No effect of monthly supplementation with 12000 IU, 24000 IU or 48000 IU vitamin D3 for one year on muscle function: The vitamin D in older people study.

Vitamin D plays a role in muscle function through genomic and non-genomic processes. The objective of this RCT was to determine the effect of monthly supplemental vitamin D3 onmuscle function in 70+ years old adults. Participants (n = 379) were randomized to receive, 12,000 IU, 24,000 IU or 48,000 IU of vitamin D3 monthly for 12 months. Standardized Hand Grip Strength (GS) and Timed-Up and Go (TUG) were measured before and after vitamin D3 supplementation. Fasting total plasma 25 hydroxyvitamin D (25OHD) and Parathyroid Hormone (PTH) concentrations were measured by Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS) and immunoassay, respectively. Baseline plasma 25OHD concentrations were 41.3 (SD 19.9), 39.5 (SD 20.6), 38.9 (SD 19.7) nmol/L; GS values were 28.5 (SD 13.4), 28.8 (SD 13.0) and 28.1 (SD 12.1) kg and TUG test values were 10.8 (SD 2.5), 11.6 (SD 2.9) and 11.9 (SD 3.6) s for the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. Baseline plasma 25OHD concentration < 25 nmol/L was associated with lower GS (P = 0.003). Post-interventional plasma 25OHD concentrations increased to 55.9 (SD 15.6), 64.6 (SD15.3) and 79.0 (SD 15.1) nmol/L in the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively and there was a significant dose-related response in post-interventional plasma 25OHD concentration (p<0.0001). Post-interventional GS values were 24.1 (SD 10.1), 26.2 (SD10.6) and 25.7 (SD 9.4) kg and TUG test values were 11.5 (SD 2.6), 12.0 (SD 3.7) and 11.9 (SD 3.2) s for 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. The change (Δ) in GS and TUG from pre to post-intervention was not different between treatment groups before and after the adjustment for confounders, suggesting no effect of the intervention. Plasma 25OHD concentration was not associated with GS and TUG test after supplementation. In conclusion, plasma 25OHD concentration < 25 nmol/L was associated with lower GS at baseline. However, monthly vitamin D3 supplementation with 12,000 IU, 24,000 IU and 48,000 IU, for 12 months had no effect on muscle function in older adults aged 70+ years. Trial Registration : EudraCT 2011-004890-10 and ISRCTN35648481.

Effects of vitamin C supplementation on glycaemic control: a systematic review and meta-analysis of randomised controlled trials.

Randomised controlled trials (RCTs) have observed contrasting results on the effects of vitamin C on circulating biomarkers of glycaemic and insulin regulation. We conducted a systematic review and meta-analysis of RCTs testing the effect of vitamin C administration on glucose, HbA1c and insulin concentrations. Four databases (PubMed, Embase, Scopus and Cochrane Library) were used to retrieve RCTs published from inception until April 2016 and testing the effects of vitamin C in adult participants. The screening of 2008 articles yielded 22 eligible studies (937 participants). Overall, vitamin C did not modify glucose, HbA1c and insulin concentrations. However, subgroup analyses showed that vitamin C significantly reduced glucose concentrations (-0.44 mmol/l, 95% CI: -0.81, -0.07, P=0.01) in patients with type 2 diabetes and in interventions with a duration greater than 30 days (-0.53%, 95% CI: -0.79, -0.10, P=0.02). Vitamin C administration had greater effects on fasting (-13.63 pmol/l, 95% CI: -22.73, -4.54, P<0.01) compared to postprandial insulin concentration. Meta-regression analyses showed that age was a modifier of the effect of vitamin C on insulin concentration. Furthermore, the effect size was associated with baseline BMI and plasma glucose levels, and with the duration of the intervention. In conclusion, greater reduction in glucose concentrations observed in patients with diabetes, older individuals and with more prolonged supplementation. Personalised interventions with vitamin C may represent a feasible future strategy to enhance benefits and efficacy of interventions. Nevertheless, results need to be interpreted cautiously due to limitations in the primary studies analysed.

