Scientific Name(s): Panax ginseng C.A. Meyer., Panax quinquefolius L.
Common Name(s): American ginseng, Asian ginseng, Canadian ginseng, Chinese ginseng, Korean ginseng, Oriental ginseng, Radix ginseng
Ginseng commonly refers to P. quinquefolius L. or P. ginseng C.A. Meyer, 2 members of the family Araliaceae. Several other species are less commonly used in Asia. The ginsengs were classified as members of the genus Aralia in older texts. In the eastern and central United States and Canada, P. quinquefolius is found in rich, cool woods; a large crop is grown commercially in Wisconsin. The Asian species P. ginseng is cultivated in Korea and China. The short plant grows 3 to 7 compound leaves that drop in the fall and bears a cluster of red or yellowish fruits from June to July. The shape of the root can vary depending on the species and has been used to distinguish types of ginseng. Medicinally, the root is considered the most valuable part of the plant in providing the pharmacologically active ginsenosides. Ginsenoside content varies with the age of the root, season of harvest, and method of preservation. While at least 4 ginsenosides are detectable in most young roots, this number more than doubles after 6 years of growth. High-quality ginseng is generally collected in the fall after 5 to 6 years of growth.1, 2
P. ginseng should not be confused with Siberian ginseng (Eleutherococcus senticosus), a related species with different chemistry.1
Ginseng is perhaps the most widely recognized plant used in traditional medicine and now plays a major role in the herbal health care market. It is classified into 3 types according to processing; fresh, white (dried after peeling), and red (steamed and dried). For more than 2,000 years, various forms have been used medicinally. The name Panax derives from the Greek word for "all healing," and its properties have been so touted. Ginseng root's man-shaped figure (shen-seng means "man-root") led proponents of the doctrine of signatures, an ancient European herbalists philosophy, to believe that the root could strengthen any part of the body. Through the ages, the root has been used in the treatment of asthenia, atherosclerosis, blood and bleeding disorders, erectile dysfunction, hypertension, liver dysfunction, and colitis, as well as to relieve the effects of aging, cancer, postmenopausal disorder, and senility.3, 4, 86
Evidence of the root's general strengthening effect has been examined for its ability to raise mental and physical capacity, as well as its protectant effect against diabetes, neurosis, radiation sickness, and some cancers. Today, its popularity is widely due to the adaptogenic or stress-protective effect of the saponins.3, 4
Major compounds in ginseng include triterpene saponins, polyacetylenes, sequiterpenes, polysaccharides, peptidoglycans, nitrogen-containing compounds, and other compounds, including fatty acids, carbohydrates, and phenolic compounds.2, 5, 6 The triterpene saponins are considered the most active compounds, and some estimates report up to 150 different ginsenosides, grouped into either dammarane or oleanane groups.6 Ginsenosides Rb1, Rb, Rc, Rd, Re, Rf, and Rg1 are the most common components of commercial ginseng products.86 Many analytical methods have been described and standards published. The European Pharmacopoeia requires a minimum of 0.4% combined Rg1 and Rb1 ginsenosides, while the Chinese Pharmacopoeia requires ginseng radix (dry root) to have not less than 0.3% Rg1 and Re combined ginsenosides and not less than 0.2% Rb1.5
Most traditional ginseng herbal preparations contain ginsenosides. However, a commercially available product, known as CVT-E002, a patented aqueous extract of approximately 80% to 90% poly-furanosyl-pyranosyl-saccharides from the roots of North American ginseng (P. quinquefolius), does not contain ginsenosides.7 Adulterants are commonly found in ginseng preparations due to the high cost of authentic ginseng roots, and the presence of natural methylxanthines may also contribute to some reported physiological effects.6, 7, 8
