encyclopedia of herbal medicine

Garlic

Garlic was the top-selling herb in 2004 with greater than $27 million in sales. The German Federal Health Agency Commission E and the European Scientific Cooperative on Phytotherapy have approved garlic for the treatment of hyperlipidemia and atherosclerosis. Allicin, the ingredient believed responsible for garlic's therapeutic benefit and odor, is highly unstable. Both heat and acid destroy the enzyme allinase, which is necessary to produce allicin, and for that reason garlic is best ingested raw. Garlic is also available over-thecounter in multiple formulations (dried, powdered, oils). The best-studied form is an enteric-coated capsule of dehydrated garlic. Freeze-drying helps retain most of the active ingredients found in raw garlic. Enteric coating permits allicin to be released in the small intestine, thereby enhancing absorption and reducing the breath odor. Over-the-counter preparations are frequently standardized to yield 0.6% allicin, but allicin yield among powdered preparations varies as much as 230-fold in brands used in trials. This lack of standardization may contribute to inconsistent results in dozens of clinical trials.

Garlic appears to have small effects on cholesterol (4–12% reduction when taken short term), very minimal effect on blood pressure, and none on glucose levels. A systematic review by Ackerman funded by the Agency for Health Care Policy and Research identified 36 randomized controlled trials on the use of garlic for the treatment of cardiovascular risk factors. Among the 26 trials evaluating hyperlipidemia, small but statistically significant reductions (16 mg/dL) were found for total cholesterol at 3 months among patients treated with garlic compared with placebo. Among the eight trials with outcomes at 6 months, no significant reductions in lipids were seen with garlic compared with placebo. In a qualitative review of antithrombotic effects, a modest and short-term effect was identified. Because garlic has some activity against platelet activation, there is a theoretical risk of increased bleeding, especially if taken with aspirin, anticoagulants, or NSAIDs, but there is insufficient evidence to determine a causal association. Effects on glucose and blood pressure were absent to minimal in studies reviewed.

Ginkgo

The dried leaf of the ginkgo tree has been used medicinally for thousands of years. More than 400 studies over the past 30 years have investigated ginkgo's ability to improve blood flow in a variety of conditions, including memory impairment, dementia, peripheral vascular disease, and tinnitus. The German Commission E has approved a standardized form of ginkgo leaf extract (EGb 761) for the treatment of cognitive impairment and intermittent claudication. Multiple pharmacologically active compounds have been isolated from ginkgo, including flavonoid glycosides and terpene lactones (ginkgolides). The flavonoids have antioxidant and free radical scavenging ability. The terpene lactones (especially ginkgolide B) have platelet-activating factor antagonist activity. In addition, ginkgo extracts increase the production of nitric oxide and activate certain central neurotransmitters, including the cholinergic system, which may contribute to their beneficial effects on memory and cognition. EGb 761—the formulation that has been studied most extensively—is standardized to contain 24% flavonoid glycosides and 6% terpene lactones.

A 1998 review identified 50 trials that assessed ginkgo's efficacy on cognitive function in the elderly. Because the vast majority of trials did not require a definitive diagnosis of dementia or Alzheimer's disease, only four trials involving 424 patients met study entry criteria for meta-analysis. Results showed a modest improvement in cognitive function when compared with the placebo group—comparable to the effect of donepezil on dementia. The longest of these studies (1 year) showed stabilization of cognitive and functional abilities in 309 demented patients treated with EGb 761 compared with placebo, with no differences in adverse outcomes. In contrast, EGb 761 was no more effective than placebo in 214 elderly Dutch patients with dementia or age-associated memory impairment. There is conflicting evidence about ginkgo's ability to enhance memory in healthy individuals. A 2002 trial reported no benefits of taking 120 mg/d of ginkgo for 6 weeks on multiple measures of memory and concentration in 230 healthy older subjects. Earlier smaller studies suggest that 240 mg/d for up to 6 weeks may be helpful in enhancing memory in healthy individuals. The NIH has funded investigators at the University of Pittsburgh to determine whether ginkgo taken over 5 years can prevent or delay the development of dementia in 3000 patients 75 years of age or older.

In general, ginkgo is well tolerated in healthy adults at recommended doses for up to 6 months. Allergic skin reactions, gastrointestinal disturbances, and headache occur in fewer than 2% of patients. There are theoretical concerns about a risk of increased bleeding because antiplatelet activating factor activity has been demonstrated in vitro. Several cases of increased bleeding have been reported (some in patients also taking aspirin or warfarin). In contrast, no excess bleeding complications have been reported in any clinical trials, causality has not been clearly established, and no differences in coagulation or platelet function were noted in 50 healthy male volunteers. Caution should still be exercised in patients with bleeding disorders or who are taking anticoagulants, aspirin, or other herbs that may increase the risk of bleeding.

