Efficacy of Ginseng Supplements on Fatigue and Physical Performance: a Meta-analysis.

We conducted a meta-analysis to investigate the efficacy of ginseng supplements on fatigue reduction and physical performance enhancement as reported by randomized controlled trials (RCTs). RCTs that investigated the efficacy of ginseng supplements on fatigue reduction and physical performance enhancement compared with placebos were included. The main outcome measures were fatigue reduction and physical performance enhancement. Out of 155 articles meeting initial criteria, 12 RCTs involving 630 participants (311 participants in the intervention group and 319 participants in the placebo group) were included in the final analysis. In the fixed-effect meta-analysis of four RCTs, there was a statistically significant efficacy of ginseng supplements on fatigue reduction (standardized mean difference, SMD = 0.34; 95% confidence interval [CI] = 0.16 to 0.52). However, ginseng supplements were not associated with physical performance enhancement in the fixed-effect meta-analysis of eight RCTs (SMD = -0.01; 95% CI = -0.29 to 0.27). We found that there was insufficient clinical evidence to support the use of ginseng supplements on reducing fatigue and enhancing physical performance because only few RCTs with a small sample size have been published so far. Further lager RCTs are required to confirm the efficacy of ginseng supplements on fatigue reduction.

INTRODUCTION

Fatigue, which is a lack of energy and motivation, can be a normal and important response to physical activity, emotional stress, boredom, or lack of sleep (1). For the purpose of relieving fatigue, other than conventional medical treatments, approximately 80% of people with chronic fatigue use alternative and complementary therapies such as massage or herbal supplements in the United States (2).

Physical performance relates to the ability to complete certain physical tasks with higher intensity, faster, or with a higher power output (3). In general, the various ginseng supplements currently available in market are claimed to increase energy levels, relieve stress, enhance athletic performance and immune system functions, control blood sugar levels, improve mental functions, and promote general well-being.

According to a review, Panax ginseng, the most attractive product of the ginseng markets in South Korea, accounts for approximately 59% in the entire Korean market, and its consumption has continuously risen (4). Extracts of P. ginseng C.A. Meyer, more commonly known as Chinese or Korean Ginseng, have a long history of use in traditional medicine in several Asian countries (5). They also have become readily accepted in many Western countries where people often consume these preparations, expecting that they may offer relief and protection in the fight against stress, disease, and fatigue (56). The wide spread use of ginseng had led researchers to assess its efficacy as therapeutic and ergogenic nutritional supplements for combating fatigue and enhancing physical performance (7).

There are two major species of ginseng, Korean ginseng (P. ginseng) and American ginseng (P. quinquefolius) with various amounts and ingredients. They mainly includes ginsenosides, which are the most important ingredients (8). To date, numerous active compounds (including approximately 40 ginsenosides) have been identified in P. ginseng with various pharmacological activities, such as effects on chemical stress, immune modulation in animal studies, antitumor activities, as well as glucose metabolism and enhancement of cognitive performance (91011). However, those effects are not clinically established.

To date, several randomized controlled trials (RCTs) have reported the efficacy of ginseng supplements on fatigue reduction (12131415) and physical performance enhancement (1617181920212223). However, those findings remain inconsistent. Also, no meta-analysis has been published on this topic, so far.

This study aimed to investigate the efficacy of ginseng supplements on fatigue relief and physical performance enhancement by using a meta-analysis of RCTs.

MATERIALS AND METHODS

Literature search

In October 2015, PubMed, EMBASE, and Cochrane Library were searched by using keywords related ginseng supplements and fatigue or physical performance. Also, we searched the bibliographies of relevant articles in order to locate additional studies. We used the following keywords for the literature search: ‘ginseng,’ ‘red ginseng,’ ‘P. ginseng,’ ‘Korean ginseng,’ ‘American ginseng,’ ‘P. quinquefolius’ and ‘fatigue,’ ‘lethargy,’ ‘exhaustion,’ ‘tiredness,’ ‘weariness,’ ‘physical performance,’ and ‘exercise performance.’

Selection criteria

We included RCTs that investigated the efficacy of ginseng supplements on fatigue reduction or physical performance enhancement compared with placebos. There was no restriction on types of populations (e.g., patients with underlying diseases or healthy people) or study periods. The first published or larger study was included in the final analysis, if data were duplicated or shared in more than one study. There was no language restriction.

