Ginseng | Cam-Cancer

Ginseng

Abstract and key points

The term ginseng refers to various plant species of the genus Panax. The main species cultivated for drug production are Panax ginseng (Korean ginseng, Asian ginseng) and Panax quinquefolius (American ginseng, Wisconsin ginseng). According to the European Medicines Agency (EMA), the root of P. ginseng is classified as a traditional herbal medicinal product. Other preparations often do not contain sufficient ginsenosides or may not contain any ginseng at all. Based on clinical research data, the medical uses of ginseng include strengthening and revitalising weak or fatigued patients and any patients suffering from a reduced ability to function and concentrate.

Anti-cancer treatment

  • The very low-quality evidence of the studies regarding the use of ginseng as a tumour-specific treatment does not allow any claim to be made at this time about the effects of ginseng as an anti-tumour treatment.

Supportive/palliative care

The effects of ginseng on fatigue (n=9), quality of life (n=5) and infectious complications (n=1) have been investigated. The results differ depending on the type of ginseng and the preparation administered.

  • Fatigue: The results of two studies (high-quality evidence) indicate that preparations made from the powder of the dried root of American ginseng (P. quinquefolius) reduce symptoms of fatigue.
    The results of the five studies with Asian ginseng (P. ginseng) differed according to the treatment of the ginseng root. The results of two studies suggest that preparations made from the dried root do not alleviate symptoms of fatigue more than treatment with a placebo (high-quality evidence). The results of the other three studies using preparations from heat-treated roots indicate that these can reduce symptoms of fatigue (moderate-quality evidence).

  • Quality of life: American ginseng (P. quinquefolius): one study provides evidence to show that preparations made from the powder of the dried root improve the quality of life in patients who are undergoing or who have received chemotherapy or radiotherapy (high-quality evidence).
    Asian ginseng (P. ginseng): one study indicates that a preparation made from the dried root does not improve quality of life more than treatment with placebo (high-quality evidence), while two studies provide evidence to show that preparations from the heat-treated root do improve the quality of life (low- to moderate-quality).
  • Infectious complications: The results of one study suggest that a polysaccharide extract of American ginseng (P. quinquefolius) may not reduce the frequency of respiratory infections in patients with CLL but it may reduce the severity of symptoms (high-quality evidence).

Preparations of P. ginseng and P. quinquefolius have only been associated with minor adverse drug reactions. These depend on the dosage, occur occasionally, are reversible and manifest as gastrointestinal intolerances, headaches and sleep disorders. The risk of interactions is low.

Document history

Fully revised and updated in November 2020 by Markus Horneber.
Summary revised and updated in October 2014 by Markus Horneber.
Summary first published in July 2007, authored by Irene Fischer, Markus Horneber, Katja Boehm.

Citation

Horneber M, Ziemann J, Ritter C, KOKONbase Team, CAM Cancer Consortium. Ginseng (Panax ginseng, P. quinquefolium) [online document], http://cam-cancer.org/en/ginseng. November, 2020.

What is it?

Name, background and characterisation of the medicinal plant

The term ginseng refers to various plant species of the genus Panax L. which belongs to the Araliaceae family. Ginseng is found in Canada, stretching down to the southern United States, and also across the north east of China, Korea, east India and Japan. The root of four to seven-year-old plants is used for medical purposes. The main species cultivated for drug production are Panax ginseng C.A. Meyer (Korean ginseng, Asian ginseng) and Panax quinquefolius Meyer (American ginseng, Wisconsin ginseng). As a result, this monograph refers predominantly to these two species, although other species (P. japonicus, P. notoginseng and P. vietnamensis) are also used for medical purposes.(Schweins 2000) In addition, medicinal plants from other genera, e.g. Eleutherococcus senticosus or Pfaffia paniculata, are also colloquially referred to as ginseng. Although these species have similar alleged indications, they should be differentiated from Panax L. due to their systematology and ingredients. Ginseng is one of the most widely consumed plant products in the world.

Ingredients and quality requirements

A large variety of substance groups have been detected in the ginseng root, including saponins, polysaccharides (panaxanes and ginsenans), flavonoids, polyacetylene and essential oil as well as proteins (gintonin).

