Herbal Supplements Commonly Used as Complementary or Alternative Therapy

Ernie-Paul Barrette

In 1993, the U.S. Food and Drug Administration (FDA) proposed removing herbal therapies from the over-the-counter market, but a vigorous letter-writing campaign resulted instead in passage of the Dietary Supplement Health and Education Act (DSHEA) in 1994. DSHEA allowed the marketing of all supplements (defined broadly to include herbs, vitamins, minerals, and amino acids) to be expanded with information regarding uses based on “structure and function.” Unfortunately, DSHEA does not require any evidence of efficacy or safety, nor does it define any standards of quality. The use of alternative medicines, including herbal preparations, has dramatically increased since the passage of DSHEA. It is critical that the primary care physician be conversant with the various preparations, claims for their effectiveness and supporting evidence, and known risks, including drug interactions. This chapter therefore presents detailed reviews of evidence regarding the preparations most commonly encountered in primary care.

UNDERSTANDING THE EVIDENCE (1,2)

The number of published clinical trials of herbal medicines is substantial. Many of the trials, however, are in journals that are inaccessible or not published in English. Most lack adequate controls, have poorly defined inclusion criteria, and measure outcomes that are not validated or not clinically relevant. Many are simply too short in duration or enroll too few participants to provide substantive clinical information. This chapter reviews the best evidence supporting the use of several herbal therapies for specific indications. In addition, pertinent safety concerns are discussed.

In Germany, a commission was formed to evaluate the many herbs claimed to have therapeutic value. Members of the “Commission E” included physicians, pharmacists, naturopathic physicians, and scientists. They published several hundred monographs in the German Federal Register. These monographs have been translated and now constitute a repository of information and evidence regarding herbal preparations. This resource represents extensive experience in Europe regarding botanical medicines. Monographs with both positive and negative recommendations are included, along with discussions of adverse effects, drug interactions, use during pregnancy and nursing, specific indications, and doses. Unfortunately, no references are provided. In addition, only a positive or a negative recommendation is provided. Thus, neither the strength of the evidence nor the vigor of the recommendation can be determined.

COMMONLY USED HERBAL PREPARATIONS

Echinacea for Upper Respiratory Infections (1, 2, 3, 4 and 5)

Extracts of three species, Echinacea purpurea, E. angustifolia, and E. pallida, are promoted for both the treatment and prevention of upper respiratory infections. Echinacea was used by Native Americans as an antiseptic and analgesic and was listed in the National Formulary until the introduction of synthetic antibiotics. The Commission E recommended Echinacea for “supportive therapy for colds and chronic infections of the respiratory tract.” Unfortunately, no standardized extract exists. Multiple species, various methods of extraction, and different parts of the plant are used, and additional herbal and homeopathic agents are frequently included with preparations of Echinacea. All of these factors make a comparison of the literature and products very difficult.

Evidence for Efficacy

A systematic review from the Cochrane Collaboration collected all the trials of monopreparations of Echinacea in the prevention or treatment of the common cold. Sixteen trials, including multiple comparisons of an Echinacea preparation versus a control group, were included in the analysis. Most comparisons were to placebo, and two were to no-treatment groups. Side effects were similar to those with placebo.

For Treatment.

Fourteen trials addressed the treatment of an acute upper respiratory infection. Most trials were felt to be of reasonable to good quality. The reviewers felt that nine trials showed a significant benefit over placebo, one trial showed a trend toward benefit over placebo, and four trials showed no benefit over placebo. Due to the multiple Echinacea preparations used, firm conclusions could not be drawn. A large randomized, controlled trial (RCT) published since this review compared Echinacea (blinded and unblinded) to no treatment and placebo. Duration and symptom severity were not statistically significantly better with Echinacea.

For Prevention.

None of the three comparisons to placebo showed an effect over a placebo on the duration and severity of upper respiratory infections. The authors concluded that the benefit of Echinacea for the prevention of upper respiratory infections may exist but has not been demonstrated in rigorous randomized trials. One recent study was less supportive. The trial compared three preparations of E. angustifolia to placebo. Participants were exposed to rhinovirus. Both prophylactic treatment starting 7 days prior to viral exposure and treatment starting with viral exposure were studied. There was no statistically significant benefit of any of the three preparations for prevention or severity of symptoms.

Safety

Anaphylaxis, acute asthma, urticaria, erythema nodosum, and maculopapular rash have been reported. Because of its immunestimulating properties, Echinacea is not recommended for persons with autoimmune disorders.

Ginkgo biloba for Dementia and Memory Enhancement in Normal Older Persons (1,2,6, 7, 8, 9 and 10)

Ginkgo biloba extracts have been used in Chinese herbal medicine for centuries. Use has increased in Europe during the last 30 years, and it is now the most prescribed herbal medicine in Germany. It is among the top five herbal products consumed in the United States. Most products are based on a standardized extract, EGb 761, which contains 22% to 27% flavone glycosides (quercetin, kaempferol, isorhamnetin) and 5% to 7% terpene lactones (2.8% to 3.4% ginkgolides A, B, and C; 2.6% to 3.2% bilobalide). EGb 761 is now off patent and may be used by any manufacturer. Unfortunately, another standardized extract process is also used, LI 1370. Although LI 1370 specifies 25% flavone glycosides and 6% terpenoids, the different process may result in different concentrations of individual ingredients. It is not known whether the active ingredient is a specific component or a combination. In Germany, the Commission E approved G. biloba for use in dementia syndromes, specifically primary degenerative dementia, vascular dementia, and mixed forms. They also approved it for intermittent claudication, vertigo, and tinnitus.

