Reviewed: Moré M, Gruenwald J, Pohl U, Uebelhack R. A Rosa canina – Urtica dioica – Harpagophytum procumbens/zeyheri combination significantly reduces gonarthritis symptoms in a randomized, placebo-controlled double-blind study. Planta Med. December 2017;83(18):1384-1391. doi: 10.1055/s-0043-112750.
Knee osteoarthritis (KO), or gonarthritis, is one of the most common disorders of the musculoskeletal system. KO is characterized by the destruction of articular cartilage and results in joint pain and stiffness. The formulation MA212, or Rosaxan (medAgil Gesundheitsgesellschaft mbH; Friedrichshafen, Germany), is a liquid “food for special medical purposes” (per the EU regulatory definition) that is used to manage KO pain. The authors conducted a placebo-controlled, randomized, double-blind study to examine the safety and efficacy of MA212 in reducing pain and improving symptoms in patients with KO.
MA212 contains 20 g rosehip (Rosa canina, Rosaceae) fruit puree, 4 g rosehip juice concentrate (concentration factor 7.1) derived from fruit puree, 160 mg stinging nettle (Urtica dioica, Urticaceae) leaf dry extract (drug extract ratio [DER] 10:1), and 108 mg devil’s claw (Harpagophytum procumbens or H. zeyheri, Pedaliaceae) root extract (DER 1.5-2.5:1). Rosehip, stinging nettle, and devil’s claw have been used in folk medicine for their anti-inflammatory and pain-relieving effects. Three-dimensional high-performance liquid chromatography identified isoquercitrin, rutin, and harpagoside, which are markers specific to rosehip, nettle, and devil’s claw, respectively.
The study enrolled 92 patients (30-70 years of age) with KO who were randomly assigned to the MA212 or placebo group, with 46 patients in each group. The patients had been diagnosed with unilateral or bilateral KO with moderate pain based on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The study was conducted from July 2015 until November 2015 in two German medical practices. The patients were evaluated at baseline and after six and 12 weeks. At baseline, all patients had similar characteristics, including WOMAC pain scores. Several patients in both groups had comorbidities, such as hypertension, OA in other joints, hypothyroidism, hypercholesterolemia, and diabetes mellitus.
The test group took 40 mL of MA212 with a tablet containing 200 IU vitamin D once daily after breakfast for 12 weeks. The placebo group ingested a vegetable mixture that consisted predominantly of tomato (Solanum lycopersicum, Solanaceae) juice plus minor vegetable components to match the color and taste of MA212. Study physicians rated the compliance as “very good” for 85% and “good” for 15% of the patients in the MA212 group. For the placebo group, they rated the compliance “very good” for 51% and “good” for 49% of the patients.
Mild adverse effects were reported by 11 patients in the MA212 group and 16 in the placebo group. Two patients in the MA212 group were excluded from the valid case analysis set (VCAS) because they used an unapproved medication to treat KO pain. Two patients in the placebo group dropped out from the full analysis set (FAS) before the onset of the study. One further patient dropped out after the six-week visit but was included in the FAS for the duration of the treatment received, leaving 44 and 43 patients in the MA212 and placebo VCAS, respectively.
The authors reported significant improvements in WOMAC pain scores in both groups at weeks six and 12 (P < .001) compared with baseline. The mean change in pain score at week 12 was 29.87 in the MA212 group and 10.23 in the placebo group, with a significant between-group difference (P < .001). Specifically, the baseline WOMAC pain score of 60.0 in the MA212 group decreased to 41.0 after six weeks and to 30.2 after 12 weeks. The placebo group began the study with an average WOMAC pain score of 60.1; those scores decreased to 52.1 after six weeks and to 49.9 after 12 weeks. After 12 weeks, 91.3% of patients in the MA212 group reported an improvement of at least 21 index points. In the placebo group, most patients experienced improvements of 1-20 points. The between-group difference was significant (P < .001).
The WOMAC scores for stiffness and function, and the overall scores, significantly improved in both groups (P < .001) but more so in the MA212 group (P < .001). VCAS analyses yielded identical significances.
Three patients in the MA212 group took acetylsalicylic acid (i.e., aspirin) daily; more patients in both groups took other analgesics as needed for various ailments other than those related to KO. The number of patients who used analgesics for KO totaled 13 in the MA212 group and 17 in the placebo group.
Both physical and mental quality of life improved significantly in the MA212 group compared with the placebo group (P < .001). These improvements “are likely to be caused by the reduced pain and stiffness, as well as the improved knee function,” wrote the authors.
The authors noted that “A significant placebo effect has been observed in the majority of osteoarthritis studies,” and that the vegetable juice content of the placebo may have had an impact on the subjects’ OA symptoms. In addition, due to the chronic nature of OA, the duration of the study was relatively short.
MA212 received a better overall rating than the placebo by physicians and by patients (P < .001 for both), and its tolerability was rated superior to placebo by physicians and patients (P = .005 for both). The authors concluded that “This study demonstrates excellent efficacy for MA212 in gonarthritis patients.”