Ginseng (Asian)

• How It Works

  Panax ginseng may be effective in treating erectile dysfunction and diabetes. Whether it can improve strength and stamina remains unknown.

  The active ingredients in ginseng are called ginsenosides, which show definite activity in the nervous systems of animals, with both stimulatory and inhibitory effects. Certain ginsenosides are able to stimulate the immune system in mice. They may also have anti-cancer activity. In addition, ginseng can prevent tumors in mice, including ovarian, lung, liver, and skin cancers. Some studies suggest that this effect may also occur in humans. In one study, Korean individuals who consumed ginseng extract had a decreased risk of all types of cancers.

  Other experiments have suggested that ginseng may increase the production of nitric oxide, a vasodilator, in the heart, lung, and kidneys. In addition, studies in animals showed that ginseng can lower blood cholesterol and triglyceride levels. Clinical trials suggest that ginseng can reduce muscle injury and inflammation after exercise.

  Because ginseng was shown to have estrogenic effects, patients with hormone-sensitive cancers should consult their physicians before using it.

• Purported Uses
  • To treat angina
    Some laboratory studies show that ginseng can increase the synthesis of nitric oxide, a vasodilator, but clinical trials have not been conducted to determine if ginseng is useful in treating angina.
  • To treat diabetes
    Ginseng may help to increase the effect of insulin as well as reduce insulin resistance in type II diabetic patients.
  • To treat HIV and AIDS
    Research shows that P. ginseng stimulates certain aspects of the immune system, and although one small clinical trial supports this use, more research is necessary.
  • To stimulate the immune system
    Clinical data support this use, but the long-term effects of P. ginseng are still not known.
  • To treat sexual dysfunction
    A clinical trial showed benefits of P. ginseng for male erectile dysfunction.
  • To improve strength and stamina
    Clinical trials do not support this use.
• Patient Warnings
  • Use of Panax ginseng should be stopped at least one week before surgery.
• Do Not Take If
  • You are taking monoamine oxidase inhibitors (MAOIs) (If combined with MAOIs, Panax ginseng can cause manic-like symptoms).
  • You are taking insulin or sulfonylureas (Panax ginseng may increase their effect, causing a drop in blood sugar).
  • You are taking warfarin or other blood thinners (Panax ginseng may lessen their effects).
  • You are taking Raltegravir (Panax ginseng may increase its effects).
• Side Effects
  • Dry mouth
  • Tachycardia (fast heart rate)
  • Nausea
  • Vomiting
  • Diarrhea
  • Insomnia
  • Nervousness
  • In a case report, a young man with no history of mental illness became manic following chronic consumption of 250 mg of Panax ginseng capsules three times a day. His symptoms resolved when he stopped taking the herb.
  • Gynecomastia (developing breasts) has been reported in a 12-year-old boy after ingesting ginseng extract for body building.
  • A 46-year-old woman developed orobuccolingual dyskinesia (OBLD) that interfered with her speech, tongue-biting and eating difficulties, following consumption of a formula containing black cohosh and ginseng. Her symptoms resolved after discontinuing use of the formula.
  • Perioperative bleeding was reported in a 72-year-old woman following cardiac surgery due to severe coagulopathy induced by high oral intake of ginseng before surgery.
• Brand Name

  Ginsana®, G115®, Ginsai®

• Scientific Name

  Panax ginseng

• Clinical Summary

  Panax ginseng is an herb native to East Asia and Russia. It is also cultivated for its medicinal properties and the root is widely used as a “Yang” tonic in traditional medicine ⁽¹⁾. Patients take ginseng to improve athletic performance, strength and stamina, and as an immunostimulant. Some use it to treat diabetes, cancer, HIV/AIDS, and a variety of other conditions. Ginsenosides, the saponin glycosides, are thought responsible for Panax ginseng’s medicinal effects. They have both stimulatory and inhibitory effects on the CNS, alter cardiovascular tone, and increase humoral and cellular-dependent immunity ⁽²⁾.

  Ginseng has been used in the treatment of erectile dysfunction ⁽⁴⁾, has the potential to increase the hypoglycemic effects of insulin and sulfonylureas as well as reduce insulin resistance in type II diabetic patients ⁽⁵⁾, to enhance immune response ^(19) (21); and to benefit patients with pre-hypertension and hypertension ⁽⁴²⁾. It was also shown to improve menopausal symptoms, and may positively affect cardiovascular health in postmenopausal women ⁽³⁰⁾. Data from randomized clinical trials indicate that ginseng helps alleviate idiopathic chronic fatigue ⁽³³⁾, and may alleviate cold hypersensitivity of hands and feet in women ⁽³⁹⁾.

