S-Equol is a metabolite resulting from the conversion of daidzein, a soya phyto-oestrogen, by the gut microflora. The potential protective effects of equol in breast cancer are still under debate. Consequently, we investigated the effects of equol on DNA methylation of breast cancer susceptibility genes (BRCA1 and BRCA2) and oncosuppressors in breast cancer cell lines (MDA-MB-231 and MCF-7) and in a dystrophic breast cell line (MCF-10a) following exposure to S-equol (2 μm) for 3 weeks. We demonstrated by quantitative analysis of methylated alleles a significant decrease in the methylation of the cytosine phosphate guanine (CpG) islands in the promoters of BRCA1 and BRCA2 after the S-equol treatment in MCF-7 and MDA-MB-231 cells and a trend in MCF-10a cells. We also showed that S-equol increases BRCA1 and BRCA2 protein expression in the nuclei and the cytoplasm in MCF-7, MDA-MB-231 and MCF-10a cell lines by immunohistochemistry. The increase in BRCA1 and BRCA2 proteins was also found after Western blotting in the studied cell lines. In summary, we demonstrated the demethylating effect of S-equol on the CpG islands inside the promoters of BRCA1 and BRCA2 genes, resulting in an increase in the level of expressed oncosuppressors in breast cancer cell lines.

Indian diets derive almost 60 % of their protein from cereals with relatively low digestibility and quality. There have been several surveys of diets and protein intakes in India by the National Nutrition Monitoring Board (NNMB) over the last 25 years, in urban and rural, as well as in slum dwellers and tribal populations. Data of disadvantaged populations from slums, tribals and sedentary rural Indian populations show that the protein intake (mainly from cereals) is about 1 gm/kg/day. However, the protein intake looks less promising in terms of the protein digestibility corrected amino acid score (PDCAAS), using lysine as the first limiting amino acid, where all populations, particularly rural and tribal, appear to have an inadequate quality to their protein intake. The protein: energy (PE) ratio is a measure of dietary quality, and has been used in the 2007 WHO/FAO/UNU report to define reference requirement values with which the adequacy of diets can be evaluated in terms of a protein quality corrected PE ratio. It is likely that about one third of this sedentary rural population is at risk of not meeting their requirements. These levels of risk of deficiency are in a population with relatively low BMI populations, whose diets are also inadequate in fruits and vegetables. Therefore, while the burden of enhancing the quality of protein intake in rural India exists, the quality of the diet, in general, represents a challenge that must be met.

Cisplatin (cis-diamminedichloroplatinum (II) (CDDP)) is a commonly used chemotherapeutic drug for the treatment of numerous forms of cancer, but it has pronounced adverse effects, namely nephrotoxicity, ototoxicity, neurotoxicity, hepatotoxicity, diarrhoea and nausea. CDDP-induced emesis and diarrhoea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants, possesses multiple biological activities, such as antioxidant and anti-inflammatory properties. In the present study, we investigated the protective effect of chrysin against CDDP-induced jejunal toxicity. The plausible mechanism of CDDP-induced jejunal toxicity includes oxidative stress, p53 and apoptosis via up-regulating the expression of caspase-6 and -3. Chrysin was administered to Wistar rats orally in maize oil. A single intraperitoneal injection of CDDP was given and the animals were killed after 24 h of CDDP injection. Chrysin ameliorated CDDP-induced lipid peroxidation, increase in xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6-phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin attenuated CDDP-induced goblet cell disintegration, enhanced expression of p53 and apoptotic tissue damage. Histological findings further substantiated the protective effects of chrysin against CDDP-induced damage in the jejunum. The results of the present study demonstrate that oxidative stress and apoptosis are closely associated with CDDP-induced toxicity and chrysin shows the protective efficacy against CDDP-induced jejunum toxicity possibly via attenuating the oxidative stress and apoptotic tissue damage.

