Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention.

BACKGROUND: Human prostate tissues are vulnerable to oxidative DNA damage. The risk of prostate cancer is lower in men reporting higher consumption of tomato products, which contain high levels of the antioxidant lycopene. We examined the effects of consumption of tomato sauce-based pasta dishes on lycopene uptake, oxidative DNA damage, and prostate-specific antigen (PSA) levels in patients already diagnosed with prostate cancer. METHODS: Thirty-two patients with localized prostate adenocarcinoma consumed tomato sauce-based pasta dishes for the 3 weeks (30 mg of lycopene per day) preceding their scheduled radical prostatectomy. Serum and prostate lycopene concentrations, serum PSA levels, and leukocyte DNA oxidative damage (ratio of 8-hydroxy-2'-deoxyguanosine [8-OHdG] to 2'-deoxyguanosine [dG]) were assessed before and after the dietary intervention. DNA oxidative damage was assessed in resected prostate tissue from study participants and from seven randomly selected prostate cancer patients. All statistical tests were two-sided. RESULTS: After the dietary intervention, serum and prostate lycopene concentrations were statistically significantly increased, from 638 nM (95% confidence interval [CI] = 512 to 764 nM) to 1258 nM (95% CI = 1061 to 1455 nM) (P<.001) and from 0.28 nmol/g (95% CI = 0.18 to 0.37 nmol/g) to 0.82 nmol/g (95% CI = 0.57 to 1.11 nmol/g) (P <.001), respectively. Compared with preintervention levels, leukocyte oxidative DNA damage was statistically significantly reduced after the intervention, from 0.61 8-OHdG/10(5) dG (95% CI = 0.45 to 0.77 8-OHdG/10(5) dG) to 0.48 8-OHdG/ 10(5) dG (95% CI = 0.41 to 0.56 8-OHdG/10(5) dG) (P =.005). Furthermore, prostate tissue oxidative DNA damage was also statistically significantly lower in men who had the intervention (0.76 8-OHdG/10(5) dG [95% CI = 0.55 to 0.96 8-OHdG/10(5) dG]) than in the randomly selected patients (1.06 8-OHdG/10(5) dG [95% CI = 0.62 to 1.51 8-OHdG/10(5) dG]; P =.03). Serum PSA levels decreased after the intervention, from 10.9 ng/mL (95% CI = 8.7 to 13.2 ng/mL) to 8.7 ng/mL (95% CI = 6.8 to 10.6 ng/mL) (P<.001). CONCLUSION: These data indicate a possible role for a tomato sauce constituent, possibly lycopene, in the treatment of prostate cancer and warrant further testing with a larger sample of patients, including a control group.

Chemical composition and potential health effects of prunes: a functional food?

Prunes are dried plums, fruits of Prunus domestica L., cultivated and propagated since ancient times. Most dried prunes are produced from cultivar d'Agen, especially in California and France, where the cultivar originated. After harvest, prune-making plums are dehydrated in hot air at 85 to 90 degrees C for 18 h, then further processed into prune juice, puree, or other prune products. This extensive literature review summarizes the current knowledge of chemical composition of prunes and their biological effects on human health. Because of their sweet flavor and well-known mild laxative effect, prunes are considered to be an epitome of functional foods, but the understanding of their mode of action is still unclear. Dried prunes contain approximately 6.1 g of dietary fiber per 100 g, while prune juice is devoid of fiber due to filtration before bottling. The laxative action of both prune and prune juice could be explained by their high sorbitol content (14.7 and 6.1 g/100 g, respectively). Prunes are good source of energy in the form of simple sugars, but do not mediate a rapid rise in blood sugar concentration, possibly because of high fiber, fructose, and sorbitol content. Prunes contain large amounts of phenolic compounds (184 mg/100 g), mainly as neochlorogenic and chlorogenic acids, which may aid in the laxative action and delay glucose absorption. Phenolic compounds in prunes had been found to inhibit human LDL oxidation in vitro, and thus might serve as preventive agents against chronic diseases, such as heart disease and cancer. Additionally, high potassium content of prunes (745 mg/100 g) might be beneficial for cardiovascular health. Dried prunes are an important source of boron, which is postulated to play a role in prevention of osteoporosis. A serving of prunes (100 g) fulfills the daily requirement for boron (2 to 3 mg). More research is needed to assess the levels of carotenoids and other phytochemicals present in prunes to ensure correct labeling and accuracy of food composition tables in order to support dietary recommendations or health claims.

