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13 Articles in Volume 11, Issue #6
A Diet for Patients With Chronic Pain
A Practical Approach to the Management Of Diabetic Neuropathy
Book Review: Handbook of Pain Assessment, Third Edition
Diagnosis of Neck and Upper Extremity Pain
Diet and Nutrition For Patients With Pain—The Time Is Here
Dislocated Shoulder: Approaches to Lessen The Pain of Reduction Techniques
Guide to Dietary Supplements Most Commonly Used in Pain Management
New Device Combines Acupuncture With Four Other Technologies to Alleviate Pain
PPM Editorial Board Outlines Nutritional Advice for Chronic Pain Patients
Prospective Study of a Lumbar Back Brace In an Interventional Pain Practice
Q&A: The Legal Implications Of Medical Marijuana
Smoking and Pain
The Skeptical Radiology Nurse

Guide to Dietary Supplements Most Commonly Used in Pain Management

Dietary supplements can be a useful part of an integrative approach to the treatment of pain.

Patients with chronic pain who seek medical advice about choosing a vitamin or supplement need to be educated about the risks/benefits of these agents. This article reviews the evidence for the most common supplements used to treat pain, recognizing the importance of an appropriate work-up, including a comprehensive history, physical examination, and relevant diagnostic studies to establish a correct diagnosis and treatment plan. Although in some cases there is overlap, pain supplements can be divided into those used to treat fibromyalgia, headache, or joint pain—osteoarthritis (OA) or rheumatoid arthritis (RA) (Tables 1 and 2). Treatments for other pain entities, such as low back pain, pain from acute injuries, and cancer-related pain are beyond the scope of this article.

Table 1: Dietary Supplements for Various Types of Pain Conditions

 

Fibromyalgia

Reviews of dietary supplements for the treatment of fibromyalgia have found some supplements to be of benefit for specific indications, such as anthocyanidins for sleep disturbances and topical capsaicin (0.025%) for joint tenderness but not for overall pain.1,2 However, the results of clinical trials of soy, malic acid, and some Chinese medicines have either been inconclusive or negative.1-3 For the treatment of fibromyalgia, some of the best evidence supports the use of S-adenosylmethionine (SAMe), a compound that exists naturally as a result of mammalian metabolism but is used in supraphysiologic doses for some medical conditions.4 A review of seven clinical trials found that SAMe benefits fibromyalgia-related depression and tender point pain severity.4

The amino acid 5-hydroxytryptophan (5-HTP) crosses the blood–brain barrier and may have effects on serotonin levels. The agent was researched in two small clinical trials more than 20 years ago.5 In the first trial, an open- label, 3-month study using 100 mg of 5-HTP three times daily in 50 people, researchers reported improvements in number of tender points, anxiety, sleep, and pain scores compared with baseline (P<0.001).6 The second trial, a double-blind, placebo-controlled trial, documented similar improvements in symptoms after 1 month of 5-HTP at a dosage of 100 mg three times daily.7 Concerns about eosinophilia myalgia syndrome due to a suspect batch of 5-HTP more than 20 years ago still compels clinicians to use reputable 5-HTP manufacturers.

Figure 1. Treatment algorithm for fibromyalgia.

Headache

Most research on dietary supplements has explored the use of supplements to prevent or treat migraine headaches.9 One agent, vitamin B2 (riboflavin) practically has become standard of care in the prevention of migraines. One study demonstrated that 400 mg per day of riboflavin significantly decreased migraine frequency (P=0.005) and the number of days with headache (P=0.012) in 55 people after 3 months of treatment.10

Another supplement that is commonly used to prevent migraines is feverfew (Tanacetum parthenium), although reviews have shown conflicting results about its efficacy.11,12 Variability in the type of feverfew tested—from powdered herb in capsules to alcohol extracts—can lead to a range in concentrations of parthenolide, the active component.13 One research group found that a feverfew C02 extract (MIG-99), at a dosage of 6.25 mg three times daily, decreased migraine frequency over 16 weeks.14 From the baseline of 4.76 attacks per month, migraine frequency decreased by 1.9 attacks in the MIG-99 group and by 1.3 attacks in the placebo group (P=0.0456).

A rhizome extract of the butterbur plant (Petasites hybridus) also has shown efficacy for migraine prevention, likely due to smooth muscle relaxation and leukotriene inhibition.15 Clinical trials have shown that 50 to 75 mg twice daily of a standardized butterbur extract (Petadolex, Weber & Weber) decreased the number of migraine attacks per month and led to fewer patients needing migraine medication treatments.16,17 A standardized extract (eg, Petadolex) free of the hepatotoxic pyrrolizidine alkaloids must be used.