Comparison of the portion size and frequency of consumption of 156 foods across seven European countries: insights from the Food4ME study.

There are no standardised serving/portion sizes defined for foods consumed in the European Union (EU). Typical serving sizes can deviate significantly from the 100 g/100 ml labelling specification required by the EU legislation. Where the nutritional value of a portion is specified, the portion size is determined by the manufacturers. Our objective was to investigate the potential for standardising portion sizes for specific foods, thereby ensuring complementarity across countries. We compared portion size for 156 food items measured using a food frequency questionnaire across the seven countries participating in the Food4me study. The probability of consuming a food and the frequency of consumption differed across countries for 93% and 58% of the foods, respectively. However, the individual country mean portion size differed from the average across countries in only 16% of comparisons. Thus, although dietary choices vary markedly across countries, there is much less variation in portion sizes. Our results highlight the potential for standardisation of portion sizes on nutrition labels in the EU.

Serum 25-hydroxyvitamin D concentration and its determinants in the very old: the Newcastle 85+ Study.

SUMMARY: Data on vitamin D status in very old adults are lacking. The aim of this study was to assess 25-hydroxyvitamin D [25(OH)D] concentrations and its predictors in 775 adults aged 85 years old living in North-East England. Low 25(OH)D was alarmingly high during winter/spring months, but its biological significance is unknown. INTRODUCTION: Despite recent concerns about the high prevalence of vitamin D deficiency in much of the British adult and paediatric population, there is a dearth of data on vitamin D status and its predictors in very old adults. The objective of the present study was to describe vitamin D status and its associated factors in a broadly representative sample of very old men and women aged 85 years living in the North East of England (55° N). METHODS: Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were analysed in 775 participants in the baseline phase of the Newcastle 85+ cohort study. Season of blood sampling, dietary, health, lifestyle and anthropometric data were collected and included as potential predictors of vitamin D status in ordinal regression models. RESULTS: Median serum 25(OH)D concentrations were 27, 45, 43 and 33 nmol/L during spring, summer, autumn and winter, respectively. The prevalence of vitamin D deficiency according to North American Institute of Medicine guidelines [serum 25(OH)D <30 nmol/L] varied significantly with season with the highest prevalence observed in spring (51%) and the lowest prevalence observed in autumn (23%; P < 0.001). Reported median (inter-quartile range) dietary intakes of vitamin D were very low at 2.9 (1.2-3.3) µg/day. In multivariate ordinal regression models, non-users of either prescribed or non-prescribed vitamin D preparations and winter and spring blood sampling were associated with lower 25(OH)D concentrations. Dietary vitamin D intake, disability score and disease count were not independently associated with vitamin D status in the cohort. CONCLUSION: There is an alarming high prevalence of vitamin D deficiency (<30 nmol/L) in 85-year-olds living in North East England at all times of the year but particularly during winter and spring. Use of vitamin D containing preparations (both supplements and medications) appeared to be the strongest predictor of 25(OH)D concentrations in these very old adults.

Ageing modifies the effects of beetroot juice supplementation on 24-hour blood pressure variability: An individual participant meta-analysis.

