Six-Weeks Very Low-calorie Diet (VLCD) Improves Glycaemic Control Without Reducing Plasma Branched-chain Amino Acids (BCAA) or Keto-Acids (BCKA) in Obese Men

Elevated plasma leucine, isoleucine and valine (BCAA) are associated with diabetes, obesity and insulin resistance (IR). Here, we evaluated the effects of 6-weeks very-low calorie diet (VLCD) upon fasting BCAA in overweight (OW) non-diabetic men, to explore associations between circulating BCAA and IR, before and after a weight loss intervention.Fasting plasma BCAA were quantified in an OW ( n = 26; BMI 32.4±3 kg/m 2 ; mean age 44±9 y) and a normal-weight (NW) group ( n = 26; BMI 24±3.1 kg/m 2 ; mean age 32±12 y). Ten of the OW group (BMI 32.2±4 kg/m 2 ; 46±8 y) then underwent 6-weeks of VLCD (600-800 kcal/d). Fasting plasma BCAA (gas-chomatography mass spectrometry), insulin sensitivity (HOMA-IR) and body-composition (DXA) were assessed before and after VLCD. Total BCAA were elevated in OW individuals (sum leucine/isoleucine/valine: 457 ± 85 µM) compared to NW control individuals (365 ± 78 µM, P <0.001). Despite significant weight loss (baseline 103.9 ± 12.3 kg to 93 ± 9.6 kg and BMI 32.3 ± 4 kg/m 2 to 28.9 ± 3.6 kg/m 2 ), no changes were observed in BCAA after 6 weeks of VLCD. Moreover, although VLCD resulted in a significant reduction in HOMA-IR (baseline 1.19±0.62 to 0.51±0.21 post-VLCD; P < 0.001), Pearson’s r revealed no relationships between BCAA and HOMA-IR, either before (leucine R 2 2.49, P = 0.9; isoleucine R 2 1.2, P = 0.9; valine R 2 0.004, P = 0.8) or after VLCD (leucine R 2 0.003, P = 0.9; isoleucine R 2 0.006, P = 0.8; valine R 2 0.002, P = 0.7).Plasma BCAA are elevated in OW compared to NW individuals. However, while 6-weeks VLCD reduced body weight and IR in OW individuals, this was not associated with reductions in BCAA. This suggests exisiting links between BCAA and insulin resistance in OW individuals, are more complex and are not normalised by simply losing weight.