Topical herbal therapies for treating osteoarthritis (review)

Background Before extraction and synthetic chemistry were invented, musculoskeletal complaints were treated with preparations from medicinal plants. They were either administered orally or topically. In contrast to the oral medicinal plant products, topicals act in part as counterirritants or are toxic when given orally. Objectives To update the previous Cochrane review of herbal therapy for osteoarthritis from 2000 by evaluating the evidence on effectiveness for topical medicinal plant products. Search methods Databases for mainstream and complementary medicine were searched using terms to include all forms of arthritis combined with medicinal plant products. We searched electronic databases (Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, CINAHL, ISI Web of Science, World Health Organization Clinical Trials Registry Platform) to February 2013, unrestricted by language. We also searched the reference lists from retrieved trials. Selection criteria Randomised controlled trials of herbal interventions used topically, compared with inert (placebo) or active controls, in people with osteoarthritis were included. Data collection and analysis Two review authors independently selected trials for inclusion, assessed the risk of bias of included studies and extracted data. Main results Seven studies (seven different medicinal plant interventions; 785 participants) were included. Single studies (five studies, six interventions) and non‐comparable studies (two studies, one intervention) precluded pooling of results. Moderate evidence from a single study of 174 people with hand osteoarthritis indicated that treatment with Arnica extract gel probably results in similar benefits as treatment with ibuprofen (non‐steroidal anti‐inflammatory drug) with a similar number of adverse events. Mean pain in the ibuprofen group was 44.2 points on a 100 point scale; treatment with Arnica gel reduced the pain by 4 points after three weeks: mean difference (MD) ‐3.8 points (95% confidence intervals (CI) ‐10.1 to 2.5), absolute reduction 4% (10% reduction to 3% increase). Hand function was 7.5 points on a 30 point scale in the ibuprofen‐treated group; treatment with Arnica gel reduced function by 0.4 points (MD ‐0.4, 95% CI ‐1.75 to 0.95), absolute improvement 1% (6% improvement to 3% decline)). Total adverse events were higher in the Arnica gel group (13% compared to 8% in the ibuprofen group): relative risk (RR) 1.65 (95% CI 0.72 to 3.76). Moderate quality evidence from a single trial of 99 people with knee osteoarthritis indicated that compared with placebo, Capsicum extract gel probably does not improve pain or knee function, and is commonly associated with treatment‐related adverse events including skin irritation and a burning sensation. At four weeks follow‐up, mean pain in the placebo group was 46 points on a 100 point scale; treatment with Capsicum extract reduced pain by 1 point (MD ‐1, 95% CI ‐6.8 to 4.8), absolute reduction of 1% (7% reduction to 5% increase). Mean knee function in the placebo group was 34.8 points on a 96 point scale at four weeks; treatment with Capsicum extract improved function by a mean of 2.6 points (MD ‐2.6, 95% CI ‐9.5 to 4.2), an absolute improvement of 3% (10% improvement to 4% decline). Adverse event rates were greater in the Capsicum extract group (80% compared with 20% in the placebo group, rate ratio 4.12, 95% CI 3.30 to 5.17). The number needed to treat to result in adverse events was 2 (95% CI 1 to 2). Moderate evidence from a single trial of 220 people with knee osteoarthritis suggested that comfrey extract gel probably improves pain without increasing adverse events. At three weeks, the mean pain in the placebo group was 83.5 points on a 100 point scale. Treatment with comfrey reduced pain by a mean of 41.5 points (MD ‐41.5, 95% CI ‐48 to ‐34), an absolute reduction of 42% (34% to 48% reduction). Function was not reported. Adverse events were similar: 6% (7/110) reported adverse events in the comfrey group compared with 14% (15/110) in the placebo group (RR 0.47, 95% CI 0.20 to 1.10). Although evidence from a single trial indicated that adhesive patches containing Chinese herbal mixtures FNZG and SJG may improve pain and function, the clinical applicability of these findings are uncertain because participants were only treated and followed up for seven days. We are also uncertain if other topical herbal products (Marhame‐Mafasel compress, stinging nettle leaf) improve osteoarthritis symptoms due to the very low quality evidence from single trials. No serious side effects were reported. Authors' conclusions Although the mechanism of action of the topical medicinal plant products provides a rationale basis for their use in the treatment of osteoarthritis, the quality and quantity of current research studies of effectiveness are insufficient. Arnica gel probably improves symptoms as effectively as a gel containing non‐steroidal anti‐inflammatory drug, but with no better (and possibly worse) adverse event profile. Comfrey extract gel probably improves pain, and Capsicum extract gel probably will not improve pain or function at the doses examined in this review. Further high quality, fully powered studies are required to confirm the trends of effectiveness identifed in studies so far