OBJECTIVES: Abnormal circadian oscillations of blood pressure (BP) and nocturnal-diurnal BP differences (i.e., dipping) increase cardiovascular risk. Whether inorganic nitrate supplementation influences 24-hr BP variability is currently unknown. We studied the effects of high-nitrate beetroot juice supplementation on BP variability measured by 24-hr ambulatory BP monitoring (24-hr ABPM) in older subjects. METHODS: Data from four independent randomised clinical trials were collated. Eighty-five older participants (age range: 55-76 years) were included in the final database. Two trials had an open-label, parallel design and two trials had a cross-over, double-blind design. Participants were randomised to either beetroot juice or placebo. Changes in 24-hr ABPM (daily, diurnal, nocturnal), variability (weighted-SDs), night-dipping, morning surge for systolic and diastolic BP were measured. Meta-analysis was conducted to obtain pooled estimates of the effect size for each BP outcome. Sub-group analyses were conducted to evaluate the influence of age, BMI, gender, BP status and changes in nitrite concentrations on the effect size. RESULTS: The pooled effect of beetroot juice on all BP outcomes was not significant. Beetroot juice ingestion determined a significant decrease in nocturnal systolic BP variability in subjects aged less than 65 y (2.8 mmHg, -4.5 -1.0, p = 0.002) compared to the older group (≥ 65 y; 1.0 mmHg, -2.2 4.2, p = 0.54). A greater change in NO2(-) concentrations after beetroot supplementation was associated with significant differences for nocturnal mean (-3.4 mmHg, -0.6 -2.4, p = 0.02) and variability (-0.8 mmHg, -1.5 -0.06, p = 0.03) of systolic BP. CONCLUSIONS: The vascular responsiveness to inorganic nitrate may be modified by mechanisms of vascular ageing influencing the reducing capacity to convert inorganic nitrate into nitrite and tissue-specific responses to dietary nitrate supplementation.

25-hydroxyvitamin D and increased all-cause mortality in very old women: the Newcastle 85+ study.

OBJECTIVE: To investigate the associations between low and high concentrations of baseline serum 25-hydroxyvitamin D [25(OH)D] and all-cause mortality in very old (≥85 years) men and women over 6 years. DESIGN, SETTING AND SUBJECTS: Prospective mortality data from 775 participants in the Newcastle 85+ Study were analysed for survival in relation to 25(OH)D (season-specific quartiles and predefined cut-off values) and sex using Cox proportional hazards models. The models were fitted to the entire and restricted (nonusers of vitamin D-containing supplements and medication) cohorts. RESULTS: For the entire cohort, mortality was higher in both the lowest and highest 25(OH)D season-specific quartiles [SQ1: hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.01-1.69, P = 0.04; SQ4: HR 1.44, 95% CI 1.12-1.85, P = 0.004] compared with the combined middle quartiles (SQ2 + SQ3), after adjustment for sociodemographic factors. The increased risk for the highest quartile remained significant after further adjustment for lifestyle variables (SQ4: HR 1.37, 95% CI 1.06-1.77, P = 0.02) and was seen only in women in sex-specific analyses. Similarly, in sensitivity analyses with predefined 25(OH)D cut-off values, the highest 25(OH)D concentration (≥75 nmol L(-1) ) was associated with a 2.4-fold increased risk of mortality in women (restricted cohort) after adjusting for all covariates. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with increased risks of mortality over 6 years in the very old; this effect was particularly noticeable in women, including those who reported taking vitamin D-containing supplements/medication.

Serum 25-hydroxyvitamin D and cognitive decline in the very old: the Newcastle 85+ Study.

BACKGROUND AND PURPOSE: Studies investigating the association between 25-hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking. METHODS: Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini-Mental State Examination) and attention-specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25(OH)D quartiles. RESULTS: Those in the lowest and highest season-specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06-2.60, P = 0.03; 1.62, 95% confidence interval 1.02-2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, ß = 0.023, P = 0.01; highest, ß = 0.021, P = 0.02), Digit Vigilance Task (lowest, ß = 0.009, P = 0.05; highest, ß = 0.01, P = 0.02) and Power of Attention (lowest, ß = 0.017, P = 0.02; highest, ß = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, ß = 0.021, P = 0.02; highest, ß = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment.

Nutrition and DNA repair--potential molecular mechanisms of action.

