Background

Ginseng is an herbal medication derived from the root of the Panax genus of plants. It has been used for several thousands years in Asia and its purported medicinal properties have reached mythic proportions. The use of ginseng in America dates back to the eighteenth century. Daniel Boone traded ginseng, and in his diary, George Washington mentioned gathering the herb.

Among the species used for pharmacological effects, Asian ginseng (Panax ginseng), American ginseng (Panax quinquefolius), and Japanese ginseng (Panax japonicus) are commonly described. Other “varieties” such as Siberian ginseng (Eleintherococcus senticosus) and Brazilian ginseng (Pfaffia paniculata) are unique plants with different pharmacological effects that may nevertheless be included in commercially available ginseng preparations.

Uses

Brekham, an early pioneer in the study of ginseng, labeled it an “adaptogen” because it appeared to protect the body against stress and restore homeostasis. Ginseng has been advocated for virtually every purpose including general health, fatigue, immune function, cancer, cardiovascular disease, diabetes mellitus, cognitive function, viral infections, sexual function, and athletic performance. Although ginseng has therapeutic potential and measurable pharmacological activity, compelling evidence is lacking to support its use for any specific indication. The German Commission E has approved ginseng as therapy for fatigue and decreased concentration and work capacity.

Phytochemistry and pharmacology

Constituents found in most ginseng species include ginsenosides, polysaccharides, peptides, polyacetylenic alcohols, and fatty acids. Most pharmacological actions are attributed to the ginsenosides that belong to a group of compounds known as steroidal saponins, steroid molecules with attached sugar residues. More than 30 ginsenosides have been isolated.

The pharmacological profile of ginseng is broad and incompletely understood because of the many heterogeneous and sometimes opposing effects of different ginsenosides. The underlying mechanism of action of the ginsenosides appears to be similar to that for steroid hormones. Actions on virtually every organ system have been described.

One of the most promising therapeutic uses of ginseng surrounds the regulation of carbohydrate metabolism and blood glucose. In patients with type 2 diabetes mellitus, ginseng lowered postprandial blood glucose compared to placebo when taken 40 minutes before or at the same time as a glucose challenge. In healthy subjects without diabetes mellitus, ginseng lowered postprandial blood glucose compared to placebo only if taken 40 minutes before glucose challenge.

Data from animal studies suggest that ginseng may have beneficial effects in the central nervous system. Ginsenosides prevented scopolamine-induced memory deficits in laboratory animals by increasing central cholinergic activity. They may also protect neurons from ischemic damage and facilitate learning and memory by enhancing nerve growth. The effect of ginseng on pain pathways needs further investigation. Ginsenosides had non-opioid-mediated analgesic properties in laboratory animals, but attenuated the analgesic effects of opiates. Ginsenosides appear to modulate neurotransmission through -aminobutyric acid (GABA), and by inhibiting neurotransmitter reuptake.

The results of investigations of the cardiovascular effects of ginseng are often contradictory, depending on the compounds tested and the organ system in which they are tested. Stimulation of endogenous nitric oxide release has been implicated in the cardiovascular and antioxidant effects of ginsenosides. In humans, normal doses of ginseng did not appear to affect blood pressure and heart rate, although extremely high doses were associated with hypertension. Ginseng may protect against myocardial reperfusion injury. In a preliminary study, cardioplegia solution containing ginseng extract improved post-bypass myocardial function in patients having mitral valve surgery.

Ginsenosides have anticarcinogenic and immunomodulatory effects. Several individual ginsenosides suppressed tumor cell growth, induced cell differentiation, regulated programmed cell death, and inhibited metastasis. Results of a cohort study showed that ginseng consumers had a lower risk for several different types of cancer compared to those who did not consume ginseng, suggesting that ginseng may have non-organ-specific anticarcinogenic effects. Ginsenosides also enhanced humoral and cell-mediated immune responses in laboratory animals- and potentiated the response to vaccination in humans.

The pharmacokinetics of ginsenosides Rg1, Re, and Rb2 have been investigated in rabbits. The elimination half-lives of these three ginsenosides ranged from 0.8 hr for ginsenoside Re to 7.4 hr for ginsenoside Rb2. The degree of protein binding may explain the wide variation in half-lives between different ginsenosides.

Safety

Early descriptions of a “ginseng abuse syndrome” characterized by hypertension and central nervous system excitation have since been challenged, although a number of case reports caution against the indiscriminate use of ginseng. The estrogen-like effects of ginseng have been associated with postmenopausal vaginal bleeding and mastalgia. An interaction between ginseng and the monoamine oxidase inhibitor phenelzine resulted in headache, tremors, and mania. There is a case report of angiogram-confirmed, self-limited cerebral arteritis associated with ginseng overdose. Ginseng was also associated with a significant decrease in warfarin anticoagulation in one case. It is not known whether ginseng can cause the same side-effects as those described from long-term steroid use.

Another potential safety issue surrounding the use of ginseng concerns its effects on coagulation pathways. Ginsenosides inhibit platelet aggregation in vitro and prolong both thrombin time and activated partial thromboplastin time in rats. These findings await confirmation in humans.

Use during pregnancy or by nursing mothers is not recommended.

Preparations and dosage

Ginseng root is either dried to yield “white ginseng” or steamed and then dried to yield “red ginseng.” Commercial ginseng extract preparations standardized to ginsenoside content are available. The recommended daily dosage is 100-200 mg of ginseng extract once daily. Dosages of ginseng extract up to 600 mg three times daily have been advocated.