Variances in cultivation and processing methods, as well as the individual genetics of each plant source, result in varying chemical compositions among commercial products. This may contribute to the lack of consensus among studies on the pharmacology and efficacy of ginseng and should be considered when conducting and interpreting research.2, 9 A second factor that may have produced erratic results is the discovery that ginsenosides (specifically Rb1, Rb2, Rc, and Rd) are metabolized extensively by the human gut microflora and that some of the resulting metabolites are pharmacologically active, such as compound K. Colonic bacteria can remove the 3 sugars from ginsenoside Rb1 in stepwise fashion, and the deglycosylated compounds are then esterified in the liver with the fatty acids stearic, palmitic, and oleic acid. These esters persist in the liver for as long as 24 hours.10, 86 Thus, differences in an individual's gut flora may lead to differing pharmacological responses to ginseng preparations. Additionally, ginsenoside bioavailability as well as the content of ginsenoside metabolites (ie, compound K, Rh1, Rg3, protopanaxatriol, protopanaxadiol) of red ginseng were found to be increased with the fermented product.86
Uses and Pharmacology
Reviews of the effects of ginseng have been published. Most studies have used whole-root preparations, with considerable variations due to uncertain species identification, age of the roots, and curing process used. Variations in saponins between the species also may contribute to the lack of consensus among researchers on ginseng's pharmacology.2, 6, 11
Both ginsenosides and polyacetylenes have demonstrated anticarcinogenic effects in vitro, including direct cytotoxic and growth inhibitory effects, induction of differentiation, and inhibition of metastasis. High concentrations of M1, an active metabolite of Rb1, Rb2, and Rc, induced cell death of mouse melanoma cells by regulating proteins involved in apoptosis. Ginsenosides Rh2 and Rh3 induced differentiation of promyelocytic leukemia cells into granulocytes; Rg3 inhibited adhesion and invasion of melanoma cells and decreased pulmonary metastasis.6, 12, 13
Epidemiological data support a protective effect of ginseng on nonspecific organ cancers.6, 14 A long-term study of ginseng 1 g taken weekly for 3 years among adults with long-term atrophic gastritis showed no effect on the overall relative risk of cancer. In the male subgroup analysis, there was a reduction in the risk of non–organ-specific cancers.14
Trials evaluating the effect of ginseng (both P. quinquefolius and P. ginseng) on cancer-related fatigue at doses of 800 mg to 2 g/day over 4 to 12 weeks have shown effects for some, but not all, aspects of mental and physical functioning.15, 16, 75, 91 Ginseng may improve some of the adverse effects of chemotherapy-related transcatheter arterial chemoembolization.17
A systematic review of herbal medicines as adjuvants to the FOLFOX4 regimen used for treating colorectal cancer was conducted to identify evidence of safety and efficacy as well as management of chemotherapy side effects. A total of 13 Chinese randomized clinical trials involving 940 patients were included, which compared herbal medicines plus FOLFOX4 combination to the FOLFOX4 regimen alone in patients with advanced (stage IV) colorectal cancer. Although 58 different herbs and/or extracts were used, Panax ginseng was one of the 6 most common herbs found in treatment preparations (n = 5 in studies). Tumor response rate, overall survival at 1 year, time to progression, quality of life, body weight, nausea/vomiting, and neutropenia improved significantly (P values ranged from P < 0.00001 to P = 0.01) with herbal adjuvants. Ginseng was included in each of the studies contributing to these results.82
The American Society of Clinical Oncology clinical practice guideline adaptation for the screening, assessment, and management of fatigue in adult survivors of cancer (2014) notes that results from small pilot studies on the effectiveness of supplements, such as ginseng, for managing cancer-related fatigue are equivocal.81
Ginseng saponins have been reported to act as selective calcium antagonists and enhance the release of nitric oxide from endothelial and neuronal cells. In vitro studies have shown that total ginseng saponins extracted from Panax notoginseng and P. quinquefolius inhibited calcium entry through receptor-operated calcium channels without affecting calcium entry through voltage channels or intracellular calcium release.6, 18
In studies involving rabbits and dogs, ginsenosides Ro and Rb from P. ginseng offered a protective effect in myocardial ischemia and reperfusion injuries. This effect may be partly mediated by increased release of prostacyclin and by activation of nitric oxide synthase and subsequent release of nitric oxide. An inhibitory effect on platelet aggregation and on the conversion of fibrinogen to fibrin has been demonstrated, and the prevention of atheroma in rabbits fed a high-cholesterol diet has been observed.6, 19