At its most fundamental, cancer is a genetic disease in the sense that the primary events in tumorigenesis involve damage to the genome. The genome is subject to damage continuously from both exogenous agents and endogenous processes but this becomes functionally important only if the damage is not detected and resolved in a timely and effective manner. In mammals there are 5 DNA repair pathways, encoded by approximately 150 genes, which appear to have arisen early in evolution and which are highly conserved. Given the substantial epidemiological and experimental evidence that variation in dietary intake accounts for a significant proportion of the variance in cancer prevalence, an a priori case can be made that dietary factors may influence the effectiveness of DNA repair. A review of the literature has identified 4 observational and 8 intervention studies in human subjects where DNA repair (or a component thereof) has been measured in relation to nutrition. This rather limited evidence base precludes drawing definitive conclusions, but the fact that there were significant effects of dietary supplements in 5 out of the 8 intervention studies suggests that food components and/or nutritional status may influence DNA repair. This review considers possible molecular mechanisms through which such factors could modulate repair.

Beta-carotene and arachidonic acid induced DNA methylation and the regulation of pro-chemotactic activity of endothelial cells and its progenitors.

DNA methylation is one of the important mechanisms regulating gene expression. Since beta-carotene (BC) was shown to have pro-chemotactic activity and stimulates expression of pro-angiogenic genes, this study was undertaken to define the possible changes in DNA methylation in endothelial cell and its progenitors in the presence of BC. The culture medium for human umbilical vein endothelial cells (HUVEC) and endothelial progenitor cells (EPC) was supplemented with BC (1 - 10 microM) with the presence of arachidonic acid (AA) (3 microM). Global DNA methylation tended to be lower in both endothelial cell lines, after incubation with BC and AA. HUVEC incubated with AA demonstrated the lowest DNA methylation. The decrease of DNA methylation in EPC, induced by BC, was concentration-dependent. The microarray study revealed, that the angiogenesis and homing-related genes were mostly influenced by BC and AA in investigated cells. Our results indicate that BC and AA-induced DNA hypomethylation in EPC and HUVEC, might be a mechanism which may alter gene expression in endothelial cells what in certain conditions may be connected with the suggested pro-malignant effect of this compounds.

Zinc transporters in the mouse placenta show a coordinated regulatory response to changes in dietary zinc intake.

The aim of the study was to determine if the expression of zinc transporters in the mouse placenta is regulated by dietary zinc, commensurate with regulating the supply of zinc to the fetus. Mice were fed diets differing only in the concentration of zinc (moderately zinc-restricted (ZnR)--15 mg Zn/kg; zinc-adequate (ZnA)--50 mg Zn/kg; zinc-supplemented (ZnS)--150 mg Zn/kg) from the onset of pregnancy until collection of tissue at day 17. Compared with mice fed the other diets, fetal weight was reduced in the ZnR group and total non-embryonic weight gain was reduced in mice fed the ZnS diet. Transcript levels of metallothionein and the zinc transporters ZnT1, ZnT4 and ZIP1 were reduced in the placenta of mice fed both the ZnR and ZnS diets compared with mice fed the ZnA diet. Placental ZnT7 and fetal liver metallothionein transcript levels did not differ significantly between mice fed the three diets and placental ZnT5 was reduced in mice fed the ZnS compared with the ZnA diet but did not differ significantly between the ZnA and ZnR diets. The pattern of mRNA expression in placenta was reflected at the protein level for ZnT1. Levels of ZnT5 protein were also highest in mice fed the ZnA diet. Both ZnT1 and ZnT5 were detected in the human villous syncytiotrophoblast by immunohistochemistry. The data indicate that the expression of zinc transporters in mouse placenta is responsive to dietary zinc supply but this modulation of expression is insufficient to maintain optimum fetal nutrition at even a modest level of dietary zinc restriction.

Methylation of the ESR1 CpG island in the colorectal mucosa is an 'all or nothing' process in healthy human colon, and is accelerated by dietary folate supplementation in the mouse.

