PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of medicinesLink to Publisher's site
 
Medicines (Basel). 2015 June; 2(2): 106–126.
Published online 2015 June 8. doi:  10.3390/medicines2020106
PMCID: PMC5533164

Safety Analysis of Panax Ginseng in Randomized Clinical Trials: A Systematic Review

James D. Adams, Academic Editor

Abstract

Background: Panax ginseng C.A. Meyer is one of the most frequently used herbs in the world. The roots of Panax ginseng have been used as a traditional tonic and medicine for thousands of years in Korea and China. Today, ginseng root is used as a dietary supplement and complementary medicine and for adjuvant therapeutics worldwide. The efficacy of ginseng has been studied in a wide range of basic research and clinical studies. However, it has been reported that the results from clinical studies are conflicting, and they depend on the parameters of the protocol design including the conditions of the participants and the types of ginseng used such as red ginseng, white ginseng, fermented ginseng and cultured ginseng. Meanwhile, in addition to clinical efficacy, the safety of ginseng is a highly important matter for customers. With globally increasing demand for Panax ginseng as a dietary supplement or complementary medicine, it is necessary to provide information on its safe use to customers to improve their health conditions. Although the safety of Panax ginseng in pre-clinical studies is well known, the evaluation of safety in clinical studies has so far been insufficient. This systematic review was conducted to assess the safety of ginseng in randomized controlled clinical trials (RCT) over the last 10 years. We chose the last 10 years because many clinical trials have been conducted in the past 10 years, and it will help to understand the recent trends in RCTs of ginseng.

Methods: Articles on ginseng studies were searched with keywords in MEDLINE and four other Korean online database sites. Studies with ginseng as a monopreparation were selected while studies with single administration, preparations combined with other herbs or drug combinations were excluded from the selected studies. Data from the selected studies meeting the criteria were extracted and reviewed in terms of study design, condition and number of participants, type of ginseng, dosage, duration, main results, adverse events and adverse reactions.

Results: Forty-four studies met the selection criteria. These studies covered the efficacy of ginseng in areas such as cardiovascular function, glucose metabolism, sexual function, anti-oxidation, anti-fatigue and psychomotor function. Twenty-nine studies showed positive results while fifteen studies showed no effect. Sixteen studies reported adverse events while five studies had no adverse events. Twenty-three studies did not mention any adverse events. The main adverse events of ginseng reported were general symptoms such as hot flushes, insomnia and dyspepsia with no significant difference in frequency and symptoms between the ginseng and placebo groups. The symptoms were mild and temporary with no serious or severe adverse events.

Conclusion: Panax ginseng showed a very safe profile in a limited number of RCTs with a small number of participants with various conditions ranging from healthy participants to patients with symptoms. However, to increase the usefulness and lower the health risk of Panax ginseng to customers, clinical trials on a larger scale and with a higher standard are necessary to define its efficacy and safety as a dietary supplement or complementary medicine.

Keywords: Panax ginseng, randomized controlled clinical trial, safety

1. Introduction

Panax ginseng has been used not only as a medicine but also as a restorative and prophylactic remedy for thousands of years in Asia. Ginseng is classified as fresh ginseng (raw ginseng), white ginseng (dried after peeling) and red ginseng (steamed and dried) depending on how it is processed. Ginsenosides are the most studied active components in ginseng. About 40 types of ginsenosides are contained in ginseng along with non-saponin compounds like acidic polysaccharides and polyacetylenes [1,2,3]. Much basic research on the range of efficacies of ginseng, including its immune-enhancing, anti-fatigue, and anti-cancer functions and improvements to cardiovascular function, is ongoing, along with numerous studies on its mechanisms [4].

Currently, the demand for ginseng as a functional food has been increasing not only in Asian countries like Korea, China and Japan but also in Western countries. Despite this trend, RCTs evaluating the efficacy of ginseng as a functional food and as an evidence-based complementary medicine are still very limited. Therefore, it is necessary to evaluate the efficacy and safety of ginseng along with the increased consumption of ginseng as a functional food, adjuvant or complementary medicine. A number of clinical studies on the efficacy and safety of ginseng in randomized controlled clinical trials have been reported [5,6]. The object of this systematic review is to summarize the randomized clinical studies of the past 10 years, focusing on the safety of ginseng to promote its usefulness as a functional food or complementary medicine.

2. Methods

2.1. Data Sources and Selection

A systematic literature search was conducted on MEDLINE, Korean Studies Information Services System (KISS), NuriMedia database (DBPIA), Korea Institute of Science and Technology Information (KISTI) and the literature search system of the authors’ own institute. Keywords used in the searches were “Panax ginseng” or “clinical” or “randomized” or “controlled” or “human study”. The search period ranged from January 2005 to November 2014. Further publications until December 2014 were also searched. Two independent reviewers (JW and YK) assessed all titles and abstracts with a pre-defined inclusion criteria using the following united keywords: Panax ginseng, ginseng, controlled, trial.

