Furio Brighenti

Nibbling versus Gorging: Metabolic Advantages of Increased Meal Frequency

We studied the effect of increasing the frequency of meals on serum lipid concentrations and carbohydrate tolerance in normal subjects. Seven men were assigned in random order to two metabolically identical diets. One diet consisted of 17 snacks per day (the nibbling diet), and the other of three meals per day (the three-meal diet); each diet was followed for two weeks. As compared with the three-meal diet, the nibbling diet reduced fasting serum concentrations of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B by a mean (+/- SE) of 8.5 +/- 2.5 percent (P less than 0.02), 13.5 +/- 3.4 percent (P less than 0.01), and 15.1 +/- 5.7 percent (P less than 0.05), respectively. Although the mean blood glucose level and serum concentrations of free fatty acids, 3-hydroxybutyrate, and triglyceride were similar during both diets, during the nibbling diet the mean serum insulin level decreased by 27.9 +/- 6.3 percent (P less than 0.01) and the mean 24-hour urinary C-peptide output decreased by 20.2 +/- 5.6 percent (P less than 0.02). In addition, the mean 24-hour urinary cortisol excretion was lower by 17.3 +/- 5.9 percent (P less than 0.05) at the end of the nibbling diet than at the end of the three-meal diet. The blood glucose, serum insulin, and C-peptide responses to a standardized breakfast and the results of an intravenous glucose-tolerance test conducted at the end of each diet were similar. We conclude that in addition to the amount and type of food eaten, the frequency of meals may be an important determinant of fasting serum lipid levels, possibly in relation to changes in insulin secretion.

Determination of the glycaemic index of foods: interlaboratory study.

Objective: Practical use of the glycaemic index (GI), as recommended by the FAO/WHO, requires an evaluation of the recommended method. Our purpose was to determine the magnitude and sources of variation of the GI values obtained by experienced investigators in different international centres.Design: GI values of four centrally provided foods (instant potato, rice, spaghetti and barley) and locally obtained white bread were determined in 8–12 subjects in each of seven centres using the method recommended by FAO/WHO. Data analysis was performed centrally.Setting: University departments of nutrition.Subjects: Healthy subjects (28 male, 40 female) were studied.Results: The GI values of the five foods did not vary significantly in different centres nor was there a significant centre×food interaction. Within-subject variation from two centres using venous blood was twice that from five centres using capillary blood. The s.d. of centre mean GI values was reduced from 10.6 (range 6.8–12.8) to 9.0 (range 4.8–12.6) by excluding venous blood data. GI values were not significantly related to differences in method of glucose measurement or subject characteristics (age, sex, BMI, ethnicity or absolute glycaemic response). GI values for locally obtained bread were no more variable than those for centrally provided foods.Conclusions: The GI values of foods are more precisely determined using capillary than venous blood sampling, with mean between-laboratory s.d. of approximately 9.0. Finding ways to reduce within-subject variation of glycaemic responses may be the most effective strategy to improve the precision of measurement of GI values.

Effect of consumption of a ready-to-eat breakfast cereal containing inulin on the intestinal milieu and blood lipids in healthy male volunteers

Objective: To investigate the effect of a breakfast cereal containing inulin on blood lipids and colonic ecosystem in normolipidemic young men.Setting: Department of Food Science and Microbiology,University of Milan, Italy.Subjects: Twelve healthy male volunteers, age 23.3±0.5 y, body mass index (BMI) 25.7±1.2 kg/m2 (mean±s.e.m.).Interventions: Subjects consumed daily, for three periods of four weeks, 50 g of a rice-based ready-to-eat cereal (placebo) and the same cereal containing 18% inulin (test) in substitution of their habitual breakfast, then returned to the habitual diet (wash-out). They followed no other dietary restrictions.Results: No changes in body weight, dietary habits, faecal and bile acid output, faecal short-chain fatty acid (SCFA) and faecal pH, were observed at the end of each period, whereas plasma total cholesterol and triacylglycerols significantly decreased at the end of test period by 7.9±5.4 (P<0.05) and 21.2±7.8% (P<0.005) respectively. Meal glucose tolerance test (MTT) resulted in the same incremental area under the curve for both cereals (IAUC test 124±35; placebo 118±33 mmol·min/l, ns). Inulin markedly enhanced breath H2 excretion (IAUC test 280±40; placebo 78±26 ppm·h, P<0.005), as well as faecal concentration of L-lactate. Total facultative anaerobes significantly decreased after test, and bifidobacteria increased after correction for total anaerobes (P<0.05). Changes in blood lipids were negatively correlated with bifidobacteria counts and positively with secondary bile acid excretion (P<0.05).Conclusions: Inulin seems to have a lipid lowering potential in normolipidemic men possibly mediated by mechanisms related to colonic fermentation.Sponsorship: National Research Council of Italy, grant number 95.00773.PF41.

