Version May 2024
INTRODUCTION — A considerable variety of complementary and alternative medicine (CAM) modalities have been suggested for managing patients with rheumatologic, autoimmune, and musculoskeletal disorders (table 1).
The efficacy and safety of CAM therapies are reviewed here, including those for which reasonable data are available and selected others that are popular. Overviews of herbal medicines, dietary supplements, acupuncture, and spinal manipulation are presented elsewhere. (See "Overview of herbal medicine and dietary supplements" and "Overview of the clinical uses of acupuncture" and "Spinal manipulation in the treatment of musculoskeletal pain".)
ROLE OF CAM REMEDIES IN RHEUMATIC DISEASE CARE — Interest in complementary and alternative medicine (CAM) remedies can be perceived as a challenge and opportunity for clinicians; while these interventions are not usually important therapeutically, the popularity of CAM informs us of the need to be sensitive, responsive, and empathetic to our patients and their needs. Our patients' persistent attraction to CAM therapies also reminds us that we still need to better identify causes and cures for the rheumatic diseases.
The clinician's response to use of complementary and alternative remedies should include education of the patient and maintenance of communication with the patient regarding these issues.
Despite the substantial interest in these therapies, the authors do not consider that anything markedly transformative has emerged from the field of CAM remedies for managing patients with rheumatic diseases [1-22]. Rheumatologists not universally recommending CAM therapies for their patients are not withholding clinically important, useful, or proven interventions or adjunctive therapies. Nevertheless, familiarity and appreciation of general principles and modalities of CAM are likely to be useful for clinicians.
TERMINOLOGY — Terms for complementary and alternative medicine (CAM) remedies have evolved. The term "integrative" medicine is increasingly used. Contemporary "complementary and alternative medicine" was formerly simply called "quackery" and was ridiculed. Attitudes of both the public and scientific community have changed over the years, and CAM became an acceptable label, particularly with the establishment of the Office of Alternative Medicine at the National Institutes of Health (NIH) in 1992 (despite considerable opposition at that time from the scientific community). The program was first called the National Center for Complementary and Alternative Medicine and subsequently renamed the National Center for Complementary and Integrative Health [1,5,21,22].
"Complementary" and "alternative" have been generally adopted in place of more pejorative terms [1,21,22]. The label "integrative" medicine, which is commonly used, is intended to reflect inclusion of evidence-based therapies into conventional practice, regardless of their origin [21,22]. This term is not always applied to therapies with scientific rigor and sometimes portrays them with more euphemism than available data would suggest. A taxonomy for CAM has also been described [23].
This discussion will adhere to convention and use the term "complementary and alternative medicine," or CAM, because of the wide acceptance of this label, although the authors prefer the terms "mainstream" and "nonmainstream" to categorize these therapies [1,5,21,22]. Other terms, such as "unproven remedies," are also problematic. As examples, there have been "mainstream" routine practices that historically were not supported by evidence or proven safe (eg, tonsillectomy and adenoidectomy, certain arthroscopic and back operations, irradiation for acne or ankylosing spondylitis, and iced saline lavage for gastrointestinal bleeding) [1,21,22]. Other therapies are evidence-based but remain eschewed by certain cultures (and are "nonmainstream"; eg, balneotherapy) [1,21,22].
EPIDEMIOLOGY AND PATTERN OF USE — Complementary and alternative medicine (CAM) has broad popularity and appeal; most patients with rheumatic and musculoskeletal diseases will consider or use CAM therapies [3,24-29]. Surveys of patients followed in private- and university-based rheumatology practices found that approximately two-thirds had used some form of complementary or alternative therapy [3,24]. In the United States, 28 to 94 percent of rheumatic disease patients have been estimated to have tried CAM [3]. In a 2011 report, 38 percent of all adults in the United States had used CAM, at a total cost of $34 billion/year or $122/person/year, accounting for 1.5 percent of total health expenditures and 11 percent of out-of-pocket expenditures on health care [3]. Thus, regardless of the clinician's attitude or "belief" in CAM, clinician familiarity with CAM remedies being used by rheumatologic patients is necessary to care properly for patients and to communicate effectively with patients and colleagues. (See "Overview of herbal medicine and dietary supplements", section on 'United States' and "Overview of herbal medicine and dietary supplements", section on 'International'.)
Survey data have found that CAM users have generally tended to be women who were well educated and economically comfortable [30]. CAM therapies have been used for chronic, as opposed to life-threatening, medical conditions [30]. In particular, CAM therapies were frequently used by patients with rheumatologic conditions such as arthritis, chronic back pain, and other painful musculoskeletal disorders [3,31].
One large survey noted that, over the course of a year, there were more patient visits to CAM practitioners than to primary care clinicians in the United States, yet a majority of CAM users did not inform their medical doctors of their use of alternative therapies [32]. Additionally, in another study, almost 50 percent of CAM users did so without any professional supervision [33], with patients more likely to choose non-practitioner-based CAM therapy than practitioner-based CAM therapy [33].
