Oxidative stress is recognized as one of the major contributors of increased risk of cancer. Many recent population studies have established a close link between dietary intake of tomatoes, a major source of the carotenoid antioxidant lycopene, and lowered risk of cancer. A study was conducted on 19 healthy human subjects to evaluate the uptake and in vivo antioxidant properties of lycopene, using a randomized, crossover design. Dietary lycopene was provided by tomato juice, spaghetti sauce, and tomato oleoresin for a period of one week 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 thiobarbituric acid-reactive substances, protein thiols, and 8-oxodeoxyguanosine contents of lymphocyte DNA were assayed to measure lipid, protein, and DNA oxidation. Lycopene was the major carotenoid present in the serum. Dietary supplementation of lycopene resulted in a significant increase in serum lycopene level and diminished amounts of serum thiobarbituric acid-reactive substances. Although not statistically significant, a tendency of lowered protein and DNA oxidation was observed. There was also indication that the lycopene levels increased in a dose-dependent manner in the case of spaghetti sauce and tomato oleoresin. These results indicate that lycopene is readily absorbed from tomato products and may act as an in vivo antioxidant. It may, therefore, play an important role in the prevention of cancer.

High rates of coronary artery disease have been reported in the Asian Indians who have migrated to other countries. Although many coronary artery disease risk factors (diabetes, high serum cholesterol, lipoprotein[a], and smoking) have been suggested, studies of coronary artery disease risk factors in Asian Indians living in USA are only a few. We investigated coronary artery disease risk factors in 110 Asian Indian physicians living in USA by questionnaire and measurement of their serum lipids and fat-soluble antioxidant vitamins. Differences in risk factors between genders, vegetarian diets and diabetic status were also studied. We found that lipoprotein(a) (mean=20 mg/dl), low density lipoprotein cholesterol, and diabetes (prevalence of 7.5%) are more important risk factors for coronary artery disease, but not smoking, when compared to other Americans. Higher levels of low density lipoprotein cholesterol, retinol, alpha-tocopherol, cryptoxanthin and lycopene, and lower levels of high density lipoprotein cholesterol were found in the males than in females. Comparable levels of lipoprotein(a) were found for males and females. Vegetarians, compared to non-vegetarians, had similar levels of lipids and fat-soluble antioxidants. Lower levels of retinol, lutein/zeaxanthin and lycopene were found in the diabetics compared to non-diabetics. These findings suggest that (1) the control of low density/high density lipoprotein cholesterol levels could be important in prevention of coronary artery disease in Indian males, (2) the vegetarian diets of Asian Indians do not favourably influence the serum lipid and antioxidant levels, and (3) increased serum levels of antioxidants may be beneficial for diabetics. Furthermore, for the first time, we show that serum levels of lutein/zeaxanthin and lycopene are significantly lower in the diabetics.

The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-beta]pyridine NPhIP) is a major dietary component in individuals eating cooked meats or fish. This heterocyclic amine requires biochemical activation, mainly through cytochrome P4501A2, and can be detoxified chiefly by 4'hydroxylation through other cytochromes, and be in turn converted through phase 2 enzymes to readily excreted conjugates. The active form of PhIP is mutagenic in Salmonella typhimurium TA98 and is a useful substrate to study the possible chemoprotective action of phytochemicals. We found that black and green tea depressed the mutagenicity of PhIP in dose-related fashion, and decaffeinated tea was less powerful an inhibitor. This led to the study of caffeine, that displayed effective dose-related inhibition of the mutagenicity of PhIP. Other antioxidants such as lycopene, the active antioxidant from tomatoes, and daidzein and genistein from soy products, also had a dose-related inhibition of the mutagenicity of PhIP. We conclude that PhIP is a good substrate found in several human foods to determine the protective effect of phytochemicals from vegetables, and beverages.