The ginsenosides or panaxosides, which belong to the triterpene saponins, are characteristic for this plant genus. The most important ginsenosides include the panaxadiols Rb1, Rb2, Rc and Rd and the panaxatriols Re, Rf, Rg1, Rg2 and Rh. The content varies depending on where it is grown, the age of the plant and the parts of the plant examined. Rb1 and Rg1 are the dominant ginsenosides in the root. (EMA 2014)

The Ginseng root (Ginseng radix) monograph of the European Pharmacopoeia defines a content of at least 0.40% ginsenosides, calculated as Rb1 and Rg1. The drug consists of the whole or cut roots of P. ginseng. There are two commercial varieties, white and red ginseng, which differ in the way they are processed. White ginseng is prepared by bleaching the root with SO2 after harvesting and then drying the root, while red ginseng is prepared by steaming the roots for two to three hours at 120–130⁰C before drying. Depending on the processing, the concentration and type of ginsenosides change. (Jia 2009). According to the European Pharmacopoeia, the purity criteria for both varieties are the loss of active ingredients during the drying process (≤ 10%), ash (≤ 7%) and ash insoluble in hydrochloric acid (≤ 7%) and the exclusion of P. quinquefolius.

A dry extract can be produced from the ginseng root using a water-ethanol mixture (35-90% v/v). For purity, the corresponding Ginseng dry extract (Ginseng extractum siccum) monograph requires a loss on drying of no more than 7% and a minimum content of the ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, Rg1 and Rg2 (combined as Rb1) of no less than 4%.

Alleged indications

Ginseng is one of the plant adaptogens that allegedly strengthen the "non-specific resistance to stress" of the organism. (Panossian 2017). Based on clinical research data, the medical uses of ginseng include strengthening and revitalising in cases of weakness and fatigue as well as re­duced performance and concentration. (EMA 2014).

In randomised studies, the effects on the following parameters were investigated:

  • athletic performance and recovery after exercise (Engels 2001),
  • short-term memory and the ability to concentrate (Reay 2010, Reay 2006, Lee 2016),
  • frequency of respiratory infections in adults and children (McElhaney 2006, Sutherland 2010, Vohra  2008),
  • fatigue in patients with multiple sclerosis (Etemadifar 2013, Kim 2011),
  • glucose tolerance and hypertensive blood pressure. (Lee 2017, Ogawa-Ochiai 2018)

In traditional Chinese medicine, ginseng is used to maintain the so-called yin-yang balance, with P. ginseng as a "warming" substance to strengthen the yang and P. quinquefolius as a "cooling" substance to strengthen the yin.(EMA 2014, Jia 2009).

In integrative cancer care, ginseng is discussed for its influence on disease progression, cancer-specific symptoms (fatigue, infectious complications) and chemotherapy-induced adverse effects, e.g. myelotoxicity. For further details, please refer to chapter "Clinical effectiveness”.

Application and dosage

The preparations are generally distributed over the counter; ginseng is available in different dosage forms and quantities of active ingredients in pharmacies, health food stores, chemists or even online. In addition to preparation as a tea, ginseng root is mostly used in the form of liquid, concentrated and dry extracts and more rarely as a drug powder, in proprietary medicinal products such as tablets and capsules.

The daily dose recommended by the European Commission is 1–2g of dried root of P. ginseng with a minimum content of 1.5% ginsenosides or equivalent preparations. (Kommision E BGA/BfArM 1991).

In Asia, the recommended doses are higher than in Europe, for example, the Chinese Pharmacopoeia recommends a daily dose of 3–9g.

Ginseng should be taken once or twice a day with plenty of liquid. The adaptogenic effects should become apparent after approximately four weeks but should weaken again with long-term treatment. Therefore, it is recommended that treatment is stopped after three months for a specified period.

Mechanisms of action

From the large number of studies, only those mechanisms of action that relate to clinical applications are presented below. The modulation of the neurohormonal system of the hypothalamic-pituitary axis, the central monoaminergic system and the immune system are discussed as the cause of the adaptogenic effects of ginseng root. (Rasheed 2008, Radad 2011, Panossian 2010).

Several studies with healthy subjects indicate improved oxidation of free fatty acids by skeletal muscles as well as reduced plasma levels of IL-6, creatinine phosphokinase and cortisol as possible positive effects of preparations with P. ginseng in improving physical strength. (Chen 2012).

Since not all mechanisms of action can be attributed to the ginsenosides, it is assumed that other ingredients which bind to the lysophosphatidic acid (LPA) receptor are involved, such as gintonin. (Choi  2015).

In cell culture and animal experiments, another group of substances in ginseng, polyacetylenes, exhibit cytotoxicity on tumour cell lines depending on time and dose. (Matsunaga 1990, Guo 2009, Kim 2016).