2.2. Eligibility of Studies

Studies were selected in accordance with the following criteria: (1) randomized controlled clinical trial; (2) Panax ginseng as a monopreparation as the intervention; (3) subjects with no other medication or supplement intake; (4) single administration excluded; (5) studies using other parts of ginseng besides the root excluded; (6) administration routes other than oral intake such as intravenous or dermal application excluded; and (7) articles in languages other than English or Korean excluded.

2.3. Data Extraction

The data were extracted from the articles according to the predefined criteria: study design, condition and number of participants, type of ginseng, dosage, duration, main results and adverse events.

3. Results

3.1. Included Studies

Out of 595 articles that were initially chosen from MEDLINE and four other Korean DB sites using the keywords, 45 articles met all the criteria (Figure 1). To put more emphasis on safety rather than efficacy, studies that used ginseng with other herbal medicines or took other drugs together were excluded from the review because ginseng and other herbal medicines or drugs could cause interactions resulting in adverse events. The 45 articles meeting the criteria of this study are summarized in Table 1.

Figure 1
Flow diagram of the publication selection process. RCT: Randomized controlled clinical trials.
Table 1
Summary of randomized controlled studies of Panax ginseng for a 10 year period (2005–2014).

Because two of the 45 articles were from the same clinical trial study [7,8], 44 studies met all the criteria for the time period from 2005 to 2014. One study was single-blind [9], and the rest were double-blind studies. There were 7 studies with crossover design while the rest were parallel design studies. The areas of study for the included studies were as follow: sexual function (6 studies), glucose metabolism (5 studies), cardiovascular function (4 studies), psychomotor function (3 studies), fatigue (4 studies), antioxidant function (3 studies), obesity (3 studies), sleep (3 studies), menopausal symptoms (2 studies), cancer (1 study), respiratory system (1 study), hearing (1 study), fibromyalgia (1 study), safety and tolerability (1 study), dry mouth (1 study), somatic symptoms (1 studies), androgenic alopecia (1 study), general symptoms (1 study), gynecological complains (1 study), and depression (1 study).

3.2. Participants

In total, 3092 participants were involved in the 44 selected studies. The median number of participants was 53 (range: 15–643). Participants were aged between 18 and 79 years. Among the 22 studies conducted on healthy subjects, 9 studies involved only male subjects, 2 studies involved only female subjects, and 11 studies included both genders. There were 6 studies on menopausal females, 5 studies on obesity, diabetes or metabolic disorders, 4 studies on erectile dysfunction, and one study each on chronic gastritis, chronic fatigue, female sexual dysfunction, chronic rhinitis, fibromyalgia, dry mouth, and alopecia, respectively. There was one study on healthy Koreans and Chinese for general symptoms and adverse events.

3.3. Interventions

Out of 29 recent studies on Korean red ginseng, 23 studies used the powder type, 5 used the extract type and 1 used a ginsenoside-fortified ginseng extract. Four studies used Panax ginseng extract (G115), 1 study used powder, 3 studies used 20% ethanol extract, 5 studies used fermented red ginseng powder and 2 studies used cultured ginseng.

Daily intake dosages varied based on the type of ginseng. The Panax ginseng extract (G115) intake was 100–400 mg, while the 20% ethanol ginseng extract intake was 1–2 g. The dosage for Korean red ginseng powder was 0.9–6 g, with the most common dosage being 3 g in 8 studies. Korean red ginseng extract intake was between 200 mg and a maximum of 60 g per day. Fermented red ginseng powder intake was 1.5–2.7 g, and cultured ginseng extract intake was 2 g. One study administrated 3 g of Panax ginseng and Panax quinquefolium each to compare the adverse events between Korean and Chinese participants.

The duration of ginseng intake was 7–11 days for the short-term studies (4 studies), and the maximum duration was 3 years. About 50% of the studies had intakes of 8 or 12 weeks. There were 13 studies with an 8-week intake, 9 studies with a 12-week intake, 7 studies with a 4-week intake, 6 studies with a 2-week intake, 2 studies with a 6-week intake, and one study each with a 24-week, 3-week, and 3-year intake.

3.4. Efficacy

According to the primary endpoint results, 29 studies showed statistical significance between the placebo groups and ginseng groups, while 15 studies did not show any effects. Two studies from the 15 studies showed no effect on the biomarkers but did show an improved quality of life.

Study results showed that Korean red ginseng extract inhibited platelet aggregation in healthy subjects [13]. There was no significant thermal effect from ginseng caused by improved blood circulation in females with a low Female Sexual Function Index (FSFI) value [12] and in healthy subjects [10]. There was also no effect on blood pressure in patients with metabolic syndrome [11].

