat portion of milk had the highest association with prostate cancer mortality rates (R2 = 0.73, p < 0.001 for men aged 65-74 years). CONCLUSIONS: These results support the results of several cohort studies which found the non-fat portion of milk to have the highest association with prostate cancer, likely due to the calcium, and tomatoes to reduce the risk of prostate cancer, most likely due to lycopene.

BACKGROUND: The large differences in cardiovascular disease rates between Eastern and Western Europe have largely developed over the last few decades, and are only partly explained by classical risk factors. This study was set up to identify other potential determinants of these differences. METHODS: This was an ecological study comparing random samples of men aged 45-64 years selected from three cities representing populations with different rates of cardiovascular mortality: Pardubice (Czech Republic), Augsburg (Bavaria, Germany), and Jerusalem (Israel). In total, 191 (response rate 70%), 153 (70%) and 162 (62%) men, respectively, participated. All centres followed the same study protocol. Lifestyle, anthropometry and biochemical risk factors were assessed by identical questionnaires, standardized medical examination, and central analyses of fasting blood samples. RESULTS: The mortality rates in the study populations, as well as the prevalence of coronary heart disease in study samples, were highest in Czech, intermediate in Bavarian and low in Israeli men. This pattern was replicated across the three samples by mean blood pressure (P < 0.001), cigarette smoking (not significant), triglycerides (P < 0.05), fibrinogen or D-dimer levels (P < 0.05). On the other hand, the prevalence of diabetes and obesity were similar; total and high density lipoprotein (HDL)-cholesterol, apolipoprotein B, lipoprotein (Lp(a)) and glucose did not differ between Czech and Bavarian men; and Czechs had particularly low levels of serum insulin and factor VIIc. Israelis had low fasting glucose and total cholesterol, as well as HDL-cholesterol levels and a high Lp(a) (each P < 0.001) compared with the two other samples. Striking differences were found for plasma homocysteine (10.5 in Czechs versus 8.9 mumol/l in Bavarians, P < 0.001) and for alpha-carotene (geometric mean in Czechs 16, Bavarians 21 and Israelis 30 micrograms/l), beta-carotene (60, 110 and 102 micrograms/l), and lycopene (84, 177 and 223 micrograms/l), respectively; all P-values < 0.001). Adjustment for obesity or smoking did not change these estimates. There were no differences in the levels of tocopherol and retinol. CONCLUSIONS: Czech men had high levels of blood pressure, triglycerides, fibrinogen and D-dimer but many other traditional risk factors, as well as indicators of metabolic disorders and vitamins A and E, did not differ between the study samples. The low levels of carotenoids and high concentrations of homocysteine in Czech men seem to reflect their low dietary intakes of fruit and vegetables. The results provide indirect support for the importance of dietary factors in the East-West morbidity and mortality divide.

AIM OF THE STUDY: The present study was conducted to investigate changes in the plasma concentration of carotenoids and carotenoid oxidation products, vitamin A, alpha- and gamma-tocopherol, and ubiquinone-10 during a dietary intervention trial with 23 male healthy volunteers. METHOD: A two week carotenoid depletion period was followed by a daily consumption of 330 mL tomato juice (40 mg lycopene), then by 330 mL carrot juice (15.7 mg alpha-carotene and 22.3 mg beta-carotene), and then by a 10 g spinach powder preparation (11.3 mg lutein and 3.1 mg beta-carotene) served with main meals for two weeks, respectively. Blood samples were collected in the morning after an overnight fasting and carotenoids, vitamin A, tocopherols, and ubichinone were analyzed by reversed-phase HPLC. RESULTS: During the tomato juice intervention, plasma concentrations of trans- and cis-lycopene increased 3-fold compared to the depletion period. Lycopene oxidation products could be demonstrated in plasma and were significantly elevated compared to control (p < 0.001). After two weeks of carrot juice consumption, alpha-carotene and beta-carotene concentrations increased 8.6- and 3.2-fold, respectively. Finally, during the spinach consumption period the lutein concentration increased 2-fold, while the beta-carotene concentrations were still elevated 2-fold. CONCLUSIONS: The moderate change in dietary habits, e.g., the consumption of 330 mL of carotenoid-rich vegetable juices caused significant changes in the plasma carotenoid concentrations, indicating a high bioavailability of carotenoids from these processed vegetable products. The changes in plasma carotenoid concentrations reflected the carotenoid composition of the consumed foods. However, particularly during the tomato juice intervention period the occurrence of lycopene oxidation products and cis-lycopene isomers in plasma was eminent. The formation may be due to antioxidant reactions of lycopene in the organism.

Lycopene, the major tomato carotenoid, has been found to inhibit proliferation of several types of cancer cells, including those of breast, lung, and endometrium. By extending the work to the HL-60 promyelocytic leukemia cell line, we aimed to evaluate some mechanistic aspects of this effect. Particularly, the possibility was examined that the antiproliferative action of the carotenoid is associated with induction of cell differentiation. Lycopene treatment resulted in a concentration-dependent reduction in HL-60 cell growth as measured by [3H]thymidine incorporation and cell counting. This effect was accompanied by inhibition of cell cycle progression in the G0/G1 phase as measured by flow cytometry. Lycopene alone induced cell differentiation as measured by phorbol ester-dependent reduction of nitro blue tetrazolium and expression of the cell surface antigen CD14. Results of several recent intervention studies with beta-carotene, which have revealed no beneficial effects of this carotenoid, suggest that a single dietary component cannot explain the anticancer effect of diets rich in vegetables and fruits. Thus another goal of our study was to examine whether lycopene has the ability to synergize with other natural anticancer compounds, such as 1,25-dihydroxyvitamin D3, which when used alone are therapeutically active only at high and toxic concentrations. The combination of low concentrations of lycopene with 1,25-dihydroxyvitamin D3 exhibited a synergistic effect on cell proliferation and differentiation and an additive effect on cell cycle progression. Such synergistic antiproliferative and differentiating effects of lycopene and other compounds found in the diet and in plasma may suggest the inclusion of the carotenoid in the diet as a cancer-preventive measure.