Lipopolysaccharide (LPS) may play an important role in chronic diseases through the activation of inflammatory responses. The type of diet consumed is of major concern for the prevention and treatment of these diseases. Evidence from animal and human studies has shown that LPS can diffuse from the gut to the circulatory system in response to the intake of high amounts of fat. The method by which LPS move into the circulatory system is either through direct diffusion due to intestinal paracellular permeability or through absorption by enterocytes during chylomicron secretion. Considering the impact of metabolic diseases on public health and the association between these diseases and the levels of LPS in the circulatory system, this review will mainly discuss the current knowledge about high-fat diets and subclinical inflammation. It will also describe the new evidence that correlates gut microbiota, intestinal permeability and alkaline phosphatase activity with increased blood LPS levels and the biological effects of this increase, such as insulin resistance. Although the majority of the studies published so far have assessed the effects of dietary fat, additional studies are necessary to deepen the understanding of how the amount, the quality and the structure of the fat may affect endotoxaemia. The potential of food combinations to reduce the negative effects of fat intake should also be considered in future studies. In these studies, the effects of flavonoids, prebiotics and probiotics on endotoxaemia should be investigated. Thus, it is essential to identify dietetic strategies capable of minimising endotoxaemia and its postprandial inflammatory effects.

Maternal exposure to environmental agents throughout pregnancy may change certain metabolic processes during the offspring's mammary gland development and alter the epigenome. This may predispose the offspring to breast cancer later in life. The purpose of the present study was to examine the effect of maternal protein restriction on the regulation of cyclin-dependent kinase inhibitor 1 (p21) gene expression in the mammary gland of rat offspring. Timed-mated Sprague–Dawley rats were fed one of the two isoenergetic diets, control (C, 18 % casein) or low protein (LP, 9 % casein), during gestation. Compared with the C group, LP offspring showed a decrease of p21 in the mammary gland at both the mRNA and protein levels. Chromatin immunoprecipitation assay demonstrated that the down-regulation of p21 transcription in LP offspring was associated with reduced acetylation of histone H3 and dimethylation of H3K4 within the p21 promoter region, but was not associated with acetylation of histone H4 or histone methylation. DNA methylation analysis using bisulphite sequencing did not detect differences in methylation at the p21 promoter between the offspring of the C and LP groups. We conclude that maternal protein restriction inhibits p21 gene expression in the mammary gland of offspring through histone modifications at the promoter region of the p21 gene.

Contrary to concerns that fructose may have adverse metabolic effects, there is evidence that small, ‘catalytic’ doses ( ≤ 10 g/meal) of fructose decrease the glycaemic response to high-glycaemic index meals in human subjects. To assess the longer-term effects of ‘catalytic’ doses of fructose, we undertook a meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library. Analyses included all controlled feeding trials ≥ 7 d featuring ‘catalytic’ fructose doses ( ≤ 36 g/d) in isoenergetic exchange for other carbohydrates. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences (MD) with 95 % CI. Heterogeneity was assessed by the Q statistic and quantified by I2. The Heyland Methodological Quality Score assessed study quality. A total of six feeding trials (n 118) met the eligibility criteria. ‘Catalytic’ doses of fructose significantly reduced HbA1c (MD − 0·40, 95 % CI − 0·72, − 0·08) and fasting glucose (MD − 0·25, 95 % CI − 0·44, − 0·07). This benefit was seen in the absence of adverse effects on fasting insulin, body weight, TAG or uric acid. Subgroup and sensitivity analyses showed evidence of effect modification under certain conditions. The small number of trials and their relatively short duration limit the strength of the conclusions. In conclusion, this small meta-analysis shows that ‘catalytic’ fructose doses ( ≤ 36 g/d) may improve glycaemic control without adverse effects on body weight, TAG, insulin and uric acid. There is a need for larger, longer ( ≥ 6 months) trials using ‘catalytic’ fructose to confirm these results.

Zingiber officinale (ZO), commonly known as ginger, has been traditionally used in the treatment of diabetes mellitus. Several studies have reported the hypoglycaemic properties of ginger in animal models. The present study evaluated the antihyperglycaemic effect of its aqueous extract administered orally (daily) in three different doses (100, 300, 500 mg/kg body weight) for a period of 30 d to streptozotocin (STZ)-induced diabetic rats. A dose-dependent antihyperglycaemic effect revealed a decrease of plasma glucose levels by 38 and 68 % on the 15th and 30th day, respectively, after the rats were given 500 mg/kg. The 500 mg/kg ZO significantly (P < 0·05) decreased kidney weight (% body weight) in ZO-treated diabetic rats v. control rats, although the decrease in liver weight (% body weight) was not statistically significant. Kidney glycogen content increased significantly (P < 0·05) while liver and skeletal muscle glycogen content decreased significantly (P < 0·05) in diabetic controls v. normal controls. ZO (500 mg/kg) also significantly decreased kidney glycogen (P < 0·05) and increased liver and skeletal muscle glycogen in STZ-diabetic rats when compared to diabetic controls. Activities of glucokinase, phosphofructokinase and pyruvate kinase in diabetic controls were decreased by 94, 53 and 61 %, respectively, when compared to normal controls; and ZO significantly increased (P < 0·05) those enzymes' activities in STZ-diabetic rats. Therefore, the present study showed that ginger is a potential phytomedicine for the treatment of diabetes through its effects on the activities of glycolytic enzymes.

