Nitrate and nitrite in the diet: how to assess their benefit and risk for human health.

Nitrate is a natural constituent of the human diet and an approved food additive. It can be partially converted to nitrogen monoxide, which induces vasodilation and thereby decreases blood pressure. This effect is associated with a reduced risk regarding cardiovascular disease, myocardial infarction, and stroke. Moreover, dietary nitrate has been associated with beneficial effects in patients with gastric ulcer, renal failure, or metabolic syndrome. Recent studies indicate that such beneficial health effects due to dietary nitrate may be achievable at intake levels resulting from the daily consumption of nitrate-rich vegetables. N-nitroso compounds are endogenously formed in humans. However, their relevance for human health has not been adequately explored up to now. Nitrate and nitrite are per se not carcinogenic, but under conditions that result in endogenous nitrosation, it cannot be excluded that ingested nitrate and nitrite may lead to an increased cancer risk and may probably be carcinogenic to humans. In this review, the known beneficial and detrimental health effects related to dietary nitrate/nitrite intake are described and the identified gaps in knowledge as well as the research needs required to perform a reliable benefit/risk assessment in terms of long-term human health consequences due to dietary nitrate/nitrite intake are presented.

Prevention of colon carcinogenesis by apple juice in vivo: impact of juice constituents and obesity.

It is estimated that 75-85% of all chronic diseases are linked to lifestyle-related and environmental factors. The development of colon cancer is positively associated with obesity and inversely associated with the intake of dietary fibre, fruit and vegetable. Apple juice is the most widely consumed fruit beverage in Germany. It contains a specific spectrum of polyphenols and other components that may reduce the risk of colon cancer. Epidemiologic studies suggest an inverse correlation between apple consumption and colon cancer risk, although the mechanisms for these observations are not clear. The present review summarizes the preventive potential of apple juices and different apple constituents on biomarkers related to colon carcinogenesis with special focus on the in vivo evidence and the cancer promoting condition of obesity. However, under the cancer promoting condition of obesity, apple juice did not show cancer-preventive bioactivity. In our experiments a cancer-preventive bioactivity of apple juice is lacking in rats under the cancer-promoting condition of obesity. To further investigate, whether this lack of efficacy observed in obese rats might be representative for obese individuals human intervention studies on high risk groups such as obese or diabetic individuals are of interest and will be conducted.

Effects of adipocyte-secreted factors on cell cycle progression in HT29 cells.

BACKGROUND: Obesity is a chronic sub-inflammatory condition which is a risk factor for several cancer diseases, e.g. colon cancer. Adipose tissue secretes biologically active factors like leptin with a known pro-inflammatory or mitogenic activity. Both, chronic inflammation and an increased cell proliferation are considered to play an important role in colon carcinogenesis. Diverse phytochemicals were shown to have cell growth inhibiting effects. AIM OF THE STUDY: The aim was to investigate whether adipocytes could mediate a proliferative capacity to HT29, a human colon adenocarcinoma cell line, and whether phytochemicals could modulate this effect. METHODS: Infranatants of adipocyte cultures from different donors were prepared and the effects of those conditioned adipocyte media (CAM) on HT29 cell growth were measured. Additionally, cell cycle progression was analyzed by flow cytometry after CAM treatment and ERK 1/2 phosphorylation was analyzed. RESULTS: CAM from a subgroup of adipose tissue donors stimulated HT29 cell growth, whereas others did not. This effect seems to be mediated via the ERK 1/2 pathway. Furthermore, CAM caused changes in cell cycle distribution with a shift of HT29 cells from G1- into the S-phase. This effect could be mimicked by leptin (1 nM). Co-incubation of CAM-treated HT29 cultures with beta-carotene or EGCG did not have a significant impact on cell cycle progression, whereas genistein (30 microM) tended to inhibit the CAM-stimulated transition of cells into the S-phase. CONCLUSION: This study confirmed the mitogenic activity of leptin in HT29 cells, although leptin secretion from adipocytes is not likely to be responsible for CAM-stimulated cell growth in our test system. The investigated phytochemicals seem to have only a minor influence on CAM-mediated cell cycle progression.