A nationwide telephone survey found that the use of CAM increased with the number of patients' medical conditions and the number of clinician visits [32]. Patients who reported poor health had substantially higher rates of use of CAM therapies than those who perceived themselves to be in better health (52 versus 33 percent). Studies of patients with specific rheumatologic conditions such as fibromyalgia, osteoarthritis, and systemic lupus erythematosus have found that most CAM users tended to be individuals with longer duration of disease, poorer functional status, and higher levels of pain [25]. It is likely that different individuals selected different CAM treatments for differing reasons.
FACTORS DRIVING USE — Patients reported using complementary and alternative medicine (CAM) therapies for a number of reasons, including being more congruent with their own values and beliefs about their health and lives. These reasons include [1,3,21,22,26,34]:
●A view of CAM therapies as consonant with their lifestyle and/or belief system
●An effort to seek a holistic approach to medical care
●A perception of CAM treatments as safer and more natural than prescription drugs
●Yearning for certainty and simplicity
●Hoping for a cure or pain relief
●A desire for a sense of control over their illness
●A desire to avoid adverse effects from therapies
●Rejection of or dissatisfaction with conventional medical care for many reasons, including:
•Perceived lack of empathy of practitioners
•Cost and toxicities of mainstream therapies
•Uncertainties about outcomes
Further, some studies suggested that patients preferring CAM tended to be more psychologically distressed and considered their health poorer than others [28,35]. A majority of patients used CAM to complement conventional care rather than substitute for it [1,3,21,22,27].
GENERAL SAFETY CONCERNS — It is a prevalent misconception among patients and the general public that complementary and alternative medicine (CAM) therapies are "natural" and "harmless" [3,31,36]. However, CAM products can be dangerous due to any of several factors, including contaminants, drug interactions, and direct adverse effects. The regulatory approaches to herbal medications and supplements in the United States and in other countries and the implications for drug safety are described separately. (See "Overview of herbal medicine and dietary supplements", section on 'Regulation in the United States' and "Overview of herbal medicine and dietary supplements", section on 'International regulation'.)
Patients have suffered from infections, injections, and adverse effects of contaminants of CAM modalities such as arsenic, lead, mercury, caffeine, analgesics, phenylbutazone, glucocorticoids, nonsteroidal antiinflammatory drugs (NSAIDs), and ephedrine [1,3,37-41]. Rarely, patients have died due to CAM remedies and their components. Additionally, there are potential interactions between many herbal therapies and conventional medications, some clinically important, that are not always recognized. (See "Overview of herbal medicine and dietary supplements", section on 'Herb-drug interactions'.)
There are also direct adverse effects of certain CAM therapies. Examples include bleeding, pain, hematoma, and, rarely, pneumothorax from acupuncture [42] and headache, local discomfort, dizziness, and a rare cerebrovascular accident from manipulation [43]. (See "Overview of the clinical uses of acupuncture", section on 'Adverse events' and "Spinal manipulation in the treatment of musculoskeletal pain", section on 'Risks of spinal manipulation'.)
In one study, some patients received up to 19 remedies, discontinued their formal treatment 11 times, visited CAM providers up to 180 times, and spent the equivalent of 1.3 days' wages on CAM, all of these in one year [44]. There are also risks from patients not communicating with their rheumatologist or other clinicians about CAM use [1,3,43,44].
Although some have argued that patients should be permitted to try CAM therapies because they are often thought to be at least innocuous, the authors' views are that it is irresponsible to use therapies generally not established as acceptably safe and effective by a preponderance of good evidence. The following concerns are relevant:
●There are documented instances of patients who received therapies other than those promised and who suffered from adverse results, including deleterious interactions with conventional pharmacotherapy, marrow aplasia, serious infections from contaminants, and death [3,45,46].
●Patients seeking CAM remedies may inappropriately neglect their illness and established therapies that have proven to be effective [1,3].
●Expenditures on CAM remedies may divert scarce personal and health care resources from more appropriate uses.
●Similar to variability in efficacy and tolerability of well-established rheumatic disease drugs for the diverse population of rheumatic disease patients, it is highly unlikely that there will be "one size fits all" CAM recommendations for rheumatic disease patients, especially given the heterogeneity of their conditions.
SELECTED COMPLEMENTARY AND ALTERNATIVE REMEDIES — A number of different complementary and alternative (CAM) modalities are used by patients with rheumatic diseases (table 1) [2,3,21,22,47,48]. Representative examples of CAM remedies are reviewed here, which are organized into the following categories:
●Therapies known not to be of clinical benefit.
●Therapies that have not been adequately studied.
●Therapies with limited but inadequate or inconsistent evidence.
●Therapies generally accepted to be of clinical value but which are recommended with varying degrees of enthusiasm for reasons of culture and/or efficacy. These treatments would no longer meet the definition of CAM, but some clinicians would still view them in that way.