A diet rich in carotenoid-containing foods is associated with a number of health benefits. Lycopene provides the familiar red color to tomato products and is one of the major carotenoids in the diet of North Americans and Europeans. Interest in lycopene is growing rapidly following the recent publication of epidemiologic studies implicating lycopene in the prevention of cardiovascular disease and cancers of the prostate or gastrointestinal tract. Lycopene has unique structural and chemical features that may contribute to specific biological properties. Data concerning lycopene bioavailability, tissue distribution, metabolism, excretion, and biological actions in experimental animals and humans are beginning to accumulate although much additional research is necessary. This review will summarize our knowledge in these areas as well as the associations between lycopene consumption and human health.

In a nested case-control study the stored, frozen sera from 22 cases of cancer of the pancreas and 44 matched control subjects were assayed for retinol, retinol-binding protein, total carotenoids, beta-carotene, lycopene, vitamin E (alpha-tocopherol), and selenium. Prediagnostic serum levels of lycopene and Se were lower among cases than among matched control subjects. These differences remained after adjustment was made for possible confounding by smoking, educational level, and the other measured serum levels. Low levels of serum vitamin E appeared to have a protective effect but a chance association between vitamin E and cancer of the pancreas could not reasonably be excluded. The association between cancer of the pancreas and serum Se was significant when the data were analyzed as a whole but its effect was seen principally in men.

In 1974 and 1975, serum specimens were collected from 25,802 volunteers in Washington County, Maryland. The serum was kept frozen at -73 degrees C until the time of assay. Prediagnostic samples from 436 cancer cases and 765 matched control subjects have been assayed. Nine sites have been studied: colon, rectum, pancreas, lung, melanoma, basal cell of skin, breast, prostate, and bladder. Serum beta-carotene levels showed a strong protective association with lung cancer, suggestive protective associations with melanoma and bladder cancer, and a suggestive but nonprotective association with rectal cancer. Serum vitamin E levels had a protective association with lung cancer; none of the other sites showed impressive associations. Low levels of serum lycopene were strongly associated with pancreatic cancer and less strongly associated with cancer of the bladder and rectum.

Crohn's disease (CD) is frequently complicated by various nutritional
disturbances. Although it is important to correct these disturbances, the
nutritional status of CD patients has been poorly documented, especially
concerning vitamin status. The aims of this study were (a) to measure the serum
concentrations of vitamin A and six other carotenoids (lutein, zeaxanthin,
alpha-, beta-carotene, alpha-, beta-cryptoxanthin) in patients with CD and to
compare them with those in healthy controls and (b) to follow the changes of
serum carotenoid levels in CD patients during treatment. Twenty-eight patients
with CD and 23 healthy persons were included in this study. The results of
twelve patients were followed up through one year. The patients were free of any nutritional treatment. The serum concentrations of carotenoids were measured with high-pressure liquid chromatography (HPLC). The serum concentrations of five carotenoids were significantly lower in the patients than in the controls (vitamin A, zeaxanthin: P < 0.001; alpha-, beta-carotene: P < 0.01; lutein: P < 0.05). The carotenoid status of the followed patients advanced to the normal range, but this increase was not significant. These findings suggest that there is a deficiency of vitamin A and its provitamins in Crohn' s disease prior to
treatment. However, because we did not evaluate the vitamin intake in this
study, we could not conclude which of the factors--poor intake, increased
requirement, or malabsorption--was more important in decreasing of carotenoid
levels.

High vegetable and fruit (V&F) consumption has been associated with a lower risk of several cancers. However, little is known about the ability of individuals to
increase their intakes markedly. In this 1-year randomized, controlled diet
intervention study of men and women with a recent history of adenomas, the
intervention group (n = 100) was asked to increase V&F intake to at least eight
servings per day; the control group (n = 101) continued eating their usual diet.
End-point measures included V&F intake assessed by 3-day diet records, plasma carotenoids, serum lipids, urinary sodium and potassium, and body weight. The intervention group increased their daily V&F intake an average of 5.5 servings over 1 year; the control group had an average decrease of 0.5 servings per day (P < 0.001). Plasma total carotenoids, alpha-carotene, beta-carotene, beta-cryptoxanthin, and lutein/zeaxanthin were each statistically significantly elevated over baseline (11-54%) in the intervention group compared with the control group over the duration of follow-up (P < 0.001). Urinary potassium excretion was elevated 14% over baseline in the intervention group compared with no change in the control group (P < 0.001). Modest decreases in the intervention but not the control group were observed for total and low-density lipoprotein cholesterol. Plasma lycopene, triglycerides, high-density lipoprotein cholesterol, body weight, and urinary sodium were not affected by the intervention. V&F intake was significantly increased in this motivated
population at higher risk of colon cancer and maintained for at least 12 months,
as assessed using diet records and an ensemble of biomarkers.

