Short-term dietary reduction of branched-chain amino acids reduces meal-induced insulin secretion and modifies microbiome composition in type 2 diabetes: a randomized controlled crossover trial.
Level 2 - randomized trial
Randomized, double-blind, placebo-controlled crossover trial
PubMed 31667519 · doi:10.1093/ajcn/nqz191
What was done
In a randomized, placebo-controlled, double-blind crossover trial, patients with well-controlled type 2 diabetes consumed isocaloric diets (protein: 1 g/kg body weight) for 4 weeks. Protein requirements were met with standard food supplemented up to 60% by an amino acid mixture either containing all amino acids or lacking branched-chain amino acids (BCAAs), keeping BCAA intake above recommended minimums. Metabolic and tissue outcomes were evaluated using mixed meal tolerance tests (MMT), hyperinsulinemic-euglycemic clamps (HECs), skeletal muscle and adipose tissue biopsies, and fecal microbiome profiling.
What was found
The BCAA-restricted diet reduced circulating BCAAs by 17% during fasting (P < 0.001), 13% during clamp (P < 0.01), and 62% during the MMT (P < 0.001). Whole-body and hepatic insulin sensitivity measured by clamp did not differ between diets. Following BCAA reduction, the oral glucose sensitivity index was 24% higher (P < 0.01), circulating FGF-21 was 21% higher (P < 0.05), and meal-induced insulin secretion was 28% lower (P < 0.05). Adipose tissue mTOR expression decreased by 13% and the mitochondrial respiratory control ratio increased 1.7-fold (both P < 0.05). The gut microbiome exhibited enriched Bacteroidetes and depleted Firmicutes.
Why it matters
This demonstrates that moderate dietary BCAA restriction selectively alters postprandial insulin secretion, adipose mitochondrial energetics, and gut microbiome composition in type 2 diabetes, even without changes in clamp-measured systemic insulin resistance.
Limits
The abstract does not state the sample size (n). The intervention was brief (4 weeks) and restricted to well-controlled type 2 diabetes patients. The protocol relied heavily on synthetic amino acid formulas (up to 60% of protein intake), which limits direct generalizability to whole-food dietary modifications, and long-term efficacy and safety remain unmeasured.
Cited by
- supports Short-term human studies show that restricting protein high in branched-chain amino acids leads to metabolic improvements.