Therapies known to be of no clinical benefit
Antibiotics and antimicrobials — Various antibiotics and other antimicrobials advocated as CAM have not been shown to be useful in the routine treatment of patients with chronic rheumatic diseases. The medication that is an exception is minocycline (and this discussion is not pertinent to diseases known to be due to an active infection, like septic arthritis due to a bacterial infection such as Staphylococcus aureus or certain patients with Lyme disease).
A suggested rationale for the use of antimicrobials for rheumatic disease is the longstanding attractive, but unproven, hypothesis arguing for a microbial etiology for rheumatoid arthritis (RA), systemic lupus erythematosus, and perhaps other rheumatic diseases. Antimicrobials might be useful therapeutically if this hypothesis were true. They might also be effective by virtue of mechanisms of action other than being antimicrobial. As examples, they might have antiinflammatory, immunomodulatory, and/or antirheumatic effects by perturbing gene expression, immune responses, cells, mediators, pathways, signal transduction and transcription, and other biologic processes, also including the microbiome [49]. The following are illustrative examples.
●Tetracyclines – Tetracycline therapy was originally tried because of a putative mycoplasma etiology for RA. Such therapy was considered ineffective for many years. This issue was revisited, however, since later scientific work found that tetracyclines, particularly minocycline, may have significant physiologic effects, including reducing collagenase activity, lessening bone resorption, and affecting T-cell and neutrophil function. In addition, these drugs were found to be antiproliferative, antiinflammatory, and antiarthritic in animal and possibly human arthritis. Studies documented efficacy of these agents for RA [50] but not consistently for osteoarthritis [51]. This is an example of a therapy for RA that was once "complementary" or "alternative" but is now "integrative" or "mainstream" for RA but of no benefit for osteoarthritis. (See "Alternatives to methotrexate for the initial treatment of rheumatoid arthritis in adults".)
●Other antibiotics – A number of antibiotics other than tetracyclines have been suggested as CAM remedies but not been found to be of consistent or proven value for treating rheumatic disorders. These included nitroimidazoles, ceftriaxone, ampicillin, amantadine, clarithromycin, clindamycin, and combination antibiotics [22,52-57].
●Treatment (nonsurgical) of periodontal infection – Nonsurgical therapy for periodontal infection, without recent or concurrent use of antibiotics, has been suggested as a strategy to favorably influence clinical outcomes in patients with RA, given the growing interest in a role for the microbiome generally, and periodontal disease specifically, in the etiopathogenesis of RA [58]. There has been speculation that formal study of antibiotic therapy, from this perspective, might be of interest [49,58,59].
Apheresis (for uncomplicated rheumatic diseases) — Once investigational and considered widely in the management of autoimmune and rheumatic disorders, apheresis is now usually reserved for use only in a limited number of conditions for which there has been some evidence of benefit and "as a last resort in desperate situations when conventional therapies have failed or are likely to fail," particularly for certain patients with antiphospholipid antibody syndrome, pulmonary hemorrhage, hyperviscosity syndrome, cryoglobulinemia, thrombotic thrombocytopenic purpura, Guillain-Barré syndrome, and Goodpasture syndrome [22,60]. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology".)
Copper bracelets — Copper salts have been antirheumatic in clinical trials, but their use was associated with many adverse effects [21,61,62]. As a result, copper salts have not evolved as an important therapeutic agent.
DMSO and hyperbaric oxygen — Dimethyl sulfoxide (DMSO) and hyperbaric oxygen were not of proven value for RA [21,22,63-66].
Therapies that have not been studied — A number of potential CAM therapies, suggested to have antirheumatic properties, lack scientific evidence to determine their benefits and the nature of their potential risks. These include cetyl myristoleate (CMO), methylsulfonylmethane (MSM), shark cartilage, Zinaxin (an herbal remedy made from ginger extracts), and others [2,21,22,67-69].
Therapies with limited but inadequate or inconsistent evidence
Acupuncture — Acupuncture has not been found effective in patients with RA [70-73] and is not a risk-free procedure. A review of reported complications included two deaths due to needle injuries to the heart and 90 pneumothoraces, of which two were fatal [74]. There have been numerous studies of acupuncture for osteoarthritis, some randomized and controlled. These are not easy to interpret because it is not clear what constitutes the optimal control for the intervention. Several trials suggested benefit [13-16,18,75,76]. Acupuncture is discussed in detail separately. (See "Overview of the clinical uses of acupuncture".)
Ayurveda — Ayurveda is an ancient Indian medical system utilizing a variety of products and practices. Two Ayurvedic mixtures, borage, garlic, Phytodolor, Uncaria tomentosa, and selenium have been studied, but critical reviews have not considered that there was satisfactory evidence of efficacy [77,78]. These studies were small, and the effects were modest at best and need confirmation in standardized trials [78,79]. One randomized pilot trial, involving a total of 43 patients with RA, found classic Ayurveda, methotrexate, and their combination to be approximately equivalent, although the trial involved only a small number of patients and the results were imprecise [79]. Data for osteoarthritis have shown benefit but remain limited [80,81].