Korean red ginseng powder reduced insulin and C-peptide during oral glucose tolerance tests (OGTT) in patients with mild diabetes [14]. Fermented red ginseng also decreased blood glucose, glycated hemoglobin (HbA1C) and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) levels during OGTT in healthy or postmenopausal females [15,16], but Korean red ginseng extract had no effect on glucose metabolism in overweight subjects or newly diagnosed type 2 diabetes mellitus (T2DM) patients [17]. G115 had no effect on blood glucose-related markers in healthy subjects [18].

Korean red ginseng extract improved working memory in the psychomotor function study [21], but there was no effect from Korean red ginseng powder on the neurocognitive function tests in healthy subjects [19]. Panax ginseng extract G115 showed no effect on working memory [20].

There was a decrease in cancer risk in chronic atrophic gastritis patients with 3 years of intervention with the Korean red ginseng extract in an 8-year follow-up study [22].Korean red ginseng powder and the 20% ethanol ginseng extract showed antioxidative effects in postmenopausal females or healthy subjects [23,24,25].

Twenty percent ethanol ginseng extract improved fatigue scores and showed antioxidative effects in chronic fatigue patients [26]. Korean red ginseng extract decreased creatine kinase (CK) and interleukin 6 (IL-6) levels after uphill tread mill exercise [27]. However, Korean red ginseng extract and ginseng powder did not affect maximal oxygen uptake (VO2max) or physical performance in healthy subjects [28,29].

One study showed that Korean red ginseng powder improved the FSFI values for sexual arousal and the Global Assessment Questionnaire (GAQ) values in menopausal females [30], but another study showed no effect on the FSFI values in women with sexual dysfunction [32]. A group of studies showed Korean red ginseng powder and cultured ginseng extract improved erectile dysfunction [31,33,34,35].

Korean red ginseng powder improved menopausal symptoms such as hot flushes and decreased blood cholesterol and LDL-cholesterol levels in menopausal females [36,37].

Korean red ginseng powder had no effect on metabolic biomarkers such as insulin sensitivity in non-diabetic healthy subjects with BMIs greater than 23 kg/m2 [38], and did not improve BMIs in a study on obese female subjects (BMI ≥ 25 kg/m2) [7]. However, it showed a genotype-dependent improvement in BMI and quality of life [8]. Korean red ginseng extract reduced the frequency of acute respiratory illnesses but not the symptom durations [39]. Fermented red ginseng improved the quality of life although it did not show any improvement related to allergic rhinitis symptoms [40].

Korean red ginseng powder and fermented red ginseng improved the effective sleep time and sleep efficiency [41,42,43]. Korean red ginseng powder improved somatic symptoms [48], hair thickness and hair density [49]. It did not improve dry mouth symptoms in xerostomatic patients, but an intergroup analysis showed improvement in dry mouth symptoms in menopausal females [47]. Korean red ginseng powder also reduced urinary BPA and MDA levels in young females and reduced the severity of gynecological complaints [9]. Fermented red ginseng improved cognitive depression in postmenopausal females [51]. Panax ginseng extract (G115) reduced noise-induced temporary threshold shifts in textile workers [44], but had no effect on pain and fatigue in patients with fibromyalgia [45].

3.5. Safety

Adverse events from the selected studies are summarized in Table 2. From the 44 selected studies, 23 studies did not report on adverse events, 5 studies reported no adverse events, and 16 studies reported adverse events. Two studies in particular focused on safety. One study compared the adverse events of red ginseng and white ginseng prepared from Panax ginseng with those of American ginseng prepared from Panax quinquefolium for a 4-week intervention using 3 g in healthy Korean and Chinese subjects [50]. In that study, there was no difference in the frequencies of the adverse events in the Korean subjects among the three ginseng types. However, a significant increase of chest discomfort was reported after the intake of American ginseng in Chinese subjects. In the other safety study with a 4-week intervention using 1 or 2 g of 20% ethanol ginseng extract of Panax ginseng, the four most frequently reported adverse events were dyspepsia, hot flushes, insomnia and constipation. However, there were no differences compared with the placebo group and no changes in hematologic and biochemical markers [46].

Table 2
Frequency of adverse events in this review.

In the study with a long-term intervention of 3 years in chronic atrophic gastritis patients, the adverse events were headaches, increased heartbeat, rashes, sweating, raised blood pressure and nasal bleeding. However, there was no significant difference in frequency between the placebo and ginseng groups, which were 12% and 9.9%, respectively [22].

