- Asian and American ginseng (P. ginsengand P. quinquefolius) are frequently used medicinal plants
- Evidence is available that ginseng helps against cancer-related fatigue
- Preliminary evidence suggests a benefit of ginseng against infections complications
- Evidence that ginseng works as an anti-cancer agent or protects from chemotherapy-associated adverse effects is weak
- P. ginseng and P. quinquefolius appear to be well tolerated
This summary reports on the most prevalently used species of the genus Panax (C. Linnaeus): Korean or Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius)
Ginseng is claimed to be an adaptogen, which enhances the “state of non-specific resistance” in stress. Ginsenosides, which are steroid glycosides comprising of a sugar and a triterpene part are the putative main active compounds of ginseng.
In traditional medicine it is used as a tonic for strengthening and invigoration in cases of fatigue and weakness as well as for reduced performance and concentration. In some countries, preparations of Asian and American ginseng are available as licensed drugs.
There is evidence from several randomized controlled trials that extracts from both ginseng species helps against cancer-related fatigue. Preliminary evidence suggests that P. quinquefolius might be of benefit to prevent respiratory infections in patients with chronic lymphocytic leukaemia. The evidence that extracts from Panax species prolongs survival, has impact on tumour response, reduces chemotherapy-associated adverse effects or increases quality of life is weak.
Ginseng is usually well tolerated with only minor and easily reversible adverse effects. Possible interactions between ginseng preparations and MAO inhibitors, warfarin and antidiabetics have been reported in the literature.
Summary revised and updated in October 2014 by Markus Horneber.
Summary first published in July 2007, authored by Irene Fischer, Markus Horneber, Katja Boehm.
Markus Horneber, CAM-Cancer Consortium. Ginseng (Panax ginseng, P. quinquefolium) [online document], http://cam-cancer.org/en/ginseng. October 20, 2014.
Description and names
Herbal drugs called "Ginseng" are derived from roots of different species of the genus Panax (C. Linnaeus) which belong to the Araliaceae plant family. Scientific names are Panax ginseng C.A. Meyer and Panax quinquefolius L.
This summary is restricted to Korean or Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius). Other commonly used Panax species are P. japonicus, P. notoginseng and P. vietnamensis. Not every plant termed as ginseng does really belong to the genus Panax. In colloquial terms plants of other genera such as, for instance, Eleutherococcus senticosusand Pfaffia paniculata are also labelled as “Siberian ginseng” and “Brazilian ginseng” respectively. As a result of a farm bill passed by the US Congress, the FDA ruled that the term "ginseng" could only be associated with the genus Panax.
Roots from P. ginseng and P. quinquefolius (for the purpose of this summary called "ginseng") are commercially produced mainly by cultivation and contain ginsenosides, polysaccharides, fatty acids, vitamins, essential oils, trace elements and amino acids1.
Ginsenosides are the putative main active compounds and are nearly exclusively found in Panax species. The content of ginsenosides is seen as a measurement of the quality of a ginseng root. Preferably, the plant is harvested once at 4-7 years old and all parts of the root (primary root, lateral roots and rootlets including their peel) are processed. Ginsenosides are bitter-tasting, surface active steroid glycosides which comprise of a sugar part and a triterpene part the so-called aglycone. The major aglycones are protopanaxadiol and protopanaxatriol, both tetracyclic triterpenes from the dammarane-type. Ginsenosides are labeled with letters and index numbers according to chromatography and there are seven major ginsenosides present inP. ginseng the protopanaxatriols (Rg1, Re, and Rf) and the protopanaxadiols (Rb1, Rc, Rb2, and Rd)P. quinquefolius contains the same ginsenosides, with the exception of Rf2.
The type and content of ginsenosides are indicative of the species and, depending on the part of the root, the age of the plant and the manufacturing process (e.g. red or white ginseng), can vary considerably3. The terms red or white ginseng are not taxonomic references but indicate how the ginseng roots had been treated (steamed = red; dried = white).
Ginsenosides are deglycosylated in the digestive tract and the aglycone part is metabolized. Resorption and bioavailability of ginsenosides and their metabolites are low4.
Application and dosage
There are many types and grades of ginseng, depending on the origin, root maturity, parts of the root used, and methods of raw material preparation or processing. For medical purposes, primarily the crème-coloured roots (harvested at 4-7 years old) are used, mostly as capsules or tablets with dried powders or extracts for oral application5.
According to the German Commission E daily doses of 1-2 g of dried root with a minimum content of 1.5% ginsenosides are recommended6.
In Asia, dosage recommendations are higher than in Europe, the Chinese pharmacopeia for instance recommends 3-9 g root and thus a daily dosage of 45-136 mg ginsenosides. Ginseng is supposed to be consumed 1-2 times daily with plenty of liquid. It is recommended that its application is interrupted after 3 months for a certain period of time.
In two recent clinical trials with cancer patients, extracts from P. quinquefolius were orally applied with daily doses ranging from 400mg to 2000mg for periods from 8 to 12 weeks7,8.