Solubilization and stabilization of carotenoids using micelles: delivery of lycopene to cells in culture.

The use of the organic cosolvents tetrahydrofuran and dimethylsulfoxide was found to be unsuitable for prostate tumor cell cultures because of solvent cytotoxicity and the poor solubility and instability of lycopene. For example, the half-life of lycopene in organic/aqueous solution was found to be less than 2 h. Therefore, a micellar preparation of lycopene was developed for the solubilization and stabilization of lycopene in cell culture media. Neither the micelles themselves nor lycopene solubilized in micelles at concentrations up to 10 microg/mL in the cell culture media produced cytotoxicity or inhibition of cell proliferation in either LNCaP human prostate cells or Hs888Lu human lung cells. Lycopene solubilized in micelles was stable for at least 96 h under standard cell culture conditions so that a constant lycopene supply could be provided to the cells. During the culture process, lycopene was taken up by LNCaP cells and reached a plateau at approximately 12 h. Micelles provide a convenient, inexpensive, and nontoxic vehicle for dissolving and stabilizing carotenes such as lycopene in tissue culture media and then delivering them to cells growing in culture.

Diet modification affects DNA oxidative damage in healthy humans.

DNA 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a promising biomarker for oxidative damage. We assessed its responsiveness to diet in 32 nonsmoking, healthy subjects (12 male, 20 female) aged 31+/-7.6 years. They consumed two liquid formula diets (Ensures) as the sole source of nutrition for 10-d in a randomized crossover design, with 5-d control solid food diets as washout before each liquid diet period. Reformulated Ensure (Re-En) had a vitamin E/ PUFA of 3.5 compared to standard Ensure (En) of 1.1. We hypothesized that subjects would have lower leukocyte 8-OHdG/deoxyguanosine (dG) ratios while consuming Re-En compared to En. But 8-OHdG/dG ratios did not change with the consumption of either Re-En or En. The mean ratios of 8-OHdG/dG after 10 days of Re-En and En consumption were (2.12+/-0.68)x10(-5) and (2.16+/-0.63)x10(-5), respectively. However, there was a 22% decrease in 8-OHdG/dG by the end of the study and a significant downward trend of leukocyte 8-OHdG among all subjects throughout all nutrient-rich diet phases as the study progressed (Test for trend: p = .04; paired t-test: p = .07). Because all the experimental diets provided antioxidant nutrients at higher quantities than typically consumed by a U.S. age-matched population, this study adds to the few in vivo studies that show a decrease in DNA damage in healthy nonsmoking subjects through dietary intervention.

A survey of serum and dietary carotenoids in captive wild animals.

Accumulation of carotenoids varies greatly among animal species and is not fully characterized. Circulating carotenoid concentration data in captive wild animals are limited and may be useful for their management. Serum carotenoid concentrations and dietary intakes were surveyed and the extent of accumulation categorized for 76 species of captive wild animals at Brookfield Zoo. Blood samples were obtained opportunistically from 275 individual animals immobilized for a variety of reasons; serum was analyzed for alpha- and beta-carotene, lutein + zeaxanthin, lycopene, beta-cryptoxanthin and canthaxanthin. Total carotenoid content of diets was calculated from tables and chemical analyses of commonly consumed dietary components. Diets were categorized as low, moderate or high in carotenoid content as were total serum carotenoid concentrations. Animals were classified as unknown, high, moderate or low (non-) accumulators of dietary cartenoids. Nonaccumulators had total serum carotenoid concentrations of 0-101 nmol/L, whereas accumulators had concentrations that ranged widely, from 225 to 35,351 nmol/L. Primates were uniquely distinguished by the widest range of type and concentration of carotenoids in their sera. Most were classified as high to moderate accumulators. Felids had high accumulation of beta-carotene regardless of dietary intake, whereas a wide range of exotic birds accumulated only the xanthophylls, lutein + zeaxanthin, canthaxanthin or cryptoxanthin. The exotic ungulates, with the exception of the bovids, had negligible or nondetectable carotenoid serum concentrations despite moderate intakes. Bovids accumulated only beta-carotene despite moderately high lutein + zeaxanthin intakes. Wild captive species demonstrated a wide variety of carotenoid accumulation patterns, which could be exploited to answer remaining questions concerning carotenoid metabolism and function.