  Ginseng has been investigated for its anticancer potential as well. Ginsenosides showed antiproliferative effects in vitro ^(25) (26). Epidemiological data show improved survival and quality of life with ginseng use, in breast cancer patients ⁽³⁾; and inverse association between ginseng consumption and reduction in the risk of endometrial cancer in breast cancer survivors ⁽³⁸⁾. In addition, two case-controlled studies indicate a positive association between consumption and reduction in the incidence of all cancers ^(11) (12). Randomized studies show safety and effectiveness of ginseng for reducing genotoxicity and improving quality of life in patients with epithelial ovarian cancer ⁽⁴³⁾, but did not find any benefit in alleviating cancer-related fatigue in advanced cancer patients ⁽⁴⁴⁾.

  Because ginseng was shown to have estrogenic effects ⁽²³⁾, patients with hormone-sensitive cancers should consult their physicians before using it. Panax ginseng should not be confused with American ginseng or Siberian ginseng, which have different medicinal properties.

• Purported Uses
  • Angina
  • Diabetes
  • Health maintenance
  • AIDS
  • Immunostimulation
  • Pain
  • Sexual dysfunction
  • Strength and stamina
• Mechanism of Action

  Ginsenosides have been shown responsible for many of ginseng’s effects, including analgesic effects when administered parenterally ⁽¹²⁾. Animal studies suggest that the ginsenoside Rb1 improves the release of acetylcholine and enhances post-synaptic uptake of choline ⁽²⁾. Ginsenosides also compete for binding sites on GABA receptors in vitro. They prolong drug-induced sleeping time in mice and exhibit additional depressant effects on the central nervous system ⁽²⁾. Ginseng may improve nitric oxide synthesis in endothelium of the heart, lung, kidneys, and in the corpus cavernosum ⁽¹³⁾.

  Oral intake of ginseng was shown to reduce muscle injury and inflammation following exercise in humans, marked by reductions in the levels of creatine kinase, beta-glucuronidase, and glucose-6-phosphate dehydrogenase (G6PDH) ⁽¹⁴⁾. In animal studies, ginseng saponins lowered total plasma cholesterol and triglyceride levels ⁽¹⁵⁾.

  Anticancer activity has also been observed in vitro with several ginsenosides. Differentiation of HL-60 (promyelocytic cells) was induced in ginsenosides Rh2- and Rh3-treated cells ⁽²⁾; Rg3 exerted its effects in part by blocking the nuclear translocation of the protein ß-catenin in colon cancer cells, most of which turned cancerous via activation of the Wnt/ß-catenin signaling pathway ⁽²⁵⁾; Rp1 reduced breast cancer cell proliferation by decreasing the stability of the insulin like growth factor 1 receptor (IGF-1R) protein in breast cancer cells ⁽²⁶⁾.

• Warnings

  Ginseng use should be discontinued at least one week before surgery ⁽¹⁶⁾.

• Adverse Reactions
  • Dry mouth, tachycardia, nausea, vomiting, diarrhea, insomnia, and nervousness have been reported following consumption of ginseng  ⁽¹⁾.
  • A 26-year-old male with no history of mental illness became manic following chronic consumption of 250 mg panax ginseng capsules three times a day. His symptoms, including irritability, insomnia, flight of ideas, and rapid speech, resolved following discontinuation of supplement ⁽¹⁷⁾.
  • Gynecomastia has been reported in a 12-year-old boy after ingesting ginseng extract for body building ⁽³¹⁾.
  • A 46-year-old woman developed orobuccolingual dyskinesia (OBLD) that interfered with her speech, tongue-biting and eating difficulties, following consumption of a formula containing black cohosh and ginseng. Her symptoms resolved after discontinuing use of the formula ⁽³⁴⁾.
  • Two cases of ginseng-associated manic psychosis have been reported ⁽³⁵⁾.
  • Pulmonary embolism has been reported in a 41-year-old woman after taking panax pills ⁽⁴⁰⁾.
  • Perioperative bleeding was reported in a 72-year-old woman following cardiac surgery due to severe coagulopathy induced by high oral intake of ginseng before surgery  ⁽⁴⁵⁾.
• Herb-Drug Interactions

  Insulin and sulfonylureas: P. ginseng may increase the hypoglycemic effect of insulin and sulfonylureas ⁽⁵⁾.
  Anticoagulants: P. ginseng may antagonize the effects of anticoagulants ^{(6) (7) (8)}.
  Monoamine oxidase inhibitors (MAOIs): P. ginseng may cause manic-like symptoms when combined with MAOIs ⁽⁹⁾.
  Imatinib: P. ginseng may increase risk of hepatotoxicity ⁽²⁴⁾.
  Cytochrome P450 (CYP) 3A4 substrates: Certain ginsenosides can induce CYP3A4 and may increase the clearance of substrate drugs ^(28) (29). However, effects in humans may not be clinically significant ⁽⁴¹⁾.
  Raltegravir: Elevated plasma levels of raltegravir, an antiretroviral drug, were reported in a patient following concurrent use of raltegravir and ginseng ⁽³²⁾.