Cereals and legumes are staple foods in India and are limiting in lysine and sulphur amino acids, respectively. Available lysine loss, due to Maillard-type reactions that may occur during food preparation, exacerbates the problem of lysine deficiency particularly in cereals. Consequently, determining the contents of digestible essential amino acids, particularly lysine, is important. True ileal digestibilities of most amino acids (including total and reactive lysine) were determined for ten food ingredients and eleven foods commonly consumed in India. Semi-synthetic diets each containing either an ingredient or the prepared food as the sole protein source were formulated to contain 100 g kg− 1 protein (75 g kg− 1 for rice-based diets) and fed to growing rats. Titanium dioxide was included as an indigestible marker. Digesta were collected and the amino acid content (including reactive lysine) of diets and ileal digesta determined. Available (digestible reactive) lysine content ranged from 1·9–15·4 g kg− 1 and 1·8–12·7 g kg− 1 across the ingredients and prepared foods respectively. True ileal amino acid digestibility varied widely both across ingredients and prepared foods for each amino acid (on average 60–92 %) and across amino acids within each ingredient and prepared food (overall digestibility 31–96 %). Amino acid digestibility was low for many of the ingredients and prepared foods and consequently digestibility must be considered when assessing the protein quality of poorer quality foods. Given commonly encountered daily energy intakes for members of the Indian population, it is estimated that lysine is limiting for adults in many Indian diets.

The development of lower-glycaemic index (GI) foods requires simple, palatable and healthy strategies. The objective of the present study was to determine the most effective dose of a novel viscous fibre supplement (PGX®) to be added to starchy foods to reduce their GI. Healthy subjects (n 10) consumed glucose sugar (50 g in water × 3) and six starchy foods with a range of GI values (52–72) along with 0 (inert fibre), 2·5 or 5 g granular PGX® dissolved in 250 ml water. GI testing according to ISO Standard 26 642-2010 was used to determine the reduction in GI. PGX® significantly reduced the GI of all six foods (P < 0·001), with an average reduction of 19 % for the 2·5 g dose and 30 % for the 5 g dose, equivalent to a reducing the GI by 7 and 15 units, respectively. Consuming small quantities of the novel functional fibre PGX®, mixed with water at the start of a meal, is an effective strategy to reduce the GI of common foods.

Consumption of a high-fat diet (HFD) enriched in saturated fat induces excessive weight gain due to adiposity, which can lead to metabolic complications, as well as increased risk of fatty liver disease and CVD. The present study investigated the underlying mechanism and dose–response effects of resveratrol (RV) on obesity, hepatic steatosis and dyslipidaemia in mice fed a HFD. Male C57BL/6J mice were fed a normal diet or a HFD (20 % fat, w/w) combined with 0·005 or 0·02 % (w/w) RV for 10 weeks. As expected, mice fed a HFD developed obesity, as shown by increased body weight gain, visceral fat, hepatic fat and plasma cholesterol. RV significantly reduced visceral fat and plasma NEFA. In the liver of HFD-fed mice, RV significantly reduced TAG and cholesterol, as well as lipid droplet number and size. A low dose of RV (0·005 %) appeared to be more effective than a higher dose of RV (0·02 %) for suppressing adiposity and hepatic steatosis development with a significant decrease in body weight gain, plasma TAG and total cholesterol levels. These changes were seemingly attributable to a suppression of the fatty acid (FA) synthase, glucose-6-phosphate dehydrogenase, and phosphatidate phosphohydrolase and/or an activation of FA oxidation in the liver and epididymal adipose tissue. In conclusion, daily consumption of a low dose of RV is effective for protecting against diet-induced obesity, hepatic steatosis and dyslipidaemia in HFD-fed mice.