Phytoestrogens and phytoestrogen metabolites differentially modulate immune parameters in human leukocytes.

Phytoestrogens (PE) including isoflavones and lignans, are a group of substances of plant origin which can act as estrogen agonists or antagonists. While the immunomodulatory effects of isoflavones have been studied, little is known about the impact of lignans and other PE metabolites on the immune system. The aim of the present study was to assess whether PE and their metabolites modulate human leukocyte functions in vitro. We investigated the effects of genistein, daidzein, matairesinol, and secoisolariciresinol, including metabolites such as equol, O-desmethylangolensin, enterodiol, and enterolactone on natural killer cell activity, proliferation, cytokine secretion, as well as apoptotic and necrotic rate of human leukocytes. Genistein, daidzein, and its metabolite equol were the most potent inhibitors of leukocyte functions. Ten micromolars of genistein decreased proliferation, lytic activity of natural killer cells, and cytokine secretions. The latter proved to be the most sensitive marker of immune functions. Lignans and their metabolites had minor effects on the immune system. The antiestrogens Tamoxifen and Fulvestrant did not block the inhibition of cytokine secretion by genistein and equol. In conclusion, while physiological concentrations of isoflavones have minor effects on cytokine secretion, lignans including their major metabolites do not modulate human leukocyte functions in vitro.

Zeaxanthin is bioavailable from genetically modified zeaxanthin-rich potatoes.

The carotenoid zeaxanthin accumulates in the human macula lutea and protects retinal cells from blue light damage. However, zeaxanthin intake from food sources is low. Increasing zeaxanthin in common foods such as potatoes by traditional plant breeding or by genetic engineering could contribute to an increased intake of this carotenoid and, consequently, to a decreased risk of age-related macular degeneration. Our aim was to investigate whether zeaxanthin from genetically modified zeaxanthin-rich potatoes is bioavailable in humans. Three men participated in this randomized, controlled double-blinded, crossover pilot study. All subjects consumed 1,100 g of mashed potatoes, either genetically modified (Solanum tuberosum L. var. Baltica GM47/18; 3 mg zeaxanthin) or wild-type control potatoes (Solanum tuberosum L. var. Baltica; 0.14 mg zeaxanthin). A second treatment was followed after a 7-day wash-out period. The concentration of zeaxanthin was significantly increased in chylomicrons after consumption of genetically modified potatoes and 0.27 mg of the 3 mg zeaxanthin dose could be detected in chylomicrons. Consumption of control potatoes had no effect on concentrations of zeaxanthin in chylomicrons. After normalization of chylomicron zeaxanthin for plasma triacylglycerol, the time course of zeaxanthin concentrations peaked at 7 h after consumption of genetically modified potatoes. There were no significant differences in the concentrations of other major potato carotenoids such as lutein and beta-carotene in chylomicrons after consumption of genetically modified and wild type control potatoes. Thus, consumption of zeaxanthin-rich potatoes significantly increases chylomicron zeaxanthin concentrations suggesting that potentially such potatoes could be used as an important dietary source of zeaxanthin.

Effects of carrot and tomato juice consumption on faecal markers relevant to colon carcinogenesis in humans.