Total antioxidant capacity of the diet is inversely and independently related to plasma concentration of high-sensitivity C-reactive protein in adult Italian subjects

Inflammation, a risk factor for cardiovascular disease, is associated with low plasma levels of antioxidant vitamins. In addition to vitamins, other antioxidants modulate the synthesis of inflammatory markers in vitro and contribute to the total antioxidant capacity (TAC) of a diet. However, the relationship between dietary TAC and markers of inflammation has never been evaluated in vivo. We investigated the relationship between dietary TAC and markers of systemic (high-sensitivity C-reactive protein (hs-CRP), leucocytes) and vascular (soluble intercellular cell adhesion molecule-1) inflammation in 243 non-diabetic subjects. General Linear Model (GLM) analysis showed a significant (P=0.005) inverse relationship between hs-CRP and quartiles of energy-adjusted dietary TAC, even when recognized modulating factors of inflammation, namely alcohol, fibre, vitamin C, alpha-tocopherol, beta-carotene, BMI, waist circumference, HDL-cholesterol, hypertension, insulin sensitivity and plasma beta-carotene, were included in the model as covariates (P=0.004). The relationship was stronger for subjects with hypertension (P=0.013 v. P=0.109 for normotensive individuals). Among dietary factors, TAC was significantly higher (5.3 (sd 3.0) v. 4.9 (sd 2.7) mmol Trolox/d; P=0.026) in subjects with low plasma hs-CRP (range: 0.0-4.1 mg/l) than in subjects with high plasma hs-CRP (range: 4.2-27.8 mg/l). We conclude that dietary TAC is inversely and independently correlated with plasma concentrations of hs-CRP and this could be one of the mechanisms explaining the protective effects against CVD of antioxidant-rich foods such as fruits, whole cereals and red wine. This could be of particular significance for subjects with high blood pressure.

Bioavailability and catabolism of green tea flavan-3-ols in humans

OBJECTIVE The aim of this study was to investigate green tea flavan-3-ol catabolism and plasma pharmacokinetic and urinary excretion by high-performance liquid chromatography with tandem mass spectrometry to evaluate their absolute bioavailability by taking into account all known and some unknown catabolites deriving from their interaction with the gastrointestinal tract and its host microflora. METHODS A feeding study was carried out in 20 healthy human volunteers who ingested 400 mL of a ready-to-drink green tea containing approximately 400 μmol of flavan-3-ols. Urine and plasma were collected for 4 and 24h, respectively, and 39 relevant catabolites were identified in these biological fluids by tandem mass spectrometry. RESULTS In biological fluids, 39 relevant flavan-3-ol catabolites were identified. In plasma, (-)-epigallocatechin-3-gallate was the only unmetabolized compound and the highest in absolute concentration compared with (-)-epigallocatechin and (-)-epicatechin conjugates. Colonic microflora-derived polyhydroxyphenyl-γ-valerolactones were by far the main urinary catabolites, averaging 10 times greater concentratin than flavan-3-ol conjugates. The calculated bioavailability was equal to 39% and it is interesting to notice the great variability in urinary excretion of colonic metabolites among participants, probably related to differences in their own colonic microflora. CONCLUSION This study demonstrates that green tea catechins are more bioavailable than previously observed when colonic ring fission metabolites are taken into consideration. Regular consumption of ready-to-drink green tea containing flavan-3-ols allows a non-marginal exposure of the human body to these catabolites, somehow justifying the numerous beneficial actions described as linked to green tea intake.

