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Metabolic changes during the perinatal period are known to promote obesity and type-2 diabetes in adulthood via perturbation of the microbiota. The risk factors for metabolic disorders include a high-fat diet (HFD) and exposure to pesticide residues. The objective of the present study was to evaluate the effects of perigestational exposure to a HFD and chlorpyrifos (CPF) on glycemia, lipid profiles, and microbial populations in Wistar dams and their female offspring. We also tested a preventive strategy based on treatment with the prebiotic inulin.From 4 months before gestation to the end of the lactation period, six groups of dams were exposed to either a standard diet, a HFD alone, CPF alone, a combination of a HFD and CPF, and/or inulin supplementation. All female offspring were fed a standard diet from weaning to adulthood. We measured the impacts of these exposures on glycemia, the lipid profile, and the microbiota (composition, metabolite production, and translocation into tissues).HFD exposure and CPF + HFD co-exposure induced dysmetabolism and an imbalance in the gut flora in both the dams and the female offspring. Inulin mitigated the impact of exposure to a HFD alone but not that of CPF + HFD co-exposure.Our results provide a better understanding of the complex interactions between environmental pollutants and diet in early life, including in the context of metabolic diseases.

myfood24 is an innovative dietary assessment tool originally developed in English for use in the United Kingdom. This online 24 h recall, a tool commonly used in nutritional epidemiology, has been developed into different international versions. This paper aims to describe the creation of its French version. We used a consistent approach to development, aligned with other international versions, using similar methodologies. A nutritional database (food item codes, portion groups and accompaniments, etc.) was developed based on commonly used French food composition tables (CIQUAL 2017). Portion sizes were adapted to French dietary habits (estimation, photographs of French portion sizes, assessment of the photograph series and their angle (aerial vs. 45 degrees)). We evaluated the new tool, which contained nearly 3000 food items with 34 individuals using the System Usability Scale. We validated the French food portion picture series using EFSA criteria for bias and agreement. The results of the picture evaluation showed that the angle with which photos are taken had limited impact on the ability to judge portion size. Estimating food intake is a challenging task. Evaluation showed “good” usability of the system in its French version. myfood24 France will be a useful addition to nutritional epidemiology research in France.

Minor compounds in vegetable oils are of health interest due to their powerful biological antioxidant properties. In order to extend the shelf life of sunflower oil, it is generally subjected to a refining process that can affect these desirable compounds. The main purpose of this study was to determine the effect of this chemical/physical refining process on selected minor components of sunflower oil in order to establish the nutritional quality and health properties of the oil. The oxidative stability, contents of fatty acids, tocopherols, phytosterols, reducing capacity, β-carotene, chlorophyll, and squalene were studied during six refining steps. Quantitative data showed the evolution of oil quality according to its degree of refinement. The results showed a significant decrease for all of the minor compounds analyzed, with losses in carotenoids of 98.6%, 8.5% in tocopherols, 19.5% in phytosterols and 45.0% in squalene. The highest reductions were recorded for the compounds that alter the most the visual aspects of the oil (waxes, carotenoids and chlorophylls) whereas reduction was limited for the compounds with no impact on the organoleptic quality. The losses in the compounds of health interest should be minimized by improving the refining processes and/or having a greater content of those molecules in crude oil by breeding new performing varieties.

Minor compounds in vegetable oils are of health interest due to their powerful biological antioxidant properties. In order to extend the shelf life of sunflower oil, it is generally subjected to a refining process that can affect these desirable compounds. The main purpose of this study was to determine the effect of this chemical/physical refining process on selected minor components of sunflower oil in order to establish the nutritional quality and health properties of the oil. The oxidative stability, contents of fatty acids, tocopherols, phytosterols, reducing capacity, β-carotene, chlorophyll, and squalene were studied during six refining steps. Quantitative data showed the evolution of oil quality according to its degree of refinement. The results showed a significant decrease for all of the minor compounds analyzed, with losses in carotenoids of 98.6%, 8.5% in tocopherols, 19.5% in phytosterols and 45.0% in squalene. The highest reductions were recorded for the compounds that alter the most the visual aspects of the oil (waxes, carotenoids and chlorophylls) whereas reduction was limited for the compounds with no impact on the organoleptic quality. The losses in the compounds of health interest should be minimized by improving the refining processes and/or having a greater content of those molecules in crude oil by breeding new performing varieties.

