Ian T. Johnson

Polyphenols: antioxidants and beyond

Research on the effects of dietary polyphenols on human health has developed considerably in the past 10 y. It strongly supports a role for polyphenols in the prevention of degenerative diseases, particularly cardiovascular diseases and cancers. The antioxidant properties of polyphenols have been widely studied, but it has become clear that the mechanisms of action of polyphenols go beyond the modulation of oxidative stress. This supplemental issue of The American Journal of Clinical Nutrition, published on the occasion of the 1st International Conference on Polyphenols and Health, offers an overview of the experimental, clinical, and epidemiologic evidence of the effects of polyphenols on health.

The nutritional significance, biosynthesis and bioavailability of glucosinolates in human foods

The glucosinolates are a large group of sulphur-containing compounds which occur in all the economically important varieties of Brassica vegetable. Their common structure comprises a β-D-thioglucose group, a sulphonated oxime moiety and a variable side-chain derived from methionine, tryptophan or phenylalanine. When the plant tissue is damaged the glucosinolates are hydrolysed by the endogenous enzyme ‘myrosinase’ (thioglucoside glycohydrolase EC 3:2:3:1), to release a range of breakdown products including the bitter, biologically active isothiocyanates. Although these compounds exert antinutritional effects in animals there is also substantial evidence that they are the principal source of anticarcinogenic activity in Brassica vegetables, and this provides a strong motive for the manipulation of glucosinolate levels in vegetables for human consumption. This review provides an overview of the evidence for a beneficial role for glucosinolates in human health, and describes the current state of knowledge regarding the genetics and biosynthesis of glucosinolates, their chemical analysis, their behaviour during cooking and processing, and their bioavailability to humans. As the genetic basis of glucosinolate biosynthesis becomes more apparent, and tools for marker-assisted plant breeding become more available, the selective breeding of horticultural brassicas with different levels and types of glucosinolates, whether by conventional means or genetic manipulation, is becoming a practical possibility. However before this strategy becomes commercially viable, the health benefits of glucosinolates for human beings must be unequivocally established. © 2000 Society of Chemical Industry

Quercetin Glucosides Interact With the Intestinal Glucose Transport Pathway

Flavonols are efficient antioxidants with the potential to protect biological macromolecules from oxidative damage in vivo, and if absorbed into the circulation they may protect against cardiovascular disease. Although flavonol aglycones are present in foods at low concentrations, their glycosides are abundant in onions, apples, beans and tea, and are thought to be stable under the conditions of the human stomach and small bowel. There is, however, recent evidence to suggest that intact glycosides of quercetin may be absorbed from the small intestine by a mechanism involving the glucose transport pathway. In the present study we tested this hypothesis by measuring the effect of quercetin glycosides on the rate of efflux of galactose from the jejunal mucosa. Everted sacs of rat jejunum preloaded with 14C-galactose were exposed to quercetin glycosides isolated from onions. Quercetin mono- and diglucosides were shown to accelerate the carrier-mediated efflux of galactose via a sodium-dependent pathway. HPLC analysis confirmed the stability of the glycosides under conditions simulating those in the upper alimentary tract. These studies suggest that purified quercetin glucosides are capable of interacting with the sodium dependent glucose transport receptors in the mucosal epithelium and may therefore be absorbed by the small intestine in vivo.

Effect of gel-forming gums on the intestinal unstirred layer and sugar transport in vitro.

The effect of two gel-forming polysaccharide gums, guar gum and Na-carboxymethyl-cellulose (CMC), on glucose transport in vitro was investigated using everted sacs of rat jejunum. The gums were added to the mucosal bathing media to give apparent viscosities in the range of 1-110 Pascal seconds X 10(-3), mPa.s(cP). Serosal glucose transport fell steeply by about 60% as the viscosities of the mucosal media rose to 20mPa.s, and levelled off thereafter. A similar effect was observed in sacs preincubated with guar gum (15 minutes) and exposed to glucose in a subsequent guar-free incubation. Glucose transport with and without the addition of guar gum was found to be sensitive to mucosal stirring, so that, when shaken at 130 oscillations per minute, sacs exposed to guar gum (0.25 %, viscosity c.a. 16 mPa.s (cP) transported glucose at a similar rate to sacs incubated without guar at 80 oscillations per minute. By measuring the time course for the establishment of osmotic induced potentials, it was shown that incubation with guar or CMC led to an increase in the apparent thickness of the unstirred fluid layer overlying the mucosa (guar-free thickness = 317 +/- 15 mu, guar treated thickness = 468 +/- 25 mu). It is suggested that the presence of a polysaccharide gum in the fluid film surrounding the villi increases its viscosity, and thus gives rise to a thickening of the rate-limiting unstirred layer. If such an effect occurs in vivo, this could contribute to the diminished post-prandial glycaemia observed in human subjects fed guar gum.