Coenzyme Q10 (CoQ10), with a dosage range of 150 to 300 mg per day, and magnesium, 300 to 600 mg per day also have been studied for migraine prevention.13,18,19 These two nutritents have been found to decrease migraine frequency and severity, the number of headache days, and, in the case of CoQ10, days with nausea. In addition, both CoQ10 and magnesium are considerations for pediatric migraines, whereas magnesium is also used for migraine headaches associated with mentruation.

Figure 2. Treatment algorithm for headache.

Joint Pain

As demonstrated by in vitro research, many dietary supplements affect the production or activity of pro-inflammatory mediators, in some cases via cyclooxygenase-1 or -2 (COX-1, COX-2) or lipoxygenase (LOX) inhibition. For example, turmeric (Curcuma longa), with the active ingredient curcumin, has been shown to inhibit numerous inflammatory mediators, such as nuclear factor-kappa B (NF-κB), prostaglandin-E2, leukotrienes, and nitric oxide.20 References are made in review articles to preliminary clinical trials (one used 1,200 mg of curcumin daily in patients with RA), but more definitive research is needed to establish dosages and efficacy.21

Figure 3. Treatment algorithm for joint pain.

Boswellia (Boswellia serrata) often is combined with turmeric. In one crossover trial in 30 patients with knee OA, the boswelia group (333 mg three times daily) had less swelling, pain, and loss of joint movement compared with the control group (P<0.001), although no radiologic changes in the knee joint were observed.22 Another boswellia extract (5-Loxin, PL Thomas) was studied in 75 patients with knee OA. Patients were randomly assigned to receive either 100 or 250 mg of 5-Loxin or a placebo daily for 90 days. At the end of the study, both doses of 5-Loxin conferred clinically and statistically significant improvements in pain scores and physical function scores in OA patients (P<0.001-0.002), noted the investigators. Significant improvements in pain score and functional ability were recorded in the treatment group supplemented with 250 mg 5-Loxin as early as 7 days after the start of treatment.23

Ginger (Zingiber officinale) rhizome contains compounds such as shogaols that inhibit pro-inflammatory prostaglandins. Preliminary clinical trials have reported improvement in knee pain. In a placebo-controlled study, ginger combined with galanga (Alpinia galanga) was given to 261 people with knee OA. The researchers reported less knee pain in the treatment group compared with the control group (63% vs 50%; P=0.048).24 In another study, ginger extract was found to be less effective than 400 mg of ibuprofen three times daily in improving pain scores in patients with knee or hip OA.25 Overall, there are conflicting results about ginger’s effectiveness in the literature.26,27

Glucosamine and chondroitin, primarily used for knee OA, have been studied in numerous clinical trials and systematic reviews; the positive effects of glucosamine on symptoms and joint space narrowing in OA found in reviews seem to be tempered by the inclusion of higher-quality studies. The recent 2-year GAIT (Glucosamine/chondroitin Arthritis Intervention Trial) found insignificant trends for improvement in joint pain with celecoxib (Celebrex) 200 mg per day and glucosamine hydrochloride (500 mg three times daily); there was no effect with chondroitin sulfate (400 mg three times daily), or with the glucosamine-chondroitin combination.28 It is possible that glucosamine sulfate may be more effective than the hydrochloride form, but that is still being debated, as are the exact mechanisms of action.29,30 The ongoing LEGS (Long Term Evaluation of Glucosamine Sulphate) study is assessing the efficacy of this formulation.

Methylsulfoylmethane (MSM) has been studied in OA, in both oral and topical formulations, often in combination with other nutraceuticals.31 A few clinical trials have been conducted, including a placebo-controlled pilot study of 50 people with knee pain. Compared with placebo, MSM (3 g twice daily) produced significantly less pain and impairment after 3 months (P<0.05).32 High-quality trials, especially with parallel pharmaceutical treatment groups, are needed.

Devil’s claw (Harpagophytum procumbens) is an African plant that has been used traditionally for arthritis, low back pain, and headache.33 The anti-inflammatory activities of Devil’s claw are thought to be due to an iridoid glycoside, harpagoside, possibly through its inhibition of various inflammatory mediators via NF-κB and COX-2 inhibition.33 Systematic reviews have found that harpagoside dosages of 50 to 100 mg per day may be effective in decreasing spine, knee, and hip pain.2,27

Avocado-soybean unsaponifiables (ASU) are derived from the unsaponifiable fraction of avocado and soybean oil and contain phytosterols, β-sterols, stigasterol, and campestrol. Four clinical trials of ASU found positive effects for knee or hip OA over 3 to 6 months (less pain and swelling); although joint space width did not change overall, a subgroup analysis may have found a reduction in progressive joint space loss in people with advanced joint space narrowing.22,34 All four trials used 300 to 600 mg daily of the Piascledine 300 formulation of ASU.