Serum carotenoids and tocopherols and incidence of age-related nuclear cataract.

BACKGROUND: It is not known whether the protective effects of antioxidants on cataract observed in experimental animals are relevant to age-related opacities in humans. OBJECTIVE: The relations of serum carotenoids and tocopherols to the incidence of age-related nuclear cataract were investigated in a random sample of 400 adults, 50-86 y of age, in the Beaver Dam Eye Study. DESIGN: Nuclear opacity was assessed by using lens photographs taken at baseline (in 1988-1990) and follow-up (in 1993-1995). Nonfasting concentrations of individual carotenoids and alpha- and gamma-tocopherol, were determined from serum obtained at baseline. A total of 252 persons were eligible for incident cataract, of whom 57 developed nuclear cataract in at least one eye. Results were adjusted for age, smoking, serum cholesterol, heavy drinking, adiposity, and, in the tocopherol models, dietary linoleic acid intake. RESULTS: Only serum tocopherol (the sum of alpha- and gamma-tocopherol, in micromol/mmol cholesterol) was associated with cataract. For total serum tocopherol, persons in tertile 3 had a lower risk of cataract than persons in tertile 1 [odds ratio (OR): 0.4; 95% CI: 0.2, 0.9; P = 0.03 for linear trend]. Although serum carotenoids were not significantly associated with nuclear cataract, marginal inverse associations with lutein (OR: 0.3; 95% CI: 0.1, 1.2; P = 0.13 for linear trend) and cryptoxanthin (OR: 0.3; 95% CI: 0.1, 1.3; P = 0.11 for linear trend) were suggested in people < or = 65 y of age. CONCLUSIONS: Findings were compatible with the possibility that nuclear cataract may be linked inversely to vitamin E status, but neither strongly supported nor negated the hypothesized inverse association of nuclear cataract with serum carotenoids.

Oxidative stress in critical care: is antioxidant supplementation beneficial?

Reactive oxygen species (ROS) are constantly produced in human beings under normal circumstances. Antioxidant systems help defend the body against ROS but may be overwhelmed during periods of oxidative stress, which can cause lipid peroxidation, damage to DNA, and cell death. Critical illness, such as sepsis or adult respiratory distress syndrome, can drastically increase the production of ROS and lead to oxidative stress. Sources of oxidative stress during critical illness include activation of the phagocytic cells of the immune system (the respiratory burst), the production of nitric oxide by the vascular endothelium, the release of iron and copper ions and metalloproteins, and the vascular damage caused by ischemia reperfusion. Only indirect measurements of ROS are available, but the presence of oxidative stress in critical illness is supported by clinical studies. In general, serum antioxidant vitamin concentrations seem to decrease and measures of oxidative stress seem to increase in critically ill populations. Oxidative stress has been associated with sepsis, shock, a need for mechanical ventilation, organ dysfunction, acute respiratory distress syndrome, disseminated intravascular coagulation, surgery, and the presence of an acute-phase response. In addition, higher levels of oxidative stress seem to occur in patients with more notable injuries. Dietary supplementation with antioxidant vitamins seems to be the logical answer to decreasing serum antioxidant concentrations, but antioxidants may have adverse effects. The benefit of supplementing antioxidants in critically ill populations has not been shown and requires further study.