The aim of the present study was to evaluate the anti-diabetic mechanism of Asparagus officinalis, a dietary agent used for the management of diabetes. Streptozotocin (90 mg/kg) was injected in 2-d-old Wistar rat pups to induce non-obese type 2 diabetes. After confirmation of diabetes on the 13th week, diabetic rats were treated with a methanolic extract of A. officinalis seeds (250 and 500 mg/kg per d) or glibenclamide for 28 d. After the treatment, fasting blood glucose, serum insulin and total antioxidant status were measured. The pancreas was examined by haematoxylin–eosin staining and immunostained β- and α-cells were observed using a fluorescence microscope. Treatment of the diabetic rats with the A. officinalis extract at doses of 250 and 500 mg/kg suppressed the elevated blood glucose in a dose- and time-dependent manner. The 500 mg/kg, but not 250 mg/kg, dose significantly improved serum insulin levels in the diabetic rats. The insulin:glucose ratio was significantly increased at both doses in the A. officinalis-treated rats. Both qualitative and quantitative improvements in β-cell function were found in the islets of the A. officinalis-treated rats. The extract showed potent antioxidant activity in an in vitro assay and also improved the total antioxidant status in vivo. In most cases, the efficacy of A. officinalis (500 mg/kg) was very similar to a standard anti-diabetic drug, glibenclamide. Thus, the present study suggests that A. officinalis extract exerts anti-diabetic effects by improving insulin secretion and β-cell function, as well as the antioxidant status.

The aims of the present study were to examine the serum amino acid profiles in obese and non-obese women and investigate the relationships between the serum amino acids and inflammation and oxidative stress in a human case–control study. Serum amino acids, inflammatory biomarkers (C-reactive protein and IL-6) and oxidative biomarkers (superoxide dismutase, malondialdehyde and glutathione peroxidase) were measured and compared in 235 obese women and 217 non-obese controls. The relationships between serum amino acids and inflammatory and oxidative biomarkers were examined using multiple linear regression. Among the amino acids determined, serum histidine, arginine, threonine, glycine, lysine and serine were found to be significantly lower in obese women as compared to non-obese controls (P < 0·001). The difference was the greatest for histidine (P < 0·001). In obese women, both histidine and arginine were negatively associated with inflammation and oxidative stress. In non-obese controls, histidine was negatively associated with oxidative stress. The findings in this study indicate that the metabolism of amino acids is abnormal in obese women in whom histidine and arginine have close relationships with inflammation and oxidative stress.

Foods high in monounsaturated fat, such as olive oil, and endurance exercise are both known to independently reduce postprandial TAG concentrations. We examined the combined effects of exercise and dietary fat composition on postprandial TAG concentrations in nine healthy pre-menopausal females (age 26·8 (sd 3·3) years, BMI 22·3 (sd 2·0) kg/m2). Each participant completed four, 2 d trials in a randomised order: (1) butter–no exercise, (2) olive oil–no exercise, (3) butter–exercise, (4) olive oil–exercise. On day 1 of the exercise trials, participants walked or ran on a treadmill for 60 min. On the no-exercise trials, participants rested on day 1. On day 2 of each trial, participants rested and consumed an olive oil meal (saturated fat 15 % and unsaturated fat 85 %) or a butter meal (saturated fat 71 % and unsaturated fat 29 %) for breakfast. Venous blood samples were obtained in the fasted state and for 6 h postprandially on day 2. A significant main effect on physical activity (exercise or control) was obtained for plasma TAG concentration (three-way ANOVA, P = 0·043), and the total area under the concentration v. time curve for TAG was 26 % lower on the olive oil–exercise trial (4·40 (sd 0·40) mmol × 6 h/l) than the butter–no exercise trial (5·91 (sd 1·01) mmol × 6 h/l) (one-way ANOVA, P = 0·029). These findings suggest that the combination of exercise and a preference for monounsaturated dietary fat intake in the form of olive oil may be most beneficial for reducing postprandial TAG concentrations.

Consumption of Phaseolus vulgaris bean species such as pinto, black, navy or kidney may be beneficial in the prevention and treatment of chronic diseases. In particular, conditions that are promoted by increased glycaemic stress (hyperglycaemia and hyperinsulinaemia) including diabetes, CVD and cancer seem to be reduced in individuals who eat more of these beans. The present paper discusses the influence of P. vulgaris species on glycaemic response and the impact that relationship may have on the risk of developing diabetes, CVD and cancer.