History / providers
For thousands of years P. ginseng has been regarded in Asia as a panacea, promoting health and longevity3. At the beginning of the 18th century the Jesuit father Lafitau discovered P. quinquefolius just outside present day Montreal. The plant has been used for hundreds of years by Native Americans as a medicinal plant9. P. quinquefolius is mainly cultivated in some parts of Canada, in a number of states in the U.S., predominantly Wisconsin and New York, and now also in China. P. ginseng is mainly produced in South Korea, with an annual production of more than 11 thousand tons1. Ginseng products which are advertised for healing purposes can be purchased almost anywhere, for instance, at chemists’, in health food stores, drug stores and over the Internet. Ginseng preparations differ in their composition, preservative agents and binding agents1.
Claims of efficacy and alleged indications
Ginseng is claimed to be an adaptogen. The definition of plant adaptogens is based on empirical knowledge from traditional medicinal systems. In Traditional Chinese Medicine, ginseng has been used for thousands of years for balancing what is referred to as the so-called “Yin-Yang” equilibrium. P. ginseng is supposed to act as a “warming” substance and thereby strengthen what is called “Yang”; whereas P. quinquefolius is claimed to have a “cooling” effect and strengthens “Yin”10,11.
Today, adaptogens are defined as drugs enhancing the “state of non-specific resistance” in stress12. Medicinal uses of ginseng that are supported by clinical data include strengthening and invigoration in cases of fatigue and weakness as well as in states of reduced performance and concentration, with some other studies researching treatment of cancer, cardiovascular disease, and diabetes13.
Mechanisms of action
The detailed mechanisms underlying the clinical effects of ginseng still need to be fully elucidated. Some of the effects possibly result from a modulation of the hypothalamus-pituitary axis or of the central monoamine neurotransmitter system14. Ginsenosides are known to exhibit several effects on the central nervous system including increased survival of neurons after different injuries15.
Other data suggest that the immunomodulatory activities of ginseng are responsible for its adaptogenic effects16.
The results of several trials with healthy subjects indicate that benefits in physical performance and exercise capacity through preparations from Panax species, namely P. ginseng, may include improved capacity of skeletal muscle to oxidize free fatty acids, reduced plasma IL-6, creatine phosphokinase, and cortisol levels17.
Findings from animal studies suggest antiangiogenic effects of ginsenoside Rg318,19. Preparations from P. quinquefoliusinhibited tumorigenesis in a mouse model of inflammation-associated colonic cancer. Those effects were thought to derive from ability of ginseng to downregulate EGFR and ErbB2 activation and Cox-2 expression20. Anti-inflammatory effects of ginsenosides seem to be mediated through the glucocorticoid receptor and through inhibitory effects on LPS-induced MAPK activation21. Data from laboratory studies suggest that the ginsenoside Rg3 also has proliferation inhibiting effects on a human colon cancer cell line (HCT 116). The inhibition of ß-catenin, a protein which is overexpressed and mutated in many cancer cells, were discussed as the putative underlying mechanism22. Current results suggest that protopanaxadiol, the aglycone part of Rg3 effectively suppresses signaling pathways which are known to be involved in several steps of the development and progression of cancer: the NF-κB, JNK and MAPK/ERK pathways23,24.
The hypoglycaemic effects of ginseng are thought to be caused by polypeptides and glycans via stimulation of hepatic glucose utilization, stimulation of insulin secretion and enhanced insulin receptor sensitivity25.
Prevalence of use
Ginseng is one of the most consumed plant products worldwide and in the United States, ginseng has been ranked as the fourth top-selling herbal remedy1,48. In a population-based cohort study with breast cancer patients shortly after diagnosis in Shanghai, 14% of women reported use of extracts from P. ginseng or P. quinquefolius at 6 months follow-up49.
The content of ginsenosides for the root according to the European Pharmacopoeia has to be a minimum of 0.40 per cent for the sum of ginsenosides Rg1 (C42H72O14,2H2O; Mr 837) and Rb1 (C54H92O23,3H2O; Mr 1163) (dried drug) and for the dry extract a minimum of 4.0 per cent of the sum of ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, Rg1 and Rg2, expressed as ginsenoside Rb1 (C54H92O23; Mr 1109).
In Germany for instance, P. ginseng has been licensed as an over-the-counter (OTC) drug by the Federal Institute for Pharmaceuticals (Bundesinstitut für Arzneimittel, BfArm). For those OTC drugs licensed in Germany a minimum content of 1.5% ginsenosides is required.
Costs and expenditures
Costs vary depending on the quality of the ginseng. Daily costs for drugs licensed in Germany amount to approximately 1-3 Euros.
For details of the included randomised controlled trials (RCT) please see Table of included studies.
Effects on survival, tumour response or performance status
A metaanalysis published in Chinese with an English abstract including seven studies with a total of 535 lung cancer patients (NSCLC) reported benefits in response rates, performance index and median survival when ginseng was added to standard chemotherapy. The authors concluded that „due to the poor quality and small sample of the included trials more large-scale multi-center randomized trials are needed“. All included studies used so called „Shenyi Capsules“ which contain „mainly ginsenoside Rg3“ according to the manufacturer50.