Cannabis and cannabinoids — The use of medical cannabis and related compounds for pain and other indications is described separately. (See "Treatment of chronic non-cancer pain in older adults", section on 'Cannabis and cannabinoids' and "Cannabis use and disorder: Epidemiology, pharmacology, comorbidities, and adverse effects".)
Diet and nutritional therapies — Dietary interventions do not have a clear, defined role in therapy for most patients with chronic inflammatory arthritis, osteoarthritis, or systemic autoimmune rheumatic disease, given the relative lack of evidence to support the efficacy of food, diet, or nutritional therapy for patients with these heterogenous conditions [2,21].
Studies regarding the role of nutrition and dietary intake in the development and treatment of rheumatic diseases are complicated by many factors that are not present in traditional drug trials. Among these are reliance upon patient-reported dietary intake surveys, the difficulty of defining an appropriate control group, the unclear length of time needed to appreciate the effect of diet on disease activity, high drop-out rates and feasibility issues in long-term (and often costly) studies, differences in food preparation and subsequent effect on nutritional value (and potential physiologic effects), lack of standardization between various nutritional supplements, and confounding factors associated with generally healthy lifestyle patterns. Such confounding factors include abstinence from tobacco use, moderate alcohol intake, and health-promoting sleep and social patterns. Reverse causation may also confound the picture, in which a "predisease" state may affect a patient's dietary choices in the weeks or months leading to formal disease diagnosis.
There are several specific situations in which nutrition has a clear role in the management of rheumatic diseases:
●In patients with gout, dietary composition and specific foods and drink are well established as risk factors for hyperuricemia, incident gout, or symptomatic flares of acute gout. Modification of these factors can influence disease development and expression, and attention to these issues is an important element of disease management. (See "Nonpharmacologic strategies for the prevention and treatment of gout".)
●There are rare patients with rheumatic diseases whose symptoms have been linked to certain foods or food products. These can only be identified with certainty by randomized, blinded, provocative, clinical challenge trials. There is also insufficient evidence to support the use of elimination or other diets for unselected patients with rheumatic diseases.
●Diets rich in fish or fish oil supplements (or certain vegetable oils) or that were "healthy" have provided marginal clinical benefit to patients, compared with normal diets. These trials have suggested small quantitative benefits of approximately one to three tender and/or swollen joints; such differences have been statistically significant, but usually not clinically important.
●As obesity has been associated with higher disease activity in inflammatory arthritis as well as a poor response to biologic medications, particularly tumor necrosis factor (TNF) inhibitors, patients with obesity should be counseled to pursue weight loss for maximum disease control [82,83].
Food, diet, and nutrition have been of considerable interest to both patients with rheumatic diseases and to clinicians since at least the time of Hippocrates. The potential for such interventions to be inexpensive, simple, accessible, safe, and enabling for patients makes them particularly appealing, but for many years, these were considered to be a prime example of "quackery" [84]. A general overview of dietary supplements is provided elsewhere. (See "Overview of herbal medicine and dietary supplements".)
Most of the available information in this area with respect to arthritis is from trials that have been inadequately blinded or poorly controlled, in part due to the challenges of trial design with interventions involving food, diet, or nutrition. However, there is evidence that some patients with rheumatic disease may be allergic to certain foods or antigens in their environment and have symptoms that might be a manifestation of allergy, "delayed allergy," or other hypersensitivity (such as milk, and possibly shrimp, nitrates, or others) [2,85-88]. Antibodies (cross-)reacting with microbial or food antigens, like citrullinated proteins, may also play a role in the pathogenesis of disease [89]. Additionally, certain types of diets with particular amounts of calories, protein, fatty acids, with particular quality or quantity of ingredients, may affect the immunologically mediated inflammation and pain that occurs with arthritis [2,88,90].
The effect of diet composition on the gut microbiome is also a topic of increasing interest, with the hypothesis that dietary intake may modulate the environment of the gut microbiome (including absolute and relative populations of certain microbiota and/or their production of bacterial metabolites, as well as alterations in intestinal permeability), which leads to downstream effects on the systemic immune system, and ultimately rheumatic disease development [91,92]. However, it remains to seen whether an altered gut microbiome ("dysbiosis") is a cause or consequence of systemic autoimmune disease. An understanding of the link between the gut environment and rheumatic disease pathophysiology is in its nascency, and additional data are needed to explain the role, if any, of nutrition and diet on this complex relationship.
Specific adverse effects of food, diet, or nutrition upon patients with arthritis are illustrated by the following:
●Inflammatory arthritis associated with cows' milk antigens – The strongest evidence that specific food intake may influence inflammatory arthritis comes from well-designed trials in individual selected (and likely rare) patients [85,87]. As an example, in one patient with symptoms and findings of inflammatory arthritis (30 minutes of morning stiffness, nine tender and three swollen joints) while on her regular diet, a three-day fast resulted in resolution of virtually all clinical manifestations of disease [87]. The clinical manifestations could then be reinduced by milk challenge but not with other foods. This patient was shown to have cellular and serologic immunologic sensitivity to cows' milk antigens.