• References

  1. Huang KC. The Pharmacology of Chinese Herbs, 2^nd ed. New York: CRC Press; 1999.

  2. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-93.

  3. Cui Y, Shu XO, Gao YT, et al. Association of ginseng use with survival and quality of life among breast cancer patients. Am J Epidemiol 2006;163:645-53.

  4. de Andrade E, de Mesquita AA, Claro Jde A, et al. Study of the efficacy of Korean Red Ginseng in the treatment of erectile dysfunction. Asian J Androl. Mar 2007;9(2):241-244.

  5. Ma SW, Benzie IF, Chu TT, et al. Effect of Panax ginseng supplementation on biomarkers of glucose tolerance, antioxidant status and oxidative stress in type 2 diabetic subjects: results of a placebo-controlled human intervention trial. Diabetes Obes Metab. Mar 18 2008.

  6. Lee SH, Ahn YM, Ahn SY, et al. Interaction between warfarin and Panax ginseng in ischemic stroke patients. J Altern Complement Med. Jul 2008;14(6):715-721.

  7. Jiang X, Williams KM, Liauw WS, et al. Effect of St John’s wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol. 2004 May;57(5):592-9.

  8. Jiang X, Blair EY, McLachlan AJ. Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach. J Clin Pharmacol. Nov 2006;46(11):1370-1378.

  9. Brinker F. Herb Contraindications and Drug Interactions. 3rd ed. Sandy (OR): Eclectic Medical Publications; 2001.

  10. Baranov AI. Medicinal uses of ginseng and related plants in the Soviet Union: recent trends in the Soviet literature. J Ethnopharmacol 1982;6:339-53.

  11. Shin HR, Kim JY, Yun TK, Morgan G, Vainio H. The cancer-preventive potential of panax ginseng: a review of human and experimental evidence. Cancer Causes Control 2000;11:565-76.

  12. Yun TK, Choi SY. Non-organ specific cancer prevention of ginseng: a prospective study in Korea. Int J Epidemiol 1998;27:359-64.

  13. Cheng TO. Panax (ginseng) is not a panacea. Arch Intern Med 2000;160:3329.

  14. Nah JJ, Hahn JH, Chung S, et al. Effect of ginsenosides, active components of ginseng, on capsaicin-induced pain-related behavior. Neuropharmacology 2000;39:2180-4.

  15. Cabral de Oliveira AC, et al. Protective effects of panax ginseng on muscle injury and inflammation after eccentric exercise. Comp Biochem Physiol C Toxicol Pharmacol 2001;130:369-77.

  16. Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA 2001;286:208-16.

  17. Engelberg D, McCutcheon A, Wiseman S. A case of ginseng-induced mania. J Clin Psychopharmacol 2001;21:535-6.

  18. Vogler BK, Pittler MH, Ernst E. The efficacy of ginseng. A systematic review of randomised clinical trials. Eur J Clin Pharmacol 1999;55:567-75.

  19. Cho YK, et al. Long-term intake of Korean red ginseng in HIV-1-infected patients: development of resistance mutation to zidovudine is delayed. Int Immunopharmacol 2001;1:1295-305.

  20. Cardinal BJ, Engels HJ. Ginseng does not enhance psychological well-being in healthy, young adults: results of a double-blind, placebo-controlled, randomized clinical trial. J Am Diet Assoc 2001;101:655-60.

  21. Scaglione F, et al. Efficacy and safety of the standardized ginseng extract G115 for potentiating vaccination against common cold and-or influenza syndrome. Drugs Exp Clin Res 1996;22:65-72.

  22. Inoue M, Wu CZ, Dou DQ, et al. Lipoprotein lipase activation by red ginseng saponins in hyperlipidemia model animals. Phytomedicine. 1999 Oct;6(4):257-65.

  23. Lee Y, Jin Y, Lim W, et al. A ginsenoside-Rh1, a component of ginseng saponin, activates estrogen receptor in human breast carcinoma MCF-7 cells. J Steroid Biochem Mol Biol. 2003 Mar;84(4):463-8.

  24. Bilgi N, Bell K, Ananthakrishnan AN, et al. Imatinib and Panax ginseng: a potential interaction resulting in liver toxicity. Ann Pharmacother. 2010 May;44(5):926-8.

  25. He BC, Gao JL, Luo X, et al. Ginsenoside Rg3 inhibits colorectal tumor growth through the down-regulation of Wnt/ß-catenin signaling. Int J Oncol. 2011 Feb;38(2):437-45.

  26. Kang JH, Song KH, Woo JK, et al. Ginsenoside Rp1 from Panax ginseng Exhibits Anti-cancer Activity by Down-regulation of the IGF-1R/Akt Pathway in Breast Cancer Cells. Plant Foods Hum Nutr. 2011 Jul 12.