Pesticides have long been used in agriculture and household treatments. Pesticide residues can be found in biological samples for both the agriculture workers through direct exposure but also to the general population by indirect exposure. There is also evidence of pesticide contamination in utero and trans-generational impacts. Whilst acute exposure to pesticides has long been associated with endocrine perturbations, chronic exposure with low doses also increases the prevalence of metabolic disorders such as obesity or type 2 diabetes. Dysmetabolism is a low-grade inflammation disorder and as such the microbiota plays a role in its etiology. It is therefore important to fully understand the role of microbiota on the genesis of subsequent health effects. The digestive tract and mostly microbiota are the first organs of contact after oral exposure. The objective of this review is thus to better understand mechanisms that link pesticide exposure, dysmetabolism and microbiota. One of the key outcomes on the microbiota is the reduced Bacteroidetes and increased Firmicutes phyla, reflecting both pesticide exposure and risk factors of dysmetabolism. Other bacterial genders and metabolic activities are also involved. As for most pathologies impacting microbiota (including inflammatory disorders), the role of prebiotics can be suggested as a prevention strategy and some preliminary evidence reinforces this axis.

The intestinal microbiota has a key role in human health via the interaction with the somatic and immune cells in the digestive tract environment. Food, through matrix effect, nutrient and non-nutrient molecules, is a key regulator of microbiota diversity. As a food contaminant, the pesticide chlorpyrifos (CPF) has an effect on the composition of the intestinal microbiota and induces perturbation of microbiota. Prebiotics (and notably inulin) are known for their ability to promote an equilibrium of the microbiota that favours saccharolytic bacteria. The SHIME® dynamic in vitro model of the human intestine was exposed to CPF and inulin concomitantly for 30 days, in order to assess variations in both the bacterial populations and their metabolites. Various analyses of the microbiota (notably temporal temperature gradient gel electrophoresis) revealed a protective effect of the prebiotic through inhibition of the enterobacterial (E. coli) population. Bifidobacteria were only temporarily inhibited at D15 and recovered at D30. Although other potentially beneficial populations (lactobacilli) were not greatly modified, their activity and that of the saccharolytic bacteria in general were highlighted by an increase in levels of short-chain fatty acids and more specifically butyrate. Given the known role of host-microbiota communication, CPF's impact on the body's homeostasis remains to be determined.

Previous work have indicated a lipid-lowering effect of esterified astaxanthin (AX) from algae Haematococcus pluvialis . The aim of this study was to set up a murine model of pre-obesity diet-induced dyslipidaemia to investigate the lipid-lowering effect of free-form AX from yeast Phaffia rhodozyma fermentation. After 6 weeks on high-fat diet, 32 male C57BL/6 mice were divided into 4 groups fed (1) a standard or (2–4) a high-fat diet (HFD) supplemented or not with AX at 0.03% or 0.06% for 8 weeks. Animals were anesthetized and sacrificed and biological samples (plasma and internal organs) collected and stored at −80 °C. The plasma concentrations of triglycerides and cholesterol were determined and gene expression measured for markers of energy metabolism in the liver and adipose tissue. Statistical analyses were performed using SPSS software and the significance set at p