Clinical trials evaluating the effect of ginseng on the cardiovascular system are limited. Hypotensive and hypertensive effects have been postulated. In a short-term study in healthy adults, ginseng 3 g had no effect on blood pressure but lowered the arterial augmentation index20 while a 12-week study among hypertensive adults found no effect of ginseng on 24-hour blood pressure or on renal function.21 Shenfu injection, a mixture of ginseng and monkshood, has been used to prevent reperfusion injury following mitral valve replacement.22 Sanchi (P. notoginseng) is widely used in traditional Chinese medicine in acute ischemic stroke. The saponins in sanchi are similar to those found in P. ginseng and are classified as dammarane saponins (Rb1 and Rg1 primarily). A review of clinical trials found limited evidence of effect of sanchi on short-term effects of ischemic stroke, but noted that the trials were of limited methodological quality.23
In a double-blind controlled trial, 64 adults with well-controlled type 2 diabetes and hypertension received 3 g of American ginseng or placebo for 12 weeks. Ginseng significantly improved arterial stiffness by 5.3% (P = 0.041) and systolic blood pressure by 11.7% (P < 0.001); no effect was noted on diastolic blood pressure.79
Rb1 and Rg1 appear to play a major role in CNS stimulatory and inhibitory effects and may modulate neurotransmitters. Cholinergic activity, implicated in mediating learning and memory processes, is affected by certain ginsenosides. Antioxidant, anti-inflammatory, antiapoptotic, and immune stimulatory effects are suggested to contribute to a protective effect in neurodegenerative disorders.24
Animal studies show that Rb1, Rg1, and Re prevent scopolamine-induced memory deficits, and that Rb1 and Rg1 appear to increase central choline uptake and facilitate the release of acetylcholine from hippocampal tissues. Results from a study in aged rats suggest that daily oral administration of P. ginseng extract 8 g/kg/day for 12 days improved learning performance. In animal tissues, ginseng extract inhibited gamma-aminobutyric acid (GABA), glutamine, dopamine, noradrenalin, and serotonin uptake in a concentration-dependent manner.6, 24, 25, 26
Limited high-quality clinical trials have been conducted, and systematic reviews include data from very few studies.11, 27 An anxiolytic effect via GABA modulation was suggested to be responsible for an observed improvement in sleep disorders for fermented ginseng.28 Among healthy adults, short-term effects of P. ginseng and P. quinquefolius include increased mental performance, increased calmness, and decreased mental fatigue.29, 30, 31 A review of the effect of ginseng on cognitive function in Alzheimer disease found an effect in favor of ginseng for the mini-mental status examination and Alzheimer Disease Assessment Scale for the 2 included studies.27, 32 A 2010 Cochrane systematic evidence review examining ginseng’s effect on cognition found it difficult to pool the available data due to heterogeneity of studies. The reviewers stated that there was some evidence to suggest benefit of ginseng in healthy people for improvement in cognitive function, behavior, and quality of life. There was a lack of high-quality evidence to support ginseng’s use in patients with dementia.76
The American Psychiatric Association (APA) guideline watch for the treatment of patients with Alzheimer disease and other dementias (2014) did not find enough definitive new evidence to change the 2007 guideline recommendations for alternative agents, including ginseng.90
Widespread usage of ginseng and the availability of limited clinical trial data make animal studies largely redundant.
Evidence appears to support the modulation of insulin sensitization and secretion based on cholinergic, dopaminergic, adrenergic, and nitric oxide actions found with ginsenosides. These have been noted to affect glucose metabolism in animal studies.24, 33, 34
Limited quality clinical trials have been conducted among adults with diabetes, with the majority of studies evaluating ginseng in healthy volunteers. Improvements in blood glucose measures and glycemic control have been reported in some33, 34, 35, 36, 37 but not all31, 38, 39 studies.
Widespread usage of ginseng and the availability of limited clinical trial data make animal studies largely redundant.
