Guide to Dietary Supplements Most Commonly Used in Pain Management
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.
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.
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.
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
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