High intakes of carotenoid-rich fruits and vegetables are associated with a reduced risk of various cancers including colon cancer. A human intervention study with carrot and tomato juice should show whether a diet rich in carotenoids, especially high in beta-carotene and lycopene, can modify luminal processes relevant to colon carcinogenesis. In a randomised cross-over trial, twenty-two healthy young men on a low-carotenoid diet consumed 330 ml tomato or carrot juice per d for 2 weeks. Intervention periods were preceded by 2-week depletion phases. At the end of each study period, faeces of twelve volunteers were collected for chemical analyses and use in cell-culture systems. Consumption of carrot juice led to a marked increase of beta-carotene and alpha-carotene in faeces and faecal water, as did lycopene after consumption of tomato juice. In the succeeding depletion phases, carotenoid contents in faeces and faecal water returned to their initial values. Faecal water showed high dose-dependent cytotoxic and anti-proliferative effects on colon adenocarcinoma cells (HT29). These effects were not markedly changed by carrot and tomato juice consumption. Neither bile acid concentrations nor activities of the bacterial enzymes beta-glucosidase and beta-glucuronidase in faecal water changed after carrot and tomato juice consumption. Faecal water pH decreased only after carrot juice consumption. SCFA were probably not responsible for this effect, as SCFA concentrations and profiles did not change significantly. In summary, in the present study, 2-week interventions with carotenoid-rich juices led only to minor changes in investigated luminal biomarkers relevant to colon carcinogenesis.

Bioavailability of astaxanthin stereoisomers from wild (Oncorhynchus spp.) and aquacultured (Salmo salar) salmon in healthy men: a randomised, double-blind study.

The objective of the present study was to investigate the bioavailability and the configurational isomer distribution of the carotenoid astaxanthin (AST) in human plasma after ingestion of wild (Oncorhynchus spp.) and aquacultured (Salmo salar) salmon. In a randomised and double-blind trial, twenty-eight healthy men consumed 250 g wild or aquacultured salmon daily for 4 weeks which provided 5 mug AST/g salmon flesh. The plasma AST concentrations as well as the isomer distribution were measured by HPLC using a reversed and a chiral stationary phase. After 6 d of intervention with salmon, plasma AST concentrations reached a plateau of 39 nmol/l after consumption of wild salmon and of 52 nmol/l after administration of aquacultured salmon. At days 3, 6, 10 and 14 -- but not at day 28 -- the AST concentrations in human plasma were significantly greater after ingestion of aquacultured salmon. After administration of wild salmon, the (3S,3'S) isomer predominated in plasma (80 %), whereas after intake of aquacultured salmon the meso form (3R,3'S) prevailed (48 %). Therefore, the AST isomer pattern in human plasma resembles that of the ingested salmon. However, after consumption of both wild and aquacultured salmon for 28 d the relative proportion of the (3S,3'S) isomer was slightly higher and the (3R,3'R) form lower in human plasma compared with the isomer distribution in salmon flesh. A selective process of isomer absorption could be responsible for the observed differences in the relative proportions of the (3S,3'S) and (3R,3'R) isomers in human plasma compared with salmon flesh.

Consumption of prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis has minor effects on selected immune parameters in polypectomised and colon cancer patients.

Probiotics (PRO) modulate immunity in humans, while the effect of prebiotics (PRE) and synbiotics (SYN) on the human immune system are not well studied yet. The objective of this study was to investigate whether daily intake of a SYN modulates immune functions. In a randomised double-blind, placebo-controlled trial, thirty-four colon cancer patients who had undergone 'curative resection' and forty polypectomised patients participated. Subjects of the SYN group daily received encapsulated bacteria (1 x 10(10) colony-forming units of Lactobacillus rhamnosus GG (LGG) and 1 x 10(10) colony-forming units of Bifidobacterium lactis Bb12 (Bb12)) and 10 g of inulin enriched with oligofructose. Controls received encapsulated maltodextrin and 10 g of maltodextrin. Prior to intervention (T1), and 6 (T2) and 12 weeks after the start of the intervention (T3), phagocytic and respiratory burst activity of neutrophils and monocytes, lytic activity of natural killer cells and production of interleukin (IL)-2, IL-10 and IL-12, as well as tumour necrosis factor-alpha and interferon-gamma (IFN-gamma) by activated peripheral blood mononuclear cells (PBMC) were measured. In faeces, the concentrations of transforming growth factor-beta1 and prostaglandin E2 were measured. IL-2 secretion by activated PBMC from the polyp group increased significantly between T1 or T2 and T3 (P < 0.05). In the cancer group, SYN treatment resulted in an increased capacity of PBMC to produce IFN-gamma at T3 (P < 0.05). Other immunity-related parameters were not affected by SYN treatment, neither in the cancer nor in the polyp group. In conclusion, supplementation with this SYN has minor stimulatory effects on the systemic immune system of the two study groups. Further studies in humans should aim to focus on the gut-associated immune system.