Evidence supporting the efficacy of ginseng in improving physical performance is conflicting. Physical performance in young, active volunteers did not improve in 4 studies; however, other studies reported a decrease in heart rate and an increase in maximal oxygen uptake.11, 40 One comprehensive literature search evaluated P. ginseng preparations in data from human studies. Properly controlled studies using higher doses (standardized to 2 g/day of dried root) administered for at least 8 weeks and in larger subject numbers more often exhibited improvement in physical or psychomotor performance. Benefit of ginseng may be greater in untrained subjects or in those older than 40 years.41
Immunomodulatory and adaptogenic effects
Animal studies have shown that ginseng extracts can prolong swimming time, prevent stress-induced ulcers, stimulate the proliferation of hepatic ribosomes, increase natural killer-cell activity, and possibly enhance the production of interferons.42 Increased spleen B lymphocyte proliferation and serum immunoglobulin production have been documented in animal models. Increased peritoneal exudate macrophage production of the cytokines IL-1, tumor necrosis factor–alpha, and IL-6, and the production of nitric oxide has also been reported.43, 44
Studies in healthy volunteers measuring T-lymphocyte immunomodulation yield equivocal results.11, 26 Studies in healthy sedentary men and healthy physically active men have found no effect of ginseng on immune markers.40, 45 Modulation of CD8+ T cells and interleukin production was reported in sedentary men beginning to exercise.45 A possible effect of ginseng on the CD4+ T cell count in HIV-positive men was reported.46
Clinical trials supported by the manufacturers of a patented P. quinquefolius preparation suggest a lowered incidence of influenza with the use of ginseng as a prophylactic, especially among elderly patients.47, 48, 49, 50, 51, 77 Dosage studies have taken place to evaluate the effect of ginseng in children with upper respiratory tract infections.52
Compared to baseline and placebo, administration of 6 g/day of the acidic polysaccharide Y-75 (Ginsan) from P. ginseng for 14 weeks resulted in significantly enhanced natural killer cell cytotoxic activity in 72 healthy volunteers. Red blood cell phagocytic activity was also significantly increased at 14 weeks compared with placebo.83
A double-blind, placebo-controlled, randomized clinical trial investigated antifatgue effects of P. ginseng (20% ethanol extract) in 90 adults with idiopathic chronic fatigue. Fatigue severity measured by numerical self-rating scores was significantly improved by 1 and 2 g daily doses; additionally, the 2 g/day doses significantly reduced visual analogue scores. Serum levels of antioxidants and biomarkers associated with oxidative stress (ie, reactive oxygen species, malondialdehyde) were also decreased significantly by both ginseng doses compared with placebo.73
Multiple sclerosis-associated fatigue
Fatigue is a common and frequently bothersome problem in patients with multiple sclerosis (MS), and a randomized, double-blind, placebo-controlled crossover pilot study (n = 47) was conducted. Patients received 6-week courses of ginseng or placebo, with a 2-week washout between crossover therapies. Patients were instructed to titrate therapy upward beginning with 1 capsule/day for 1 week, 2 capsules/day in week 2, and 4 capusles/day for the next 4 weeks. Capsules contained 100 mg of ginseng extract or placebo. No significant difference in benefit for MS-related fatigue reduction was seen for ginseng versus. placebo.78
P. ginseng (100 mg/day root extract, 27% ginsenosides) was compared with amitriptyline 25 mg/day and placebo in a double-blind randomized clinical trial for the treatment of fibromyalgia in adult women. Over the 12-week study period, statistically significant reductions from baseline were documented for pain, fatigue, and sleep in all 3 treatment groups (n = 38); however, no differences between groups occurred.74
Studies in postmenopausal women suggest ginseng 1 g daily (as Korean red ginseng) may increase sexual arousal possibly via a relaxing effect on the clitoral cavernosal muscle and vaginal smooth muscle.53
In men, an improvement in erectile function has been shown in a meta-analysis of clinical studies.54, 55 The American Urological Association guidelines on the management of erectile dysfunction (2005) states that herbal therapies are not recommended for the treatment of erectile dysfunction based on insufficient data. They note that evidence from a small randomized controlled trial has suggested that Korean red ginseng may be an effective treatment, but this needs to be validated by larger trials.72
The Society of Obstetricians and Gynaecologists of Canada revised clinical practice guidelines on managing menopause (2014) do not recommend ginseng for reducing menopausal symptoms based on a lack of evidence to support clinical benefit.88 Likewise, the Endocrine Society clinical practice guidelines for the treatment of symptoms of the menopause (2015) recommend counseling patients on the lack of consistent evidence for benefit of complementary medicine therapies, including ginseng, as an alternative nonhormonal therapy for vasomotor symptoms (weak recommendation; low quality evidence).89
Ginseng root is standardized according to ginsenosides content, and can be chewed or taken as a powder, liquid extract, decoction, or infusion.
