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Caloric restriction improves glycaemic control without reducing plasma branched-chain amino acids or keto-acids in obese men

Sayda, M. H.; Abdul-Aziz, M. H.; Gharahdaghi, N.; Wilkinson, D. J.; Greenhaff, P. L.; Philips, B. E.; Smith, K.; Idris, I.; Atherton, P. J.


M. H. Sayda

M. H. Abdul-Aziz

N. Gharahdaghi

Professor of Translational Physiology

Professor of Metabolic Mass Spectrometry

Professor of Diabetes and Metabolic Medicine

Professor of Clinical, metabolic & Molecular Physiology


Higher plasma leucine, isoleucine and valine (BCAA) concentrations 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 BCAAs were quantified in an OW (n = 26; BMI 32.4 ± 3 kg/m2; mean age 44 ± 9 y) and a normal-weight (NW) group (n = 26; BMI 24 ± 3.1 kg/m2; mean age 32 ± 12.3 y). Ten of the OW group (BMI 32.2 ± 4 kg/m2; 46 ± 8 y) then underwent 6-weeks of VLCD (600–800 kcal/day). Fasting plasma BCAA (gas chromatography-mass spectrometry), insulin sensitivity (HOMA-IR) and body-composition (DXA) were assessed before and after VLCD. Total BCAA were higher 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 to 93 ± 9.6 kg and BMI 32.2 ± 4 to 28.9 ± 3.6 kg/m2), no changes were observed in BCAAs 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 R2: 2.49e−005, p = 0.98; isoleucine R2: 1.211−e006, p = 0.9; valine R2: 0.004, p = 0.85) or after VLCD (leucine R2: 0.003, p = 0.86; isoleucine R2: 0.006, p = 0.82; valine R2: 0.002, p = 0.65). Plasma BCAA are higher 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 that studies demonstrating links between BCAA and insulin resistance in OW individuals, are complex and are not normalised by simply losing weight.


Sayda, M. H., Abdul-Aziz, M. H., Gharahdaghi, N., Wilkinson, D. J., Greenhaff, P. L., Philips, B. E., …Atherton, P. J. (2022). Caloric restriction improves glycaemic control without reducing plasma branched-chain amino acids or keto-acids in obese men. Scientific Reports, 12, Article 19273.

Journal Article Type Article
Acceptance Date Oct 4, 2022
Online Publication Date Nov 11, 2022
Publication Date Nov 11, 2022
Deposit Date Oct 19, 2022
Publicly Available Date Nov 23, 2022
Journal Scientific Reports
Electronic ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 12
Article Number 19273
Keywords Obesity; Insulin sensitivity; Amino Acids; Health
Public URL
Publisher URL


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