Adverse events occurring during the clinical trials were reported to have no relation with the test sample; allergic reactions such as cold allergy were reported in the ginseng group, but the author stated that it was not related to the ginseng intervention [13]. Adverse events such as voice disorder, ophthalmalgia, perinea pain and renal stones in the erectile dysfunction study were shown to have no relation with the test sample [31]. In a 12-week intervention study with healthy subjects, there were no statistical differences between the placebo and ginseng groups for adverse events, and specific events were not observed (p = 0.378) [39]. The observed adverse events of gastritis, arthritis and urticaria during the study period had no causal relationship to the ginseng intake [39]. Vaginal bleeding was reported in the study on sexual dysfunction in menopausal females [30]. One case of hypoglycemia was reported in the glucose metabolism study with healthy subjects [15].

Adverse events reported in the RCTs were described as general symptoms which were also observed in the placebo group. General symptoms for adverse events such as hot flushes, insomnia, dyspepsia, skin disorders, dried mouth, diarrhea, headaches, chest discomfort, constipation, nasal bleeding, dizziness, rapid heartbeat and anorexia were reported in both ginseng and placebo groups.

Overall, there was no statistical significance between the ginseng and placebo groups on the frequency or symptoms of adverse events, and no serious or severe adverse events were reported. The symptoms were mild and temporary, which ceased when ginseng administration was discontinued.

4. Discussion

Panax ginseng C.A. Meyer not only has been used as a traditional tonic and medicine for thousands of years in Asia, but also as a dietary supplement and complementary medicine and for adjuvant therapeutics worldwide. It is necessary to provide information on its safety along with its clinical efficacy to consumers as the demand for ginseng increases.

From clinical trials on the efficacy and safety of ginseng, randomized controlled clinical trials over the past 10 years were searched for in online databases and the reported adverse events were investigated. Because the use of other herbal medicines or drugs combined with ginseng could cause interactive adverse events, we selected 45 articles that used ginseng as a monopreparation as well as those meeting other criteria. However, 15 studies out of the 44 studies were shown to be not significant. For example, in five studies on blood glucose regulation, three studies showed an effect on glucose metabolism in impaired fasting glucose or impaired glucose tolerance, in menopausal female or healthy subjects [14,15,16]. The test samples, dosages and durations also varied in these studies. These results indicate that subject selection, dosage, duration and biomarkers in clinical trials are crucial for obtaining positive results. In addition, clearly stating the production process and the content of the samples used can support the reliability of the study. Although many systematic reviews on clinical trials with ginseng have been published recently, many of them have a high risk of bias due to the small number of participants [5,6,52,53].

The short-term interventions were between 7–11 days while one long-term intervention was three years. Fifty percent of the studies were between 8–12 weeks, and the rest of studies were less than six weeks. Therefore, moving forward, long-term studies of more than 12 weeks should be done on the efficacy and safety of ginseng.

Among the reviewed studies that used ginseng as a monopreparation and in which no other drugs were taken, five studies reported no adverse events, and 16 studies reported adverse events. The reported adverse events were mainly general symptoms that were observed in both the ginseng and placebo groups such as dyspepsia, hot flushes and insomnia. These adverse events were mild and temporary. There were no significant differences in the frequency and symptoms of adverse events between the placebo and ginseng groups, indicating that ginseng intake is safe generally. However, 23 studies did not report on adverse events. Because not many studies are discussing adverse events sufficiently, the evaluation of safety of Panax ginseng in this review could be limited. To fully understand the adverse events of ginseng, studies should report detailed adverse events during the trials.

In the case of adverse events from ginseng, interaction with warfarin has been reported in some case reports [54,55], but it was also reported that there was no interaction with warfarin in healthy subjects [56] and in patients receiving warfarin therapy [57,58]. Although many case reports have reported on ginseng and drug interaction, the evidence is insufficient because the studies lack clear information on the samples which were combined with other herbs or on the condition of the participants. Because many people take drugs to maintain their health and expect supplementary effects from ginseng, it will be necessary to provide clear information to ginseng consumers through studies on drug interaction, on the activities of drug metabolizing enzymes, and on drug transporters and pharmacokinetics.

Furthermore, studies on the efficacy and safety of ginseng with higher standards should be conducted to help consumers maintain health and combat diseases with ginseng as a dietary supplement or complimentary medicine.

5. Conclusions

Panax ginseng as a monopreparation showed a safe profile with no significant differences between the placebo and ginseng groups in terms of the frequency and symptoms of adverse events in RCT studies with a small number of subjects with various conditions for each patient. However, more studies with higher standards and larger-scaled clinical trials on the efficacy and safety of ginseng are necessary to provide more definite information about ginseng as a functional food or complementary medicine to the consumers.

Author Contributions

Author Contributions

YSK selected the documents and drafted the article. JYW searched and selected the documents. CKH searched and organized the document information. IMC designed the review outline and critically revised it for the content.

Conflicts of Interest

Conflicts of Interest

The authors declare no conflict of interest.