IntroductionThe loss of autonomy in elderly varies according to the individual health status, but also to the social and psychological environment. Multiple risk factors play a role, including limited access to a balanced diet, physical inactivity or a poor social network. Prevention programs must therefore be based on a multidimensional approach, but are rarely studied with regard to their effectiveness.Materials and methodsThe objective of the Auton'Al 60 program is to prevent the loss of autonomy related to diet, physical activity and mental health in elderly, aged 60 to 89, in the county of Oise, North of France. Between February and July 2018, 7 different prevention workshops were conducted in 5 geographical areas (urban and rural). A blog and a monthly newsletter have been created to limit the loss to follow- up. Evaluation was based on an in-depth interview at T0 inquiring about the level of autonomy, the dietary habits and the health status, as well as on 2 self-administered questionnaires during and at the end of the program. In addition, each workshop has been evaluated separately according to key indicators. Statistical analysis was performed using SPSS 17.Results69 workshops have been completed during 5 months. In total, 91 subjects (27.8% men - 71.9% women) participated in at least one workshop, with a mean age of 69.1 years (± 6.3). 72.6% of the subjects were present at 6 or 7 workshops, and 49.5% participated in all activities. A state of loss of autonomy was reported by 6.7% of the participants. 32.6% of the population were chronic-disease-free and 43.8% had a normal BMI (kg / m2). The prevalence of obesity was 15.7%. The program showed effectiveness to decrease the consumption of high-fat products in 52.9% as well as the consumption of sugary products in 60.9% of the participants. Furthermore, 23.2% of the subjects started a new social activity during the program. However, compared to other age groups observed fragility seemed to be particularly high in elderly aged from 66 to 69 years.ConclusionThe Auton'Al 60 program confirms the heterogeneity in the level of autonomy, health status and health behavior in elderly. The multidimensional approach has shown satisfactory effectiveness. Prevention strategies have been developed for isolated or low-income subjects and are under current evaluation.

International audience; Acacia gum, known as gum Arabic (GA), is a hydrocolloid complex, polysaccharide-based gum exudate. The gum is secreted by the trunk, branches or fruit of Acacia trees (i.e Acacia senegal and Acacia seyal) in response to a scission, injury or fungal infection. Acacia trees are natives to dry areas of the sub-saharian region, from Senegal to East Africa, of which Sudan, Chad, and Nigeria produce nearly 95% of GA exported to the world market. The dried gummy exudate, consisting of soluble fibers of low viscosity, is an interesting edible ingredient for several industrial applications (Williams & Phillips, 2009). Thanks to its technological features, the GA is extensively used in the food, pharmaceutical, printing, textile, and cosmetic industries. Added to liquid food systems, they can adjust and improve their rheological properties. GA generally function as stabilizer, emulsifier, film former, thickener, flocculant and surfacefinishing agent. These intrinsic properties make GA a recognized food additive (E414). They are found in the production of beverages, confectionery, emulsions, flavor encapsulations, bakery products and brewing (Verbeken, Dierckx, & Dewettinck, 2003). These exceptional functional properties are thought to be tightly related to the composition and characteristics of molecular structure of GA. The molecular structure of GA consists of a mixture of highly branched and acidic polysaccharides. The main linear chain is composed of a core of 1,3linked β-D-galactopyranose monomers with branches linked through C-6 but also C-4 or C-2. The branched chains consist of galactose and arabinose terminated by rhamnose and glucuronic acid (Al-Assaf et al.

Astaxanthin is a marine carotenoid that has a number of potential health benefits, including a very strong antioxidant potential. Present in the flesh of salmonids and shellfish, its natural sources currently on the market for food supplements come from the algae Haematococcus pluvialis and krill. However other natural sources can be found and may be of interest. Cellular uptake studies were performed on Caco-2/TC7 colonic cells. The cells were cultured on a semi-permeable membrane to create a polarized and functional epithelium, representative of the intestinal barrier. Four sources of astaxanthin were selected and compared; synthetic, natural extracts from bacteria, algae or yeast. Astaxanthin was incorporated at a concentration of 5µM into mixed micelles and applied to cultured cells and concentration of astaxanthin measured by HPLC in both apical and basolateral compartments. Small variations in bioavailability were observed at 3 hours. After 6 hours, only the algae source of astaxanthin was still present in the apical compartment as the esterified form. Structure-activity relationships are further discussed. Animal experiments using yeast and algae sources in different types of matrices confirm the role of source and formulation in the bioavailability potential of astaxanthin.

The idea that sugar feeds the tumor cells is relayed by some health professionals and media alike. Patients may be torn between what they read in the media and their food preferences during and after treatment. With this survey, we aim at understanding the perception and overall consumption patterns of sugar in cancer patients together with possible physiological and psychological triggers. We decided not to include quantitative nutritional measures of the sugar consumption. The survey was distributed in a hospital setting and through a cancer support online network. Results have shown that opinion on sugar was globally "average". However, there were differences depending on sex and age. Half of the patients declared having a decreased consumption of sugar and sweet products while 26% declared an increased consumption. When looking at psychological triggers to consumption, the weight of fatigue and worry increased after cancer diagnosis compared to before. Environmental triggers such as mixed messages from health professionals or the media need to be further investigated. In line with ESPEN guidelines, we advise to maintain moderate sugar intake as part of a healthy diet to prevent malnutrition as a first line of defense against cancer-associated morbidity and mortality.