BAKCGROUND: A predictable consequence of cholestasis is malabsorption of
fat-soluble factors, (vitamins A, D, E, K) and other free radical scavengers,
such as carotenoids. It has been suggested that oxygen-derived free radicals may be involved in the pathogenesis of chronic liver damage. AIMS: (i) To evaluate retinol, alpha-tocopherol and carotenoid plasma levels in two groups of patients with chronic cholestatic liver disease (primary biliary cirrhosis and primary sclerosing cholangitis); (ii) to compare the respective plasma levels with those of the general population; (iii) to correlate the plasma levels with disease
severity. METHODS: A total of 105 patients with chronic cholestasis were
included in the study: 86 with primary biliary cirrhosis (81 female, five male,
mean age 55.5 11 years), 19 with primary sclerosing cholangitis (seven
female, 12 male, mean age 35 11 years; six patients had associated
inflammatory bowel disease); 105 sex- and age-matched subjects from the general population in the same geographical area (88 female, 17 male, mean age 51.3.5 10 years) served as controls. Carotenoids (lutein zeaxanthin, lycopene, beta-carotene, alpha-carotene, beta-cryptoxanthin), retinol and alpha-tocopherol were assayed by high-pressure liquid chromatography. A food frequency questionnaire was administered to each subject to evaluate the quality and the quantity of dietary compounds. Data were processed by analysis of variance and linear regression analysis, as appropriate. RESULTS: Both primary biliary cirrhosis and primary sclerosing cholangitis patients had significantly lower levels of retinol, alpha-tocopherol, total carotenoids, lutein, zeaxanthin, lycopene, alpha- and beta-carotene than controls (P < 0.0001). Among the cholestatic patients, no significant difference in the concentration of
antioxidants was observed between primary biliary cirrhosis and primary
sclerosing cholangitis subjects. Anti-oxidant plasma levels were not affected by
the severity of the histological stage in primary biliary cirrhosis, but a
negative correlation was found between total carotenoids and both alkaline
phosphatase (ALP) and gammaglutamyl transpeptidase (GGT) (P < 0.013 and P <0.018, respectively). Within the primary sclerosing cholangitis group, no
correlation was found between total carotenoids and cholestatic enzymes.
Nutritional intake in cholestatic patients was comparable to controls, including
fruit and vegetable intake. CONCLUSIONS: Although no clinical sign of deficiency is evident, plasma levels of antioxidants are low in cholestatic patients even in early stages of the disease. This is probably due to malabsorption of fat-soluble vitamins, as well as other mechanisms of hepatic release, suggesting the need for dietary supplementation.

BACKGROUND: The aim of this study was to evaluate prospectively whether there are differences in spectrometrically measurable parameters of the fundus between patients with early and late age-related maculopathy (ARM), the children of the ARM patients (F1 generation) and normals. METHOD: Using the "Jenaer Imaging Spectrometer", retinal oxygen saturation, xanthophyll, and intrinsic fluorescence were measured; the spatial distribution of xanthophyll was
determined using the Rodenstock SLO 101 model. RESULTS: Xanthophyll is reduced in late ARM as compared to the F1 generation and the control group (alpha <0.01). The different fluorescence spectra, measured at shortwave and at longwave excitation, suggest the presence of more than one fluorophore. Furthermore, the components of the fluorophores seem to be different between patients with ARM and their F1 generation. The longwave autofluorescence is age-dependent only in late ARM (r2 = 0.81). For the first time, we found an alteration in oxygen saturation in retinal vessels in patients with ARM. CONCLUSIONS: Xanthophyll is reduced only in late ARM. Autofluorescence and oxygen saturation are different between ARM patients, the F1 generation and normals, however, we were not able to identify a genetically based predisposition concerning the parameters studied.