Evidence for Efficacy

The body of research regarding potential mechanisms of action is extensive; these include scavenging free radicals, blocking platelet-activating factor, increasing blood flow, stabilizing membranes, and decreasing capillary fragility, among others.

For Use in Alzheimer Disease.

A rigorous Cochrane Collaborative meta-analysis, rejecting all but four studies on methodologic grounds, found data “inconsistent and unconvincing” for a cognitive benefit in persons with dementia. Since this meta-analysis, large well-designed trials have failed to show a statistically or clinically significant benefit either for treatment of established disease or for prevention. For example, a very large RCT in the United States compared G. biloba with placebo for the prevention of dementia in both normals and those with mild cognitive impairment. The trial enrolled 3,069 volunteers age 75 and older with mean follow-up of 6.1 years. The incidence of dementia was not decreased with G. biloba use in either group (see also Chapter 173).

For Use in Normal Older Persons.

Promoters of G. biloba claim that the substance improves memory and cognitive performance in normal older persons. Many seniors take Ginkgo-containing products in the hope of improving their mental functioning, making Ginkgo one of the top-selling herbal remedies in the United States. However, trials have not shown consistent benefit for nondemented older persons. In the best randomized trial, 230 patients of age 60 years or older and without significant neurologic or psychiatric illness were randomized to either Ginkgo, 40 mg three times daily, or matching placebo. Participants completed 14 standardized tests of memory, language, and concentration before the trial and at the end of 6 weeks. All 14 tests of cognitive function, as well as ratings by participants’ family members, showed no difference between the groups. Less well-designed studies that suggest mild benefit are often quoted in support of Ginkgo use. As noted, there is no evidence of benefit in prevention of dementia.

Safety

Because one of the known effects of G. biloba is antagonism of platelet-activating factor, it is not surprising that several cases of severe bleeding during its use have been reported. These include spontaneous bilateral subdural hematomas, subarachnoid hemorrhage, subdural hematoma, intracerebral hemorrhage, and spontaneous hyphema. Because of these antiplatelet effects and the reports of associated bleeding complications, Ginkgo should be avoided in patients with bleeding disorders and in those taking warfarin or drugs with anticoagulant or antiplatelet effects.

Kava-Kava for Anxiety (1,2,11, 12, 13, 14, 15, 16, 17 and 18)

The botanical name of kava-kava is Piper methysticum (“intoxicating pepper”). Kava-kava has been used in Pacific Island
communities for centuries for its relaxing and tranquilizing effects. It continues to be used in Micronesia, Melanesia, and Polynesia. Captain James Cook first reported its use to the west. The Commission E has given kava a positive rating for the “condition of nervous anxiety, stress, and restlessness.”

Evidence for Efficacy

Kava was first studied by German scientists in the 19th century, and in the 1950s, animal studies showed a sedative, analgesic, anticonvulsant, and muscle-relaxant effect. The active agents are believed to be the kavalactones (pyrones), primarily kawain, dihydrokawain, methysticin, and dihydromethysticin. Although the results of early studies with D, L-kawain suggested a benefit in treating anxiety, all recent trials have used an extract standardized to the content of kavalactones. A systematic review and metaanalysis of kava for the treatment of anxiety included seven trials. The authors concluded that kava was superior to placebo for the short-term treatment of anxiety. Methodologic limitations of several of these trials, however, limit enthusiasm for kava. The best evidence supporting the use of kava is a double-blinded, randomized, controlled multicenter trial comparing kava (100 mg three times daily, 70% kavalactones) with placebo. Enrollment consisted of 101 patients with generalized anxiety disorder, adjustment disorder with anxiety, agoraphobia, and specific phobia as defined in the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders. The trial lasted 24 weeks and used Hamilton Rating Scale for Anxiety (HAMA) scores with an intent-to-treat analysis as the primary outcome. The HAMA score improved in both arms, but the improvement was significantly greater with kava (30.7 to 17.1) than with placebo (31.4 to 20.3; p = 0.02) by 8 weeks. Both arms showed continued improvement for 16 weeks and then plateaued. The benefit of kava persisted from 8 weeks to the end of the trial. At 24 weeks, the HAMA scores remained improved with kava (kava, 30.7 to 9.7; placebo 31.4 to 15.2; p < 0.001). Adverse effects were minimal.

Safety

In large, observational trials, adverse effects have been rare. In several small trials, a worsening of cognitive function and coordination were seen, as expected with benzodiazepines but not with kava. Heavy, prolonged use of kava results in a well-described skin disorder characterized by dry, yellow scaling. There are case reports of dystonic reactions in five patients, including torticollis, generalized choreoathetosis, and oral-lingual dyskinesia. A single controversial report described a semicomatose state in a man who combined kava with alprazolam. Of greatest concern are the reports of hepatotoxicity, including fulminant liver failure requiring transplantation.

Milk Thistle for Hepatitis and Cirrhosis (1,19, 20, 21 and 22)

Milk thistle (Silybum marianum) has a 2,000-year history of use by herbalists. Although it was reported to relieve many conditions, it is currently promoted primarily for liver and biliary disorders. The active ingredient is called silymarin, which is composed of three isomeric compounds (silibinin, silydianin, and silychristin). From 20% to 40% of silymarin is concentrated in the bile. Milk thistle has been used in Europe for 30 years. The Commission E recommends its use as supportive treatment for chronic inflammatory liver conditions.

Only gold members can continue reading. Log In or Register to continue