Dietary exposure to the organophosphorothionate pesticide chlorpyrifos (CPF) has been linked to dysbiosis of the gut microbiota. We therefore sought to investigate whether (i) CPF’s impact extends to the intestinal barrier and (ii) the prebiotic inulin could prevent such an effect. In vitro models mimicking the intestinal environment (the SHIME®) and the intestinal mucosa (Caco-2/TC7 cells) were exposed to CPF. After the SHIME® had been exposed to CPF and/or inulin, we assessed the system’s bacterial and metabolic profiles. Extracts from the SHIME®’s colon reactors were then transferred to Caco-2/TC7 cultures, and epithelial barrier integrity and function were assessed. We found that inulin co-treatment partially reversed CPF-induced dysbiosis and increased short-chain fatty acid production in the SHIME®. Furthermore, co-treatment impacted tight junction gene expression and inhibited pro-inflammatory signaling in the Caco-2/TC7 intestinal cell line. Whereas, an isolated in vitro assessment of CPF and inulin effects provides useful information on the mechanism of dysbiosis, combining two in vitro models increases the in vivo relevance.

The purpose of the present study was to establish the prebiotic effect of a new xylo-oligosaccharide (XOS) and of an inulin-and-XOS mixture (INU–XOS) and to determine their effect on endotoxaemia (lipopolysaccharides (LPS)) and immune parameters. In this randomised, parallel, placebo-controlled, double-blind study, sixty healthy volunteers were randomly assigned to three groups, receiving either 5 g XOS, INU–XOS (3 g inulin +1 g XOS) or an equivalent weight of wheat maltodextrin (placebo) during 4 weeks. Faecal samples were collected to assess the effects of these products on microbiota, as well as SCFA composition, enzymatic activities and secretory IgA production. Circulating LPS was measured in plasma samples, and whole blood was incubated with LPS to measure cytokine expression. Consumption of XOS alone increased the faecal concentrations of Bifidobacterium and butyrate and activities of α-glucosidase and β-glucuronidase, while decreasing the concentrations of acetate and p-cresol. Consumption of XOS in combination with inulin did not decrease the concentrations of acetate and p-cresol, but increased in addition the faecal concentrations of total SCFA and propionate. Furthermore, consumption of XOS in combination with inulin decreased LPS concentrations in blood and attenuated LPS-induced increases in gene expression in IL-1β and LPS-induced decreases in gene expression in IL-13 in blood. In conclusion, consumption of XOS alone or in combination with inulin results in beneficial albeit different changes in the intestinal microbiome on a high-fat diet. In addition, consumption of XOS in combination with inulin attenuates the proinflammatory effects of a high-fat diet in the blood of healthy subjects.

Whether or not folic acid supplementation promotes the progression of colorectal preneoplastic lesions to cancer is an important public health issue, given mandatory fortification and widespread supplemental use of folic acid in North America. We investigated the effect of folic acid supplementation on the progression of aberrant crypt foci (ACF), the earliest precursor of colorectal cancer. Male Sprague-Dawley rats (n = 152) were placed on a control diet (2 mg folic acid/kg diet) at weaning and ACF were induced by azoxymethane. Six weeks post-ACF induction, rats were randomized to receive 0, 2, 5 or 8 mg folic acid/kg diet. At 34 weeks of age, rats were killed, and colorectal tumor parameters, plasma folate and homocysteine (a sensitive inverse indicator of tissue folate status) concentrations and rectal epithelial proliferation were determined. Although the number of ACF increased as dietary folic acid levels increased (P = 0.015), the incidence of colorectal tumors did not differ significantly among the four dietary groups. However, tumor multiplicity was positively correlated with dietary folic acid levels (r = 0.32; P = 0.002) and inversely with plasma homocysteine concentrations (r = -0.32; P = 0.005). Tumor burden was positively correlated with dietary folic acid levels (r = 0.35; P = 0.001) and plasma folate concentrations (r = 0.33; P = 0.008) and inversely with plasma homocysteine concentrations (r = -0.42; P < 0.001). Rectal epithelial proliferation was positively correlated with dietary folic acid levels (r = 0.39; P < 0.001) and plasma folate concentrations (r = 0.34; P < 0.001) and inversely with plasma homocysteine concentrations (r = -0.37; P < 0.001). Our data suggest that folic acid supplementation may promote the progression of ACF to colorectal tumors.