ESR1 is frequently silenced by CGI (CpG island) methylation, both in human colorectal tumours and, in an age-dependent manner, in healthy mucosa. It is not clear, however, whether methylation of individual cytosines occurs randomly within the epithelial genome, or preferentially within individual cells as an 'all-or-nothing' phenomenon. CGI methylation can be quantified in human DNA residues recovered from faecal samples. We used bisulphite genomic sequencing of human DNA from this source and from a colorectal cancer cell line (SW48) to show that the ESR1 CGI is methylated in an allele-specific manner. This provides support for the 'all or none' mechanism for methylation of this gene, and shows how age-dependent methylation of the ESR1 CGI leads rapidly to silencing of the gene within the cells, and hence the colonic crypt within which it occurs. Preliminary studies with a rodent model suggest the rate of age-dependent methylation of ESR1 is modifiable by dietary folate.

Homeostatic regulation of zinc transporters in the human small intestine by dietary zinc supplementation.

BACKGROUND: The role of intestinal transporter regulation in optimising nutrient absorption has been studied extensively in rodent and cell line models but not in human subjects. AIMS: The aim of the present study was to investigate the response in vivo of zinc transporters in the human enterocyte to dietary zinc supplementation. SUBJECTS: Eighteen patients who had previously undergone ileostomy, all free of any symptoms of inflammatory bowel disease. METHODS: Subjects took a daily zinc supplement of 25 mg for 14 days in a double blind, placebo controlled, crossover trial. The effect of the supplement on expression in ileal biopsies of the zinc transporters SLC30A1, SLC30A4, SLC30A5, SLC39A1, SLC39A4, and metallothionein was measured by reverse transcription-polymerase chain reaction RT-PCR. Expression of SLC30A1, SLC30A5, and SLC39A4 was also examined by immunoblotting. RESULTS: The zinc supplement reduced SLC30A1 mRNA (1.4-fold) together with SLC30A1, SLC30A5, and SLC39A4 protein (1.8-fold, 3.7-fold, and to undetectable levels, respectively) in ileal mucosa and increased metallothionein mRNA (1.7-fold). The supplement had no effect on expression of SLC30A4 or SLC39A1 mRNA. Localisation of SLC30A5 at the apical human enterocyte/colonocyte membrane and also at the apical membrane of Caco-2 cells was demonstrated by immunohistochemistry. Commensurate with these observations in zinc supplemented human subjects, SLC30A1, SLC30A5, and SLC39A4 mRNA and protein were reduced in Caco-2 cells cultured at 200 muM compared with 100 muM zinc. CONCLUSIONS: These observations indicate that, in response to variations in dietary zinc intakes, regulated expression of plasma membrane zinc transporters in the human intestine contributes to maintenance of zinc status.

Comparative gastrointestinal and plasma cholesterol responses of rats fed on cholesterol-free diets supplemented with guar gum and sodium alginate.

The present study investigated the digestion and cholesterol-lowering effects of the water-soluble NSP guar gum (GG) and sodium alginate (SA) in laboratory animals. Groups of five male Wistar strain rats were fed semi-purified cholesterol-free diets containing 0, 50 or 100 g NSP source/kg for 21 d which comprised a 14-d adaptation period followed by a 7-d balance period. Weight gain over the balance period and food conversion ratio decreased linearly with increasing NSP intake ( and respectively). DM digestibility decreased with increasing NSP intake and this effect was greater for SA-containing diets compared with GG-containing diets At the lower inclusion rate, 0.9-1.0 of the additional NSP was digested, but this value fell to 0.8 for both NSP sources at the 100 g/kg inclusion rate, implying that the capacity for near complete digestion of the test NSP had been exceeded. Intestinal tissue mass was increased in response to inclusion of both NSP sources. Caecal digesta pH decreased linearly with additional GG, but increased slightly with consumption of SA. Total caecal short-chain fatty acid concentrations (micromol/g caecal contents) increased markedly with 50 g GG/kg but did not increase further with 100 g GG/kg, and were slightly lower than control values in rats consuming SA. Plasma cholesterol concentration fell linearly with increasing NSP in the diet and the effect was similar for both GG and SA. Total output of faecal bile acids rose in rats fed 50 g GG/kg and 50 g SA/kg (59 micromol/7 d v. 24 micromol/7 d for control rats) with no further increase at the higher inclusion rate. These results show that SA has a strong hypocholesterolaemic effect in rats which is similar to that of GG, and that this effect is most likely to be mediated through an interruption in the entero-hepatic circulation of bile acids and not through increased hepatic supply of propionate from fermentation of the NSP in the large bowel.