There is an increased interest in investigating the relationship between the gut microbiota and energy homeostasis. Probiotics are health beneficial microbes mainly categorised under the genus Lactobacillus and Bifidobacterium, which when administered in adequate amounts confer health benefits to the host, and have been implicated in various physiological functions. The potential role of probiotics in energy homeostasis is a current and an emerging area of research. In the present study, Lactobacillus acidophilus NCDC 13 was used to evaluate its anti-obesity potential in diet-induced obese (C57BL/6) mice. The probiotic bacterial culture was administered in Indian yogurt preparation called ‘dahi’, prepared using native starter cultures, and compared with control dahi containing only dahi starter cultures. The dietary intervention was followed for 8 weeks, and whole-body fat composition, and liver and muscle adiposity were measured using MRI. Changes in gut microbiota were assessed by fluorescent in situ hybridisation in faeces and caecal contents. The feeding of the probiotic brought no changes in body-weight gain, food and dahi intake when compared with the control dahi-fed animals. No significant changes in body fat composition, liver and muscle adiposity were also observed. At the end of the dietary intervention, a significant increase (P < 0·05) in the number of total Bifidobacterium was observed in both faeces and caecal contents of mice as a result of probiotic dahi administration. Thus, L. acidophilus NCDC 13 supplementation could be beneficial in shifting the gut microbiota balance positively. However, its anti-obesity potential could not be established in the present study and warrants further exploration.

Over the past 20 years, the popularity of soyafoods has increased in part because of research suggesting that these foods convey health benefits independent of their nutrient content. For example, in 1999, the US Food and Drug Administration approved a health-claim for soyafoods and CHD based on the hypocholesterolaemic effects of soya protein. However, soyafoods have become controversial in recent years because of concerns that their uniquely rich phyto-oestrogen (isoflavone) content may cause untoward effects in some individuals. Most notable in this regard is the concern that soyafoods are contraindicated for breast cancer patients and women at high risk of developing this disease. Furthermore, the hypocholesterolaemic effects of soya protein have been challenged. However, the results of recently published meta-analyses indicate that soya protein directly lowers circulating LDL-cholesterol levels by approximately 4 %. There is also intriguing evidence that soyafoods reduce CHD risk independent of their effects on lipid levels. In regard to the breast cancer controversy, recently published clinical and epidemiological data do not support observations in rodents that soyabean isoflavones increase breast cancer risk. In postmenopausal women, isoflavone exposure does not adversely affect breast tissue density or breast cell proliferation. Furthermore, both US and Chinese prospective epidemiological studies show that post-diagnosis soya consumption is associated with an improved prognosis. Therefore, soyafoods should be considered by women as healthy foods to include in diets aimed at reducing the risk of CHD regardless of their breast cancer status.

Dietary Zn recommendations vary widely across Europe due to the heterogeneity of approaches used by expert panels. Under the EURopean micronutrient RECommendations Aligned (EURRECA) consortium a protocol was designed to systematically review and undertake meta-analyses of research data to create a database that includes ‘best practice’ guidelines which can be used as a resource by future panels when setting micronutrient recommendations. As part of this process, the objective of the present study was to undertake a systematic review and meta-analysis of previously published data describing the relationship between Zn intake and status in adults. Searches were performed of literature published up to February 2010 using MEDLINE, Embase and the Cochrane Library. Data extracted included population characteristics, dose of Zn, duration of study, dietary intake of Zn, and mean concentration of Zn in plasma or serum at the end of the intervention period. An intake–status regression coefficient ($\circ {>\beta }$$$) was estimated for each individual study, and pooled meta-analysis undertaken. The overall pooled $\circ {>\beta }$$$ for Zn supplementation on serum/plasma Zn concentrations from randomised controlled trials and observational studies was 0·08 (95 % CI 0·05, 0·11; P < 0·0001; I2 84·5 %). An overall $\circ {>\beta }$$$ of 0·08 means that for every doubling in Zn intake, the difference in Zn serum or plasma concentration is $2^{ \circ {>\beta }}$$$ (20·08 = 1·06), which is 6 %. Whether the dose–response relationship, as provided in the present paper, could be used as either qualitative or quantitative evidence to substantiate the daily Zn intake dose necessary to achieve normal or optimal levels of biomarkers for Zn status remains a matter of discussion.