Selection of relevant studies

Two of the authors independently evaluated the eligibility of all studies retrieved from the databases based on the pre-determined criteria. Disagreements between evaluators were resolved by discussion. From the trials included in the final analysis, we extracted the following data: study name, journal, species of ginseng supplements, funding and ginseng supplements source of studies, geographic location, duration of intervention, dose of ginseng supplements, tool name used to measure the efficacy of ginseng supplements, the number of participants, and main results.

Assessment of methodological quality

We assessed the methodological quality of the included studies using a validated scale for RCTs developed by Jadad and colleagues (24). This 5-point quality scale allocates points for randomization (1 point if study is described as randomized, additional 1 point if table of random numbers or computer-generated randomized was used), double-blind (1 point if described as double-blind, additional 1 point if masking such as identical placebo was used), and follow-up (1 point if the numbers and reasons of withdrawal are described for each group) in the report of an RCT. Trials having scores of 2 or less were considered as low-quality and scores of 3 to 5 as high-quality (24).

Main and subgroup analyses

We investigated the overall efficacy of ginseng supplements on relieving fatigue and enhancing physical performance. Also, we conducted subgroup analyses by funding source, ginseng supplements source, species of ginseng supplements, duration of ginseng supplements, geographic location of studies, and dose of intervention.

Statistical analyses

We investigated the efficacy of ginseng supplements on relieving fatigue and enhancing physical performance before and after intervention compared with placebo. Because of the different scales for fatigue reduction or physical performance enhancement across the studies, we used standardized mean difference (SMD) as a main effect size to calculate those differences between the intervention and control groups. SMD is a difference in means between the two groups divided by standard deviation (SD). SMD was calculated as follows: SMD = (M1 − M2)/pooled SD

Where M1 is a mean of fatigue reduction in the intervention group, M2 is a mean of fatigue reduction in the control group, and pooled SD is a pooled intervention specific standard deviation (25). If the intervention group has a higher fatigue relief than the control group, SMD will have a positive value. In order to estimate heterogeneity across studies, we used Higgins I2, which measures the percentage of total variation across studies. Negative values of I2are set at zero; I 2 ranges between 0% (no observed heterogeneity) and 100% (maximal heterogeneity). An I2value greater than 50% is considered as having substantial heterogeneity (26). The SMD with 95% confidence intervals (CI) was calculated on the basis of either the fixed- or random-effects models. When substantial heterogeneity was not observed, the SMD calculated based on the fixed-effects model was reported. When substantial heterogeneity was observed, the SMD based on the random-effects model was reported. Stata SE version 12.1 software package (StataCorp, College Station, TX, USA) was used for statistical analysis.

RESULTS

Selection of trials

A total of 155 articles were retrieved after searching three databases and relevant bibliographies (Fig. 1). After excluding duplicated articles and reviewing articles based on those title and abstracts, we reviewed 25 articles with full texts and then included 12 trials in the final analysis. We excluded 13 articles because of insufficient data (n = 13).

Fig. 1

Flow diagram for identification of relevant clinical trials.

General characteristics of the included trials

Table 1 illustrates general characteristics of the 12 articles included in the final analysis. The included trials involved a total of 659 participants. The intervention periods ranged from 4 weeks to 12 weeks. They were published from 1996 through 2013 and conducted in America (n = 7), Korea (n = 2), Iran (n = 1), Thailand (n = 1), and Poland (n = 1). They used Korean ginseng (14-20. 22, 23), P. notoginseng (21), and American Ginseng (12, 13). Six different measurement tools were used in the studies. The questionnaires used for the assessment of fatigue were the Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF), Modified Fatigue Impact Scale (MFIS), Numerical Rating Scale (NRS), and the Short Form 36 Health Survey Version 2 (SF-36v2). The tests used for the assessment of physical performance were the Incremental Bicycle Ergometer Exercise and Wingate test.

Table 1

General characteristics of studies in the final analysis (n = 12)