Dietary strategies to reduce the burden of cancer and cardiovascular disease in the UK.

The importance attributed to dietary change as a means of helping to achieve the major goals of the UK's public health policy as articulated in the Health of the Nation White paper (Department of Health, 1992) is less apparent in the most recent strategy document (Department of Health, 1999). Greater emphasis is given to amelioration of the socio-economic circumstances that are believed to contribute to inequalities in health. Better understanding of the elements of foods and diets which help protect health together with better evidence of effective dietary interventions are essential if the opportunities to use diet to reduce the burden of non-communicable diseases are to be realised. This is likely to need new research strategies that take advantage of emerging information from genomics and proteomics to produce evidence of safety, efficacy and applicability. Ethical exploitation of the rapid growth in interest in 'functional foods' by the food industry will require a level of investment in biomedical research unusual in the past.

Nutrition in cancer prevention.

Although variation in diet may account for approximately one third of the variation in cancer incidence worldwide, epidemiologic studies have proven to be a blunt instrument for identifying causal relationships between intakes of specific food constituents and cancer risk at specific sites. Diets rich in fruits and vegetables seem to be protective, but the adverse effects of beta carotene supplementation trials on lung cancer incidence in smokers caution against the attribution of benefit to single substances. Important diet-gene interactions may exist, as illustrated by differential responses to variation in folate status in those with methylenetetrahydrofolate reductase polymorphisms. Targeting initial intervention studies in those with explicit genetic predisposition to cancer may have both greater cost-effectiveness and fewer ethical difficulties than do similar studies in the general public.

Dose-response effects of raw potato starch on small-intestinal escape, large-bowel fermentation and gut transit time in the rat.

This study was designed to quantify starch digestion within the small and large bowels separately when raw potato starch (RPS) was included at 0-240 g/kg in diets fed to growing male Wistar rats. RPS was incorporated in the diets at the expense of maize starch which was expected to be almost completely digested in the small bowel. The digestibility of the maize starch was 0.99 but only 0.28 of the RPS was digested before the terminal ileum so that with increasing intakes of RPS there was a progressive increase in starch supply to the large bowel (LB). Of this starch 0.77, 0.72 and 0.73 was fermented in the large bowel when RPS constituted 80, 160 and 240 g/kg diet respectively. With increasing RPS intake, there was a curvilinear response in molar proportion of butyrate in caecal contents with a maximum value at about 80 g RPS/kg diet. The molar proportion of acetate increased linearly, that of propionate was unchanged, whilst proportions of the minor short-chain fatty acids all declined markedly with increasing RPS intake. The novel marker Bacillus stearothermophilus spores (BSS) was compared with CrEDTA in estimation of whole-gut mean transit time (MTT) when given together in a single test meal. Whilst estimates of MTT for the two markers were strongly correlated within individual rats (r2 0.72), BSS produced estimates that were 13 h longer than those based on CrEDTA. Neither marker detected a change in MTT with increasing RPS intake but, with both, the rate constant (k1) for the 'largest mixing pool' declined significantly (P < 0.001) as dietary RPS concentration was changed from 0-240 g/kg.

Tissue hypertrophy and epithelial proliferation rate in the gut of rats fed on bread and haricot beans (Phaseolus vulgaris).