Background: Galactooligosaccharides are selectively fermented by the beneficial member of the colonic microflora contributing to the health of the host. Objective: We assessed the prebiotic potential of a novel galactooligosaccharide produced through the action of -galactosidases, originating from a probiotic Bifidobacterium bifidum strain, against a galactooligosaccharide produced through the action of an industrial -galactosidase and a placebo. Design: Fifty-nine healthy human volunteers participated in this study. Initially, the effect of the matrix on the prebiotic properties of a commercially available galactooligosaccharide (7 g/d) was assessed during 7-d treatment periods with a 7-d washout period in between. During the second phase, 30 volunteers were assigned to a sequence of treatments (7 d) differing in the amount of the novel galactooligosaccharide (0, 3.6, or 7 g/d). Stools were recovered before and after each intervention, and bacteria numbers were determined by fluorescent in situ hybridization. Results: Addition of the novel galactooligosaccharide mixture significantly increased the bifidobacterial population ratio compared with the placebo (P 0.05), whereas 7 g/d of the novel galactooligosaccharide significantly increased the bifidobacterial ratio compared with the commercial galactooligosaccharide (P 0.05). Moreover, a significant relation (P 0.001) between the bifidobacteria proportion and the novel galactooligosaccharide dose (0, 3.6, and 7 g/d) was observed. This relation was similar to the effect of the novel galactooligosaccharide on the prebiotic index of each dose. Conclusions: This study showed that galactooligosaccharide mixtures produced with different -galactosidases show different prebiotic properties and that, by using enzymes originating from bifidobacterial species, an increase in the bifidogenic properties of the prebiotic product is achievable. Am J Clin Nutr 2008;87: 785–91.

The presence of pesticide residues in food is a public health problem. Exposure to these substances in daily life could have serious effects on the intestine-the first organ to come into contact with food contaminants. The present study investigated the impact of a low dose (1 mg/day in oil) of the pesticide chlorpyrifos (CPF) on the community structure, diversity and metabolic response of the human gut microbiota using the SHIME (R) model (six reactors, representing the different parts of the gastrointestinal tract). The last three reactors (representing the colon) were inoculated with a mixture of feces from human adults. Three time points were studied: immediately before the first dose of CPF, and then after 15 and 30 days of CPF-oil administration. By using conventional bacterial culture and molecular biology methods, we showed that CPF in oil can affect the gut microbiota. It had the greatest effects on counts of culturable bacteria (with an increase in Enterobacteria, Bacteroides spp. and clostridia counts, and a decrease in bifidobacterial counts) and fermentative activity, which were colon-segment-dependent. Our results suggest that: (i) CPF in oil treatment affects the gut microbiota (although there was some discordance between the culture-dependent and culture-independent analyses); (ii) the changes are "SHIME (R)-compartment" specific; and (iii) the changes are associated with minor alterations in the production of short-chain fatty acids and lactate.

A moderate thiamine deficiency that does not affect weight gain or produce the classical signs of thiamine deficiency may have adverse health effects. We assessed the effect of marginally thiamine-deficient diets by measuring the effects of the diets on an enzyme marker for thiamine adequacy and markers for plasma and tissue exposure to potential endogenous carbonyl toxins. Five groups of male F344 rats were fed an AIN76-based diet containing thiamine at 2, 2.9, 5.2, 11, or 18 mg/kg diet. The animals were killed at 70 days by carbon dioxide inhalation, and cardiac blood, liver, colon, and brain samples were obtained. Erythrocytes were analyzed for transketolase activity; plasma for glyoxal, methylglyoxal, hydroimidazolone, nitrotyrosine, and protein carbonyl adducts; and tissue extracts for the 3 protein adducts. Thiamine pyrophosphate–dependent transketolase activity was inversely correlated with dietary thiamine of less than 5.2 mg/kg diet. Plasma methylglyoxal and protein adduct concentrations also increased significantly at dietary thiamine levels or at thiamine level of less than 2.6 mg/kg diet. The brain, liver, and colon showed similar trends, with evident tissue specificity. Diets marginally deficient in thiamine increase the endogenous formation of carbonyl products at thiamine levels only slightly below the requirement levels, 4 mg/kg diet (0.25 mg/kJ diet).