●Other food triggers for arthritis – An association of arthritis with certain foods and other exposures has been found with a range of different substances [86-88]. As examples, palindromic rheumatism has been associated with sodium nitrate ingestion; Behçet syndrome with black walnuts; systemic lupus erythematosus-like symptoms from canavanine in alfalfa (which may cross-react with native deoxyribonucleic acid (DNA) or activate B lymphocytes) in some monkeys in one experiment, and with hydrazine; and RA with many substances including house dust, tobacco, smoke, petrochemicals, tartrazine, dairy products, wheat, corn, and beef. In addition, rheumatoid-like synovitis in rabbits has been induced by dietary cows' milk [93].
Beneficial effects of food, diet, or nutrition upon patients with arthritis are illustrated by the following:
●Effects of different diets – There is no compelling evidence that any diet other than a healthy, balanced one is consistently helpful to patients with arthritis. As an example, study of a popular diet (the elimination of red meat, additives, preservatives, fruit, dairy products, herbs, spices, and alcohol) for patients with arthritis found no consistent salutary effect on disease activity for patients with RA and did not affect patients with osteoarthritis [86]. A "healthy" diet provided marginal benefit for patients with RA (by a few tender/swollen joints) [94,95], as has a diet rich in fish [95,96] or a "Mediterranean diet" [90]. Adherence to a "Mediterranean diet" was inversely associated with risk of RA for men and for seropositive RA [97] and could reduce high risk of RA among ever-smoking women [98]. Importantly, a certain dietary pattern found to be a risk factor for or against disease development does not guarantee that it will play a significant role in treatment once the disease process has fully manifested itself.
●Effects on mediators of inflammation – Some observations have suggested that dietary factors that modify arachidonic acid-derived prostaglandin or leukotriene generation have the potential to affect inflammatory and immunologic responses and as a result may also have potential to ameliorate symptoms of rheumatic diseases, although consistent clinically important therapeutic benefit remains to be demonstrated. As examples:
•A Mediterranean diet has been described as providing benefit to patients with RA. In comparison with a typical "Western" diet, a Mediterranean diet generally derives fewer calories from animal fat and more from cereals and vegetable oils, particularly olive oil. Liberal intake of fresh fruits and beans as well as a moderate daily consumption of wine is also typical of this type of diet. The possible effects of a Mediterranean diet were the subject of a study in which 51 patients with RA were randomly assigned to a Mediterranean diet or to an omnivorous cuisine for 12 weeks [90]. While those subjects who ate a Mediterranean diet had more improvement in some measures of disease activity, other indicators were unchanged. There were few notable differences observed between patient global assessments or disease activity scores (DAS) among patient groups; the DAS28 in treated patients decreased by 0.56. Since the intervention and assessment were not blinded in any fashion, a significant placebo effect in the group assigned to the Mediterranean diet could not be excluded.
•Fish or plant oils have also been shown to be modulators of inflammation in patients with systemic lupus erythematosus and in RA. Recent studies suggested that omega polyunsaturated fatty acid intake may [99] while adherence to other dietary elements may not [100] affect expression or outcomes of patients with systemic lupus erythematosus and lupus nephritis. (See 'Fish and botanic oils' below.)
●Effects of nutritional supplements – A number of substances, typically administered as components of nutritional supplements, have been reported to be helpful for patients with arthritis, including copper, zinc, L-histidine, and vitamin B (table 1). In general, however, the evidence in support of such claims is scant [2,21]. As an example, some patients with RA have been reported to benefit from oral zinc; however, the improvement was modest, inconsistent, and was not confirmed in other studies [2,21]. In addition, although the administration of L-histidine helped a small set of patients with RA [2,21], it has not emerged as an important antirheumatic agent.
Evidence to support the efficacy of vitamin C for arthritis patients is also lacking [2,21]. Concentrations of vitamin B6 were reduced in the serum of patients with RA [101], and levels of pyridoxal 5' phosphate, the active metabolite of B6, were inversely correlated with disease activity [102]. However, the authors are unaware of studies attempting to examine the possible therapeutic effects of these nutriments in patients with arthritis or musculoskeletal or rheumatic diseases [2,21].
Glucosamine and chondroitin sulfate — Effects of glucosamine and chondroitin sulfate, which have been the subjects of multiple trials of varying quality and advocated for use in osteoarthritis, are described in detail separately. (See "Management of knee osteoarthritis", section on 'Nutritional supplements'.)
Herbal remedies — Various herbal preparations have been and continue to be examined for possible benefit for arthritis and musculoskeletal diseases, but none of these can be recommended as a convincingly reproducible, safe, effective, and clinically important therapy for patients with rheumatic diseases. A general overview of herbal medicine is provided elsewhere. (See "Overview of herbal medicine and dietary supplements".)
An example of an herbal therapy with potential benefit in RA is an alcohol extract of Tripterygium wilfordii Hook F (TwHF), a Chinese herbal remedy, which has immunosuppressive properties [22,103-106]. Well-designed randomized trials demonstrated clinical benefit for patients with RA, noninferiority to methotrexate, and that TwHF and methotrexate in combination were better than monotherapy.