Oral herbal therapies for treating osteoarthritis (review)

Background Medicinal plant products are used orally for treating osteoarthritis. Although their mechanisms of action have not yet been elucidated in full detail, interactions with common inflammatory mediators provide a rationale for using them to treat osteoarthritic complaints. Objectives To update a previous Cochrane review to assess the benefits and harms of oral medicinal plant products in treating osteoarthritis. Search methods We searched electronic databases (CENTRAL, MEDLINE, EMBASE, AMED, CINAHL, ISI Web of Science, World Health Organization Clinical Trials Registry Platform) to 29 August 2013, unrestricted by language, and the reference lists from retrieved trials. Selection criteria Randomised controlled trials of orally consumed herbal interventions compared with placebo or active controls in people with osteoarthritis were included. Herbal interventions included any plant preparation but excluded homeopathy or aromatherapy products, or any preparation of synthetic origin. Data collection and analysis Two authors used standard methods for trial selection and data extraction, and assessed the quality of the body of evidence using the GRADE approach for major outcomes (pain, function, radiographic joint changes, quality of life, withdrawals due to adverse events, total adverse events, and serious adverse events). Main results Forty‐nine randomised controlled studies (33 interventions, 5980 participants) were included. Seventeen studies of confirmatory design (sample and effect sizes pre‐specified) were mostly at moderate risk of bias. The remaining 32 studies of exploratory design were at higher risk of bias. Due to differing interventions, meta‐analyses were restricted to Boswellia serrata (monoherbal) and avocado‐soyabean unsaponifiables (ASU) (two herb combination) products. Five studies of three different extracts from Boswellia serrata were included. Moderate‐quality evidence from two studies (85 participants) indicated that 90 days treatment with 100 mg of enriched Boswellia serrata extract improved symptoms compared to placebo. Mean pain was 40 points on a 0 to 100 point VAS scale (0 is no pain) with placebo, enriched Boswellia serrata reduced pain by a mean of 17 points (95% confidence interval (CI) 8 to 26); number needed to treat for an additional beneficial outcome (NNTB) 2; the 95% CIs did not exclude a clinically significant reduction of 15 points in pain. Physical function was 33 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) 0 to 100 point subscale (0 is no loss of function) with placebo, enriched Boswellia serrata improved function by 8 points (95% CI 2 to 14); NNTB 4. Assuming a minimal clinically important difference of 10 points, we cannot exclude a clinically important benefit in some people. Moderate‐quality evidence (one study, 96 participants) indicated that adverse events were probably reduced with enriched Boswellia serrata (18/48 events versus 30/48 events with placebo; relative risk (RR) 0.60, 95% CI 0.39 to 0.92). Possible benefits of other Boswellia serrata extracts over placebo were confirmed in moderate‐quality evidence from two studies (97 participants) of Boswellia serrata (enriched) 100 mg plus non‐volatile oil, and low‐quality evidence from small single studies of a 999 mg daily dose of Boswellia serrata extract and 250 mg daily dose of enrichedBoswellia serrata. It was uncertain if a 99 mg daily dose of Boswellia serrata offered benefits over valdecoxib due to the very low‐quality evidence from a small single study. It was uncertain if there was an increased risk of adverse events or withdrawals with Boswellia serrata extract due to variable reporting of results across studies. The studies reported no serious adverse events. Quality of life and radiographic joint changes were not measured. Six studies examined the ASU product Piasclidine®. Moderate‐quality evidence from four studies (651 participants) indicated that ASU 300 mg produced a small and clinically questionable improvement in symptoms, and probably no increased adverse events compared to placebo after three to 12 months treatment. Mean pain with placebo was 40.5 points on a VAS 0 to 100 scale (0 is no pain), ASU 300 mg reduced pain by a mean of 8.5 points (95% CI 1 to 16 points); NNTB 8. ASU 300 mg improved function (standardised mean difference (SMD) ‐0.42, 95% CI ‐0.73 to ‐0.11). Function was estimated as 47 mm (0 to 100 mm scale, where 0 is no loss of function) with placebo, ASU 300 mg improved function by a mean of 7 mm (95% CI 2 to 12 mm); NNTB 5 (3 to 19). There were no differences in adverse events (5 studies, 1050 participants) between ASU (53%) and placebo (51%) (RR 1.04, 95% CI 0.97 to 1.12); withdrawals due to adverse events (1 study, 398 participants) between ASU (17%) and placebo (15%) (RR 1.14, 95% CI 0.73 to 1.80); or serious adverse events (1 study, 398 participants) between ASU (40%) and placebo (33%) (RR 1.22, 95% CI 0.94 to 1.59). Radiographic joint changes, measured as change in joint space width (JSW) in two studies (453 participants) did not differ between ASU 300 mg treatment (‐0.53 mm) and placebo (‐0.65 mm); mean difference of ‐0.12 (95% CI ‐0.43 to 0.19). Moderate‐quality evidence from a single study (156 participants) confirmed possible benefits of ASU 600 mg over placebo, with no increased adverse events. Low‐quality evidence (1 study, 357 participants) indicated there may be no differences in symptoms or adverse events between ASU 300 mg and chondroitin sulphate. Quality of life was not measured. All other herbal interventions were investigated in single studies, limiting conclusions. No serious side effects related to any plant product were reported. Authors' conclusions Evidence for the proprietary ASU product Piasclidine® in the treatment of osteoarthritis symptoms seems moderate for short term use, but studies over a longer term and against an apparently active control are less convincing. Several other medicinal plant products, including extracts of Boswellia serrata, have moderate‐quality evidence for trends of benefits that warrant further investigation in light of the fact that the risk of adverse events appear low. There is no evidence that Piasclidine® significantly improves joint structure, and limited evidence that it prevents joint space narrowing. Structural changes were not tested for with any other herbal intervention. Further investigations are required to determine optimum daily doses producing clinical benefits without adverse events