The polysaccharides from P. quinquefolius are known to have immunomodulatory properties that are mediated by toll-like receptors and cause the possible anti-infective effects. (Wang 2001, Wang 2004, Predy 2006).

The polysaccharides are also potentially significant in the effects of ginseng on fatigue and exhaustion. In animal experiments, the polysaccharide fractions from P. ginseng and P. quinquefolius led to increased performance in the "forced swim test", improved mitochondrial function and a reduction in biochemical markers for oxidative stress. (Wang  2010, Wang 2014).

Legal issues and cost

According to the EMA, the root of P. ginseng is classified as a traditional herbal medicinal product. Other preparations often do not contain sufficient ginsenosides or may not contain any ginseng at all. For this reason, standardised preparations of pharmaceutical quality should be used to ensure they have a good effect and tolerability, the monthly costs of which can be up to €100.

Does it work?

Anti-tumour treatment

The very low-quality evidence of the studies regarding the use of ginseng as a tumour-specific treatment does not allow any statement to be made at this time about the effects of ginseng as an anti-tumour treatment.

Statements in guidelines

-

Description of the studies included

A review article investigated the effects of ginsenoside Rg3 in the treatment of non-small cell lung cancer (NSCLC). The authors included 20 clinical trials that were published only in Chinese. (Xu 2016). They saw limitations in the methodological quality of the majority of the studies ("the randomization and concealment allocation of most studies were not clear (...), the study periods were generally short, and none of the included trials included long-term follow-up.") and concluded that the very low quality of evidence does not allow a claim to be made regarding the effects of Rg3 on NSCLC.

A randomised study of 414 patients with NSCLC in stages III and IV published afterwards reported a longer median survival time (12 vs. 8.5 months) if ginsenoside Rg3 was also administered during chemotherapy. Only the abstract of this study has been published in English, therefore the quality of the evidence cannot be assessed. (Zhang 2018).

Supportive/palliative care

Nine interventional studies investigated the effects on fatigue of pharmaceutically manufactured preparations from the two types of ginseng, Asian (P. ginseng) and American ginseng (P. quinquefolius). (Barton 2010, Barton 2013, Yennurajalingam 2017, Jiang 2017, Kim 2017, Pourmohamadi 2018, Younus 2003, High 2012, Kim 2020, Martoni 2018). Four of these studies and one further study also examined the effect on quality of life factors. (Barton 2010, Yennurajalingam 2017, Jiang 2017, Kim 2017, Kim 2006). An interventional study investigated the effects of a polysaccharide extract from American ginseng (P. quinquefolius) on infectious complications in chronic lymphocytic leukaemia. (High 2012). The results of these interventional studies differ depending on the type of ginseng and the preparation administered.

  • Fatigue: The results of two studies show a trend that preparations made from the powder of the dried root of American ginseng (P. quinquefolius) reduce symptoms of fatigue (high-quality evidence). (Barton 2010, Barton 2013).
    The results of five studies with Asian ginseng (P. ginseng) differed according to the type of treatment of the ginseng root. The results of Yennurajalingam et al (Yennurajalingam  2017) and Martonie et al. (Martoni 2018) indicate that preparations made from the dried ginseng root do not alleviate symptoms of fatigue more than treatment with a placebo (high-quality evidence). The results of the other three studies using preparations from the heat-treated root indicate that symptoms of fatigue can be reduced (moderate-quality evidence). (Jiang 2017, Kim 2017, Kim 2020).
    Although the results of two other randomised studies provide evidence for the effects of ginseng on fatigue, only an abstract is published for one study and this does not specify the type of ginseng used. (Younus 2003). The other study (Pourmohamadi 2018) does not go into detail about the preparation made from P. ginseng.

  • Quality of life: American ginseng (P. quinquefolius): one study provides evidence that preparations made from the powder of the dried root improve the quality of life in patients who are undergoing or have received chemotherapy or radiotherapy (high-quality evidence). (Barton 2010).
    Asian ginseng (P. ginseng): one study indicates that a preparation made from the dried root does not improve quality of life more than treatment with placebo (high-quality evidence), (Yennurajalingam 2017) while two studies provide evidence to show that preparations from the heat-treated root do improve the quality of life (low- to moderate-evidence). (Jiang  2017, Kim 2006).
  • Infectious complications: The results of one study suggest that a polysaccharide extract of American ginseng (P. quinquefolius) may not reduce the frequency of respiratory infections in patients with CLL but it may reduce the severity of symptoms (High 2012).

