Six Non-Essential Amino Acids Improves Joint Pain and Stiffness in Healthy Subjects with Joint Discomfort

by | Oct 27, 2022 | 2022, Amino Acids, Joint Health

Written by Taylor Woosley, Staff Writer. 12-week supplementation of 12 g of 6 non-essential amino acids (alanine, aspartic acid, glutamic acid, glycine, proline, and serine) resulted in improved VAS, JKOM, and JOA scores, suggesting that the treatment group experienced improved joint pain, discomfort, and stiffness both in a resting state and during normal activity. 

joint healthHealthy limb joints are important for maintaining health and attaining longevity1. The joint is an organ constituted mainly of cartilage, synovial fibroblasts, and bone tissue2. Joint tissue is primarily composed of the extracellular matrix (ECM) produced by cells and contains chondroitin, keratosulfate, and various types of collagens3. Long-term biomechanical stress on the joint can lead to acute or chronic overuse of the joint and, if not treated, to injuries or chronic degenerative diseases4.

Collagen supplements are rich in amino acids such as glycine, proline, and hydroxyproline; all of which play important roles in the building of joint cartilage and may also have anti-inflammatory and antioxidant effects5. Amino acids are organic substances which are the basic unit for protein synthesis in cellular metabolism6. Amino acids are broadly classified as non-essential or essential depending on the body’s ability to synthesize them in sufficient quantities, with certain amino acids needing to be supplied in the diet under certain conditions such as extreme trauma or metabolic stress7.

Takeuchi et al. conducted a randomized, double-blind, placebo-controlled, parallel group study to evaluate the effects of non-essential amino acids on joint conditions. 50 healthy subjects experiencing joint discomfort were given a supplement containing six non-essential amino acids (alanine, aspartic acid, glutamic acid, glycine, proline, and serine) (n=25) or placebo (n=25) (4 g three times per day) for 12 weeks. A 12-week posttreatment observation period was also included in the study. Subject inclusion consisted of being aged 20-64 years, living normally but with joint discomfort in one or both knee joints, with desired grading on the measurements of VAS, JKOM, and JOA scores in the pre-study screening test. Subjects were allocated to either the six amino acids (6AA) supplementation group (consisting of DL-alanine (1.16 g), sodium L-aspartate (0.56 g), L-glutamic acid (0.51 g), glycine (0.56 g), L-serine (0.51 g), and L-proline (0.68 g)) or to the control group (consisting of a maltitol supplement).

Baseline measures of subjective symptoms and blood urine parameters were taken at week 0 (W0), prior to intervention; week 4 (W4); and week 12 (W12), after the intervention. The primary outcome was the condition of the participants’ knee joints based on VAS, JKOM, and JOA scales. The VAS is a self-report measure of a subject’s subjective experience of pain. The JKOM is an assessment tool for the measure of pain, discomfort, and stiffness in the knee. The JOA is utilized to evaluate knee conditions from the clinician’s point of view. Secondary outcomes included serum levels of the cartilage type II collagen degradation products, C-terminal telopeptide of type II collagen (CTX-II) and type II collagen cleavage neoepitope (C2C), and uric acid and plasma levels of tumor necrosis factor-alpha (TNF-α).

A Student’s t-test was utilized to assess the statistical significance of between-group differences, comparing changes from baseline W0 to W4 and from W0 to W12. Linear mixed models (LMMs) were applied with random intercepts to analyze the time course of effects. Significant findings of the study are as follows:

  • The 6AA group showed a significantly greater reduction than placebo in all VAS scores from W0 to W4 and W12. This difference was significant when analyzed by the unpaired t-test and LMM (p<0.05)
  • The 6AA group had significantly lower scores than the control group on the JKOM at W4 and W12. In domain V, the 6AA groups showed a significantly greater improvement in scores than the control group at the end of the study period (p=0.0052).
  • The LMM analysis found significantly greater reductions in JOA scores for the 6AA group than for the placebo (p=0.021).
  • Regarding changes in secondary outcome measures, only uric acid was significantly different between the 6AA and placebo groups.

Findings of the study show that intake of 6AA for 12 weeks resulted in a significantly greater improvement in VAS scores and total JKOM scores. Improvements in both scores demonstrate that pain, discomfort, and stiffness in knee joints was reduced only in the 6AA treatment group. Study limitations include the use of self-report measures of medical conditions which cannot be regarded as objective, the lack of dietary records which could offer further insight into the amount of non-essential amino acids present in the participant’s diet, and the use of only one dose being tested.

Source: Takeuchi, Fumika, Michihiro Takada, Yasuo Kobuna, Hirohisa Uchida, and Yusuke Adachi. “Effects of Non-Essential Amino Acids on Knee Joint Conditions in Adults: A Randomised, Double-Blind, Placebo-Controlled Trial.” Nutrients 14, no. 17 (2022): 3628.

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

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Posted October 26, 2022.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

Resources:

  1. Fujii Y, Liu L, Yagasaki L, Inotsume M, Chiba T, Asahara H. Cartilage Homeostasis and Osteoarthritis. Int J Mol Sci. Jun 5 2022;23(11)doi:10.3390/ijms23116316
  2. Malek N, Starowicz K. Joint problems arising from lack of repair mechanisms: can cannabinoids help? Br J Pharmacol. May 2019;176(10):1412-1420. doi:10.1111/bph.14204
  3. Takeuchi F, Takada M, Kobuna Y, Uchida H, Adachi Y. Effects of Non-Essential Amino Acids on Knee Joint Conditions in Adults: A Randomised, Double-Blind, Placebo-Controlled Trial. Nutrients. Sep 2 2022;14(17)doi:10.3390/nu14173628
  4. Zdzieblik D, Brame J, Oesser S, Gollhofer A, König D. The Influence of Specific Bioactive Collagen Peptides on Knee Joint Discomfort in Young Physically Active Adults: A Randomized Controlled Trial. Nutrients. Feb 5 2021;13(2)doi:10.3390/nu13020523
  5. Mobasheri A, Mahmoudian A, Kalvaityte U, et al. A White Paper on Collagen Hydrolyzates and Ultrahydrolyzates: Potential Supplements to Support Joint Health in Osteoarthritis? Curr Rheumatol Rep. Oct 30 2021;23(11):78. doi:10.1007/s11926-021-01042-6
  6. Lee DY, Kim EH. Therapeutic Effects of Amino Acids in Liver Diseases: Current Studies and Future Perspectives. J Cancer Prev. Jun 2019;24(2):72-78. doi:10.15430/jcp.2019.24.2.72
  7. Hope HC, Salmond RJ. The Role of Non-essential Amino Acids in T Cell Function and Anti-tumour Immunity. Arch Immunol Ther Exp (Warsz). Oct 12 2021;69(1):29. doi:10.1007/s00005-021-00633-6