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Background: Protein induces an increase in insulin concentrations when ingested in combination with carbohydrate. Increases in plasma insulin concentrations have been observed after the infusion of free amino acids. However, the insulinotropic properties of different amino acids or protein (hydrolysates) when coingested with carbohydrate have not been investigated. Objective: The aim of this study was to define an amino acid and protein (hydrolysate) mixture with a maximal insulinotropic effect when co-ingested with carbohydrate. Design: Eight healthy, nonobese male subjects visited our laboratory, after an overnight fast, on 10 occasions on which different beverage compositions were tested for 2 h. During those trials the subjects ingested 0.8 g · kg Ϫ1 · h Ϫ1 carbohydrate and 0.4 g · kg Ϫ1 ·h Ϫ1 of an amino acid and protein (hydrolysate) mixture. Results: A strong initial increase in plasma glucose and insulin concentrations was observed in all trials, after which large differences in insulin response between drinks became apparent. After we expressed the insulin response as area under the curve during the second hour, ingestion of the drinks containing free leucine, phenylalanine, and arginine and the drinks with free leucine, phenylalanine, and wheat protein hydrolysate were followed by the largest insulin response (101% and 103% greater, respectively, than with the carbohydrate-only drink; P < 0.05). Conclusions: Insulin responses are positively correlated with plasma leucine, phenylalanine, and tyrosine concentrations. A mixture of wheat protein hydrolysate, free leucine, phenylalanine, and carbohydrate can be applied as a nutritional supplement to strongly elevate insulin concentrations.Am J Clin Nutr 2000;72:96-105. KEY WORDSInsulin secretion, amino acid supplementation, protein hydrolysates, leucine, arginine, phenylalanine, glutamine, healthy men INTRODUCTIONThe synergistically stimulating effect of the combined intake of carbohydrates and protein on plasma insulin concentrations was described for the first time in the 1960s (1, 2) and was confirmed later by Nuttall et al (3,4). The insulinotropic effect of intravenous amino acid administration was also studied in the 1960s by . Infusion of several amino acids led to significant increases in plasma insulin. A mixture of 10 amino acids and equimolar quantities of arginine or leucine only were found to be the most potentiating. Floyd et al also observed a synergistic effect when glucose was administered intravenously with these amino acids. After different combinations of amino acids were investigated, the combined intravenous administration of arginine-leucine and arginine-phenylalanine, together with glucose, resulted in the largest increase in plasma insulin concentrations. Several in vitro studies using incubated ␤-cells of the pancreas showed strong insulinotropic effects of arginine, leucine, phenylalanine, and leucine in combination with glutamine (11)(12)(13)(14)(15)(16)(17)(18)(19)(20).A strong elevation of plasma insulin concentrations ...

AbstractÐBoth carcinogenic and anticarcinogenic properties have been reported for the synthetic antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). The association between dietary intake of BHA and BHT and stomach cancer risk was investigated in the Netherlands Cohort Study (NLCS) that started in 1986 among 120,852 men and women aged 55 to 69 years. A semi-quantitative food frequency questionnaire was used to assess food consumption. Information on BHA or BHT content of cooking fats, oils, mayonnaise and other creamy salad dressings and dried soups was obtained by chemical analysis, a Dutch database of food additives (ALBA) and the Dutch Compendium of Foods and Diet Products. After 6.3 years of follow-up, complete data on BHA and BHT intake of 192 incident stomach cancer cases and 2035 subcohort members were available for case-cohort analysis. Mean intake of BHA or BHT among subcohort members was 105 and 351 "g/day, respectively. For consumption of mayonnaise and other creamy salad dressings with BHA or BHT no association with stomach cancer risk was observed. A statistically non-signi®cant decrease in stomach cancer risk was observed with increasing BHA and BHT intake [rate ratio (RR) highest/lowest intake of BHA=0.57 (95% con®dence interval (CI): 0.25±1.30] and BHT=0.74 (95% CI: 0.38±1.43). In this study, no signi®cant association with stomach cancer risk was found for usual intake of low levels of BHA and BHT. #

Background: Dietary supplement use is increasing, but there are few comparable data on supplement intakes and how they affect the nutrition and health of European consumers. The aim of this study was to describe the use of dietary Correspondence: G Skeie, Institute of Community Medicine, University of Tromsø, N-9037 Tromsø, Norway. E-mail: Guri.Skeie@uit.no Guarantor: G Skeie Contributors: GS performed statistical analyses and wrote the article. NS was the overall coordinator of this project and of the EPIC nutritional databases (ENDB) project. GS, ML, PA, PJ, VP, AP, EMN, KA, TP, MN, MT, KN, JH, LW, ES, AO, SN, VH, GD, CC, DE contributed to the reclassification of data from their respective countries, and gave input on statistical analyses, interpretation of results and drafting of the article. TB, AH, HV, PW, MCBR, PF, EL, NS gave input on the statistical analyses, interpretation of results and drafting of the manuscript. The other co-authors were local EPIC collaborators involved in the design of the study and data collection. ER is the overall coordinator of the EPIC study. All co-authors provided comments and suggestions on the article and approved the final version. Results: Between countries, the mean percentage of dietary supplement use varied almost 10-fold among women and even more among men. There was a clear north-south gradient in use, with a higher consumption in northern countries. The lowest crude mean percentage of use was found in Greece (2.0% among men, 6.7% among women), and the highest was in Denmark (51.0% among men, 65.8% among women). Use was higher in women than in men. Vitamins, minerals or combinations of them were the predominant types of supplements reported, but there were striking differences between countries. Conclusions: This study indicates that there are wide variations in supplement use in Europe, which may affect individual and population nutrient intakes. The results underline the need to monitor consumption of dietary supplements in Europe, as well as to evaluate the risks and benefits.