Salix alba, or white willow, one of the plants from which aspirin (acetylsalicylic acid, ASA) and related compounds were discovered and derived, contains glycosides (salicin, salicortin, fragilin, and tremulacin) and the primary metabolite, salicylic acid, that act as nonselective COX-1/COX-2 inhibitors.35,36 Two reviews detailed the use of Salix alba (120-240 mg per day of salicin) for back pain,37,38 while a third review looked at herbal preparations for OA, finding positive effects for one herbal product containing 100 mg of powdered Salix alba bark and four other plants.39 A multifaceted trial in 127 people with knee or hip OA randomized to 240 mg of salicin daily (from S. daphnoides bark), diclofenac 100 mg daily, or placebo, and 26 people with RA randomized to either 240 mg of salicin daily or placebo, found no reduction in pain with salicin for either OA or RA after 6 weeks.40 In the OA arm, pain scores decreased by 8 mm (17%) in the willow bark group and by 23 mm (47%) in the diclofenac group compared with 5 mm (10%) in the placebo group. In the RA arm, the mean reduction of pain on the visual analog scale (VAS) was 8 mm (15%) in the willow bark group compared with 2 mm (4%) in the placebo group. The difference was not statistically significant, noted the investigators. It is possible that Salix alba is more effective than Salix daphnoides. Estimates are that 240 mg of salicin is equivalent to 50 mg of ASA,41 leading most experts to consider Salix alba as an adjunctive therapy for pain, at best.

The two species of cat’s claw, or uña de gato (Uncaria tomentosa and U. guianensis), contain a variety of compounds, including pentacyclic oxindole alkaloids, that have antioxidant and anti-inflammatory effects via suppression of TNF-α and NF-κB.42 In a double-blind trial, 40 patients with RA were randomized to receive either a 20 mg capsule of U. tomentosa root extract (Krallendorn) or placebo three times daily for 6 months.43 Patients taking cat’s claw had a greater reduction in painful joints than the control group (53.2% vs 24.1%, respectively; P=0.044), but there were no differences in the number of swollen joints, the duration of morning stiffness, or laboratory parameters. Another trial randomized 45 people with knee OA to 100 mg per day of a freeze-dried preparation of U. guianensis bark (30 patients) or placebo (15 patients) for 4 weeks.44 The cat’s claw group had significantly less knee pain with activity, even after just 1 week of treatment.

Baikal, or Chinese, skullcap (Scuttelaria baicalensis/barbata), has traditional use as an anti-inflammatory. Recently, an extract of the root has been combined with the bark of Acacia catechu in a blend called flavocoxid (Limbrel, Primus Pharmaceuticals) containing from the two plants respectively, baicalin and catechin—flavonoids with anti-oxidant and anti-inflammatory activity. In one double-blind clinical trial, 103 people with knee OA were given either 500 mg twice daily of flavocoxid or naproxen; both groups improved equally from baseline (P<0.01), but without a control group, it is difficult to determine how much of that improvement is due to placebo effect.45

SAMe also has been studied in people with OA and was the subject of an 11-study meta-analysis.46 Two of the 11 studies allowed the researchers to conclude that SAMe versus placebo improves functional limitations (effect size 0.31; 95% confidence interval, 0.098-0.519) but not pain. However, when compared with nonsteroidal anti-inflammatory drugs (NSAIDs), SAMe was as effective as NSAIDs in addressing both pain and functional limitations, and had less side effects than NSAIDs. There was a significant amount of heterogeneity in the included studies (ie, dosing, length, etc.), prompting the researchers to recommended further clinical trials.

Omega-3 fatty acids, especially the marine-derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are thought to lessen inflammation by competing with arachidonic acid as substrates for metabolism by COX and LOX.47 Most of the clinical trials have focused on fish oil (at least 2.7 g EPA plus DHA daily, results may not be apparent for 3 to 4 months) in RA, although there also has been research on flax seeds or flax seed oil; benefits have been noted in patient-assessed pain, morning stiffness, number of affected joints, and NSAID use.48,49

Table 2: Suggested Supplements for Fibromyalgia, Migraine, and Arthritisa

Table 2: Suggested Supplements for Fibromyalgia, Migraine, and Arthritisa

Conclusion

There are many dietary supplements, with varying degrees of supporting scientific evidence, for pain conditions such as fibromyalgia, headache, and joint pain. In some cases, after addressing any relevant nutraceutical-pharmaceutical interactions, such products can be a useful part of an integrative approach to the treatment of pain, while the medical community awaits further research to refine and improve the use of these vitamins, herbs, and other compounds.

Last updated on: September 2, 2011
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