Dietary Glycemic Load and Index and Risk of Coronary Heart Disease in a Large Italian Cohort: The EPICOR Study

BACKGROUND Dietary glycemic load (GL) and glycemic index (GI) in relation to cardiovascular disease have been investigated in a few prospective studies with inconsistent results, particularly in men. The present EPICOR study investigated the association of GI and GL with coronary heart disease (CHD) in a large and heterogeneous cohort of Italian men and women originally recruited to the European Prospective Investigation into Cancer and Nutrition study. METHODS We studied 47 749 volunteers (15 171 men and 32 578 women) who completed a dietary questionnaire. Multivariate Cox proportional hazards modeling estimated adjusted relative risks (RRs) of CHD and 95% confidence intervals (CIs). RESULTS During a median of 7.9 years of follow-up, 463 CHD cases (158 women and 305 men) were identified. Women in the highest carbohydrate intake quartile had a significantly greater risk of CHD than did those in the lowest quartile (RR, 2.00; 95% CI, 1.16-3.43), with no association found in men (P = .04 for interaction). Increasing carbohydrate intake from high-GI foods was also significantly associated with greater risk of CHD in women (RR, 1.68; 95% CI, 1.02-2.75), whereas increasing the intake of low-GI carbohydrates was not. Women in the highest GL quartile had a significantly greater risk of CHD than did those in the lowest quartile (RR, 2.24; 95% CI, 1.26-3.98), with no significant association in men (P = .03 for interaction). CONCLUSION In this Italian cohort, high dietary GL and carbohydrate intake from high-GI foods increase the overall risk of CHD in women but not men.

Antiglycative and neuroprotective activity of colon-derived polyphenol catabolites

SCOPE Dietary flavonoids and allied phenolic compounds are thought to be beneficial in the control of diabetes and its complications, because of their ability to inhibit oxidative stress, protein glycation and to act as neuroprotectants. Following ingestion by humans, polyphenolic compounds entering the large intestine undergo extensive metabolism by interaction with colonic microbiota and it is metabolites and catabolites of the parent compounds that enter the circulatory system. The aim of this study was to investigate the inhibitory activity of some colonic microbiota-derived polyphenol catabolites against advanced glycation endproducts formation in vitro and to determine their ability, at physiological concentrations, to counteract mild oxidative stress of cultured human neuron cells. METHODS AND RESULTS This study demonstrated that ellagitannin-derived catabolites (urolithins and pyrogallol) are the most effective antiglycative agents, whereas chlorogenic acid-derived catabolites (dihydrocaffeic acid, dihydroferulic acid and feruloylglycine) were most effective in combination in protecting neuronal cells in a conservative in vitro experimental model. CONCLUSION Some polyphenolic catabolites, generated in vivo in the colon, were able in vitro to counteract two key features of diabetic complications, i.e. protein glycation and neurodegeneration. These observations could lead to a better control of these events, which are usually correlated with hyperglycemia.

Glycemic index, glycemic load and glycemic response: An International Scientific Consensus Summit from the International Carbohydrate Quality Consortium (ICQC)

BACKGROUND AND AIMS The positive and negative health effects of dietary carbohydrates are of interest to both researchers and consumers. METHODS International experts on carbohydrate research held a scientific summit in Stresa, Italy, in June 2013 to discuss controversies surrounding the utility of the glycemic index (GI), glycemic load (GL) and glycemic response (GR). RESULTS The outcome was a scientific consensus statement which recognized the importance of postprandial glycemia in overall health, and the GI as a valid and reproducible method of classifying carbohydrate foods for this purpose. There was consensus that diets low in GI and GL were relevant to the prevention and management of diabetes and coronary heart disease, and probably obesity. Moderate to weak associations were observed for selected cancers. The group affirmed that diets low in GI and GL should always be considered in the context of diets otherwise understood as healthy, complementing additional ways of characterizing carbohydrate foods, such as fiber and whole grain content. Diets of low GI and GL were considered particularly important in individuals with insulin resistance. CONCLUSIONS Given the high prevalence of diabetes and pre-diabetes worldwide and the consistency of the scientific evidence reviewed, the expert panel confirmed an urgent need to communicate information on GI and GL to the general public and health professionals, through channels such as national dietary guidelines, food composition tables and food labels.