References

1. Christensen L.P. Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Adv. Food Nutr. Res. 2009;55:1–99. [PubMed]
2. Sun Y. Structure and biological activities of the polysaccharides from the leaves, roots and fruits of Panax ginseng C.A. Meyer: An overview. Carbohydr. Polym. 2011;85:490–499. doi: 10.1016/j.carbpol.2011.03.033. [Cross Ref]
3. Liu J.H., Lee C.S., Leung K.M., Yan Z.K., Shen B.H., Zhao Z.Z., Jiang Z.H. Quantification of two polyacetylenes in radix ginseng and roots of related Panax species using a gas chromatography-mass spectrometric method. J. Agric. Food Chem. 2007;55:8830–8835. doi: 10.1021/jf070735o. [PubMed] [Cross Ref]
4. Lee J., Zhao Y., Liang X.J. Current evaluation of the millennium phytomedicine—Ginseng (II): Collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine. Curr. Med. Chem. 2009;16:2924–2942. [PMC free article] [PubMed]
5. Lee N.H., Son C.G. Systematic review of randomized controlled trials evaluating the efficacy and safety of ginseng. J. Acupunct. Meridian Stud. 2011;4:85–97. doi: 10.1016/S2005-2901(11)60013-7. [PubMed] [Cross Ref]
6. Shergis J.L., Zhang A.L., Zhou W., Xue C.C. Quality and risk of bias Panax ginseng randomized controlled trial: A review. Am. J. Chin. Med. 2013;41:231–252. doi: 10.1142/S0192415X13500171. [PubMed] [Cross Ref]
7. Kwon D.H., Bose S., Song M.Y., Lee M.J., Lim C.Y., Kwon B.S., Kim H.J. Efficacy of Korean red ginseng by single nucleotide polymorphism in obese women: Randomized, double-blind, placebo-controlled trial. J. Ginseng Res. 2012;36:176–189. doi: 10.5142/jgr.2012.36.2.176. [PMC free article] [PubMed] [Cross Ref]
8. Kwon D.H., Lee M.J., Lim J.Y., Bose S., Lee S.J., Kim H.J. Efficacy of red ginseng by oriental medical obesity syndrome differentiation on obese women: randomized, double-blind, placebo-controlled trial. J. Korean Med. Obes. Res. 2011;11:1–14.
9. Yang M., Lee H.S., Hwang M.W., Jin M. Effects of Korean red ginseng (Panax ginseng. C.A. Meyer) on bisphenol A exposure and gynecologic complaints: Single blind, randomized clinical trial of efficacy and safety. BMC Complement. Altern. Med. 2014;14:265. doi: 10.1186/1472-6882-14-265. [PMC free article] [PubMed] [Cross Ref]
10. Kang J.H., Lee N., Ahn Y.H., Lee H. Study on improving blood flow with Korean red ginseng substances using digital infrared thermal imaging and Doppler sonography: Randomized, double blind, placebo-controlled clinical trial with parallel design. J. Tradit. Chin. Med. 2013;33:39–45. doi: 10.1016/S0254-6272(13)60098-9. [PubMed] [Cross Ref]
11. Park B.J., Lee Y.J., Lee H.R., Jung D.H., Na H.Y., Kim H.B., Shim J.Y. Effects of Korean red ginseng on cardiovascular risks in subjects with metabolic syndrome: A double-blind randomized controlled study. Korean J. Fam. Med. 2012;33:190–196. doi: 10.4082/kjfm.2012.33.4.190. [PMC free article] [PubMed] [Cross Ref]
12. Choi M.S., Jeong J.C., Park J.K., Ahn H.Y., Kim D.I. A study on thermal effect and medication compliance of red ginseng extract. J. Oriental Obstet. Gynecol. 2009;22:223–235.
13. Shin K.S., Lee J.J., Jin Y.R., Yu J.Y., Park E.S., Im J.H., You S.H., Oh K.W., Lee M.K., Wee J.J., et al. Effect of Korean red ginseng extract on blood circulation in healthy volunteers: A randomized, double-blind, pacebo-controlled trial. J. Ginseng Res. 2007;31:109–116.
14. Bang H.J., Kwak J.H., Ahn H.Y., Shin D.Y., Lee J.H. Korean red ginseng improves glucose control in subjects with impaired fasting glucose, impaired glucose tolerance, or newly diagnosed type 2 diabetes mellitus. J. Med. Food. 2014;17:128–134. doi: 10.1089/jmf.2013.2889. [PMC free article] [PubMed] [Cross Ref]
