Clinical effects of inulin supplementation for knee osteoarthritis pain

Recent research suggests that the gut microbiome may regulate chronic pain processing (1-3). Inulin, a prebiotic fiber, can modulate the composition and activity of the gut microbiota, leading to increased production of short-chain fatty acids (SCFAs) such as butyric acid through fermentation. Given the potential influence of the gut microbiome on pain sensitisation, this study aimed to evaluate the clinical effects of inulin supplementation on pain, physical function, and pain sensitivity in individuals with knee osteoarthritis (OA). In a 6-week, randomized, controlled trial with a 2x2 factorial design, individuals with knee OA pain received either 20g/day of inulin or 10g/day of maltodextrin (placebo), with or without digital physiotherapy. The primary outcome was pain intensity measured by the numerical rating scale (NRS). Secondary outcomes included functional performance (30- second chair-stand [30-CST], timed-up-and-go [TUG], grip strength), pain sensitivity assessed via quantitative sensory testing (QST), and serum short-chain fatty acids (SCFAs), including butyrate. Inulin supplementation significantly reduced pain compared to placebo (inulin: baseline- adjusted mean 3.3 [95% C.I. 2.5-4.1] vs. placebo: 4.4 [95% C.I. 3.6-5.2]; β = -1.11, Cohen’s d = 0.57, p = 0.045). It also led to improvement in grip strength (inulin: baseline-adjusted mean 38.6 [95% C.I. 36.5-40.8] vs. placebo: 34.0 [95% C.I. 31.9-36.1]; Cohen’s d = 0.68, p = 0.002), whereas no significant effects were observed for 30-CST and TUG. In addition, inulin improved markers of central sensitisation, with a higher proportion of individuals showing increased pressure pain thresholds at the superolateral knee (inulin: average improved 40.0% [SD 10.09] vs placebo: 11.1% [SD 3.0], p = 0.009) and enhanced temporal summation responses (inulin: average improved 74.0% [SD 18.7] vs placebo: 51.8% [SD 14.0], p = 0.025). Furthermore, inulin uniquely increased circulating butyric acid levels (baseline: mean 1054 [SD 502.1] vs follow-up: mean 1282 [SD 451.2], p = 0.0248). No significant correlations were identified between SCFA levels and pain or functional outcomes, suggesting that the effects of inulin may be mediated through alternative mechanisms. Inulin supplementation led to moderate improvements in pain, grip strength, and pain sensitivity in individuals with knee osteoarthritis, suggesting a potential role in modulating central pain mechanisms independent of SCFA production.