Flavonoids alter P-gp expression in intestinal epithelial cells in vitro and in vivo.

Flavonoids are secondary plant metabolites included in our diet but are also provided in a growing number of supplements. They are suggested to interact with intestinal transport systems including phospho-glycoprotein (P-gp) which mediates the efflux of a variety of xenobiotics back into the gut lumen. In human intestinal Caco-2 cells, we tested the effects of 14 different flavonoids on P-gp expression in vitro. Protein expression levels were quantified by Western blotting, flow cytometry, and real-time PCR. Except apigenin, all flavonoids at concentrations of 10 microM increased P-gp expression in Western blotting experiments when cells were exposed to the compounds over 4 wk. Flavone was one of the most effective P-gp inducers in Caco-2 cells and its effects were, therefore, also assessed for changes in P-gp in vivo in the gastrointestinal tract of C57BL/6 mice. P-gp expression was significantly increased by flavone (400 mg/kg body weight x day over 4 wk) in the small intestine but not in the colon which displayed intrinsically the highest expression level. In conclusion, the increase in P-gp expression caused by flavonoids in intestinal epithelial cells in vitro and also in vivo may serve as an adaptation and defense mechanism limiting the entry of lipophilic xenobiotics into the organism.

Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients.

BACKGROUND: Animal studies suggest that prebiotics and probiotics exert protective effects against tumor development in the colon, but human data supporting this suggestion are weak. OBJECTIVE: The objective was to verify whether the prebiotic concept (selective interaction with colonic flora of nondigested carbohydrates) as induced by a synbiotic preparation-oligofructose-enriched inulin (SYN1) + Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (BB12)-is able to reduce the risk of colon cancer in humans. DESIGN: The 12-wk randomized, double-blind, placebo-controlled trial of a synbiotic food composed of the prebiotic SYN1 and probiotics LGG and BB12 was conducted in 37 colon cancer patients and 43 polypectomized patients. Fecal and blood samples were obtained before, during, and after the intervention, and colorectal biopsy samples were obtained before and after the intervention. The effect of synbiotic consumption on a battery of intermediate bio-markers for colon cancer was examined. RESULTS: Synbiotic intervention resulted in significant changes in fecal flora: Bifidobacterium and Lactobacillus increased and Clostridium perfringens decreased. The intervention significantly reduced colorectal proliferation and the capacity of fecal water to induce necrosis in colonic cells and improve epithelial barrier function in polypectomized patients. Genotoxicity assays of colonic biopsy samples indicated a decreased exposure to genotoxins in polypectomized patients at the end of the intervention period. Synbiotic consumption prevented an increased secretion of interleukin 2 by peripheral blood mononuclear cells in the polypectomized patients and increased the production of interferon gamma in the cancer patients. CONCLUSIONS: Several colorectal cancer biomarkers can be altered favorably by synbiotic intervention.

Cloudy apple juice is more effective than apple polyphenols and an apple juice derived cloud fraction in a rat model of colon carcinogenesis.

