title: Effects of arginine on osteoarthritis: a pilot clinical trial
Creators: name: Haque, Nafiza Anjum
Publisher: name: Memorial University of Newfoundland
Year: 2023

description: Background: Osteoarthritis (OA) is a disease of high prevalence and economic burden, with yearly cost in Canada rising to $7.6 billion by 2031. It was recently discovered that arginine deficiency is associated with OA, suggesting arginine supplementation may be a novel nutraceutical for OA. We, therefore, undertook this phase IV, randomized, controlled and open-label two-arm clinical trial to assess the effects of arginine supplementation on cartilage degradation related gene expressions. Patients and Methods: Primary knee OA patients who were scheduled to undergo total knee replacement (TKR) in six months were approached and recruited into the study. The consented patients were then randomly assigned into two groups - a control (no supplementation) or treatment (arginine supplementation for six months). The patients in the treatment group were provided and instructed to take 1.5g of oral L-arginine supplements daily until their TKR. All study participants were interviewed at the rheumatology clinic at St. Clare’s Mercy Hospital and comprehensive questionnaire data were collected along with their blood samples. At their TKR surgery, joint tissue samples including cartilage, subchondral bone, and synovial membrane were collected with flash frozen method and stored at -80°C freezer until analysis. RNA was extracted from cartilage samples in LN2 environment with a Freezer Mill and five cartilage homeostasis related gene expressions including two cartilage matrix synthesis (COL2A1 and ACAN) and three cartilage degradation enzymes (MMP13, CTSK, and CTSB) were assessed by real time PCR. Appropriate parametric tests like T-test and paired t-test and non- parametric tests like Chi square and Mann Whitney tests were used to compare differences between treatment and control groups for gene expressions. WOMAC and SF-36 questionnaire was used to assess the health status and quality of life between the two groups at different time points. Results: In total, we recruited 48 patients, ten patients were dropped out, one was rheumatoid arthritis, and one patient had no tibial sample. The final analysis included 36 participants (n=24 control, n=12 arginine supplementation) who completed the study. There was no significant difference in age, sex, BMI, and WOMAC scores between the two groups. The arginine concentrations were lower before the trial in both groups and increased by 23.5% and 33.5% in arginine and control groups after the trial, respectively. The mean time interval that patients taking arginine was 179 days ± 150 days. RNA was extracted from affected tibial cartilage tissue and cDNA synthesis was completed. Realtime PCR was completed to check the gene expression levels of MMP13, CTSB, CTSK, ACAN and COL2A1. There was no statistical difference in the gene expression of the genes of interest between the two groups. For WOMAC and SF-36 scores, at 6 months and 12 months, both groups showed significant improvements in all measures compared to baseline, indicating an improvement in knee pain, stiffness, function, physical and mental function of the individuals. This could be explained primarily due to the surgery itself which might have had an impact on the health status of the participants. Conclusion: Our data did not show significant differences in cartilage synthesis and degradation genes between arginine supplementation and non-supplementation, which might be due to the small sample size. Further studies with a larger sample size are required to verify our findings.