A meta-analysis of six RCTs with a total of 496 Chinese non-small cell lung cancer patients (NSCLC) treated with different chemotherapy regimen found an increased response rate [odds ratio: 2.64 (95% CI: 1.70–4.11] and disease control rate [odds ratio: 3.34 (95% CI: 1.92–5.81)] if ginsenoside Rg3 was added to chemotherapy. The authors concluded that „the available evidence suggests that Rg3 plus chemotherapy improves the response rate of NSCLC patients, and well-designed RCTs with large sample size are needed“51.
A further 3 RCTs which at least had an English abstract and reported on clinical outcomes were retrieved. One study reported similar survival rates in NSCLC patients after radical surgery when ginseng was compared to chemotherapy or combined with chemotherapy27. The second study found significantly different survival times when ginseng was compared with no treatment in advanced gastric cancer patients after surgery28. The third study reported no significant differences in tumour response when ginseng was added to standard chemotherapy for advanced oesophageal cancer29. Due to the low reporting quality and the fact that two studies were available only as abstract publications all studies were judged as being at high risk of bias.
Effects on quality of life
Three double-blind, placebo-controlled and one open-label RCT with a no treatment control group (available only as an abstract publication) reported benefits of ginseng on measures of quality of life29-32.
Effects on cancer-related fatigue
Most recent data come from a trial with 364 patients with cancer of various origin undergoing or having undergone chemotherapy with curative intent within the past 2 years and moderate fatigue lasting for at least 1 month before study entry. The data support the benefit of P. quinquefolius, 2000mg daily, against CRF with clinically meaningful results after a 8-week treatment period without discernible toxicities7.
Effects on infectious complications
A recent placebo-controlled trial found that P. quinquefolius could be of some benefit for respiratory infections in patients with chronic lymphocytic leukaemia (CLL). Though extracts from P. quinquefolius did not significantly reduce the duration of acute respiratory infections or the use of antibiotics, the rate of moderate to severe infections and the intensity of symptoms were significantly diminished. In addition, patients who received ginseng exhibited seroconversion to common viruses more frequently8.
Effects on chemotherapy-associated adverse effects
One open-label trial (available only as an abstract publication) with „Shenyi Capsules“ which contain „mainly ginsenoside Rg3“ according to the manufacturer reported lower rates of bone marrow toxicity in the ginseng group and a reduced frequency of nausa and vomiting29.
Preparations from P. ginseng and P. quinquefolius are universally described as causing only minor if any adverse effects. Minor and easily reversible, undesirable effects include headaches, sleep disturbances and gastrointestinal intolerance10. The FDA has added P. quinquefolius on the GRAS (generally recognised as safe) list. Serious adverse effects are rare and have only been reported from countries where ginseng is being used as an unregulated food supplement and where it is consumed in high dosage. Recently, a case was reported of a female patient who developed prolonged QT with subsequent torsades de pointes during periods in which she had ingested large amounts of P. ginseng33.
Long-term studies in animals (up to 6 months) did not indicate any chronic toxicity34. There is evidence of teratogenicity with exposure to ginsenosides, but data are derived from animal studies and are based on exposure to isolated ginsenosides at much higher levels than achievable through normal consumption in humans35,36. There is no evidence of carcinogenic activity in rats or mice37.
There are no strict contraindications. Ginseng could induce hypoglycemia and therefore caution is usually warranted in diabetes patients. In schizophrenia, hypertension, arrhythmia, cardiovascular and cerebrovascular disease, and insomnia, ginseng might worsen the conditions, especially when used over a longer period of time10,38.
Laboratory findings about estrogenic activities of ginsenosides are inconsistent and clinical data did not suggest relevant endocrine activities39. Data from a pilot trial suggested no safety issues in children and adolescents. Little reliable data is available for the consumption of P. ginseng or P. quinquefolius during pregnancy and lactation, especially during the first trimester35.
The literature indicates possible interactions between ginseng preparations and MAO inhibitors, warfarin and antidiabetics40.
Current reviews did not report clinically relevant pharmacokinetic interactions for ginseng extracts41-43. The author of one of the reviews ranked ginseng among herbs for which “the available evidence indicates that, at commonly recommended doses, none of these herbs act as potent or moderate inhibitors or inducers of cytochrome P450 (CYP) enzymes or P-glycoprotein (ABCB1)”42.
Conditions increasing the gastric pH, e.g. use of proton pump inhibitors, lead to a reduced rate of deglycosylated ginsenosides and a subsequent reduction of gastrointestinal uptake of active metabolites44,45.
A recent case report suggested a imatinib-associated hepatotoxicity after concurrent P. ginseng ingestion46.
Unlike earlier reviews, a current test of 21 commonly sold ginseng products found that none of them was contaminated with pesticides but one product had lead contamination and three products failed to contain their claimed or minimum expected amounts of ginsenosides47.
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