15. Oh M.R., Park S.H., Kim S.Y., Back H.I., Kim M.G., Jeon J.Y., Ha K.C., Na W.T., Cha Y.S., Park B.H., et al. Postprandial glucose-lowering effects of fermented red ginseng in subjects with impaired fasting glucose or type2 diabetes: A randomized, double-blind, placebo-controlled clinical trial. BMC Complement. Altern. Med. 2014;14:237–244. doi: 10.1186/1472-6882-14-237. [PMC free article] [PubMed] [Cross Ref]
16. Lee K.J., Lee S.Y., Ji G.E. Diabetes-ameliorating effects of fermented red ginseng and causal effects on hormonal interactions: Testing the hypothesis by multiple group path analysis. J. Med. Food. 2013;16:383–395. doi: 10.1089/jmf.2012.2583. [PubMed] [Cross Ref]
17. Reeds D.N., Patterson B.W., Okunade A., Holloszy J.O., Polonsky K.S., Klein S. Ginseng and ginsenoside Re do not improve β-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes. Diabetes Care. 2011;34:1071–1076. doi: 10.2337/dc10-2299. [PMC free article] [PubMed] [Cross Ref]
18. Reay J.L., Scholey A.B., Milne A., Fenwick J., Kennedy D.O. Panax ginseng has no effect on indices of glucose regulation following acute or chronic ingestion in healthy volunteers. Br. J. Nutr. 2009;101:1679–1688. doi: 10.1017/S0007114508123418. [PubMed] [Cross Ref]
19. Yeo H.B., Yoon H.K., Lee H.J., Kang S.G., Jung K.Y., Kim L. Effects of Korean red ginseng on cognitive and motor function: A double-blind, randomized, placebo-controlled trial. J. Ginseng Res. 2012;36:190–197. doi: 10.5142/jgr.2012.36.2.190. [PMC free article] [PubMed] [Cross Ref]
20. Reay J.L., Scholey A.B., Kennedy D.O. Panax ginseng (G115) improves aspects of working memory performance and subjective ratings of calmness in healthy young adults. Hum. Psychopharmacol. Clin. Exp. 2010;25:462–471. doi: 10.1002/hup.1138. [PubMed] [Cross Ref]
21. Kennedy D.O., Reay J.L., Scholey A.B. Effects of 8 weeks administration of Korean Panax ginseng extract on the mood and cognitive performance of healthy individuals. J. Ginseng Res. 2007;31:34–43.
22. Yun T.K., Zheng S., Choi S.Y., Cai S.R., Lee Y.S., Liu X.Y., Cho K.J., Park K.Y. Non-organ-specific preventive effect of long-term administration of Korean red ginseng extract on incidence of human cancers. J. Med. Food. 2010;13:489–494. doi: 10.1089/jmf.2009.1275. [PubMed] [Cross Ref]
23. Seo S.K., Hong Y., Yun B.Y., Chon S.J., Jung Y.S., Park J.H., Cho S., Choi Y.S., Lee B.K. Antioxidative effects of Korean red ginseng in postmenopausal women: A double-blind randomized controlled trial. J. Ethnopharmacol. 2014;154:753–757. doi: 10.1016/j.jep.2014.04.051. [PubMed] [Cross Ref]
24. Kim J.Y., Park J.Y., Kang H.J., Kim O.Y., Lee J.H. Beneficial effects of Korean red ginseng on lymphocyte DNA damage, antioxidant enzyme activity, and LDL oxidation in healthy participants: A randomized, double-blind, placebo-controlled trial. Nutr. J. 2012;11:47–55. doi: 10.1186/1475-2891-11-47. [PMC free article] [PubMed] [Cross Ref]
25. Kim H.G., Yoo S.R., Park H.J., Lee N.H., Shin J.W., Sathyanath R., Cho J.H., Son C.G. Antioxidant effects of Panax ginseng C.A. Meyer in healthy subjects: A randomized, placebo-controlled clinical trial. Food Chem. Toxicol. 2011;49:2229–2235. [PubMed]
26. Kim H.G., Cho J.H., Yoo S.R., Lee J.S., Han J.M., Lee N.H., Ahn Y.C., Son C.G. Antifatigue effects of Panax ginseng C.A Meyer: A randomized, double-blind, placebo-controlled trial. PLoS ONE. 2013;8:e61271. doi: 10.1371/journal.pone.0061271. [PMC free article] [PubMed] [Cross Ref]
27. Jung H.L., Kwak H.E., Kim S.S., Kim Y.C., Lee C.D., Byurn H.K., Kang H.Y. Effects of Panax ginseng supplementation on muscle damage and inflammation after uphill treadmill running in humans. Am. J. Chin. Med. 2011;39:441–450. doi: 10.1142/S0192415X11008944. [PubMed] [Cross Ref]