Statements in guidelines

The NCCN guideline 'Cancer-related fatigue' (NCCN 2018) evaluated the results of a study (Barton 2013): "there may be some data to support the use of American ginseng".

In its statement on the use of ginseng to treat fatigue, the ASCO guideline (Bower 2014) referred to a systematic review which included only some of the studies mentioned above (Finnegan-John 2013): “(…) there is no consistent evidence of their effectiveness”.

Description of the studies included

Cancer-related fatigue

Barton et al. (Barton 2010) examined the effects of an eight-week course of treatment with American ginseng (P. quinquefolius) in three different doses (2x500mg, 2x750g, 2x1g) on fatigue and exhaustion in 282 patients with different malignant diseases in various stages. All patients had suffered from fatigue symptoms of ≥4/10 in the previous two weeks and were either still receiving or had just completed chemotherapy or radiotherapy at the time of the study. Although the eight-week treatment with American ginseng showed a trend in reducing symptoms of fatigue and exhaustion depending on dosage, the difference did not reach statistical significance compared with placebo. The effects were most pronounced in the group with the highest daily dose (2x1g daily). Depending on the dose, ginseng also had a positive effect on the quality of life but this was also not statistically significant. (high-quality evidence)

In a subsequent two-arm study, the same research group (Barton 2013) examined the effects of an eight-week course of American ginseng (P. quinquefolius) at the dose that had been most effective in the previous study (Barton 2010) (2g/day) in 346 patients with fatigue and exhaustion during or after chemotherapy or radiotherapy. After four weeks, the improvement of fatigue and exhaustion in the ginseng group was not statistically significant compared to the placebo group (P=0.07). After a further four weeks of treatment, the positive effects were significantly stronger in the ginseng group than in in the placebo group and particularly pronounced in the group of patients still receiving chemotherapy or radiotherapy. (high-quality evidence).

Yennurajalingam et al. (Yennurajalingam 2017) investigated the effects of a four-week course of treatment with Asian ginseng (P. ginseng; preparation made from the dried root with ≥7.0% ginsenosides, 2x400mg daily) on fatigue and exhaustion (primary outcome), general quality of life, anxiety, depression, physical strength and the severity of symptoms in 112 outpatients with various malignant diseases in advanced stages. All patients had complained of feeling fatigued on a scale of ≥4/10 in the last two weeks. In both groups (ginseng, placebo), all investigated outcome measures improved over the course of four weeks, but the groups did not differ greatly except for a significantly lower number of adverse events in the ginseng group (high-quality evidence).

In a small two-arm study, Kim et al. (Kim 2017) investigated the effects of a three-month course of treatment with Asian ginseng (P. ginseng; extract from the heat-treated root; 3x1000mg daily) on genotoxic changes, quality of life, fatigue, mental stress, pain and sleep disorders after chemotherapy using taxane and platinum. All 30 patients had previously undergone curative surgery for ovarian cancer and had completed adjuvant chemotherapy two months earlier. After the 12-week treatment, symptoms of fatigue, functionality and all other outcomes examined were significantly improved in the ginseng compared to the placebo group. (moderate-quality evidence).

The authors of another two-arm study (Jiang 2017) examined the effects of treatment with Asian ginseng (P. ginseng; extract from the heat-treated root, 3,000mg daily) on fatigue, quality of life, anxiety, depression and physical performance during chemotherapy. All 60 patients had lung cancer (NSCLC) in stages III-IV and received treatment with cisplatin and gemzitabine during the study. After a two-month course of treatment, the patients in the ginseng group had significantly lower fatigue symptoms compared to those who had not received any additional therapy. (low-quality evidence)

In a two-arm intervention study, Kim et al. (Kim 2020) investigated the effects of Asian ginseng (P. ginseng; extract from the heat-treated root, 2,000mg daily) on the severity of fatigue symptoms in 219 patients with colorectal carcinomas at various stages while receiving chemotherapy (mFOLFOX-6) with adjuvant or palliative intention. During the 16 weeks of treatment, the participants in the ginseng group had significantly less severe fatigue (BFI, cumulative values, AUC) compared to the placebo group.

Pourmohamadi et al. (Pourmohamadi 2018) investigated the effects of treatment with a preparation of Asian ginseng (P. ginseng, not further described, 100mg 1x daily.) on fatigue, mood and quality of life in 113 patients with non-metastatic colorectal cancer after chemotherapy. After a 30-day course of treatment, the authors reported that patients in the ginseng group were less fatigued, had a better quality of life and mood, and had fewer sleep disorders (low-quality evidence).

