Clinical Trials of Ginseng
March 1, 2002 12 minutes read
Clinical Trials of Ginseng
By Dennis V.C. Awang, PhD
Asian ginseng, perhaps the most revered of traditional Chinese medicines, is derived from the root of a perennial herb native to China, Russia, and Korea. Most of the commercially exported supply available today comes from China and Korea.1 American ginseng is native to eastern North America—from Quebec to western Manitoba in Canada, and south to northern Florida, Alabama, and Oklahoma.2 Most American ginseng is cultivated in Ontario, British Columbia, and Wisconsin.
Ginseng has long been a top seller on the dietary supplement market; sales of ginseng products amounted to almost $96 million dollars in 1998.3 True ginseng belongs to the plant genus Panax in the Araliaceae family. Ginseng (jen-seng, schin-seng, ren-shen) means "man-root" or "essence of the earth in the form of a man" the more closely the root form resembles the human form, the more greatly the Chinese prize it—and the more expensive it is. The word Panax comes from the Greek, pan meaning "all" and akos meaning "cure," reflecting the plant’s traditional reputation as a cure-all or panacea.2
Only two species, Panax ginseng C.A. Meyer (Asian ginseng) and P. quinquefolius L. (American ginseng) are significant items of commerce in the west; P. notoginseng F. H. Chen ex C. Y. Wu & K. M. Feng (Tienchi or Sanchi ginseng) is popular in Asia. At least 20 non-Panax species also have been promoted, inappropriately, as ginseng, most notably eleuthero or Siberian ginseng, Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. Eleuthero is a member of the Araliaceae plant family, but has a totally different chemical composition from those of the true ginsengs. A southern Asian vine marketed in the United States as Southern ginseng (Gyno-stemma pentaphyllum [Thunb.] Makino, Cucurbitaceae), is the only non-Panax plant that so far has been found to contain ginsenosides.4
In China, ginseng is valued as a mild drug and general tonic. It is used to improve mental and physical performance, enhance endurance, promote resistance to infection, and counter nervous debility.1 Ginseng consumption in pregnancy has long been a part of Chinese tradition, believed to provide energy for both mother and child.5
Ginseng products are commercially available in many different forms. Traditionally, the Chinese have either chewed the root or prepared a drink by simmering slices of the root in boiling water (a decoction). In China and in American Chinatowns, ginseng candy, chewing gum, and wine can be found. Most commercial extracts are prepared using alcohol-water solvent mixtures. Commercial aqueous alcoholic extracts are likely to be of unreliable quality and consistency. The most reliable dosage form is whole dried root, powdered and usually encapsulated, ingested as such, or sliced, tea-cut or powdered, steeped in boiling water. The proprietary extract G115®, contained in Ginsana®: (Pharmaton SA, Lugano, Switzerland) has been used in several clinical studies.
Standardization
Standardization of ginseng products has been almost exclusively directed at total ginsenosides—the characteristic, steroid-like sugar derivatives (triterpene saponins) that widely are regarded as the main bioactive components of the ginsengs. American ginseng contains a higher content of ginsenosides than Asian ginseng.
More than 30 ginsenosides have been identified. The most abundant ginsenoside in both American and Asian ginseng root is ginsenoside Rb1, which is reported to have a sedative effect. Ginsenoside Rg1 exerts a mild stimulant effect6 and exists at considerably lower levels in American ginseng. The Rb1:Rg1 ratio in American ginseng usually is around 10, whereas the ratio for Asian ginseng generally is between 1 and 3.7 Leaves may contain high levels of ginsenosides, but leaves and roots show significantly different patterns of composition of the main ginsenosides.8 Some scientists believe that polysaccharides (high molecular weight sugars) contribute significantly to the activity of ginseng extracts, especially their immunomodulating effects.9,10
Clinical Trials
Diabetes. A double-blind, placebo-controlled trial of (apparently Asian) ginseng extract (100 mg qd or 200 mg qd for eight weeks) in 36 newly diagnosed non-insulin dependent diabetes mellitus (NIDDM) patients found that ginseng improved mood, vigor, well-being, and psychomotor performance.11 The 200 mg dose reportedly significantly reduced fasting blood glucose and HbA1c and increased physical activity; however, baseline values are not given.