As recently shown, a cloudy apple juice (CloA) was effective to modulate colon cancer associated parameters in rats treated with 1,2-dimethylhydrazine (DMH). To identify the bioactive substance classes in CloA, we fractionated CloA to yield a total polyphenol (PF) and a cloud (CF) fraction consisting of proteins, fatty acids, polyphenols, and cell wall polysaccharides. Rats received water (control (Cont)) or CloA, PF, and CF separate or combined (PF-CF) ad libitum for 7 weeks starting one week before the first DMH-injection. As determined by comet assay, the DMH-induced genotoxicity in colonocytes of controls (Cont/DMH: 7.7 +/- 0.5%) was significantly reduced by CloA (3.3 +/- 0.3%) but not by any of the fractions. The crypt cell proliferation induced by DMH (Cont/NaCl: 7.5 +/- 0.6%; Cont/DMH: 14.9 +/- 0.8%) was significantly decreased by CloA (9.4 +/- 0.4%), PF (12.4 +/- 0.7%), CF (11.6 +/- 0.4%), and PF-CF (12.4 +/- 0.6%). Although not statistically significant, CloA tended to reduce the number of large aberrant crypt foci (ACF) (Cont/DMH: 19.0 +/- 3.7; CloA/DMH: 12.3 +/- 1.9), while none of the fractions affected ACFs. Neither CloA nor the fractions changed mRNAs of colonic cyclooxygenases (COX-1, COX-2), glutathione-associated enzymes (GST-M2, gamma-GCS, GST-P), the splenocyte CD4/CD8 ratio, natural killer cell activity, and plasma antioxidant status. These results demonstrate that CloA had a higher cancer-preventive potential than the fractions and further, besides PF, identified CF as an additional bioactive fraction of CloA.

Cellular uptake of carotenoid-loaded oil-in-water emulsions in colon carcinoma cells in vitro.

Oil-in-water emulsions allow the preparation of lipophilic compounds such as carotenoids in the liquid form. Here, the effect of a combination of some emulsifiers, such as two whey protein isolates (BiPro and BioZate), sucrose laurate (L-1695), and polyoxyethylene-20-sorbitan-monolaurate (Tween 20), on the stability of lycopene and astaxanthin in emulsions, droplet size, and cellular uptake of these carotenoids has been investigated. The degradation of lycopene was slightly more pronounced than that of astaxanthin in all emulsions. The concentration of lycopene and astaxanthin decreased by about 30% and 20%, respectively, in all emulsions after 3 weeks of storage in the dark at 4 degrees C. The kind of emulsifiers or their combinations have played an important role in the cellular uptake by the colon carcinoma cells line HT-29 and Caco-2.

Intervention with polyphenol-rich fruit juices results in an elevation of glutathione S-transferase P1 (hGSTP1) protein expression in human leucocytes of healthy volunteers.

Polyphenols are probably antigenotoxic on account of their antioxidant activities and might alter phase I and II enzymes in a way that results in chemoprotection. We investigated the hypothesis that polyphenols enhance expression of glutathione S-transferases (GSTs), which increases carcinogen detoxification and thereby provides protection against oxidative stress. HGSTP1 protein expression and GST polymorphisms were determined in leucocytes obtained during an intervention study with healthy subjects consuming two fruit juices in an 8 wk trial (polyphenol-free run in phase, juice intervention phase, washout phase, second juice intervention phase, each treatment regime lasted for 2 wk). The study had originally shown that juice intervention significantly reduced oxidative DNA damage in leucocytes at week 8 (Bub, A., Watzl, B., Blockhaus, M., Briviba, K. et al., J. Nutr. Biochem. 2003, 14, 90-98). We reanalysed the levels of DNA damage based on GST genotypes. We also treated leucocytes in vitro with mixtures of polyphenols and determined cytotoxicity and expression of 96 genes related to drug metabolism. Key results with leucocytes of the intervention study were that the initial content of hGSTP1 protein was first suppressed at weeks 4 and 6. At week 8, however, hGSTP1 protein expression was significantly increased. HGSTP1 protein levels and DNA damage were inversely correlated (p = 0.005), but there was no difference for cells obtained from subjects with hGSTM1*1 and hGSTM1*0 genotypes, nor was there any difference between cells from subjects consuming the two different juices. The treatment of leucocytes with polyphenol mixtures in vitro did not result in modulated GST gene expression or total GST activity, but in an up-regulation of other biotransformation enzymes (e. g., members of the cytochrome P450 and the sulphotransferase family). In conclusion, in vitro treatment of leucocytes led to a modulated mRNA expression of selected genes, not directly related to oxidative defence systems. In vivo, however, we observed a delayed enhancement of hGSTP1, which could be associated with an initial repression of oxidative DNA damage in leucocytes from human subjects, consuming juices with high levels of polyphenols.

