Oral hyaluronan relieves knee pain: a review

Oe M, Tashiro T, Yoshida H, et al. · Nutrition Journal

Every one of the 13 reports is tabulated as positive, though not all on symptoms: the review sorts them as seven on pain or synovitis symptoms, four on effusion or inflammation and three on knee muscle strength, and one measured only a urinary bone-turnover marker in athletes. The mechanisms it lays out are enteric bacterial breakdown to oligosaccharides that are then absorbed, technetium-labelled HA reaching joints in rats and dogs, and, without absorption, HA binding intestinal TLR4 to raise IL-10 and SOCS3 and lower pleiotrophin in a mouse model. It gives the effective intake as 48 to 240 mg/day for 2 weeks to 12 months and says the minimal dose and duration are not established.

Population

Review of 13 reports of ingested hyaluronan for knee pain, 2008 to 2015 (11 randomised placebo-controlled trials, one retrospective cohort against paracetamol and one meta-analysis of two trials), plus mechanism and safety studies

Intervention

Oral hyaluronan at 48 to 240 mg/day of HA, given as pure HA or as 80 to 4,800 mg/day of HA-containing mixtures, for 2 weeks to 12 months

Comparator

Mostly placebo

Limitations

Four of nine authors are employees of Kewpie Corporation, an HA manufacturer, and the review declares no competing interests; the trial set is largely small sponsor-run Japanese and Spanish studies, and several used HA-containing mixtures whose other components the review itself says cannot be ruled out. It does not mention CD44 or induced endogenous HA synthesis.