Branched-Chain Amino Acids and Testosterone in Older Adults With Type 2 Diabetes: Cross-Sectional and Longitudinal Findings From a Post Hoc Analysis of an Amino Acid Supplementation Trial

Erika Matsuda; Takaaki Matsuda; Kosuke Kojo; Yoshinori Osaki; Yasuhiro Suzuki; Hiroaki Suzuki; Bryan Mathis; Motohiro Sekiya; Hiroyuki Nishiyama; Hitoshi Shimano

doi:10.7759/cureus.92180

Branched-Chain Amino Acids and Testosterone in Older Adults With Type 2 Diabetes: Cross-Sectional and Longitudinal Findings From a Post Hoc Analysis of an Amino Acid Supplementation Trial

Cureus. 2025 Sep 12;17(9):e92180. doi: 10.7759/cureus.92180. eCollection 2025 Sep.

Authors

Erika Matsuda¹, Takaaki Matsuda^{2

3}, Kosuke Kojo^{4

3}, Yoshinori Osaki¹, Yasuhiro Suzuki⁵, Hiroaki Suzuki⁶, Bryan Mathis⁷, Motohiro Sekiya¹, Hiroyuki Nishiyama⁸, Hitoshi Shimano¹

Affiliations

¹ Department of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, JPN.
² Department of Endocrinology and Metabolism, University of Tsukuba Hospital, Tsukuba, JPN.
³ Tsukuba Clinical Research and Development Organization (T-CReDO), University of Tsukuba, Tsukuba, JPN.
⁴ Department of Urology, University of Tsukuba Hospital, Tsukuba, JPN.
⁵ Institute of Systems and Information Engineering, University of Tsukuba, Tsukuba, JPN.
⁶ Department of Food and Health Sciences, Faculty of Human Life Sciences, Jissen Women's University, Tsukuba, JPN.
⁷ Department of Cardiovascular Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, JPN.
⁸ Department of Urology, Institute of Medicine, University of Tsukuba, Tsukuba, JPN.

Abstract

Introduction: Branched-chain amino acids (BCAAs) and sex hormones share anabolic effects on skeletal muscle. As cross-sectional associations in older adults with type 2 diabetes (T2D) remain unclear, we analyzed potential causal effects of BCAA supplementation in this population.

Methods: This was an exploratory, post hoc analysis of a 24-week amino acid supplementation trial in older adults with T2D (BCAA 8 g or soy protein 7.5 g). Thirty-five participants (22 men, 13 women) were included. Total testosterone (TT), free testosterone (FT), and sex hormone-binding globulin (SHBG) were measured. Spearman's rank correlation assessed cross-sectional associations, and paired t-tests or Wilcoxon signed-rank tests analyzed pre- and post-supplementation changes.

Results: At baseline, men showed a negative correlation between serum BCAA and TT (ρ = -0.486) but not FT, whereas women showed positive correlations with both (ρ = 0.446 and 0.657). SHBG correlated negatively with BCAA in both sexes (ρ = -0.452 and -0.571). In the BCAA group, no significant changes in sex hormones were observed after supplementation.

Conclusions: Cross-sectional associations between serum BCAA and testosterone levels in older adults with T2D were not observed longitudinally and may not reflect direct relationships, but rather influenced by insulin resistance or SHBG levels related to body composition. As this was an exploratory analysis with a small sample size, the results should be interpreted with caution.

Keywords: aged adult; anabolic agents; body composition; branched-chain amino acids (bcaas); insulin resistance; postmenopause; sex hormone-binding globulin; testosterone (tt); type 2 diabetes mellitus (dm).