In a reader’s letter, Martoni et al. (Martoni 2018) reported an unpublished three-arm intervention study which examined the effects of Asian ginseng (P. ginseng; extract from the dried root, 250 to 500mg/day) on fatigue. The participants in the study had different types of cancer and their situations varied significantly in terms of illness and treatment. The symptoms of fatigue decreased in all three groups after the four-week treatment phase. There were no differences between the ginseng groups and the placebo group.

The results of Younus et al. (Younus 2003) are only published as an abstract and the type of ginseng used is not specified.

Quality of life

Kim et al. (Kim 2006) investigated the effects of 1x daily 3000mg red ginseng (P. ginseng) over 12 weeks on quality of life in a randomised and blinded pilot study involving 53 patients with various types of cancer in non-metastatic stages. The treatment situations of the patients who received ginseng was not considered. The authors found improved mental health (GHQ-12) and a tendency for improved physical condition (WHOQOL-BREF) in the group that had taken ginseng. (moderate-quality evidence)

Further studies on quality of life are described under "Fatigue". (Barton 2010, Yennurajalingam 2017, Jiang 2017, Kim 2017).

Infectious complications

In a blinded, randomised study, High et al. (High 2012) examined the effects of 2x daily 200mg of a patented polysaccharide extract made from American ginseng (P. quinquefolius) over eight weeks on the frequency of respiratory infections and the need for antibiotic treatment in 293 patients with early stages of CLL in "watch and wait" situations. They found no reduction in the frequency of respiratory infections but the symptoms of the disease were less pronounced when treated with the polysaccharide extract (significant for 'sore throat') and seroconversions for typical viral pathogens were more frequent. (high-quality evidence)

Is it safe?

Long-term studies in animals (up to six months) showed no evidence of chronic toxicity. (Chang 2003). Although there is evidence of teratogenic effects of ginsenosides, these data are derived from animal models and are based on studies with individual ginsenosides at much higher concentrations than those normally achieved in humans. (Seely 2008, Shin 2010). There is no evidence of carcinogenic effects in rats or mice. (National Toxicology Program 2011).

Adverse effects

Preparations of P. ginseng and P. quinquefolius have only been associated with minor adverse drug reactions. (Mancuso 2017). These depend on the dosage, occur occasionally, are reversible and manifest as gastrointestinal intolerances, headaches and sleep disorders. (Jia 2009). The FDA has placed P. quinquefolius on the GRAS list of substances generally recognised as safe. The risk of serious adverse effects is very low and their occurrence has only been reported in countries where ginseng is taken in high doses. (WHO 2010). A case report is available after a patient developed a prolonged QT interval with subsequent torsades de pointes as a result of consuming a larger amount of P. ginseng. (Torbey 2010).

Contraindications

There are no strict contraindications for the use of ginseng extracts or the drug. Since they can cause hypoglycaemia, caution is advised for diabetics. Ginseng can aggravate symptoms in patients with schizophrenia, arterial hypertension, cardiovascular disease or insomnia, especially if used over a long period of time. (Jia 2009, Brown 1997).

Laboratory data on oestrogenic effects of ginsenosides are available but are not consistent and clinical data do not show relevant endocrine effects. (Wiklund 1999).

The results of a pilot study do not reveal any safety concerns among children and adolescents. There is little reliable information available on the use of P. ginseng or P. quinquefolius during pregnancy and while breastfeeding, especially during the first trimester of pregnancy. (Seely 2008).

Interactions

When taking standardised preparations of P. ginseng in the recommended dosages of 1-1.5g, there is only a low risk of interaction with drugs whose metabolism includes CYP1A2, CYP2D6, CYP2E1 or transmembrane transport P-glycoprotein. Clinical studies suggest only slight changes in plasma levels, which probably have no clinical relevance. (Wiklund 1999) As a weak inducer of CYP3A4, Asian ginseng may, under certain circumstances, reduce the effect of substrates of this enzyme, so that a moderate interaction potential can be assumed. (Wiklund 1999). Non-standardised or specified preparations may deviate from this. Further information on interactions of ginseng and its preparations can be found in the interaction profile on ginseng (Wiklund 1999).

Other safety issues/warnings

In contrast to previous reviews, a recent study of 21 common ginseng products found that none of them are contaminated with pesticides. However, one product was found to be contaminated with lead and three products were not measured at the declared or required minimum level of ginsenosides. (ConsumerLab.com 2020)

Evidence tables
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