Biomarkers of food intake (BFIs) are a promising tool for limiting misclassification in nutrition research where more subjective dietary assessment instruments are used. They may also be used to assess compliance to dietary guidelines or to a dietary intervention. Biomarkers therefore hold promise for direct and objective measurement of food intake. However, the number of comprehensively validated biomarkers of food intake is limited to just a few. Many new candidate biomarkers emerge from metabolic profiling studies and from advances in food chemistry. Furthermore, candidate food intake biomarkers may also be identified based on extensive literature reviews such as described in the guidelines for Biomarker of Food Intake Reviews (BFIRev). To systematically and critically assess the validity of candidate biomarkers of food intake, it is necessary to outline and streamline an optimal and reproducible validation process. A consensus-based procedure was used to provide and evaluate a set of the most important criteria for systematic validation of BFIs. As a result, a validation procedure was developed including eight criteria, plausibility, dose-response, time-response, robustness, reliability, stability, analytical performance, and inter-laboratory reproducibility. The validation has a dual purpose: (1) to estimate the current level of validation of candidate biomarkers of food intake based on an objective and systematic approach and (2) to pinpoint which additional studies are needed to provide full validation of each candidate biomarker of food intake. This position paper on biomarker of food intake validation outlines the second step of the BFIRev procedure but may also be used as such for validation of new candidate biomarkers identified, e.g., in food metabolomic studies.

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To postpone cognitive decline and dementia in old age, primary prevention is required earlier in life during middle age. Dietary components may be modifiable determinants of mental performance. In the present study, habitual fruit and vegetable intake was studied in association with cognitive function and cognitive decline during middle age. In the Doetinchem Cohort Study, 2613 men and women aged 43-70 years at baseline (1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002) were examined for cognitive function twice, with a 5-year time interval. Global cognitive function and the domains memory, information processing speed and cognitive flexibility were assessed. Dietary intake was assessed with a semi-quantitative FFQ. In multivariate linear regression analyses, habitual fruit and vegetable intake was studied in association with baseline and change in cognitive function. Higher reported vegetable intake was associated with lower information processing speed (P¼0·02) and worse cognitive flexibility (P¼ 0·03) at baseline, but with smaller decline in information processing speed (P, 0·01) and global cognitive function (P¼0·02) at follow-up. Total intakes of fruits, legumes and juices were not associated with baseline or change in cognitive function. High intakes of some subgroups of fruits and vegetables (i.e. nuts, cabbage and root vegetables) were associated with better cognitive function at baseline and/or smaller decline in cognitive domains. In conclusion, total intake of fruits and vegetables was not or inconsistently associated with cognitive function and cognitive decline. A high habitual consumption of some specific fruits and vegetables may diminish age-related cognitive decline in middle-aged individuals. Further research is needed to verify these findings before recommendations can be made.

To optimize the postexercise insulin response and to increase plasma amino acid availability, we studied postexercise insulin levels after the ingestion of carbohydrate and wheat protein hydrolysate with and without free leucine and phenylalanine. After an overnight fast, eight male cyclists visited our laboratory on five occasions, during which a control drink and two different beverage compositions in two different doses were tested. After they performed a glycogen-depletion protocol, subjects received a beverage (3.5 mL. kg(-1)) every 30 min to ensure an intake of 1.2 g. kg(-1). h(-1) carbohydrate and 0, 0.2 or 0.4 g. kg(-1). h(-1) protein hydrolysate (and amino acid) mixture. After the insulin response was expressed as the area under the curve, only the ingestion of the beverages containing wheat protein hydrolysate, leucine and phenylalanine resulted in a marked increase in insulin response (+52 and + 107% for the 0.2 and 0.4 g. kg(-1). h(-1) mixtures, respectively; P: < 0. 05) compared with the carbohydrate-only trial). A dose-related effect existed because doubling the dose (0.2-0.4 g. kg(-1). h(-1)) led to an additional rise in insulin response (P: < 0.05). Plasma leucine, phenylalanine and tyrosine concentrations showed strong correlations with the insulin response (P: < 0.0001). This study provides a practical tool to markedly elevate insulin levels and plasma amino acid availability through dietary manipulation, which may be of great value in clinical nutrition, (recovery) sports drinks and metabolic research.