Further investigation into the mechanism of the beneficial antiinflammatory effects of this herbal preparation may be valuable. It has extensive effects on the immune system and immunoregulation, alkylating properties, and perturbs the pituitary adrenal axis [22]. Its use, however, may be limited by cost and/or adverse effects.
Additional herbs and dietary supplements that have been studied in patients with RA, but not associated with any clinical improvement, include black currant (Ribes nigrum), Boswellia serrata, evening primrose (eg, from Oenothera biennis and Oenothera lamarckiana), feverfew (Tanacetum parthenium), and green-lipped mussels [4,70,71,107].
Supplementation with turmeric was found to be beneficial in addition to standard of care (intravenous cyclophosphamide) for individuals with lupus nephritis in a small (n = 24) 3-month randomized trial, as both proteinuria and hematuria improved to a greater degree in the treatment arm versus the control arm [108]. While multiple murine lupus models have also supported a possible role of turmeric or curcumin (a constituent of the turmeric root) in the treatment of systemic lupus erythematosus or lupus nephritis, trials in humans are otherwise lacking [109-112].
Green tea extract (500 mg twice daily) was studied in 68 patients with systemic lupus erythematosus in addition to standard of care in a randomized trial for 12 weeks [113]. In this trial, the green tea extract arm experienced a greater decrease in disease activity compared with placebo at the end of the trial and improved fatigue. The systemic lupus erythematosus disease activity was relatively low in both arms at baseline, and while the dose used is generally recognized as safe in humans, high doses of green tea extract have been linked to hepatic dysfunction [114].
Other herbal preparations have been promoted as treatments for osteoarthritis. A 2001 systematic review concluded that there was as yet no convincing evidence of a significant benefit with Eazmov, Gitadyl, or ginger extract [77]; additional data regarding ginger have not been definitive [115,116]. By comparison, there has been limited but some evidence of efficacy (decreased pain) for a number of compounds and extracts; however, these studies were not consistently double-blind, randomized, controlled, or confirmed. They include [70,117-123]:
●Reumalex (a combination of willow bark, guaiacum resin, black cohosh, sarsaparilla, and poplar bark)
●Willow bark alone
●Pine bark
●Green-lipped mussel
●Rose hip
●Stinging nettle
●Articulin F (a proprietary combination of Boswellia serrata [Indian frankincense], Withania somnifera [winter cherry], turmeric, and zinc)
●Boswellia
●Devil's claw
●Extract of soybean and avocado unsaponifiables (ASU)
●Phytodolor (a combination of poplar bark, ash bark, and goldenrod)
●Capsaicin cream
Studies may be particularly difficult to perform for approaches like Ayurvedic treatments, which utilize complex and multiple interventions [80].
Homeopathy — Homeopathy has not been found to be of value for rheumatic or other musculoskeletal disorders, particularly in larger well-designed analyses, despite some small trials suggesting benefit [22,124]. Homeopathy is reviewed in detail separately. (See "Homeopathy".)
Laser therapy — Low-level laser therapy (ie, using low-power light sources), has been evaluated for both RA and osteoarthritis. A systematic review of published trials reported that laser treatment of the hands of patients with RA provided some short-term clinical benefit in pain and stiffness [125]. A systematic review analysis of six studies found modestly decreased pain (-1.10 points, 95% CI -1.82 to -0.39, on a scale of 1 to 10) and duration of morning stiffness (-27.5 minutes, 95% CI -2.9 to -52) for laser treatments compared with placebo [126]. By comparison, consistent benefit was not observed in those with osteoarthritis. It is difficult to provide any specific recommendations regarding low-level laser therapy because of limits to trial design and variations in protocols, including laser intensity, duration, wavelength, and frequency of treatments.
Leeches — Pain relief from the application of leeches was reported in a study of 51 patients with osteoarthritis who were randomly assigned to have leeches (Hirudo medicinalis) or topical diclofenac applied to an affected knee [127]. Significantly more pain relief was reported with leeching than with diclofenac when assessed at seven days. The benefit persisted for up to 28 days and was associated with improvements in stiffness and function. The lack of blinding of patients and assessors is a major potential source of bias and diminishes confidence in the results [128]. Dried leech bodies contain an inhibitor of thrombin-induced platelet aggregation [129]. Use of leeches also carries a risk of cellulitis and septicemia due to Aeromonas hydrophila that colonizes medicinal leeches. (See "Aeromonas infections".)
Permanent magnets — Although popular, permanent magnets appeared to be without benefit in patients with chronic low back pain, as demonstrated in a pilot randomized trial of 20 patients [130]. They also seemed to be no better than placebo in relieving wrist pain in patients with carpal tunnel syndrome [131]. Improvements in pain and function have been reported in some studies of patients with osteoarthritis of the knee or hip [132,133]. Blinding was a problem for these studies, as subjects could often discern the difference between magnetic devices and nonmagnetic or weakly magnetic (placebo) controls. Pulsed magnetic fields were not more effective than a sham treatment for patients with osteoarthritis of the knee [134].
