SAT-611 Dietary Reduction of Branched-Chain Amino Acids

Background: One of the primary risk factors for the development of diabetes is obesity. Although moderate weight loss can lead to improvements in metabolic health, reduced-calorie diets are difficult to sustain. A number of groups have shown that low protein diets are associated with metabolic health in both rodents and humans. In particular, the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are associated with insulin resistance and diabetes in humans. Blood levels of the BCAAs decrease in humans fed a low protein diet, and we recently showed that reducing either dietary BCAAs or protein rapidly restored normal body composition and insulin sensitivity to diet-induced obese mice without reducing calorie intake. We are determining the effect of a low BCAA diet in humans with prediabetes and overweight/obesity. Objectives: The primary outcome is the reduction of dietary BCAA intake by at least 50% in subjects in the low BCAA group while maintaining overall baseline calories. Secondary outcomes are compliance and tolerability of the low BCAA protein powder. Method: This is a randomized, controlled, single-blind pilot study. The intervention arm uses a low BCAA protein powder to replace two meals per day for 60 days. The control arm uses a control protein powder with standard amounts of amino acids to replace two meals per day for 60 days. We are enrolling 16 males with the following criteria: ages 35 to 65, BMI 28 to 35, and hemoglobin A1c 5.7%-6.4% or fasting glucose 101-125 mg/dL. A registered dietitian reviews a 4-day food diary prior to diet initiation and creates an individualized meal plan based on those values in order to maintain baseline calories during the study diet. Baseline measurements prior to diet initiation include waist circumference, body mass index, fasting insulin and glucose, an oral glucose tolerance test, resting metabolic rate, body composition testing using dual energy x-ray absorptiometry, jumping mechanography to assess muscle function, and a stool sample to assess the microbiome. These tests are repeated after 60 days on the diet. Safety labs are performed while on the diet and 2-3 weeks after the end of the diet. Weekly safety telephone calls occur while on the diet. The food diaries are repeated after 30 and 60 days on the diet. Results/Conclusion: Ten of sixteen subjects have completed the trial to date. One out of four subjects in the low BCAA group dropped out; the remainder successfully completed the study. BCAA intake was successfully reduced by 50%. Missed beverages were uncommon. No significant safety concerns or side effects have been noted. In conclusion, our early results suggest that replacement of two meals a day with a protein powder lacking BCAA for up to two months is a safe and feasible intervention. Ongoing analysis will determine if this intervention impacts metabolic health.