Written by Markus Horneber and the CAM-Cancer Consortium.
Updated October 20, 2014

Ginseng in the management of cancer

Abstract and key points

  • Asian and American ginseng (P. ginseng and 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.

Read about the regulation, supervision and reimbursement of herbal medicine at NAFKAMs website CAM Regulation.

What is it?

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 senticosus and 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.

Ingredients

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 acids.[1]

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 Rf.[2]

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 considerably.[3] 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 low.[4]

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 application.[5]

According to the German Commission E daily doses of 1-2 g of dried root with a mi­ni­mum content of 1.5% ginsenosides are recommended.[6]

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 weeks.[7;8]

History / providers

For thousands of years P. ginseng has been regarded in Asia as a panacea, promoting health and longevity.[3] 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 plant.[9] 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 tons.[1] 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 agents.[1]

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 stress.[12] 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 diabetes.[13]

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 system.[14] Ginsenosides are known to exhibit several effects on the central nervous system in­cluding increased survival of neu­rons after different injuries.[15]

Other data suggest that the immunomodulatory activities of ginseng are responsible for its adaptogenic effects.[16]

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 levels.[17]

Findings from animal studies suggest antiangiogenic effects of ginsenoside Rg3.[18;19] Preparations from P. quinquefolius inhibited 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 expression.[20] Anti-inflammatory effects of ginsenosides seem to be mediated through the glucocor­ticoid receptor and through inhibitory effects on LPS-induced MAPK activa­tion.[21] 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 mechanism.[22] 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 pathways.[23;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 sensitivity.[25]

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 remedy.[1,48] 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-up.[49]

Legal issues

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).[26]

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.

Does it work?

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 manufacturer.[50]

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 chemotherapy.[27] The second study found significantly different survival times when ginseng was compared with no treatment in advanced gastric cancer patients after surgery.[28] The third study reported no significant differences in tumour response when ginseng was added to standard chemotherapy for advanced oesophageal cancer.[29] 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 life.[29-32]

Effects on cancer-related fatigue

There is evidence from four RCTs that extracts of P. quinquefolius and of P. gin­seng can effectively reduce cancer-related fatigue (CrF).[7;30-32]

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 toxicities.[7]

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 frequently.[8]

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 vomiting.[29]

Is it safe?

Adverse effects

Preparations fromP. ginsengandP. quinquefoliusare universally described as caus­ing only minor if any adverse effects. Minor and easily reversible, undesir­able effects include headaches, sleep disturbances and gastrointestinal intoler­ance.[10] The FDA has addedP. quinquefoliuson the GRAS (generallyrecog­nisedassafe) 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 ofP. gin­seng.[33]

Long-term studies in animals (up to 6 months) did not indicate any chronic toxic­ity.[34] 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 hu­mans.[35;36] There is no evi­dence of carcinogenic activity in rats or mice [37]

Contraindications

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 time.[10;38]

Laboratory findings about estrogenic activities of ginsenosides are inconsistent and clinical data did not suggested relevant endocrine activities.[39] Data from a pilot trial suggested no safety issues in children and adolescents. Little reliable data is available for the consumption ofP. ginsengorP. quinquefoliusduring preg­nancy and lactation, especially during the first trimester.[35]

Interactions

The literature indicates possible interactions between ginseng preparations and MAO inhibi­tors, warfarin and antidiabetics.[40]

Current reviews did not report clinically relevant pharmacokinetic interactions for gin­seng extracts.[41-43] 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 metabolites.[44;45]

A recent case report suggested a imatinib-associated hepatotoxicity after concurrentP. gin­senginge­stion.[46]

Warnings

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 ginse­nosides.[47]

Citation

Markus Horneber, CAM-Cancer Consortium. Ginseng (Panax ginseng, P. quinquefolium) [online document]. http://cam-cancer.org/The-Summaries/Herbal-products/Ginseng-Panax-ginseng-P.-quinquefolium. October 20, 2014.

Document history

Summary revised and updated in October 2014 by Markus Horneber.
Summary first published in July 2007, authored by Irene Fischer, Markus Horneber, Katja Boehm.

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