28. Yoon S.J., Kim K.H., Kim C.J., Park H.C., Kang K.H., Kim M.J., Kang S.M., Kwak U.H., Kim H.J. Effect of red ginseng supplementation on aerobic.anaerobic performance, central and peripheral fatigue. J. Ginseng Res. 2008;32:210–219.
29. Kulaputana O., Thanakomsirichot S., Anomasiri W. Ginseng supplementation does not change lactate threshold and physical performances in physically active Thai man. J. Med. Assoc. Thail. 2007;90:1172–1179. [PubMed]
30. Oh K.J., Chae M.J., Lee H.S., Hong H.D., Park K. Effects of Korean red ginseng on sexual arousal in menopausal women: Placebo-controlled, double-blind crossover clinical study. J. Sex. Med. 2010;7:1469–1477. doi: 10.1111/j.1743-6109.2009.01700.x. [PubMed] [Cross Ref]
31. Ham W.S., Kim W.T., Lee J.S., Ju H.J., Kang S.J., Oh J.H., Her Y., Chung J.Y., Park K.S., Choi Y.D. Efficacy and safety of red ginseng extract powder in patients with erectile dysfunction: Multicenter, randomized, double-blind, placebo-controlled study. Korean J. Urol. 2009;50:159–164. doi: 10.4111/kju.2009.50.2.159. [Cross Ref]
32. Kim D.I., Choi M.S., Ahn H.Y. Efficacy and safety of red ginseng on women’s health related quality of life and sexual function. J. Ginseng Res. 2009;33:115–126.
33. Kim T.H., Jeon S.H., Hahn E.J., Paek K.Y., Park J.K., Youn N.Y., Lee H.L. Effects of tissue-cultured mountain ginseng (Panax ginseng C.A. Meyer) extract on male patients with erectile dysfunction. Asian J. Androl. 2009;11:356–361. doi: 10.1038/aja.2008.32. [PMC free article] [PubMed] [Cross Ref]
34. De Andrade E., de Mesquita A.A., Claro J.A., de Andrade P.M., Ortiz V., Paranhos M., Srougi M. Study of the efficacy of Korean red ginseng in the treatment of erectile dysfunction. Asian J. Androl. 2007;9:241–244. doi: 10.1111/j.1745-7262.2007.00210.x. [PubMed] [Cross Ref]
35. Kim H.S., Woo S.H., Jo S.H., Hahn E.J., Youn N.Y., Lee H.L. Double-blind, placebo-controlled, multi-center study for therapeutic effects of mountain Panax ginseng C.A Meyer extract in men with erectile dysfunction: A preliminary report. Korean J. Androl. 2006;24:84–88.
36. Kim S.Y., Seo S.K., Choi Y.M., Jeon Y.E., Lim K.J., Cho S., Choi Y.S., Lee B.S. Effects of red ginseng supplementation on menopausal symptoms and cardiovascular risk factors in postmenopausal woman: a double-blind randomized controlled trial. Menopause. 2012;19:461–466. doi: 10.1097/gme.0b013e3182325e4b. [PubMed] [Cross Ref]
37. Kim H.S., Yoon Y.J., Lee J.M., Lee C.H., Jang J.B., Lee K.S., Cho J.H. A clinical study on the effect of red ginseng for postmenopausal hot flushes. J. Oriental Obstet. Gynecol. 2009;22:132–139.
38. Cho Y.H., Ahn S.C., Lee S.Y., Jeong D.W., Choi E.J., Kim Y.J., Lee J.G., Lee Y.H., Shin B.C. Effect of Korean red ginseng on insulin sensitivity in non-diabetic healthy overweight and obese adults. Asia Pac. J. Clin. Nutr. 2013;22:365–371. [PubMed]
39. Lee C.S., Lee J.H., Oh M., Choi K.M., Jeong M.R., Park J.D., Kwon D.Y., Ha K.C., Park E.O., Lee N., et al. Preventive effect of Korean red ginseng for acute respiratory illness: A randomized and double-blind clinical trial. J. Korean Med. Sci. 2012;27:1472–1478. doi: 10.3346/jkms.2012.27.12.1472. [PMC free article] [PubMed] [Cross Ref]
40. Jung J.W., Kang H.R., Ji G.E., Park M.S., Song W.J., Kim M.H., Kwon J.W., Kim T.W., Park H.W., Cho S.H., et al. Therapeutic effects of fermented red ginseng in allergic rhinitis: A randomized, double-blind, placebo-controlled study. Allergy Asthma Immunol. Res. 2011;3:103–110. doi: 10.4168/aair.2011.3.2.103. [PMC free article] [PubMed] [Cross Ref]
41. Han H.J., Kim H.Y., Choi J.J., Ahn S.Y., Lee S.H., Oh K.W., Kim S.Y. Effects of red ginseng extract on sleeping behaviors in human volunteers. J. Ethnopharmacol. 2013;149:597–599. [PubMed]