Echinacea

Echinacea ranks among the top-selling herbs in the United States, accounting for more than $300 million in sales annually. Three of nine echinacea species are currently used for the treatment and prevention of upper respiratory infections. Preparations are made from roots (Echinacea pallida and Echinacea angustifolia), above-ground parts (stems, leaves, and flowers of Echinacea purpurea), or a combination of both. Multiple forms are available over-the-counter, including capsules, fresh pressed juice, tinctures, and teas. Differences in species, growing conditions, plant parts used, and extraction procedures can result in differences in chemical composition and biologic activity. Several active ingredients have been identified, including polysaccharides, glycoproteins, alkaloids, and flavonoids. In vitro and animal studies suggest that these ingredients cause stimulation of the immune system (natural killer cells, macrophages, and cytokine activity) and that they possess anti-inflammatory, free radical-scavenging, and antiviral activity.

The quality of most clinical trials has been limited by use of multiple products and doses (including formulations containing multiple herbs) and the lack of rigorous methodology. Two high-quality systematic reviews have evaluated 13 double-blind, randomized, controlled trials of echinacea for prevention or treatment of the common cold. In both reviews, there was modest benefit of echinacea compared with placebo for the acute treatment of upper respiratory infections. Subjects reported reduced symptoms or shortened duration of a viral upper respiratory tract when the herb was started within several days after onset of cold symptoms and continued for 8–10 days. A more recent study of 128 adults who took a standardized echinacea preparation at the onset of a cold and for 7 days reported 23% lower symptom severity score than those randomized to placebo. In contrast, echinacea taken for upper respiratory infection prevention has not been shown to be effective. Echinacea was no more effective in preventing experimentally induced rhinovirus infection in 48 adults inoculated with rhinovirus type 39 (RV-39). An alcohol-free form of echinacea was also no more effective than placebo in relieving upper respiratory tract infection symptoms in children ages 2–11 in a recent large clinical trial, but fewer colds developed in 430 children who received an herbal preparation containing echinacea, propolis, and vitamin C than in those who received a placebo. In general, echinacea is well tolerated, with few reported adverse events. Rare allergic reactions including rash have been reported (especially in patients with ragweed allergies), and there was a single case of recurrent erythema nodosum. The German Commission E recommends that patients who are pregnant, have autoimmune disease, or who are immunocompromised not take echinacea because of its immune-stimulating effects. The Commission also recommends that its use be limited in others to less than 4 weeks. The data supporting these recommendations are not clear.

Ginseng

Ginseng root has been used for medicinal purposes in Asia for over 2000 years. There are three major forms of ginseng in use today: Asian ginseng (Panax ginseng); American ginseng (Panax quinquefolius); and Siberian ginseng (Eleutherococcus senticosus), which is not a member of the Panax genus. The German Commission E monograph on ginseng root approves its use as “a tonic to counteract weakness and fatigue, as a restorative for declining stamina and impaired concentration, and as an aid to convalescence.” Extracts are made from dried roots and contain ginsenosides. Over 25 ginsenosides have been isolated, each with unique and sometimes oppositional effects on the cardiovascular, central nervous, and immune systems. The mechanisms of action have not been clearly delineated.

There is an extensive body of scientific literature on this subject, with over 4000 books and papers published. Multiple indications have been studied using different ginseng species, often with poor methodologic rigor. One European study identified 57 randomized controlled trials of ginseng in the world's literature, but only 16 studies were of good enough quality to be included in their systematic review. Insufficient evidence was available to support or refute the use of ginseng for any of the purported indications, including improvement of physical performance, cognitive functioning, and quality of life. Two small 2004 clinical trials suggest ginseng may improve cognitive performance in healthy persons and prevent acute respiratory illness in institutionalized older adults. A study done in 2000 suggested that one form of American ginseng may attenuate postprandial glycemia in both normal and diabetic persons, but follow-up reports from the same researchers showed no or variable effects of ginsengs with different ginsenoside composition.

Ephedra (Ma-huang)

The dried young stems of Ephedra sinica have been used for thousands of years in traditional Oriental medicine to treat respiratory disorders, especially bronchospasm and congestion. Ephedra has also been widely marketed for its stimulant and appetite suppressant effects (alone or in combination with caffeine-like herbs). Ephedra's alkaloids are structurally similar to amphetamines. A meta-analysis concluded that patients taking ephedra or ephedra plus caffeine products lost 1.3 or 2.2 more pounds per month respectively than those taking placebo. These products were associated with a twofold to threefold risk of psychiatric, autonomic, gastrointestinal symptoms, and/or heart palpitations. Of all the adverse effects caused by ingestion of herbs reported to US poison control centers, 64% were due to products containing ephedra, even though they represented only 0.82% of herbal product sales. Over 800 cases of adverse events, including more than 20 deaths, have been reported to the FDA, which has since prohibited the sales of ephedra-containing dietary supplements. Many “Ephedra-free” weight loss products contain bitter orange (citrus aurantium), which could pose similar risks because it contains synepherine, which has sympathomimetic activity.