The present study was designed to test the hypothesis that increasing short-chain fatty acid (SCFA) production in the large bowel increases gut epithelial proliferation rate (EPR). Two experiments were carried out in which rats were fed on bread (wholemeal or white)-based diets containing graded amounts of cooked haricot (Phaseolus vulgaris) beans; the latter are a rich source of fermentable carbohydrates. Consumption of beans was associated with several-fold increases in SCFA production with the greatest relative increase being for butyrate. Despite the very large increase in SCFA production, there was no evidence that this had any effect on EPR in the duodenum. Where the basal diet contained wholemeal bread (Expt 1) there was no effect of enhanced SCFA supply on EPR in either the caecum or colon, but with the white bread-based diet (Expt 2) adding beans produced increments in both SCFA supply and EPR in the caecum. Evidence that SCFA are responsible for enhanced EPR above normal levels is not convincing. In those instances where enhanced SCFA supply is associated with increased EPR, the increase may be (1) from a hypoproliferative state towards normal, (2) a transient phenomenon accompanying tissue hypertrophy or (3) a homeostatic response to increased cell loss by cell sloughing or apoptosis. It is not likely that there is any direct link with risk of colon cancer.

Digestive adaptations of rats given white bread and cooked haricot beans (Phaseolus vulgaris): large-bowel fermentation and digestion of complex carbohydrates.

Two experiments were carried out to examine the short (1-3 d) and medium (14 d) term adaptations of rat large-bowel (LB) fermentation to alterations in substrate supply brought about by including cooked haricot beans (Phaseolus vulgaris) in diets based on white bread. Changes in organic matter (OM) flow from the ileum occurred within 1 d and were stable for 14 d but the pattern of caecal short-chain fatty acids took much longer to stabilize with considerable increases in butyrate between 1 and 3 d and up to 14 d. This suggests that the metabolic activity of the LB microflora may take a considerable time to stabilize after an abrupt change in substrate supply. Despite an almost fourfold change in OM supply to the LB, the proportion of this OM apparently fermented in that organ (0.46) remained fairly constant. None of the apparent resistant starch measured in the diets could be detected in faeces. Dietary non-starch polysaccharides (NSP) were extensively fermented with similar values (0.82) for both bread and bean NSP and there was little indication of any interaction between the two diet components on NSP fermentation. An attempt was made to fractionate ileal and faecal OM to provide a basis for a quantitative model of LB stoichiometry.

Gastrointestinal responses of rats fed on white and wholemeal breads: complex carbohydrate digestibility and the influence of dietary fat content.

To obtain quantitative information on the digestibility of the non-starch polysaccharides (NSP) fraction of white and wholemeal breads, rats were fed on diets in which freeze-dried bread (white, wholemeal or mixtures of the two) provided all the complex carbohydrates. In a second experiment the possibility that dietary fat concentration might influence NSP digestibility was tested by feeding diets containing 30 or 170 g maize oil/kg and either white or wholemeal bread. Multiple linear regression analysis provided little evidence of associative effects of dietary components on NSP digestibility and in the two experiments digestibilities of NSP for white and wholemeal breads were 0.77-0.82 and 0.47-0.52 respectively. Xylose- and arabinose-containing polymers were better digested than was cellulose for both breads. Replacing white by wholemeal bread markedly increased the molar proportion of butyrate in caecal volatile fatty acids at the expense of acetate. This was associated with greater flows of organic matter to the large bowel (LB) and a reduction in caecal transit time (Expt 2). There was little detectable effect of dietary maize oil concentration on NSP digestibility or on LB fermentation. All breads contained some starch resistant to pancreatic alpha-amylase (EC 3.2.1.1) without previous treatment with dimethyl sulphoxide. The digestibility of this starch fraction was not significantly different from 1.0 for all diets except that containing wholemeal bread and the higher maize oil concentration where the apparent digestibility was 0.89.