In the present study, we aimed to examine the effects of soya oligosaccharides (SOS) and soya oligopeptides (SOP) on blood lipid levels, release of vasoactive substances, antioxidant activity and faecal bile acid (FBA) excretion in rats fed a high-fat diet (HFD). Male Sprague–Dawley rats were evenly divided into five groups according to diets as follows: regular diet (control), HFD, HFD enriched with 2 % of SOS (SOS), HFD enriched with 3 % of SOP (SOP) and HFD enriched with 2 % SOS and 3 % SOP (SOSP). The results showed that SOS and SOP significantly reduced plasma total cholesterol, LDL-cholesterol and TAG, whereas HDL-cholesterol concentration was significantly increased. Furthermore, SOS and SOP reduced plasma apoB, apoE and the apoB:apoAI ratio, whereas apoAI was significantly increased. Moreover, SOS and SOP also reduced plasma thromboxane A2 (TXA2) and the TXA2:prostacyclin (PGI2) ratio, whereas plasma PGI2 and nitric oxide were significantly increased. In addition, SOS and SOP significantly reduced serum and liver malondialdehyde concentrations and increased FBA excretion. However, we did not observe obvious influences of SOS and SOP on superoxide dismutase activities in the liver of HFD-fed rats. The combination of 2 % SOS and 3 % SOP showed a more marked effect than SOS or SOP alone in improving the lipid profile, release of vasoactive substances and increasing FBA excretion (P < 0·05). In summary, SOS and SOP might help prevent atherosclerosis through improving abnormal blood lipid levels, regulating vasoactive substances and protecting against oxidative stress.

Pulses are grain legumes that have sustained the civilisations of the world throughout their development; yet this staple food crop has fallen into disuse, particularly in Westernised societies, and decreased consumption parallels increased prevalence of CVD. The objective of the present study was to identify mechanisms that account for the cardioprotective activity of dry bean (Phaseolus vulgaris L.), one of the four primary pulse crops, which is widely produced and consumed globally. Laboratory assays that can be used for in vivo screening of dry beans and other pulses to identify those with the greatest potential to benefit human health are also reported. Sprague–Dawley rats and a diet-induced obesity model in C57Bl/6 mice were used to assess the effect of cooked dry bean incorporated into a purified diet formulation on plasma lipids and hepatic proteins involved in the regulation of lipid biosynthesis. In both animal species, short-term feeding of a bean-containing diet reduced plasma total cholesterol and LDL-cholesterol without affecting HDL-cholesterol or total TAG. Mechanisms associated with cholesterol catabolism and excretion are the likely targets of the bean effect. Unexpectedly, bean-fed obese mice experienced weight loss as well as an improved plasma lipid profile within a 12 d time frame. These findings support the use of short-term (7–14 d) assays to investigate mechanisms that account for the cardioprotective and weight regulatory effects of dry bean and to screen dry bean germplasm resources for types of bean with high protective activity. These same assays can be used to identify the bioactive components of bean that account for the observed effects.

Colorectal cancer (CRC) is a leading cause of preventable cancer deaths worldwide, with dietary factors being recognised as key risk modifiers. Foods containing dietary fibre are protective to a degree that the World Cancer Research Fund classifies the evidence supporting their consumption as ‘convincing’. The mechanisms by which fibre components protect against CRC remain poorly understood, especially their interactions with the gut microbiome. Fibre is a composite of indigestible plant polysaccharides and it is emerging that fermentable fibres, including resistant starch (RS), are particularly important. RS fermentation induces SCFA production, in particular, relatively high butyrate levels, and in vitro studies have shown that this acid has strong anti-tumorigenic properties. Butyrate inhibits proliferation and induces apoptosis of CRC cell lines at physiological concentrations. These effects are attributed to butyrate's ability to alter gene transcription by inhibiting histone deacetylase activity. However, the more recent discovery of G-protein coupled receptors that bind butyrate and other SCFA and data obtained from proteomic and genomic experiments suggest that alternative pathways are involved. Here, we review the mechanisms involved in butyrate-induced apoptosis in CRC cells and, additionally, the potential role this SCFA may play in mediating key processes in tumorigenesis including genomic instability, inflammation and cell energy metabolism. This discussion may help to inform the development of strategies to lower CRC risk at the individual and population levels.