Herbal therapy for treating rheumatoid arthritis (review)

Background Herbal medicine interventions have been identified as having potential benefit in the treatment of rheumatoid arthritis (RA). Objectives To update an existing systematic (Cochrane) review of herbal therapies in RA. Search methods We searched electronic databases Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, AMED, CINAHL, Web of Science, Dissertation Abstracts (1996 to 2009), unrestricted by language, and the WHO International Clinical Trials Registry Platform in October 2010. Selection criteria Randomised controlled trials of herbal interventions compared with placebo or active controls in RA. Data collection and analysis Two authors selected trials for inclusion, assessed risk of bias and extracted data. Main results Twelve new studies were added to the update, a total of 22 studies were included. Evidence from seven studies indicate potential benefits of gamma linolenic acid (GLA) from evening primrose oil, borage seed oil, or blackcurrent seed oil, in terms of reduced pain intensity (mean difference (MD) ‐32.83 points, 95% confidence interval (CI) ‐56.25 to ‐9.42,100 point pain scale); improved disability (MD ‐15.75% 95% CI ‐27.06 to ‐4.44%); and an increase in adverse events (GLA 20% versus placebo 3%), that was not statistically different (relative risk 4.24, 95% CI 0.78 to 22.99). Three studies compared Tripterygium wilfordii (thunder god vine) to placebo and one to sulfasalazine and indicated improvements in some outcomes, but data could not be pooled due to differing interventions, comparisons and outcomes. One study reported serious side effects with oral Tripterygium wilfordii Hook F. In the follow‐up studies, all side effects were mild to moderate and resolved after the intervention ceased. Two studies compared Phytodolor® N to placebo but poor reporting limited data extraction. The remaining studies each considered differing herbal interventions. Authors' conclusions Several herbal interventions are inadequately justified by single studies or non‐comparable studies in the treatment of rheumatoid arthritis. There is moderate evidence that oils containing GLA (evening primrose, borage, or blackcurrant seed oil) afford some benefit in relieving symptoms for RA, while evidence for Phytodolor® N is less convincing.Tripterygium wilfordii products may reduce some RA symptoms, however, oral use may be associated with several side effects. Many trials of herbal therapies are hampered by research design flaws and inadequate reporting. Further investigation of each herbal therapy is warranted, particularly via well designed, fully powered, confirmatory clinical trials that use American College of Rheumatology improvement criteria to measure outcomes and report results according to CONSORT guidelines

Efficacy and Safety of Pomegranate Medicinal Products for Cancer

Preclinical in vitro and in vivo studies demonstrate potent effects of pomegranate preparations in cancer cell lines and animal models with chemically induced cancers. We have carried out one systematic review of the effectiveness of pomegranate products in the treatment of cancer and another on their safety. The PubMed search provided 162 references for pomegranate and cancer and 122 references for pomegranate and safety/toxicity. We identified 4 clinical studies investigating 3 pomegranate products, of which one was inappropriate because of the low polyphenol content. The evidence of clinical effectiveness was poor because the quality of the studies was poor. Although there is no concern over safety with the doses used in the clinical studies, pomegranate preparations may be harmful by inducing synthetic drug metabolism through activation of liver enzymes. We have analysed various pomegranate products for their content of anthocyanins, punicalagin, and ellagic acid in order to compare them with the benchmark doses from published data. If the amount of coactive constituents is not declared, patients risk not benefiting from the putative pomegranate effects. Moreover, pomegranate end products are affected by many determinants. Their declaration should be incorporated into the regulatory guidance and controlled before pomegranate products enter the market

Best Available Evidence in Cochrane Reviews on Herbal Medicine?