Massage — A small beneficial effect of whole-body massage using a Swedish technique was suggested in a pilot study when compared with waitlisted controls [135]. This is undergoing further study. Indeed, one report examined effects of massage after exercise-induced muscle damage. Massage activated mechanosensory sensors (the mechanotransduction signaling pathways focal adhesion kinase and extracellular signal-regulated kinase), as might be expected. Massage also potentiated mitochondrial biogenesis signaling, mitigated the rise in nuclear factor kappa-B nuclear accumulation caused by exercise-induced muscle trauma, and moderated production of TNF-alpha, interleukin (IL) 6, and heat shock protein phosphorylation, all reflecting less cellular stress and inflammation and promoting recovery and healing [136]. This offered a biologic explanation and mechanism for clinical effect and represented a model approach for examining any putative therapy, whether CAM, traditional, mainstream, or nonmainstream.
Venoms — Venoms affect inflammatory and immune responses in vitro, but they have no consistently documented clinical utility [21]. Indeed, a "beekeepers" arthritis has been reported [137].
Others — Various other potential therapies have been examined in studies of limited size or quality in patients with RA, osteoarthritis, and fibromyalgia, including:
●Thalidomide [138]
●Manipulation [22,139]
●Electromagnetic radiation [22,140,141]
●Photo- (chemo)pheresis [142,143]
●Yoga [22,144-146]
●Tai chi [146-148]
●Prayer or distant healing [22,149,150]
●Botulinum toxin (for tendonitis and osteoarthritis) [151,152]
●Chicken soup [153]
Observations are not sufficiently robust except to suggest that some of these therapies are safe (yoga, tai chi, and prayer). More and better data are needed as to their efficacy.
Therapies generally thought of proven value but with variable acceptance — Some treatment modalities have been more generally accepted as exhibiting evidence of proven value but, like CAM, are only variably utilized therapeutically, often due to cultural acceptance or variability or to the degree or perception of clinical efficacy. Examples include spa therapy, use of fish or botanic oils, exercise therapies, and mind-body techniques.
Balneotherapy (mud/spa therapy) — Balneotherapy has been reasonably well studied with a number of investigations supporting safety and modest efficacy for RA, psoriatic arthritis, and osteoarthritis [22,154]. Its popularity is limited largely by cultural constraints, with patients in many countries, like the United States, expecting pharmacologic or biologic treatments for their illnesses.
Exercise — While largely beyond the scope of this discussion, exercise too is now generally accepted as part of comprehensive management programs for most patients with arthritis, both for physical and psychologic benefits [22].
Fish and botanic oils — Fish and botanic oils may exert clinical effects through their impact on mediators of inflammation [155-157]. Nutritional status exerts a profound influence on immune responsiveness and disease expression [2,21]. As an example, mice with systemic lupus erythematosus or rats with arthritis that were fed diets rich in eicosapentaenoic acid (a naturally occurring, substituted, polyunsaturated fatty acid analog) fared better than did control animals [2,21,158]. (See 'Diet and nutritional therapies' above.)
Clinical trials of fish oils and plant seed oils have suggested a modest decrease in certain symptoms in patients with RA [2,21,158,159]. Symptomatic improvement (standard RA clinical assessments, tender/swollen joint, stiffness, walk time, well-being/global assessments) of fish oil supplementation may be enhanced by limiting the dietary intake of polyunsaturated oils (eg, corn, soybean, safflower, sunflower) to 10 grams or less per day. Although capsules of fish oil are convenient, the amount of omega-3 contained in each capsule is equivalent to that found in 1 mL of cod liver oil; thus, a 20 mL dose of cod liver oil, which is the usual daily dose, provides roughly the same amount of such fatty acids as that found in 20 capsules of fish oil.
Fish oil improved outcomes in patients with recent-onset RA in a randomized "treat-to-target" protocol. Significantly fewer patients taking an average of 3.7 grams per day of eicosapentaenoic acid and docosahexanoic acid failed a triple-therapy regimen (methotrexate, hydroxychloroquine, and sulfasalazine) compared with controls not taking supplemental fish oil (11 versus 32 percent), and significantly more patients given fish oil experienced American College of Rheumatology (ACR) remission [160]. These observations suggested that fish oil might improve clinical outcomes in patients with recent-onset RA who were on triple therapy.
Another study suggested that high levels of erythrocyte-bound omega-3 fatty acids were associated with decreased progression to inflammatory arthritis among individuals who had anti-citrullinated protein antibodies but who did not have RA [161,162].
A double-blind, placebo-controlled trial of fish oil in addition to standard of care (intravenous cyclophosphamide) in patients with proliferative lupus nephritis (n = 191) found that the fish oil supplementation arm had higher rates of complete renal responses and lower proportions of those experiencing no response [163]. Hematuria, urine protein-to-creatinine ratios, glomerular filtration rates, and incidence of infection and urinary tract infection were all significantly in favor of the fish oil supplementation arm as well. Other studies with fish oil and other supplements with high omega-3 content have had varying degrees of success (or lack thereof) in lupus-specific studies [164].