No.	Source (project name)	Country location	Participants (follow-up period)	Intervention vs. Control	Type of ginseng	Main outcome measures used	Measurement tools	Mean ± SD (baseline/follow-up)
								Intervention	Placebo
1	Engels 1996	USA	19 healthy adult females (8 wk)	1,000 mg/day (n = 10) vs. placebo (n = 9)	Panax ginseng	Recovery oxygen uptake (VO2)	Incremental Bicycle Ergometer Exercise	4 ± 0.2/3.9 ± 0.3 (ml/kg per min)	4.1 ± 0.3/4 ± 0.2 (ml/kg per min)
2	Engels 1997	USA	31 healthy adult males (8 wk)	2,000 mg/day (n = 10) vs. 1,000 mg/day (n = 11) vs. Placebo (n = 10)	Panax ginseng	Maximal oxygen uptake (VO2 max)	Incremental Bicycle Ergometer Exercise	42.3 ± 1.6/41.4 ± 1.5 (ml/kg per min)	42.3 ± 3.1/42.9 ± 2.9 (ml/kg per min)
3	Ziemba 1999	Poland	15 healthy people (6 wk)	350 mg/day (n = 7) vs. placebo (n = 8)	Panax ginseng	Maximal oxygen uptake (VO2 max)	Incremental Bicycle Ergometer Exercise	3.9 ± 0.09/3.8 ± 0.14 (l/min)	3.8 ± 0.15/3.8 ± 0.15 (l/min)
4	Engels 2001	USA	20 healthy women (8 wk)	2,000 mg/day (n = 12) vs. placebo (n = 12)	Panax ginseng	Rate of fatigue	Wingate test	47.89 ± 6.73/45.5 ± 8.4	47.68 ± 8.18/48.04 ± 6.31
5	Engels 2003	USA	27 healthy students (8 wk)	2,000 mg/day (n = 15) vs. placebo (n = 12)	Panax ginseng	Mean power output	Wingate test	−0.13 ± 0.07 W/kg (Change score between before and after intervention)	−0.08 ± 0.08 W/kg (Change score between before and after intervention)
6	Liang 2005	USA	29 healthy people (4 wk)	1,350 mg/day (n = 13) vs. placebo (n = 16)	Panax notoginseng	Exercise time to exhaustion (Tmax)	Incremental Bicycle Ergometer Exercise	30.5 ± 12.8/37.6 ± 10.2 (mins)	30 ± 12.6/33.6 ± 10.5 (mins)
7	Kulaputana 2007	Thailand	57 health males (8 wk)	500 mg/day (n = 28) vs. placebo (n = 29)	Panax ginseng	Total exercise time	Incremental Bicycle Ergometer Exercise	18.6 ± 2.8/19.7 ± 2.6 (mins)	17.2 ± 2.6/18.3 ± 2 (mins)
8	Yoon 2008	Korea	14 healthy students (8 wk)	3,000 mg/day (n = 10) vs. placebo (n = 10)	Panax ginseng	Oxygen uptake (VO2)/Maximal oxygen uptake (VO2 max)	Wingate test	48.6 ± 2.3/50.1 ± 2.6 (%)	48.5 ± 1.8/49.9 ± 2.7 (%)
9	Kim 2011	USA	47 health participants (6 wk)	100 mg/day in the 1st week, 200 mg/day in the 2nd week, 400 mg/day in the following 4 weeks for intervention group vs. placebo (Crossover study)	Panax quinquefolius	Fatigue score	Modified Fatigue Impact Scale	47 ± 15/42.7 ± 15.7	47 ± 15/43.7 ± 16.7
10	Barton 2013	USA	271 men and women with cancer-related fatigue defined as a score of 4 or more (8 wk)	2,000 mg of American ginseng/day (n = 183) vs. Placebo (n = 181)	Panax quinquefolius	The subjective experience of fatigue	The Multidimensional Fatigue Symptom Inventory–Short Form.	20 ± 27 (Change score between before and after intervention)	10.3 ± 26.1 (Change score between before and after intervention)
11	Etemadifar 2013	Iran	52 female multiple sclerosis patients (12 wk)	500 mg of Korean ginseng/day (n = 26) vs. Placebo (n = 26)	Panax ginseng	Fatigue score	Modified Fatigue Impact Scale	31.69 ± 14.9/23.65 ± 12.8	22.23 ± 13.21/23.69 ± 12.94
12	Kim 2013	Korea	88 participants with idiopathic chronic fatigue (ICF) (4 wk)	2,000 mg/day (n = 29) vs. 1,000 mg/day (n = 29) vs. Placebo (n = 30)	Panax ginseng	Fatigue severity	Numerical Rating Scale	60.8 ± 10.3/41.8 ± 13.2	59.3 ± 10.6/48.8 ± 7.3

Methodological quality of trials

Table 2 illustrates the methodological quality of all 12 RCTs included in the final analysis based on the Jadad scale. All of them have 3, 4, and 5 points, which implies that all trials have a low risk of bias.