According to the Complete German Commission E Monographs, crude preparations of dried root powder 1 to 2 g can be taken daily for up to 3 months.8 In numerous clinical trials, the dosage of crude root has ranged from 0.5 to 3 g/day and the dose of extracts has generally ranged from 100 to 400 mg.2, 11, 13 Other trials have used higher dosages.38, 91
Pregnancy / Lactation
Avoid use during pregnancy and lactation due to insufficient safety evidence.2, 56 Concerns regarding estrogenic effects of ginseng have not been established, while in vitro teratogenicity in rats has been reported at artificially high doses of ginsenosides. 2, 56
An association of ginseng with androgenization in a case report is considered doubtful and more likely due to an adulterant in the preparation.56, 57 Ginseng is widely used in Asian countries among pregnant women and evidence from a cohort study and a review of clinical trials conducted in Singapore found no association between adverse events and the consumption of ginseng products in pregnant women.56
Agents with antiplatelet properties: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of agents with antiplatelet properties. Bleeding may occur. Consider therapy modification.58, 59, 60, 61
Antihypertensive agents: Herbs (hypertensive properties) may diminish the antihypertensive effect of antihypertensive agents. Monitor therapy.92
Herbs (anticoagulant/antiplatelet properties): May enhance the adverse/toxic effect of other herbs (anticoagulant/antiplatelet properties). Bleeding may occur. Consider therapy modification.58
Hypoglycemia agents: Herbs (hypoglycemic properties) may enhance the hypoglycemic effect of hypoglycemia-associated agents. Monitor therapy.93
Nonsteroidal anti-Inflammatory agents: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of nonsteroidal anti-inflammatory agents. Bleeding may occur. Consider therapy modification.58
It is estimated that more than 6 million people regularly ingest ginseng in the United States. There have been few reports of severe reactions, and a very low incidence of adverse events has been reported in clinical trials.56 Hypersensitivity and anaphylaxis have been reported69 and the QTc interval may be increased.70
Inappropriate use of P. ginseng has been described causing symptoms such as hypertension, diarrhea, sleeplessness, mastalgia, vaginal bleeding, skin rash, confusion, and depression. A "ginseng abuse syndrome" was described based on an uncontrolled study in which participants used up to 15 g ginseng daily. When the dosage was reduced to 1.7 g/day, adverse reactions resolved.2, 56
Estrogenic effects have been reported in both pre- and postmenopausal women. However, studies with standardized extracts have shown no effect on estrogenic receptors (rats) or progesterone receptors (humans).2, 56 A case of orobuccolingual dyskinesia was reported in a 46-year-old menopausal woman after using a product containing black cohosh and ginseng for over a year.80 Two cases of new onset acute manic psychosis associated with high-dose, long-term ginseng use were reported in a 23 year-old Caucasian man and 79 year-old African American man after consuming an estimated 7 and 10 times, respectively, the daily recommended traditional Chinese medicinal dose. Neither patient had a psychiatric history. Approximately 15 g/day for 1 month and 20 g/day for 2 months, respectively, were consumed prior to emergency evaluation of bizarre or inappropriate behavior and psychomotor activity, restlessness, irritability, and anxiousness. All symptoms remitted in both patients with administration of supportive care and a short course of antipsychotic medication.84
In the 2016 Scientific Statement by the American Heart Association regarding drugs that may cause or exacerbate heart failure, ginseng has been recognized as a product with possibly harmful cardiovascular effects, such as hypo- or hypertension or decreased diuretic responsiveness, and may be harmful in patients with heart failure. The guidance noted that naturoceuticals are not recommended for the management of heart failure symptoms or for the secondary prevention of cardiovascular events, and that nutritional supplements are not recommended for the treatment of heart failure [Low-quality; Limited].85
Data collected between 2004 and 2013 among 8 US centers in the Drug-induced Liver Injury Network revealed 15.5% (130) of hepatotoxicity cases was caused by herbals and dietary supplements whereas 85% (709) were related to medications. Of the 130 related cases of liver injury related to supplements, 65% were from non-bodybuilding supplements and occurred most often in Hispanic/Latinos compared to non-Hispanic whites and non-Hispanic blacks. Liver transplant was also more frequent with toxicity from non-bodybuilding supplements (13%) than with conventional medications (3%) (P<0.001). Overall, the number of severe liver injury cases was significantly higher from supplements than conventional medications (P=0.02). Of the 217 supplement products implicated in liver injury, ginseng was among the 22% (116) of the single-ingredient products.87
A doping-control urinalysis was conducted under International Olympic Committee (IOC) doping control guidelines for CVT-E002 200 and found no IOC-banned substances that might induce a positive doping-control urinalysis result.71
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