Many different dietary manipulations have been proposed as therapy in RA, but the majority are unproven. An exception to this may be that diets rich in fish oil or a diet to which eicosapentaenoic acid or docosahexaenoic acid is added may result in decreased arachidonic acid metabolites and cytokines, with a concurrent decrease in symptoms [155-157].
Mind-body therapies — Biofeedback, relaxation, meditation, and other mind-body therapies have shown varying degrees of benefit in certain situations [22,165]. As an example, one report found that mindfulness-based interventions in patients with RA helped reduce experienced disease activity (tender joints, patient global assessment, stiffness, and pain) but not objective disease activity (swollen joints and C-reactive protein [CRP]) [165]. The roles of mind-body therapies for chronic back and neck pain are described separately. (See "Management of nonradicular neck pain in adults", section on 'Psychologic and mind-body therapies' and "Subacute and chronic low back pain: Nonpharmacologic and pharmacologic treatment".)
It should be noted when reading reports of "complementary" and "alternative" remedies that the placebo effect can be quite powerful in patients with arthritis. In one preliminary report, for example, clinical improvement of as much as 50 percent occurred in up to 45 percent of patients [166].
ACR POSITION STATEMENT — One of the authors (RS Panush) developed a position statement concerning complementary and alternative medicine (CAM) for rheumatic diseases for the American College of Rheumatology (ACR) in 1998 [34] that has subsequently been updated several times, including in 2020 [167]. Salient portions of it state:
"The American College of Rheumatology (ACR) recognizes the interest in complementary and alternative medicine (CAM) by persons with arthritis. The ACR believes health care providers should be informed about more common CAM modalities such as mind-body interventions, herbal therapy, and nutritional therapy, and should be willing and able to discuss them openly with patients. The ACR supports rigorous scientific evaluation of all modalities that can improve outcomes for patients with rheumatic diseases and recommends continued support of the National Center for Complementary and Integrative Health. The ACR understands that certain characteristics of some CAM modalities make it difficult or impossible to conduct standard randomized controlled trials. For these modalities, innovative methods of evaluation are needed, as are measures and standards for the generation and interpretation of evidence. The ACR supports the integration of those modalities proven to be safe and effective by scientifically rigorous clinical trials into clinical practice. The ACR advises caution in the use of modalities not studied scientifically. In the absence of rigorous clinical trials, the ACR recommends advising patients that potential harm can occur from unproven therapies. The ACR recommends practitioners be proactive in inquiring about patients' interest and use of CAM."
SUMMARY AND RECOMMENDATIONS
●There are a very select few complementary and alternative medicine (CAM) remedies that may play a role in the routine management of select patients with rheumatic diseases. In the authors' judgment, there are no CAM therapies that have been proven to play a consistent and substantial role in the management of rheumatic diseases. More high-quality data are needed before widespread recommendations can be made in favor of certain CAM therapies. (See 'Role of CAM remedies in rheumatic disease care' above.)
●CAM has broad popularity and appeal; most patients with rheumatic and musculoskeletal diseases will consider or use CAM therapies, but often do not notify their rheumatologist or other medical clinicians. Clinicians should be familiar with the common CAM remedies available for arthritis and rheumatic disease. This will facilitate effective communication with patients and colleagues. (See 'Epidemiology and pattern of use' above.)
●Various factors contribute to the appeal of complementary and alternative remedies. These include seeking hope for understanding and a cure for or relief from physical and emotional suffering due to the effects of the medical illness, response to psychosocial distress independent of illness severity, lifestyle choice, difficulty coping with the limitations of contemporary practice, and uncertainty concerning outcomes of illness. (See 'Factors driving use' above.)
●The clinician's response to use of complementary and alternative remedies should include education of the patient and the maintenance of communication with the patient regarding these issues. Potential harms of such therapies include certain adverse effects, failure to use accepted effective interventions, and financial cost. (See 'Role of CAM remedies in rheumatic disease care' above and 'Factors driving use' above and 'General safety concerns' above.)
●There are a wide variety of complementary and alternative remedies for rheumatic disorders (table 1). Therapies can be separated into those known not to be clinically beneficial (eg, antibiotics, apheresis, copper bracelets, dimethyl sulfoxide [DMSO], hyperbaric oxygen), those that have not been studied (cetyl myristoleate [CMO], ginger, methylsulfonylmethane [MSM], shark cartilage, and certain others), those inadequately or incompletely studied (acupuncture, Ayurveda, food and diet, glucosamine and chondroitin sulfate, herbal therapies, laser therapy, leeches, magnets, manipulation, photopheresis, prayer/distant healing, pulsed electromagnetic therapy, S-Adenosyl methionine [SAMe], tai chi, venoms, yoga, and zinc), and those now generally accepted as effective and safe (exercise, fish/botanic oils, mind-body therapies, and spa/balneotherapy). (See 'Selected complementary and alternative remedies' above.)
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