Table 2

Methodological quality of trials based on the Jadad scale (n = 12)

No.	Study	Randomization	Description of randomization methods	Double-blind	Using identical placebo	Follow-up reporting	Total score
1	Engels et al. 1996	1	0	1	1	1	4
2	Engels et al. 1997	1	1	1	1	1	5
3	Ziemba et al. 1999	1	0	1	1	1	4
4	Engels et al. 2001	1	0	1	1	1	4
5	Engels et al. 2003	1	0	1	1	1	4
6	Liang et al. 2005	1	1	1	1	1	5
7	Kulaputana et al. 2007	1	0	1	1	1	4
8	Yoon et al. 2008	0	0	1	1	1	3
9	Kim et al. 2011	1	1	1	1	1	5
10	Barton et al. 2013	1	1	1	1	1	5
11	Etemadifar et al. 2013	1	1	1	1	1	5
12	Kim et al. 2013	1	1	1	0	1	4

Efficacy of ginseng supplements on fatigue reduction and physical performance enhancement

In the fixed-effects meta-analysis, ginseng supplements showed a statistically significant efficacy on fatigue reduction (SMD = 0.34; 95% CI = 0.16 to 0.52, n = 4) (Fig. 2). However, there was no significant association between ginseng supplements and physical performance enhancement (SMD = −0.01; 95% CI = −0.29 to 0.27, n = 8) (Fig. 3).

Fig. 2

Efficacy of ginseng supplements on fatigue reduction in the meta-analysis of RCTs (n = 4).

Fig. 3

Efficacy of ginseng supplements on physical performance enhancement in the meta-analysis of RCTs (n = 8).

Subgroup meta-analysis by various factors

Table 3 shows the findings from the subgroup meta-analysis by various factors for both fatigue reduction and physical performance enhancement. Overall, subgroup meta-analysis by various factors showed that ginseng supplements had an efficacy on fatigue reduction. However, the use of ginseng supplements with short duration (< 6 weeks) and lower dose (< 1,000 mg/day) showed no significant efficacy. Regarding physical performance enhancement, overall there was no efficacy of ginseng supplements.

Table 3

Efficacy of ginseng supplements on fatigue reduction and physical performance enhancement in the subgroup meta-analysis of RCTs by various factors

Factors	No. of Trials	SMD (95% CI)	Heterogeneity I2 (%)	Model used
Fatigue
Funding sources
From companies	-	-	-
From non-companies*	4	0.34 (0.16–0.52)	5.2	Fixed-effects
Ginseng supplement sources
From companies*	2	0.28 (0.08–0.49)	43.7	Fixed-effects
From non-companies*	2	0.54 (0.16–0.92)	0	Fixed-effects
Species of ginseng
Korean ginseng*	2	0.54 (0.16–0.92)	0	Fixed-effects
Non-Korean ginseng*	2	0.28 (0.08–0.49)	43.7	Fixed-effects
Duration of intervention
1–6 wk	2	0.28 (−0.23–0.80)	59.3	Random-effects
> 6 wk*	2	0.39 (0.17–0.61)	0	Fixed-effects
Geographic location of studies
Asian countries*	2	0.54 (0.16–0.92)	0	Fixed-effects
Western countries*	2	0.28 (0.08–0.49)	43.7	Fixed-effects
Dose of intervention
< 1,000 mg/day	2	0.20 (−0.12–0.53)	40.5	Fixed-effects
≥ 1,000 mg/day*	2	0.40 (0.18–0.62)	0	Fixed-effects
Physical Performance
Funding resources
From companies	1	−0.03 (−1.08–0.28)	-	Fixed-effects
From non-company	7	−0.01 (−0.30–0.28)	0	Fixed-effects
Ginseng supplement sources
From companies	3	−0.08 (−0.29–0.31)	0	Fixed-effects
From non-companies	5	0.06 (−0.34–0.47)	0	Fixed-effects
Species of ginseng
Korean ginseng	7	0.02 (−0.28–0.33)	0	Fixed-effects
Non-Korean ginseng	1	−0.21 (−0.95–0.52)	-	Fixed-effects
Duration of intervention
1–6 wk	2	0.03 (−0.57–0.63)	22.1	Fixed-effects
> 6 wk	6	−0.02 (−0.34–0.29)	0	Fixed-effects
Geographic location of studies
Asian countries	2	−0.01 (−0.47–0.46)	0	Fixed-effects
Western countries	6	−0.01 (−0.36–0.34)	8	Fixed-effects
Dose of intervention
< 1,000 mg/day	2	0.11 (−0.36–0.57)	0	Fixed-effects
≥ 1,000 mg/day	6	−0.08 (−0.43–0.27)	0	Fixed-effects

SMD = standardized mean difference, CI = confidence interval.