A prospective, comparative analysis of anti-Müllerian hormone, inhibin-B, and three-dimensional ultrasound determinants of ovarian reserve in the prediction of poor response to controlled ovarian stimulation

OBJECTIVE To compare three-dimensional ultrasound parameters, antral follicle count (AFC), ovarian volume, and ovarian vascularity indices with anti-Müllerian hormone (AMH) and other conventional endocrine markers for the prediction of poor response to controlled ovarian hyperstimulation (COH) during assisted reproduction treatment (ART). DESIGN Prospective study. SETTING University-based assisted conception unit. PATIENT(S) One hundred thirty-five women undergoing the first cycle of ART. INTERVENTION(S) Transvaginal three-dimensional ultrasound assessment and venipuncture in the early follicular phase of the menstrual cycle immediately before ART. MAIN OUTCOME MEASURE(S) Poor ovarian response and nonconception. RESULT(S) Antral follicle count (Exp(B): 0.65) and AMH (Exp(B): 0.13) were the most significant predictors of poor ovarian response on multiple regression analysis and their predictive accuracy was similar, with an area under the curve (AUC) of 0.935 and 0.905, respectively. The AFC and AMH, as a combined test, did not significantly improve the level of prediction (AUC = 0.946). The sensitivity and specificity for prediction of poor ovarian response were 93% and 88% for AFC and 100% and 73% for AMH at an optimum cutoff values of < or =10 and < or =0.99 ng/mL, respectively. Age (Exp(B): 1.191) was the only significant predictor of nonconception, although its predictive accuracy was also low (AUC = 0.674). CONCLUSION(S) The AFC and AMH are the most significant predictors of poor response to ovarian stimulation during ART. The AMH and AFC, either alone or in combination, demonstrate a similar predictive power but are not predictive of nonconception, which is dependent on the womans age.

Metabolomics of Fecal Extracts Detects Altered Metabolic Activity of Gut Microbiota in Ulcerative Colitis and Irritable Bowel Syndrome

(1)H NMR spectroscopy of aqueous fecal extracts has been used to investigate differences in metabolic activity of gut microbiota in patients with ulcerative colitis (UC) (n = 13), irritable bowel syndrome (IBS) (n = 10), and healthy controls (C) (n = 22). Up to four samples per individual were collected over 2 years giving a total of 124 samples. Multivariate discriminant analysis, based on NMR data from all three groups, was able to predict UC and C group membership with good sensitivity and specificity; classification of IBS samples was less successful and could not be used for diagnosis. Trends were detected toward increased taurine and cadaverine levels in UC with increased bile acid and decreased branched chain fatty acids in IBS relative to controls; changes in short chain fatty acids and amino acids were not significant. Previous PCR-denaturing gradient gel electrophoresis (PCR-DGGE) analysis of the same fecal material had shown alterations of the gut microbiota when comparing UC and IBS groups with controls. Hierarchical cluster analysis showed that DGGE profiles from the same individual were stable over time, but NMR spectra were more variable; canonical correlation analysis of NMR and DGGE data partly separated the three groups and revealed a correlation between the gut microbiota profile and metabolite composition.

Anticarcinogenic Factors in Plant Foods: A New Class of Nutrients?

INTRODUCTION . . , 175 MECHANISMS OF CARCINOGENESIS . . 176 BLOCKING AGENTS . . 178 PHASE I METABOLISM ACTIVATION BY MONOOXYGENASES . . 178 Free radical mediated damage . . 180 Alternative route to phase I metabolism quinone reductase (QR) . . 181 C O N J U G A T I O N BY PHASE I1 ENZYMES . . 183 INDIRECT EFFECTS V I A ENTERIC BACTERIAL METABOLISM , . 184 INDUCERS OF D N A REPAIR . . 185 SUPPRESSING AGENTS . . 186 INHIBITORS OF CELL PROLIFERATION . . 186 Modijication of intracellular signalling . . . 187 Inhibition of oncogene expression . . . 188 Polyamine metabolism . . 188 Oestrogen metabolism . . 189 DIRECT A C T I N G MODULATORS OF CELL D A M A G E . . . 190 Suppression of free radical production . . . 190 Selective cytotoxins . . 191 I N D U C E R S OF C E L L U L A R DIFFERENTIATION . . 191 ANTIMETASTATIC AGENTS . . 192 IMMUNOMODULATION . . 192 A NEW CLASS OF NUTRIENTS?. . . 192 REFERENCES . . . 194