The B vitamins are water-soluble vitamins required as coenzymes for enzymes essential for cell function. This review focuses on their essential role in maintaining mitochondrial function and on how mitochondria are compromised by a deficiency of any B vitamin. Thiamin (B1) is essential for the oxidative decarboxylation of the multienzyme branched-chain ketoacid dehydrogenase complexes of the citric acid cycle. Riboflavin (B2) is required for the flavoenzymes of the respiratory chain, while NADH is synthesized from niacin (B3) and is required to supply protons for oxidative phosphorylation. Pantothenic acid (B5) is required for coenzyme A formation and is also essential for alpha-ketoglutarate and pyruvate dehydrogenase complexes as well as fatty acid oxidation. Biotin (B7) is the coenzyme of decarboxylases required for gluconeogenesis and fatty acid oxidation. Pyridoxal (B6), folate and cobalamin (B12) properties are reviewed elsewhere in this issue. The experimental animal and clinical evidence that vitamin B therapy alleviates B deficiency symptoms and prevents mitochondrial toxicity is also reviewed. The effectiveness of B vitamins as antioxidants preventing oxidative stress toxicity is also reviewed.

We hypothesized that in marginal thiamin deficiency intracellular alpha-oxoaldehydes form macromolecular adducts that could possibly be genotoxic in colon cells; and that in the presence of oxidative stress these effects are augmented because of decreased detoxification of these aldehydes. We have demonstrated that reduced dietary thiamin in F344 rats decreased transketolase activity and increased alpha-oxoaldehyde adduct levels. The methylglyoxal protein adduct level was not affected by oral glyoxal or methylglyoxal in the animals receiving thiamin at the control levels but was markedly increased in the animals on a thiamin-reduced diet. These observations are consistent with our suggestion that the induction of aberrant crypt foci with marginally thiamin-deficient diets may be a consequence of the formation of methylglyoxal adducts.

Background: We investigated a prebiotic low-digestible carbohydrate (LDC) as a possible food ingredient to stimulate bowel functions in the treatment of inflammatory bowel disease. The study aimed to assess a fermentable dextrin fiber (Nutriose) and its relationship to the immune management of the disease and the microbiota profile in colitis-bearing piglets. Methods: In a randomized placebo-controlled parallel blind preclinical study, 32 male piglets were fed LDC (4% Nutriose) or dextrose placebo for 44 days before being challenged with trinitrobenzene sulfonic acid (TNBS) to induce colitis. We followed the microbiota profile using real-time polymerase chain reaction (PCR) targeted to 9 bacterial genera. Secretory IgA was evaluated by enzyme-linked immunosorbent assay (ELISA). Inflammatory protein profiles were monitored in blood and colonic tissues. Both histological scoring of biopsy samples and live endoscopic scoring were used to measure colitis development. Results: Prior and continuing LDC supplementation alleviated the symptoms of colitis (body weight loss, bloody stools) induced by a TNBS challenge. This effect was associated with an improvement in endoscopic and histological scores. LDC was shown to selectively downregulate some of the proinflammatory factors and their concomitant pyretic events and to stimulate the Th2-related immune pathway (IL-10 and s-IgA). Conclusions: At the dose tested, LDC is a well-tolerated prebiotic agent able to not only stimulate butyrogenic bacteria strains and reduce intestinal transit disorders and energy intake, but also to prevent chronic inflammatory intestinal injuries. Inflamm Bowel Dis 2010