Stability and biotransformation of various dietary anthocyanins in vitro.

BACKGROUND: Anthocyanins, which are found in high concentrations in fruit and vegetable, may play a beneficial role in retarding or reversing the course of chronic degenerative diseases. However, little is known about the biotransformation and the metabolism of anthocyanins so far. AIM OF THE STUDY: The aim of the study was to investigate possible transformation pathways of anthocyanins by human faecal microflora and by rat liver microsomes as a source of cytochrome P450 enzymes as well as of glucuronyltransferases. METHODS: Pure anthocyanins, an aqueous extract of red radish as well as the assumed degradation products were incubated with human faecal suspension. The incubation mixtures were purified by solid-phase extraction and analysed by HPLC/DAD/MS and GC/MS. Quantification was done by the external standard method. Furthermore the biotransformation of anthocyanins by incubation with rat liver microsomes in the presence of the cofactor NADPH (as a model for the phase I oxidation) and in the presence of activated glucuronic acid (as a model for the phase II glucuronidation) was investigated. RESULTS: Glycosylated and acylated anthocyanins were rapidly degraded by the intestinal microflora after anaerobic incubation with a human faecal suspension. The major stable products of anthocyanin degradation are the corresponding phenolic acids derived from the B-ring of the anthocyanin skeleton. Anthocyanins were not metabolised by cytochrome P450 enzymes, neither hydroxylated nor demethylated. However they were glucuronidated by rat liver microsomes to several products. CONCLUSIONS: The gut microflora seem to play an important role in the biotransformation of anthocyanins. A rapid degradation could be one major reason for the poor bioavailability of anthocyanins in pharmacokinetic studies described so far in the literature. The formation of phenolic acids as the major stable degradation products gives an important hint to the fate of anthocyanins in vivo.

Novel lycopene metabolites are detectable in plasma of preruminant calves after lycopene supplementation.

Appropriate animal models such as preruminant calves are necessary to study the complex physiological functions of carotenoids and to relate them to possible health effects in humans. In this study, the bioavailability and metabolism of lycopene from 2 dietary supplements were compared. LycoVit containing synthetic lycopene and Lyc-O-Mato containing natural tomato oleoresin were administered to 2 groups of preruminant calves (each n = 8) for 14 d in daily doses of 15 mg of lycopene. Plasma was analyzed for carotenoids before the intervention period, directly after, and each day for 5 d after the end of the intervention. All-trans and 5-cis lycopene, and 3 lycopene metabolites not previously found in calf plasma were detected. These metabolites contributed 52% of the total lycopene content measured at the end of the intervention period. Based on spectroscopic data, they might be hydrogenation products, which are formed from all-trans and/or 5-cis lycopene. In the LycoVit group, total lycopene concentrations were approximately 300% higher (286 +/- 89 nmol/L) than in the Lyc-O-Mato group (72 +/- 33 nmol/L) (P < 0.001). This indicates that, unlike in humans, lycopene from LycoVit and Lyc-O-Mato does not have equal bioavailabilities in preruminant calves. Therefore, the preruminant calf may not be a suitable animal model with which to study the biological and physiological effects of lycopene.

Basal colon crypt cells are more sensitive than surface cells toward hydrogen peroxide, a factor of oxidative stress.

Products of oxidative stress are possibly important risk factors for colon cancer. It is necessary to assess their toxicity in tumour target cells, which include the stem cells and dividing daughter cells located in the bottom of the colon crypts. Here, we investigated the sensitivity of crypt cells towards hydrogen peroxide (H(2)O(2)), a key genotoxin associated with oxidative stress. Primary rat colonocytes, were isolated from different regions of the crypts by fractionated digestion. Differentiation was determined by measuring the alkaline phosphatase activity. Deoxyribonucleic acid (DNA) damage and oxidised DNA bases were determined using the modified version Comet assay with endonuclease III. Major findings were that rat colonocytes had high levels of endogenous DNA single strand breaks, with no significant difference from basal crypt cells to surface cells. However, cells of the basal crypt had more oxidised DNA pyrimidines, which were probably a reflection of preceding in vivo exposure. An in vitro treatment with H(2)O(2) significantly increased DNA strand breaks in all fractions of rat colonocytes, but again cells of the basal crypt were more sensitive than cells of the surface epithelium. We conclude that cells from lower crypt sections are more sensitive towards H(2)O(2) than differentiated cells at the surface of the crypt.