Cochrane reviews are considered by many to be the “gold standard” or the final word in medical conversation on a topic. We explored the eleven most relevant Cochrane reviews on herbal medicine and identified that frequently herbal medicines in the included studies had not been sufficiently well characterised. If data on the effects of the plant parts are unavailable, effects of co-active ingredients need to be considered and the plausibility of the study medications for the specific indications discussed. Effect sizes calculated from exploratory studies would be best used to determine the sample sizes required for future confirmatory studies, rather than as definitive reports of intervention effects. Reviews should be comprehensive, including discussion of putative adverse events and possible drug interactions. We suggest that the guidelines for preparing Cochrane reviews be revised and offer assistance in this task

Harpgophytum procumbens for osteoarthritis and low back pain: A systematic review

BACKGROUND: The objective of this review is to determine the effectiveness of Harpagophytum procumbens preparations in the treatment of various forms of musculoskeletal pain. METHODS: Several databases and other sources were searched to identify randomized controlled trials, quasi-randomized controlled trials, and controlled clinical trials testing Harpagophytum preparations in adults suffering from pain due to osteoarthritis or low back pain. RESULTS: Given the clinical heterogeneity and insufficient data for statistical pooling, trials were described in a narrative way, taking into consideration methodological quality scores. Twelve trials were included with six investigating osteoarthritis (two were identical trials), four low back pain, and three mixed-pain conditions. CONCLUSIONS: There is limited evidence for an ethanolic Harpagophytum extract containing less than <30 mg harpagoside per day in the treatment of knee and hip osteoarthritis. There is moderate evidence of effectiveness for (1) the use of a Harpagophytum powder at 60 mg harpagoside in the treatment of osteoarthritis of the spine, hip and knee; (2) the use of an aqueous Harpagophytum extract at a daily dose of 100 mg harpagoside in the treatment of acute exacerbations of chronic non-specific low back pain; and (3) the use of an aqueous extract of Harpagophytum procumbens at 60 mg harpagoside being non-inferior to 12.5 mg rofecoxib per day for chronic non-specific low-back pain (NSLBP) in the short term. Strong evidence exists for the use of an aqueous Harpagophytum extract at a daily dose equivalent of 50 mg harpagoside in the treatment of acute exacerbations of chronic NSLBP

Efficacy and safety of Harpagophytum and Salix extract preparations

AbstractIn Europe, extracts from Harpagophytum procumbens and Salix species are widely used for the treatment of rheumatic pain. Declaration of the quantity of active principles helps to optimize treatment success. For both herbal medicinal products, pharmacological and clinical studies have proven antirheumatic effectiveness which is superior to placebo and equally effective compared to synthetic medication. Treatment of osteoarthritic and low back pain with Harpagophytum procumbens and Salix extracts is associated with a low incidence of adverse events lower than that known from NSAIDs. In terms of quality, safety and efficacy, Harpagophytum procumbens and Salix extract preparations may fulfill the requirements that characterize synthetic medication

L’efficacité et la sécurité des préparations à base d’extraits d’Harpagophytum et de Salix

RésuméEn Europe, on utilise largement des extraits d’espèces d’Harpagophytum procumbens et de Salix pour le traitement des douleurs rhumatismales. L’établissement de la quantité de principes actifs permet d’optimiser le traitement. Pour ces deux phyto-médicaments, des études cliniques et pharmacologiques ont mis en évidence une efficacité dans la lutte contre le rhumatisme qui est supérieure à celle du placebo et égale à celle des médications à base de produits de synthèse. Le traitement des douleurs lombaires liées à l’arthose par extraits d’Harpagophytum procumbens et de Salix est associé à la faible incidence des effets secondaires ; elle est en tout cas plus faible que celle observée avec les anti-inflammatoires non stéroïdiens ou AINS. En termes de qualité, de sécurité et d’efficacité, il est possible que les préparations à partir d’extraits d’Harpagophytum procumbens et de Salix puissent remplir les conditions caractérisant les médicaments de synthèse