A thermolyzed diet has the potential of providing exogenous oxidative stress in the form of advanced glycation end-products (AGE) and decreased thiamin. There is then a possibility that it could result in intracellular exposure to alpha-oxoaldehydes (glyoxal and methylglyoxal (MG)) with metabolic and genetic consequences. Two groups of Fischer 344 rats were fed the following diets: group A was given an AIN93G diet (control diet), while group B was given a thermolyzed AIN93G diet for 77 days. At the end of 77 days TK activity in red blood cells; glyoxal/MG levels in the plasma; glyoxal/MG HI protein adducts and dicarbonyls in the plasma, liver and colon tissues; glutathione levels of whole blood; and oxidative stress/inflammatory markers in the colon were measured. The thermolyzed diet resulted in: decreased thiamin status, increased plasma levels of glyoxal/MG and their adducts, increased protein dicarbonyls in the liver and plasma, lowered blood glutathione levels, increased infiltration of macrophages and increased colon nitrotyrosine levels. The thermolyzed diet increased the body burden of AGEs and decreased the thiamin status of the rats. This increased endogenous alpha-oxoaldehydes and oxidative stress has the potential to injure tissues that have low levels of antioxidant defenses such as the colon.

The B vitamins are water-soluble vitamins that are required as coenzymes for reactions essential for cellular function. This review focuses on the essential role of vitamins in maintaining the one-carbon transfer cycles. Folate and choline are believed to be central methyl donors required for mitochondrial protein and nucleic acid synthesis through their active forms, 5-methyltetrahydrofolate and betaine, respectively. Cobalamin (B12) may assist methyltetrahydrofolate in the synthesis of methionine, a cysteine source for glutathione biosynthesis. Pyridoxal, pyridoxine and pyridoxamine (B6) seem to be involved in the regeneration of tetrahydrofolate into the active methyl-bearing form and in glutathione biosynthesis from homocysteine. Other roles of these vitamins that are relevant to mitochondrial functions will also be discussed. However these roles for B vitamins in cell function are mostly theoretically based and still require verification at the cellular level. For instance it is still not known what B vitamins are depleted by xenobiotic toxins or which cellular targets, metabolic pathways or molecular toxic mechanisms are prevented by B vitamins. This review covers the current state of knowledge and suggests where this research field is heading so as to better understand the role vitamin Bs play in cellular function and intermediary metabolism as well as molecular, cellular and clinical consequences of vitamin deficiency. The current experimental and clinical evidence that supplementation alleviates deficiency symptoms as well as the effectiveness of vitamins as antioxidants will also be reviewed.

A library of 42 natural and synthetic flavonoids has been screened for their effect on cell proliferation and apoptosis in a human colonic cell line (HT-29). Examples of different classes of flavonoids have been screened, and the effects of hydroxylation, methoxylation and/or C-alkylation at various positions in the A- and B-rings have been assessed. Flavones and flavonols possess greater antiproliferative activity than chalcones and flavanones. With respect to structural modification of flavonoids, C-isoprenylation was by far the most effective, with substitution at the 8-position and longer chains, such as geranyl giving the best results. Finally, most compounds that significantly reduced cell survival also increased caspase activity, suggesting that at least part of their antiproliferative activity might be attributable to an apoptotic response.

A wide variety of plant-derived compounds, including the polyphenolic flavonoids, is present in the human diet or is consumed for medicinal reasons. Epidemiological and animal studies tend to suggest a protective effect of flavonoids against cardiovascular diseases and some types of cancer. Although flavonoids have been studied for about 50 years, the cellular mechanisms involved in their biological activity are still largely unknown. Antioxidant properties of the flavonoids have been postulated as a mechanism for putative protective effect against cardiovascular disease. Nevertheless, these properties alone are not sufficient to explain the anti-carcinogenic potential of these polyphenols. The mechanisms by which the molecules interact with cells or are absorbed by them are very important for determining the intracellular concentration and distribution of the metabolites to internal organs. With the exception of the cells lining the gastrointestinal tract, all other cells in the body are only exposed to flavonoid metabolites and degradation products. No previous studies have addressed this aspect of cellular exposure, except for some methylated metabolites. Within the last decade, reports on flavonoid activities have been largely associated with enzyme inhibition and anti-proliferative activity. From our recent work on the human colon cancer cell line HT29 and comparison with published studies, structure–function relationships demonstrate that antioxidant, enzyme inhibitor or anti-proliferative activities are dependent on particular structure motifs. The present review also presents a summary of mechanistic data on a few selected compounds.