  27. Chen JK, Chen TT. Chinese Medical Herbology and Pharmacology. California: Art of Medicine Press; 2004.

  28. Hao M, Ba Q, Yin J, et al. Deglycosylated ginsenosides are more potent inducers of CYP1A1, CYP1A2 and CYP3A4 expression in HepG2 cells than glycosylated ginsenosides. Drug Metab Pharmacokinet. 2011;26(2):201-5.

  29. Hao M, Zhao Y, Chen P, et al. Structure-activity relationship and substrate-dependent phenomena in effects of ginsenosides on activities of drug-metabolizing P450 enzymes. PLoS One. 2008 Jul 16;3(7):e2697.

  30. Kim SY, Seo SK, Choi YM, et al. Effects of red ginseng supplementation on menopausal symptoms and cardiovascular risk factors in postmenopausal women: a double-blind randomized controlled trial. Menopause. 2012 Apr;19(4):461-6.

  31. Kakisaka Y, Ohara T, Tozawa H, et al. Panax ginseng: a newly identified cause of gynecomastia. Tohoku J Exp Med. 2012;228(2):143-5.

  32. Mateo-Carrasco H, Gálvez-Contreras MC, Fernández-Ginés FD, Nguyen TV. Elevated liver enzymes resulting from an interaction between Raltegravir and Panax ginseng: a case report and brief review. Drug Metabol Drug Interact. 2012;27(3):171-5.

  33. Kim HG, Cho JH, Yoo SR, et al. Antifatigue effects of Panax ginseng C.A. Meyer: a randomised, double-blind, placebo-controlled trial.PLoS One. 2013 Apr 17;8(4):e61271.

  34. Sen A. Orobuccolingual dyskinesia after long-term use of black cohosh and ginseng. J Neuropsychiatry Clin Neurosci. 2013 Fall;25(4):E50.

  35. Norelli LJ, Xu C. Manic Psychosis Associated With Ginseng: A Report of Two Cases and Discussion of the Literature. J Diet Suppl. 2014 Apr 1. [Epub ahead of print]

  36. Jia L, Zhao Y. Current evaluation of the millennium phytomedicine—ginseng (I): etymology, pharmacognosy, phytochemistry, market and regulations. Curr Med Chem. 2009;16(19):2475-84.

  37. Lee J, Lee E, Kim D, Lee J, Yoo J, Koh B.Studies on absorption, distribution and metabolism of ginseng in humans after oral administration. J Ethnopharmacol. 2009 Feb 25;122(1):143-8.

  38. Hsu WL, Tsai YT, Wu CT, Lai JN. The Prescription Pattern of Chinese Herbal Products Containing Ginseng among Tamoxifen-Treated Female Breast Cancer Survivors in Taiwan: A Population-Based Study. Evid Based Complement Alternat Med. 2015;2015:385204.

  39. Park KS, Park KI, Kim JW, Yun YJ, Kim SH, Lee CH, Park JW, Lee JM. Efficacy and safety of Korean red ginseng for cold hypersensitivity in the hands and feet: a randomized, double-blind, placebo-controlled trial. J Ethnopharmacol. 2014 Dec 2;158 Pt A:25-32.

  40. Yigit M, Cevik E. A rare cause of pulmonary embolism: panax. Am J Emerg Med. 2015 Feb;33(2):311.e1-2.

  41. Kim DS, Kim Y, Jeon JY, et al. Effect of Red Ginseng on cytochrome P450 and P-glycoprotein activities in healthy volunteers. J Ginseng Res. 2016 Oct;40(4):375-381.

  42. Lee HW, Lim HJ, Jun JH, Choi J, Lee MS. Ginseng for Treating Hypertension: A Systematic Review and Meta-Analysis of Double Blind, Randomized, Placebo-Controlled Trials. Curr Vasc Pharmacol. 2017;15(6):549-556.

  43. Kim HS, Kim MK, Lee M, Kwon BS, Suh DH, Song YS. Effect of Red Ginseng on Genotoxicity and Health-Related Quality of Life after Adjuvant Chemotherapy in Patients with Epithelial Ovarian Cancer: A Randomized, Double Blind, Placebo-Controlled Trial. Nutrients. 2017 Jul 19;9(7). pii: E772.

  44. Yennurajalingam S, Tannir NM, Williams JL, et al. A Double-Blind, Randomized, Placebo-Controlled Trial of Panax Ginseng for Cancer-Related Fatigue in Patients With Advanced Cancer.J Natl Compr Canc Netw. 2017 Sep;15(9):1111-1120.

  45. Viviano A, Steele D, Edsell M, Jahangiri M. Over-the-counter natural products in cardiac surgery: a case of ginseng-related massive perioperative bleeding. BMJ Case Rep. 2017 Aug 7;2017.