*Statistically significant association.

DISCUSSION

In this meta-analysis of RCTs, we found that the use of ginseng supplements had the efficacy on fatigue reduction, but not physical performance enhancement. Specifically, the effect size on the efficacy of ginseng supplements on fatigue reduction (SMD = 0.34) was between the small (SMD = 0.20) and medium levels (SMD = 0.50) based on Cohen’s rule of thumb (27). However, we found that only four relevant RCTs have been published regarding fatigue reduction, and the total number of the study participants included in those trials was only 429. Thus, there was no sufficient clinical evidence to support the use of ginseng supplements on reducing fatigue and enhancing physical performance.

There are some possible biological mechanisms for the efficacy of ginseng supplements on mental and physical fatigue reduction and physical performance enhancement. Regarding mental fatigue, although a human study indicated that ginseng increases cognitive performance (28), its mechanisms remain not known, but may be related to the ginseng's glycemic properties (2930). Ginseng affects brain activity, specifically by increasing cortical levels of dopamine, noradrenalin, serotonin, and cyclic adenosine monophosphate (cAMP) (31). An in vitro study suggested that ginseng increases energy produced aerobically in the brain (32). Ginseng saponins showed moderate depressant actions on the electroencephalogram and the behavior in cats (33). As for physical fatigue and physical performance, ergogenic aids are believed to increase performance by some of the following mechanisms: renewing or increasing energy stores in the body, facilitating the biochemical reactions that yield energy, reducing or neutralizing performance-inhibiting metabolic by products, and facilitating recovery (3435). Although the mechanism on the ergogenicity of ginseng on physical performance has not been fully identified, theories include stimulation of the hypothalamic-pituitary-adrenal cortex axis and increased resistance to the stress of exercise, enhanced myocardial metabolism, increased hemoglobin levels, vasodilatation, increased oxygen extraction by muscles, and improved mitochondrial metabolism in the muscle, all of which theoretically could enhance physical performance (36373839). A clinical experimental study reported that the use of ginseng supplements before exhaustive aerobic exercise can reduce creatine kinase leakage during exercise, possibly due to ginseng's ability to reduce cellular and muscle damage (40).

However, although there are some possible biological mechanisms on the efficacy of ginseng supplements on physical performance enhancement in in vivo animal or in vitro laboratory studies, our meta–analysis of eight randomized controlled trials found that there was no sufficient evidence on the efficacy. Several explanations could be considered for this inconsistence. First, preclinical studies, including in vivo laboratory studies and animal studies might not represent the biological mechanism in the human body. Therefore, although preclinical studies showed an efficacy of ginseng supplements on physical performance enhancement, clinical circumstances could report no benefit of ginseng supplements. Second, the sample size of the final meta-analysis is a limitation to evaluate the efficacy. We only included eight RCTs with 212 participants due to a paucity of data. Third, there was heterogeneity in the participants in each trial. While two American studies including 39 participants were conducted in healthy adult females (1619), American (17) and Thailand (22) studies including 88 participants were conducted in health adult males. Finally, the dose and duration of the intervention in each trial varied from 350 mg/day/person to 3,000 mg/day/person and 4 weeks to 8 weeks among included studies.

We have limitations in the current meta-analysis. Although we found that there was a significant efficacy of ginseng supplements on fatigue reduction, no sufficient RCTs were published in order to confirm this finding. The number of the study participants was not enough to draw conclusions. Specifically, out of a total of 429 study participants from all four RCTs, 271 participants were from Barton’s study (13), which indicated a significant efficacy. Also, many RCTs were excluded from the final analysis because of insufficient data.

To the best of our knowledge, this meta-analysis is thought to be the first meta-analysis of RCTs about this issue. Although there is no sufficient clinical evidence about the efficacy of ginseng supplements for health, in some countries, especially Korea, some sellers promote the sale of ginseng supplements as if these are clinically approved effective against fatigue or some diseases, and also many people have consumed ginseng supplements in the belief that these prevent diseases and improve their health.

In summary, we found that there was insufficient clinical evidence to support the use of ginseng supplements on reducing fatigue and enhancing physical performance because only a few RCTs with a small sample size were published so far. Further lager RCTs are needed to confirm the efficacy of ginseng supplements for fatigue reduction and physical performance enhancement.