Influence of using different sources of carotenoid data in epidemiologic studies.

OBJECTIVE: This study compared distributions of carotenoid intake and diet-serum correlations using two sources of carotenoid data: the US Department of Agriculture-National Cancer Institute (USDA-NCI) carotenoid food composition database and values accompanying the Block-NCI Health Habits and History Questionnaire (HHHQ). DESIGN AND SUBJECTS: A 100-item food frequency questionnaire was used to collect dietary data from 2,152 adults, aged 43 to 85 years, who were participating in the Nutritional Factors in Eye Disease Study, a population-based study designed to evaluate nutritional factors associated with age-related eye disease. Blood samples were collected from a random sample of 400 nonfasting participants in the study. RESULTS: Median carotenoid intakes using HHHQ vs USDA-NCI data were alpha carotene (229 vs 223 micrograms/day), beta carotene (1,321 vs 1,325 micrograms/day), beta cryptoxanthin (72 vs 21 micrograms/day), lutein + zeaxanthin (653 vs 811 micrograms/day), and lycopene (593 vs 1,615 micrograms/day). all paired differences in carotenoid intake were significantly different from zero (Wilcoxon signed-rank, P < .0001). Despite these differences, the two databases similarly ranked individuals according to carotenoid intake: Spearman correlations ranged from .71 (lycopene) to .93 (alpha carotene). Differences between diet-serum correlations (adjusted for energy, body mass index, high density lipoprotein, and total cholesterol) using HHHQ vs USDA-NCI data were minor and not significant (P > .05): alpha carotene (r = .33 vs .32), beta carotene (r = .27 vs .32), beta cryptoxanthin (r = .48 vs .53), lutein+zeaxanthin (r = .28 vs .24), and lycopene (r = .29 vs .25). CONCLUSIONS: Although estimates of carotenoid intake differed significantly, only minor differences in carotenoid rankings and diet-serum correlations were observed using either data source in this population.

Update on the biological characteristics of the antioxidant micronutrients: vitamin C, vitamin E, and the carotenoids.

Under normal circumstances, free radicals that are produced through biological processes and in response to exogenous stimuli are controlled by various enzymes and antioxidants in the body. Laboratory evidence suggests that oxidative stress, which occurs when free radical formation exceeds the ability to protect against them, may form the biological basis of several acute medical problems, such as tissue injury after trauma, and chronic conditions, such as atherosclerosis and cancer. A potential role for the antioxidant micronutrients (vitamin C, vitamin E, and the carotenoids) in modifying the risk for conditions that may result from oxidative stress has stimulated intense research efforts, increased interest in micronutrient supplements, and heightened consumer interest in these compounds. Much remains to be learned, however, about the bioavailability, tissue uptake, metabolism, and biological activities of these micronutrients. These biological characteristics will ultimately determine their clinical usefulness in modulating oxidative stress. Also, whether the antioxidant mechanism explains their relationship with risk for acute and chronic disease in epidemiologic studies remains to be determined. Increased knowledge in this area of nutrition science will have an impact on both clinical dietetics practice and public health nutrition guidelines.

Serum selenium and colonic neoplastic risk.

BACKGROUND: Selenium deficiency has been associated with cancer risk in several organs. This association was investigated in neoplasia of the colorectum. DESIGN: A case-control study is reported with two patient series, colorectal cancer and colorectal adenomatous polyps, and a control group found to be free of colorectal neoplasia. Diagnosis was determined by colonoscopy and histologic review of suspected neoplasms. Serum drawn at the time of colonoscopy was subsequently assayed for selenium content, and quartiles based on selenium were defined. Crude and adjusted odds ratios with 95 percent confidence intervals for adenoma related to selenium were calculated, controlling for known or suspected risk factors including gender, age, race, body mass index, family history, tobacco use, alcohol consumption, serum beta carotene, serum alpha tocopherol, and serum ferritin. RESULTS: There were 138 controls who had no neoplastic disease, 139 adenoma patients, and 25 cancer patients. For adenoma, comparing higher quartiles of selenium to the first (lowest selenium), the adjusted odds ratio for the second quartile was 1.7 (95 percent confidence interval, 0.8-3.7), the third quartile was 1.4 (0.7-3.2), and the fourth (highest selenium) quartile was 1.8 (0.9-4). The odds ratios for cancer patients were 0.8 for the second quartile, 1 for the third quartile, and 1.7 for the fourth quartile. CONCLUSION: No trend could be detected toward a protective effect of higher levels of serum selenium for colonic benign or malignant tumors.