Three recent randomized controlled studies led by the same investigator, all using American ginseng, were conducted in Canada. A placebo-controlled crossover study compared ginseng (3 g) given 40 minutes before or with a glucose challenge in 10 healthy subjects and nine subjects with NIDDM. In subjects with NIDDM, ginseng reduced the area under the glycemic curve by 19% ± 22% when given before and by 22% ± 17% when given with a glucose challenge. In normal subjects, ginseng reduced postprandial glycemia by 18% ± 31% only when given before a glucose challenge; there was no effect when ginseng was administered concurrently.12
A crossover study in 12 non-diabetic subjects tested doses ranging from 1 g to 3 g given concurrently with, or 40, 20, or 10 minutes before, a glucose challenge. This study confirmed a reduction in the area under the glycemic curve (9.2-14.1%) only when ginseng was administered 40 minutes before glucose challenge; all doses were equivalent.13
The third study, in 10 subjects with NIDDM, tested three doses (3, 6, or 9 g) administered concurrently with, or 120, 80, or 40 minutes before, a glucose challenge. All doses reduced the area under the glycemic curve (15.9-19.7%) with no difference between doses; time of administration did not make a difference.14
Menopausal symptoms. A randomized, double-blind study of 384 menopausal women tested 100 mg of a standardized ginseng extract G115 for 16 weeks.15 There were no differences between groups with respect to hot flashes, follicle-stimulating hormone (FSH), estradiol levels, endometrial thickness, vaginal maturity index, or vaginal pH, or scores on the Psychological General Well-Being Index or the Women’s Health Questionnaire, which assesses menopausal symptoms.
Physical performance. A review of ergogenic properties of ginseng identified 11 controlled trials (10 described as double-blind, seven reported only as abstracts) of ginseng and ergogenic performance.16 Of these, seven found no effect of ginseng on outcomes while four found a positive effect; six of seven trials since 1996 found no effect.17
Stress, fatigue, mood, and memory. There is little evidence that supports ginseng use for improved mood or cognitive function; however, most trials were done in healthy individuals. A randomized double-blind placebo-controlled trial of ginseng extract (G115, 200 or 400 mg for eight weeks) in 83 healthy men and women found no effect on mood disturbance.18
A double-blind placebo-controlled study in 112 healthy subjects, ages 40-70 years, tested 400 mg of an Asian ginseng extract daily (for 8-9 weeks).19 There was no difference between groups in concentration, memory, or subjective experience.
A placebo-controlled study of a commercial ginseng-multivitamin/multimineral preparation among 60 geriatric patients found no differences between groups in length of stay, activities of daily living, cognitive function, or somatic symptoms.20
A double-blind study of a multivitamin complex with or without ginseng in 625 patients with stress or fatigue found that ginseng supplementation significantly improved quality-of-life measures at four months.21
A placebo-controlled, crossover trial (no mention is made of randomization; it is stated that half of the participants started with ginseng and half with placebo) tested the effects of Korean ginseng (1,200 mg/d for three consecutive nights) in 12 student nurses (6 female) assigned to night duty for three-night stints during one month.22 Self-rating scales were used to evaluate mood, sleep quality, degree of lethargy, and bodily symptoms (anxiety, tension, tiredness, and slowness); objective tests of psychophysiological performance were conducted. All assessments were performed the morning after the third night. Placebo and ginseng were administered at least two weeks apart. An assessment also was performed during a daytime shift, after a good night’s sleep. Night work, compared to day work, significantly and adversely affected mood and bodily symptoms, but ginseng, compared to placebo, did not improve any measures.
