+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Associations between branched chain amino acid intake and biomarkers of adiposity and cardiometabolic health independent of genetic factors: A twin study

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          Conflicting data exist on the impact of dietary and circulating levels of branched chain amino acids (BCAA) on cardiometabolic health and it is unclear to what extent these relations are mediated by genetics.


          In a cross-sectional study of 1997 female twins we examined associations between BCAA intake, measured using food frequency-questionnaires, and a range of markers of cardiometabolic health, including DXA-measured body fat, blood pressure, HOMA-IR, high-sensitivity C-reactive protein (hs-CRP) and lipids. We also measured plasma concentrations of BCAA and known metabolites of amino acid metabolism using untargeted mass spectrometry. Using a within-twin design, multivariable analyses were used to compare the associations between BCAA intake and endpoints of cardiometabolic health, independently of genetic confounding.


          Higher BCAA intake was significantly associated with lower HOMA-IR (− 0.1, P-trend 0.02), insulin (− 0.5 μU/mL, P-trend 0.03), hs-CRP − 0.3 mg/L, P-trend 0.01), systolic blood pressure (− 2.3 mmHg, P-trend 0.01) and waist-to-height ratio (− 0.01, P-trend 0.04), comparing extreme quintiles of intake. These associations persisted in within-pair analysis for monozygotic twins for insulin resistance ( P < 0.01), inflammation ( P = 0.03), and blood pressure ( P = 0.04) suggesting independence from genetic confounding. There was no association between BCAA intake and plasma concentrations, although two metabolites previously associated with obesity were inversely associated with BCAA intake (alpha-hydroxyisovalerate and trans-4-hydroxyproline).


          Higher intakes of BCAA were associated, independently of genetics, with lower insulin resistance, inflammation, blood pressure and adiposity-related metabolites. The BCAA intake associated with our findings is easily achievable in the habitual diet.

          Related collections

          Most cited references 28

          • Record: found
          • Abstract: found
          • Article: not found

          Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity.

          To evaluate whether the homeostasis model assessment (HOMA) is a reliable surrogate measure of in vivo insulin sensitivity in humans. In the present study, we compared insulin sensitivity as assessed by a 4-h euglycemic (approximately 5 mmol/l) hyperinsulinemic (approximately 300 pmol/l) clamp with HOMA in 115 subjects with various degrees of glucose tolerance and insulin sensitivity. We found a strong correlation between clamp-measured total glucose disposal and HOMA-estimated insulin sensitivity (r = -0.820, P<0.0001), with no substantial differences between men (r = -0.800) and women (r = -0.796), younger (aged <50 years, r = -0.832) and older (r = -0.800) subjects, nonobese (BMI <27 kg/m2, r = -0.800) and obese (r = -0.765) subjects, nondiabetic (r = -0.754) and diabetic (r = -0.695) subjects, and normotensive ( r = -0.786) and hypertensive (r = -0.762) subjects. Also, we found good agreement between the two methods in the categorization of subjects according to insulin sensitivity (weighted k = 0.63). We conclude that the HOMA can be reliably used in large-scale or epidemiological studies in which only a fasting blood sample is available to assess insulin sensitivity
            • Record: found
            • Abstract: found
            • Article: not found

            Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms.

            Leucine, as an essential amino acid and activator of mTOR (mammalian target of rapamycin), promotes protein synthesis and suppresses protein catabolism. However, the effect of leucine on overall glucose and energy metabolism remains unclear, and whether leucine has beneficial effects as a long-term dietary supplement has not been examined. In the present study, we doubled dietary leucine intake via leucine-containing drinking water in mice with free excess to either a rodent chow or a high-fat diet (HFD). While it produced no major metabolic effects in chow-fed mice, increasing leucine intake resulted in up to 32% reduction of weight gain (P < 0.05) and a 25% decrease in adiposity (P < 0.01) in HFD-fed mice. The reduction of adiposity resulted from increased resting energy expenditure associated with increased expression of uncoupling protein 3 in brown and white adipose tissues and in skeletal muscle, while food intake was not decreased. Increasing leucine intake also prevented HFD-induced hyperglycemia, which was associated with improved insulin sensitivity, decreased plasma concentrations of glucagon and glucogenic amino acids, and downregulation of hepatic glucose-6-phosphatase. Additionally, plasma levels of total and LDL cholesterol were decreased by 27% (P < 0.001) and 53% (P < 0.001), respectively, in leucine supplemented HFD-fed mice compared with the control mice fed the same diet. The reduction in cholesterol levels was largely independent of leucine-induced changes in adiposity. In conclusion, increases in dietary leucine intake substantially decrease diet-induced obesity, hyperglycemia, and hypercholesterolemia in mice with ad libitum consumption of HFD likely via multiple mechanisms.
              • Record: found
              • Abstract: found
              • Article: not found

              Validation of a self-administered food-frequency questionnaire administered in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study: comparison of energy, protein, and macronutrient intakes estimated with the doubly labeled water, urinary nitrogen, and repeated 24-h dietary recall methods.

              The validation of dietary assessment instruments is critical in the evaluation of diet as a chronic disease risk factor. The objective was to assess the validity of a self-administered food-frequency questionnaire by comparison with dietary recall, urinary nitrogen excretion, and total energy expenditure data. Over a 1-y period, data from twelve 24-h dietary recalls, a food-frequency questionnaire, and four 24-h urine samples were obtained from 134 study participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) Study in Potsdam, Germany. In a substudy of 28 participants, total energy expenditure from doubly labeled water measurements was assessed. Energy-adjusted, deattenuated correlation coefficients between the questionnaire and the recalls ranged from 0.54 for dietary fiber to 0.86 for alcohol. Cross-classification of quintiles of nutrient intakes from the questionnaire and recalls indicated severe misclassification to be <4%. Reported protein intake correlated with estimated protein excretion (r = 0.46). Energy intake and total energy expenditure were also significantly correlated (r = 0.48); however, all but one subject underreported their energy intake. The magnitude of underreporting varied considerably, by 22% on average, and increased slightly with increasing energy intake. A similar pattern of underreporting was observed when energy intakes from the 24-h dietary recalls were compared with total energy expenditure. These data indicate an acceptable relative validity of the food-frequency questionnaire in this study population. Compared with measurements of total energy expenditure and protein excretion, however, only moderate agreement with both the food-frequency questionnaire and the 24-h dietary recalls was observed.

                Author and article information

                Int J Cardiol
                Int. J. Cardiol
                International Journal of Cardiology
                15 November 2016
                15 November 2016
                : 223
                : 992-998
                [a ]Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, UK
                [b ]Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
                Author notes
                [* ]Corresponding author at: Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, UK.Department of Nutrition and Preventive MedicineNorwich Medical SchoolUniversity of East AngliaNorwichUK a.cassidy@

                This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

                © 2016 The Authors

                This is an open access article under the CC BY license (



                Comment on this article