Effect of beta-carotene supplementation on indices of colonic cell proliferation.

BACKGROUND: Epidemiologic studies have shown that consuming foods containing beta-carotene is associated with a decreased incidence of colon cancer. The validity of this association has recently been questioned. It is not known if the rate of colonic cell proliferation differs among individuals with or without a history of colonic polyps or cancer and if proliferation changes in response to beta-carotene. PURPOSE: This study was intended to (a) determine whether differences exist in colonic cell proliferation in individuals with and without prior colonic polyps or tumors, (b) demonstrate that beta-carotene accumulates in colonic mucosa following dietary supplementation, and (c) determine whether mucosal beta-carotene accumulation influences colonic cell proliferation. METHODS: Subjects were enrolled in the phase I study from June 1991 until February 1994. The participants included 20 individuals (11 males and nine females, aged 62.3 +/- 8.9 years [means +/- SD]) with normal colons (as judged by recent colonoscopy), 40 (24 males and 16 females, aged 59.6 +/- 10.1 years) with a history of colonic polyp(s), and 41 (30 males and 11 females, aged 67.2 +/- 9.7 years) with prior colon cancer. The subjects in the last two groups consumed either 30 mg of beta-carotene or placebo each morning for 3 months. This dose of beta-carotene has no known toxic effects, but it can increase the serum level by approximately 10-fold. beta-carotene concentration in serum and colonic tissue was quantitated by high-pressure liquid chromatography in samples collected before and after supplementation with beta-carotene or placebo. Cellular proliferation was assessed on the basis of tissue ornithine decarboxylase activity, urinary polyamine excretion, and proliferating cell nuclear antigen expression. The differences in colonic cell proliferation parameters due to beta-carotene supplementation, within and among different groups, were evaluated by the Wilcoxon matched-pairs signed ranked test and the Mann-Whitney test, respectively. All statistical tests were two-sided. RESULTS: Colonic cell proliferation did not differ in samples obtained from individuals with and without prior colonic polyp(s) or cancer. beta-carotene concentrations in serum and colonic tissue were significantly increased in groups receiving beta-carotene (P < .001). However, cell proliferation did not differ, as judged by any of the three measures, among samples from all experimental groups collected before and after supplementation with beta-carotene. CONCLUSIONS: Dietary supplementation with beta-carotene for a period of 3 months does not alter colonic cell proliferation in individuals with a history of colonic polyps or cancer. IMPLICATIONS: The mechanism by which beta-carotene might reduce colon cancer incidence does not appear to involve or result in a change in cell proliferation in the normal colonic mucosa as studied in individuals with a history of colonic polyps or cancer.

Evidence from cancer intervention and biomarker studies and the development of biochemical markers.

Evidence from intervention trials with vitamins E and C and beta-carotene are reviewed as well as evidence from trials that have used intermediate endpoints with a special emphasis on biomarkers of cancer of the colorectum. The methodologic issues that require resolution before a second generation of clinical trials are launched to assess the efficacy of these antioxidants in the prevention of cancer are identified. Specific concerns regarding the validation of pathologic biomarkers of cancer and biochemical markers of mechanism of action for the antioxidants are discussed. Cellular proliferation indexes in the colon are used as an example of pathologic biomarkers for cancer and the measurement of plasma and tissue malondialdehyde concentrations is used as an example of problems with the development of biochemical markers of oxidative stress that can be used in prevention trials. The use of DNA oxidation products as promising biomarkers is also discussed.

