The effect of oral low molecular weight liquid hyaluronic acid combination with glucosamine and chondroitin on knee osteoarthritis patients with mild knee pain An 8-week randomized double-blind placebo-controlled trial

Background: The popularity of dietary supplements for knee osteoarthritis (OA) management is on the rise; however, their effects are still debated. Methods: This study aimed to investigate the effect of an oral low molecular weight liquid hyaluronic acid supplement in the treatment of knee OA patients with mild knee pain (visual analogue scale [VAS] <= 3) in Taiwan population. This was a randomized, double-blind, placebo-controlled study. Forty-seven subjects were enrolled and randomly allocated to either the A+HA or the placebo groups. The subjects were required to drink a bottle contained 20 mL of A+HA or placebo daily throughout an 8-week study period. The efficacy was assessed by using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the 36-item Short Form Survey (SF-36). Results: At Week 8, significant reductions from baseline in the WOMAC pain (-2.6 +/- 1.68, P < .0001), stiffness (-1.2 +/- 1.50, P = .007), physical function (-5.8 +/- 4.39, P < .0001), and total (-9.4 +/- 5.82, P < .0001) scores were observed in the A+HA group but not in the placebo group. Significant differences in the mean change of WOMAC scores from baseline at Week 8 between groups were detected (P < .01). At Week 8, the A+HA group also showed significant improvements in SF-36 physical functioning (2.7 +/- 3.10, P = .001) and bodily pain (0.7 +/- 1.50, P < .05) domains. Although the A+HA group had a higher increase in the SF-36 total score than the placebo group but the difference was not statistically significant (2.1 +/- 12.75 vs 0.3 +/- 19.66, P = .12). Conclusions: Oral administration of low molecular weight liquid HA appeared to be effective for knee OA patients with mild knee pain (VAS <= 3) in the relief of knee OA symptoms, particularly in pain and physical function. Clinical Trial Registration: NCT04352322.