Paraoxonase 1 Q192R (PON1-192) polymorphism is associated with reduced lipid peroxidation in healthy young men on a low-carotenoid diet supplemented with tomato juice.

The HDL-bound enzyme paraoxonase (PON) protects LDL from oxidation and may therefore attenuate the development of atherosclerosis. We examined the effect of tomato and carrot juice consumption on PON1 activity and lipid peroxidation in healthy young volunteers with different PON1-192 genotypes (Q/R substitution at position 192). In this randomized cross-over study twenty-two healthy, non-smoking men on a low-carotenoid diet received 330 ml/d tomato juice (37.0 mg lycopene, 1.6 mg beta-carotene) or carrot juice (27.1 mg beta-carotene, 13.1 mg alpha-carotene) for 2 weeks. Intervention periods were preceded by 2-week low-carotenoid intake. We determined the PON1-192 genotype by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) and measured ex vivo LDL oxidation (lag time), plasma malondialdehyde and PON1 activity at the beginning and end of each intervention period. At baseline, lag time was higher (P<0.05) in QQ (111 (sd 9) min) than in QR/RR subjects (101 (sd 8) min). Neither tomato nor carrot juice consumption had significant effects on PON1 activity. However, tomato juice consumption reduced (P<0.05) plasma malondialdehyde in QR/RR (Delta: -0.073 (sd 0.11) micromol/l) as compared to QQ subjects (Delta:+0.047 (sd 0.13) micromol/l). Carrot juice had no significant effect on malondialdehyde irrespective of the PON1-192 genotype. Male volunteers with the QR/RR genotype showed an increased lipid peroxidation at baseline. Although tomato and carrot juice fail to affect PON1 activity, tomato juice intake reduced lipid peroxidation in healthy volunteers carrying the R-allele of the PON1-192 genotype and could thus contribute to CVD risk reduction in these individuals.

A half-marathon and a marathon run induce oxidative DNA damage, reduce antioxidant capacity to protect DNA against damage and modify immune function in hobby runners.

This study investigated whether a 21.1 km (half-marathon) or a 42.195 km (marathon) run modulates DNA damage, antioxidant capacity in lymphocytes and plasma, and the immune system in healthy hobby runners. Ten and 12 volunteers who completed the Baden-Marathon race in Karlsruhe with a running distance of 21.1 km and 41.195 km, respectively, were assessed 10 days before and immediately after the finish. There was no increase in the levels of endogenous DNA strand breaks immediately after half-marathon or marathon races. A statistically significant increase in the levels of oxidative DNA damage in lymphocytes was found using endonuclease III but not formamidopyrimidine glycolase (Fpg). The resistance of DNA to oxidative damage induced by hydrogen peroxide in isolated lymphocytes was significantly decreased after both races. The levels of plasma antioxidants such as alpha-tocopherol, beta-carotene and lycopene were close to, or higher than, those considered optimal for reducing the risk of cardiovascular diseases and there were no significant changes after the races in antioxidant capacity of LDL (lag-time test) or plasma in ORAC, TEAC or paraoxonase assays. The number and percentage of granulocytes and monocytes able to generate oxidative burst were significantly increased after both races, but the lytic activity of NK cells was significantly increased at the end of the half-marathon; no effect was observed in the marathon runners. Thus, oxidative DNA damage in lymphocytes, decreased the antioxidant capacity to protect lymphocytes against DNA strand breaks and increased the formation of reactive species by phagocytes in well-nourished hobby runners indicating moderate oxidative damage during such high-intensity exercise.