An ecological study of diet and lung cancer in the South Pacific.

Incidence rates of lung cancer have been markedly lower for Fiji than for other South Pacific countries, despite similar rates of smoking. We conducted population-based surveys in several island nations of the South Pacific (Cook Islands, Fiji, Tahiti and New Caledonia) and used data from Caucasian, Japanese, Hawaiian, Filipino and Chinese controls in a case-control study of lung cancer in Hawaii to investigate the role of diet in explaining differences in lung cancer incidence among 20 ethnic-sex groups. In a stepwise linear regression of lung cancer rates on smoking, diet and other variables, smoking, as expected, explained the majority (61%) of the variability in incidence. However, several dietary components also explained significant portions of the variance. Lutein intake explained 14% and vitamin E intake, cholesterol intake and height explained 5-7% each of the remaining variance in incidence. Associations with lutein and vitamin E were inverse, whereas those with cholesterol and height were direct. Dietary beta-carotene intake was not associated with lung cancer incidence. These ecological data provide evidence for a protective effect of lutein against lung cancer. A protective effect of dietary vitamin E and a risk-enhancing effect of dietary cholesterol are also suggested.

Pharmacokinetics of beta-carotene and canthaxanthin after ingestion of individual and combined doses by human subjects.

OBJECTIVE: This study investigated effects of ingestion of a combined dose of beta-carotene and canthaxanthin on their individual pharmacokinetics in serum. METHODS: During three 5-day study periods, two subjects ingested either a 25 mg dose of beta-carotene, a 25 mg dose of canthaxanthin, or a combined dose of 25 mg each of beta-carotene and canthaxanthin. Pharmacokinetics of the individual and combined doses were compared within subjects. RESULTS: Ingestion of a concurrent beta-carotene dose reduced the peak serum canthaxanthin concentration by 38.8 +/- 6.5%, and the 24- and 72-hour areas under the serum canthaxanthin concentration-time curves by 38.1 +/- 6.4 and 34.4 +/- 7.4%, respectively. The suggested antagonism between beta-carotene and canthaxanthin was not reciprocal; beta-carotene inhibited the appearance of canthaxanthin in serum but canthaxanthin did not inhibit the appearance of beta-carotene. CONCLUSION: Our data suggest that ingestion of a combined pharmacologic dose of beta-carotene and canthaxanthin reduces the bioavailability of the canthaxanthin dose.

Factor VII coagulant activity and cholesterol changes in premenopausal women consuming a long-term cholesterol-lowering diet.

We periodically obtained blood samples from mildly hypercholesterolemic, but otherwise healthy, premenopausal women who were recruited to participate in a study of a long-term, cholesterol-lowering diet. All meals were prepared and most meals were consumed in the study center dining facility. Tests performed on blood samples included fibrinogen, cholesterol, factor VII coagulant activity (VIIc), and other measures of factor VII. We found that when women switched from a typical American diet (37% fat, polyunsaturated fatty acid to saturated fatty acid [P/S] ratio 0.5, 300 mg cholesterol/d) to a diet lower in fat and cholesterol (American Heart Association phase 2 diet: 30% fat, P/S ratio of 1, 150 to 200 mg cholesterol/d) and maintained that diet for 20 weeks, their plasma cholesterol levels decreased by approximately 6% after 4 weeks and remained at that level until study termination. Likewise, VIIc decreased by approximately 11% while factor VII antigen, total factor VII activity, and fibrinogen concentration did not change appreciably from baseline values. Our results show that premenopausal women benefit from a diet lower in total and saturated fat by a reduction in blood cholesterol and VIIc. Extrapolation from data on men in the Northwick Park Heart Study indicates that the 11% decrease in VIIc activity would correspond to an approximately 30% decrease in risk of mortality from coronary heart disease.