Blood pressure. An apparently single-blind study of red Asian ginseng (steamed unpeeled before drying, which gives it a reddish caramel color) administered placebo for four weeks, then ginseng (1.5 g tid) for eight weeks in 45 subjects (34 completed).23 Red ginseng significantly reduced systolic, but not diastolic, blood pressure in the 26 subjects with essential hypertension who completed the trial. There was no effect in the eight subjects with white-coat hypertension who completed the trial. Two subjects dropped out because of abdominal discomfort and constipation; other reported side effects included dyspepsia, tiredness, and diaphoresis.
Adverse Effects and Interactions
No significant toxicity of ginseng has been reported in clinical trials. However, several case reports of adverse events have been published. Cerebral arteritis was diagnosed in a 28-year-old-woman who developed severe headache accompanied by nausea, vomiting, and chest tightness following ingestion of a large quantity of a rice wine extract of Asian ginseng root slices.24
A case of Stevens-Johnson syndrome was reported as possibly associated with a ginseng preparation.25 The connection seems unlikely; the patient had been a regular ginseng user and recently had been treated with both antibiotics and a non-steroidal anti-inflammatory drug.
Several sources caution that excessive use can cause insomnia or hypertension.26-28 In China, ginseng is contraindicated in hypertensive patients. Safety studies of ginseng use in pregnancy so far have not been conducted.
Estrogenic Effects
It is not clear whether or not ginseng causes estrogenic effects. The Wiklund study found no changes in endometrial thickness, vaginal maturity index, FSH, or estradiol levels.15 However, several case reports note estrogenic effects. Two cases of postmenopausal uterine bleeding have been reported. A 72-year-old woman experienced vaginal bleeding after daily ingestion of a Swiss-Austrian formula containing 200 mg of ginseng.29 A 44-year-old woman, menopausal for two years, experienced episodes of uterine bleeding temporally related to the use of a ginseng-containing Chinese face cream.30 Rechallenge caused uterine bleeding four weeks later; endometrial biopsy showed a disordered proliferative pattern. Mastalgia with diffuse nodularity was reported in a 70-year-old woman who had been taking powdered ginseng for three weeks.31 Cessation resolved symptoms, and rechallenge reproduced symptoms. None of the products associated with apparent estrogenic effects were analyzed to exclude the possibility of adulteration.
Interactions
A case report associates Asian ginseng use with decreased international normalized ratio (INR) in a patient previously stable on warfarin.32
Combining ginseng with phenelzine resulted in headache, insomnia, and tremulousness in a 64-year-old woman,33 and may have precipitated some manic symptoms in a 42-year-old depressed patient who also was taking bee pollen, lorazepam, and triazolam.34 A 35-year-old woman with a history of depression, previously stable on lithium and amitriptyline, was hospitalized for an acute manic episode 10 days after substituting one tablet of ginseng daily for her regular medications.35 It is unclear whether this was a medication withdrawal effect, an adverse effect of ginseng, or a drug interaction; the time sequence is inadequately described.
A clinical study in 14 men, used as their own controls, found that coadministration of a hot-water extract of Korean P. ginseng (3 g/65 kg body weight) with 25% alcohol (72 g/65 kg body weight) reduced blood alcohol levels an average of 35%.36
The British Herbal Compendium (BHC) advises against concurrent use of ginseng with caffeine,26 and this caution often is given by herbalists. The caution is apparently based on the belief that P. ginseng is stimulating and could potentiate the effect of other stimulants.
Summary
Additional clinical studies are needed before definitive conclusions can be drawn as to whether ginseng is beneficial to any clinical condition. At this time, there is limited evidence that ginseng may be of benefit in diabetes.
Ginseng appears to be relatively safe for healthy adults. In spite of widespread use in pregnant women in some communities, safety studies are not available. Psychiatric patients and those on anticoagulant medication should avoid its use. Diabetics who use ginseng should monitor blood sugar levels carefully, preferably under the supervision of a health professional.
References
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21. Marasco C, et al. Double-blind study of a multivitamin complex supplemented with ginseng extract. Drugs Exp Clin Res 1996;22:323-329.
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Awang DVC. Clinical trials of ginseng. Altern Ther Women's Health 2002;4:17-21.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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