Effects of the regular consumption of wholemeal wheat foods on cardiovascular risk factors in healthy people

BACKGROUND AND AIM The intake of wholemeal foods is consistently associated with reduced risk of type 2 diabetes and cardiovascular diseases in epidemiological studies, although the mechanisms of this association are unclear. Here we aim to compare in healthy subjects the metabolic effects of a diet rich in wholemeal wheat foods versus one based on the same products in refined form. METHODS AND RESULTS Fifteen healthy individuals (12 M/3 F), mean age 54.5+/-7.6 years, BMI 27.4+/-3.0 kg/m(2) (mean+/-SD), participated in a randomized sequential crossover study. After 2 weeks run-in, participants were randomly assigned to two isoenergetic diets with similar macronutrient composition, one rich in wholemeal wheat foods and the other with the same foods but in refined form (cereal fibre 23.1 vs. 9.8 g/day). After the two treatment periods (each lasting 3 weeks) plasma glucose and lipid metabolism, antioxidant activity, acetic acid, magnesium, adipokines, incretins and high-sensitivity C-reactive protein (hs-CRP) were measured at fasting and for 4h after a standard test meal (kcal 1103, protein 12%, CHO 53%, fat 35%) based on wholemeal or refined wheat foods, respectively. After the two diets there were no differences in fasting nor in postprandial plasma parameter responses; only glucose was slightly but significantly lower at 240 min after the refined wheat food meal compared to the wholemeal wheat food meal. Conversely, after the wholemeal diet both total (-4.3%; p<0.03) and LDL (-4.9%; p<0.04) cholesterol levels were lower than after the refined wheat diet at fasting. CONCLUSIONS Consumption of wholemeal wheat foods for 3 weeks reduces significantly fasting plasma cholesterol as well as LDL cholesterol levels in healthy individuals without major effects on glucose and insulin metabolism, antioxidant status and sub-clinical inflammation markers.

Post-Prandial Responses to Cereal Products Enriched with Barley β-Glucan

Background: High amounts of soluble β-glucan in barley products may exert beneficial effects on glucose tolerance and blood lipids. Objective: To investigate the acute postprandial response on plasma glucose, insulin and lipids after consumption of two experimental products made from barley flour enriched with β-glucan in comparison with similar products made from whole-wheat flour. Methods: A group of 10 healthy volunteers (5 males, age 25.4 ± 0.5 y, BMI 22.6 ± 0.7 Kg/m2) received at breakfast, in random order and in different days, portions (40g of available carbohydrate) of different cereal products or white bread consumed together with a load of 90000 UI retinol. Products were crackers and cookies made either from barley or whole-wheat flour in a 2 × 2 design, where the two factors were the cereal source of dietary fiber (DF), and the food processing. Barley products supplied 12 g DF, 50% soluble, with 3.5 g of β-glucan per portion. Whole-wheat products supplied about 14 g of dietary fiber, mainly in the insoluble form, with negligible amount of β-glucan. Fasting and post-prandial glucose and insulin were evaluated for 180 min after the meals; retinyl-palmitate (RP) and triacylglycerol (TAG) were evaluated hourly over 8 hours. Glycemic (GI) and Insulinemic (II) indexes of products were also assessed, using white bread as reference. Results: Glucose curves were significantly different between types of food processing (p < 0.01) but not between cereal sources of DF (p = 0.07). On the contrary, the effect of fiber but not of processing was evident when glucose response was expressed as Glycemic Index (effect of DF p < 0.01, effect of processing p = 0.69). Individual GI values were 78, 81, 49 and 34 for whole-wheat crackers (WWCr), whole-wheat cookies (WWc), barley crackers (BCr) and barley cookies (Bc) respectively. Insulin curves were significantly different both between type of processing and fiber source (p < 0.001 for both effects). Again, insulin indices were different between fiber but not between processing (p < 0.5 and p = 0.174 respectively). RP and TAG daily profiles were not significantly different between the factors studied. Conclusions: Products prepared from barley flour enriched with β-glucan exhibit favourable responses on glucose metabolism, and particularly on insulinemic responses. In general, cookies responded better to the addition of barley fiber than crackers. Our results highlight the complexity of the effect that barley fiber may exert when added to different food products in reducing postprandial metabolic responses.