42. Lee S.A., Kang S.G., Lee H.J., Jung K.Y., Kim L. Effect of Korean red ginseng on sleep: A randomized, placebo-controlled trial. Sleep Med. Psychophysiol. 2010;17:85–90.
43. Kitaoka K., Uchida K., Okamoto N., Chikahisa S., Miyazaki T., Takeda E., Sei H. Fermented ginseng improves the first-night effect in humans. Sleep. 2009;32:413–421. [PubMed]
44. Doosti A., Lotfi Y., Moossavi A., Bakhshi E., Talasaz A.H., Hoorzad A. Comparison of the effects of N-actyl-cysteine and ginseng in prevention of noise induced hearing loss in male textile workers. Noise Health. 2014;16:223–227. [PubMed]
45. Braz A.S., Morais L.C., Paula A.P., Diniz M.F., Almeida R.N. Effects of Panax ginseng extract in patients with fibromyalgia: A 12-week, randomized, double-blind, placebo-controlled trial. Rev. Bras. Psiquiatr. 2013;35:21–28. doi: 10.1016/j.rbp.2013.01.004. [PubMed] [Cross Ref]
46. Lee N.H., Yoo S.R., Kim H.G., Cho J.H., Son C.G. Safety and tolerability of Panax ginseng root extract: A randomized, placebo-controlled, clinical trial in healthy Korean volunteers. J. Altern. Complement. Med. 2012;18:1061–1069. doi: 10.1089/acm.2011.0591. [PMC free article] [PubMed] [Cross Ref]
47. Park J.W., Lee B.J., Bu Y.M., Yeo I.W., Kim J.S., Ryu B.H. Effects of Korean red ginseng on dry mouth: A randomized, double-blind, placebo-controlled trial. J. Ginseng Res. 2010;34:183–191. doi: 10.5142/jgr.2010.34.3.183. [Cross Ref]
48. Kang E.H., Shin W.Y., Song Y.J., Yu B.H. Effect of Korean red ginseng on somatic symptoms in a general population in Korea. J. Ginseng Res. 2009;33:219–222.
49. Kim J.H., Yi S.M., Choi J.E., Son S.W. Study of the efficacy of Korean red ginseng in the treatment of androgenic alopecia. J. Ginseng Res. 2009;33:223–228.
50. Seo J.C., Han S.W., Byun J.S., An H.D., Ha I.D., Cho G.H., Leem K.H. The effects of ginseng and American ginseng on general symptom in Koreans and Chineses–double-blind randomized controlled trials. J. Ginseng Res. 2005;29:27–36.
51. Lee K.J., Ji G.E. The effect of fermented red ginseng on depression is mediated by lipids. Nutr. Neurosci. 2014;17:7–15. doi: 10.1179/1476830513Y.0000000059. [PubMed] [Cross Ref]
52. Shergis J.L., Zhang A.L., Zhou W., Xue C.C. Panax ginseng in randomized controlled trials: A systematic review. Phytother. Res. 2013;27:949–965. doi: 10.1002/ptr.4832. [PubMed] [Cross Ref]
53. Choi J., Kim T.H., Choi T.Y., Lee M.S. Ginseng for health care: A systematic review of randomized controlled trials in Korean literature. PLoS ONE. 2013;8:1–14. doi: 10.1371/journal.pone.0059978. [PMC free article] [PubMed] [Cross Ref]
54. Coon J.T., Ernst E. Panax ginseng a systematic review of adverse effects and drug interactions. Drug Saf. 2002;25:323–344. [PubMed]
55. Izzo A.A., Ernst E. Interactions between herbal medicines and prescribed drugs: An updated systematic review. Drugs. 2009;69:1777–1798. doi: 10.2165/11317010-000000000-00000. [PubMed] [Cross Ref]
56. Jiang X., Williams K.M., Liauw W.S., Ammit A.J., Roufogalis B.D., Duke C.C., Day R.O., McLachlan A.J. Effect of St John’s wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br. J. Clin. Pharmacol. 2004;57:592–599. doi: 10.1111/j.1365-2125.2003.02051.x. [PMC free article] [PubMed] [Cross Ref]
57. Lee S.H., Ahn Y.M., Ahn S.Y., Doo H.K., Lee B.C. Interaction between warfarin and Panax ginseng in ischemic stroke patients. J. Altern. Complement. Med. 2008;14:715–721. doi: 10.1089/acm.2007.0799. [PubMed] [Cross Ref]
58. Lee Y.H., Lee B.K., Choi Y.J., Yoon I.K., Chang B.C., Gwak H.S. Interaction between warfarin and Korean red ginseng in patients with cardiac valve replacement. Int. J. Cardiol. 2010;145:275–276. doi: 10.1089/acm.2007.0799. [PubMed] [Cross Ref]

Articles from Medicines are provided here courtesy of Multidisciplinary Digital Publishing Institute (MDPI)