Effect of oat gum on the physical properties of the gastrointestinal contents and on the uptake of D-galactose and cholesterol by rat small intestine in vitro

Recent reports indicate that oats have a relatively low glycaemic effect in comparison with other carbohydrate food, and that their consumption leads to a reduction in plasma-cholesterol levels in man. These properties may be due to a soluble non-starch polysaccharide in oats. The present study was undertaken to explore the physiological properties of this material. Three groups of male Wistar rats were meal-fed on a control diet free of soluble dietary fibre for 10 d before being given a 10 g meal of either the control diet, a diet containing oat gum (beta-glucan), or finely ground rolled oats. The contents of the stomach, small intestine and caecum were later recovered and the weight, water content and viscosity were measured. The small intestinal contents from oat-gum-fed or oat-fed rats had a higher wet: dry weight ratio than that of the controls, and a higher viscosity. In in vitro studies the rate of uptake of D-galactose by jejunal rings was reduced in the presence of oat gum. The estimated Michaelis-Menten constant for the carrier-mediated component in the presence of oat gum was higher than that for controls, but the maximum transport rates were similar. Cholesterol uptake by everted jejunal sacs was progressively inhibited by increasing concentrations of oat gum in the mucosal medium. It is concluded that increased viscosity of the contents of the small intestine may contribute to the low glycaemic index and hypocholesterolaemic effects of oats in man. Oats appear to be amongst the few palatable sources of viscous dietary fibre in the conventional Western diet.

Ulcerative colitis and irritable bowel patients exhibit distinct abnormalities of the gut microbiota.

BackgroundPrevious studies suggest a link between gut microbiota and the development of ulcerative colitis (UC) and irritable bowel syndrome (IBS). Our aim was to investigate any quantitative differences in faecal bacterial compositions in UC and IBS patients compared to healthy controls, and to identify individual bacterial species that contribute to these differences.MethodsFaecal microbiota of 13 UC patients, 11 IBS patients and 22 healthy volunteers were analysed by PCR-Denaturing Gradient Gel Electrophoresis (DGGE) using universal and Bacteroides specific primers. The data obtained were normalized using in-house developed statistical method and interrogated by multivariate approaches. The differentiated bands were excised and identified by sequencing the V3 region of the 16S rRNA genes.ResultsBand profiles revealed that number of predominant faecal bacteria were significantly different between UC, IBS and control group (p < 10-4). By assessing the mean band numbers in UC (37 ± 5) and IBS (39 ± 6), compared to the controls (45 ± 3), a significant decrease in bacterial species is suggested (p = 0.01). There were no significant differences between IBS and UC. Biodiversity of the bacterial species was significantly lower in UC (μ = 2.94, σ = 0.29) and IBS patients (μ = 2.90, σ = 0.38) than controls (μ = 3.25, σ = 0.16; p = 0.01). Moreover, similarity indices revealed greater biological variability of predominant bacteria in UC and IBS compared to the controls (median Dice coefficients 76.1% (IQR 70.9 - 83.1), 73.8% (IQR 67.0 - 77.5) and 82.9% (IQR 79.1 - 86.7) respectively). DNA sequencing of discriminating bands suggest that the presence of Bacteroides vulgatus, B. ovatus, B. uniformis, and Parabacteroides sp. in healthy volunteers distinguishes them from IBS and UC patients. DGGE profiles of Bacteroides species revealed a decrease of Bacteroides community in UC relative to IBS and controls.ConclusionMolecular profiling of faecal bacteria revealed abnormalities of intestinal microbiota in UC and IBS patients, while different patterns of Bacteroides species loss in particular, were associated with UC and IBS.

Review article: nutrition, obesity and colorectal cancer

Background The age‐adjusted incidence of colorectal cancer is higher in prosperous industrialized countries than elsewhere. Dietary factors may account for 75% of sporadic colorectal cancer in the west, but the mechanisms remain obscure.