Panax ginseng and Ergogenic Profile: Randomized, Placebo Controlled Study

Introduction: Ginseng is a herbal plant that is known for its therapeutic medical importance for many diseases; it acts as a tonic and provides energy with significant reduction in mental and physical fatigue. Objectives: The aim of the present study was evaluating the ergogenic effect of Panax ginseng on normal healthy volunteers. Subjects and Methods: Randomized selection of 35 healthy volunteers with age ranged 20-30 years, they are randomly divided into two groups for assessment of the ergogenic effects of Ginseng compared with a placebo effect. Tunturi bicycle Ergometer (for assessment of exercise tolerance) was used for evaluating the ergogenic effects before and after two weeks of treatment with Ginseng or placebo. Group A: include 10 healthy volunteers regarded as a control group that treated with 500 mg/day of starch capsule as a single dose. Group B: include 25 healthy volunteers that received Ginseng capsule 500 mg /day. Results: Placebo produces insignificant effects following two consecutive weeks of treatment p >0.05. Ginseng showed more significant effects on the most of ergogenic parameters including pulse, time, distance and calorie consumption p <0.05 , but Ginseng therapy showed insignificant effects on speed and maximal oxygen consumption (Vo 2max ) variables ( p >0.05). Conclusion: Ginseng leads to significant ergogenic effects on normal healthy volunteers compared to placebo.


INTRODUCTION
Ginseng is an herbal plant that is known for its therapeutic medical importance for a long time in the regions of eastern Asia and North America that used for different purposes in medical fields, it is effective against many diseases, act as a tonic and provide energy with significant reduction in mental and physical fatigue [1].
There are several studies carried out by the researcher that dealing with the pharmacological action of Ginseng extract that improve the body performance, treat and prevent many diseases like cancer, diabetes and inflammation since; Ginseng contains ginsenoside, acid polysaccharide, polyacetylene, antioxidative aromatic in its composition, it was found that Panax ginseng contains approximately 38 types of the ginsenoid, which are responsible for the most of the Ginseng pharmacological effects [2].
Naturally, different herbs and medicine have been used for their own benefits since; many herbs improve physical performance and speed endurance as well as augmenting body fitness during intense period of acute exercise, moreover, there is a broad array of nutrients and pharmacological agents that afford physical stimulation and/or rapid recovery from intense exercise [3]. The most popular herbs that are used to boost sport performance and exercise endurance are ephedrine, Panax ginseng, caffeine and Eurycoma longifolia [4]. Most of ergogenic agents are illicit and have psychotropic effects like amphetamine [5].
Various forms of Panax ginseng are available such as a tincture, powder and whole root that have a potential role in improving physical health and performance through different mechanisms like anabolic action and stimulation of cortisol hormone secretion during acute exercise [6]. Additionally, Panax ginseng inhibits lipid peroxidation during stress induced by physical performances via free radical scavenges activity [7]. Furthermore, Panax ginseng has central stimulant effects that augment and improve alertness and reduction of fatigue, which per se enhances the body performance [8]. Many studies have revealed that Panax ginseng effects is duration and dose dependent since; chronic administrations of Panax ginseng leads to significant reduction in blood lactate levels with significant improvement in the cardio-respiratory function, this is mainly seen in individual with poor physical activity [9].
Different studies have been found that therapy with Panax ginseng amplifies and increases the exercise duration during acute exercising testing due to stress adaptation and stress attenuating effects induced by active constituents of Panax ginseng that stimulates stress hormone secretions during physical exercise [10]. So; chronic consumption of Panax ginseng lower maximal oxygen consumption during physical performances due to advancement of exercise endurance time [11].
Therefore, the aim of the present study was evaluating the ergogenic effect of Panax ginseng on normal healthy volunteers.

SUBJECTS AND METHODS
The study was conducted in Department of Clinical Pharmacology, College of Medicine, Al-Mustansiriya University. This study was approved by the specific Scientific Jury and Ethical Committee by the medical board, college of medicine, Al-Mustansiriya, all of enrolled participants gave an informed verbal consent for their participations in this study. Randomized selection of 35 healthy volunteers with age ranged between 20-30 years have been done, the volunteers have no history of any acute or chronic somatic or psychological diseases.
After enrollment in the present study, the subjects were randomly divided into two groups for assessment of the ergogenic effects of Ginseng compared with a placebo effect. Tunturi bicycle Ergometer (for assessment of exercise tolerance) at morning was used for evaluating the ergogenic effects before and after two weeks of treatment with Ginseng or placebo.
Group A: include 10 subjects (9 Males and 1 Female) healthy volunteers that regarded as a control group that treated with 500 mg/day with starch capsule as a single dose. Group B: include 25 subjects (20 Males and 5 Females) healthy volunteers that were received Ginseng capsule 500 mg /day. All participants are followed for two consecutive weeks from starting of treatments.

Inclusion Criteria
The participants that were included in this study should be fit and younger.

Exclusion Criteria
Older persons, children, smoker, alcoholics, pregnancy, lactation, hypersensitivity to Ginseng, chronic diseases such as diabetes mellitus, hypertension, ischemic heart diseases, renal or hepatic insufficiency, drug abuser and bleeding tendency.

Ergometer Measurement
All healthy participants in each groups evaluate their fitness by Ergometer measurement via Tunturi bicycle to record heart rate, distance, calorie consumption, speed and time before and after receiving placebo or Ginseng for two consecutive weeks for evaluation the ergogenic effects of Ginseng.
In this research, the exercise program involved cycling on a special bicycle Ergometer (TUNTURI 5835011 OY, LTD, Germany, class A, EN-9591+5), this device allow the researcher to measure and estimate exercise parameters such as energy expenditure, speed, distance…….. etc, heart rate was measured by the ear pulse sensor. Each volunteer do this exercise course till the time of exhaustion and before stopping this cycling exercise all data are recorded from well-ordered digital screen [12].
The volume of oxygen consumption (Vo 2max ) measured indirectly via special formula that depends on resting heart rate, body weight and age of participant [13]. Vo 2max =3.542+ (-0.014× Age) + (0.015× Body mass [Kg]) + (-0.011× Resting Heart Rate) It measures the maximum capacity for physical fitness, Vo 2max considered as the maximum amount of oxygen consumption during the exercise intensity. A mean value of VO2 max for male athletes is 3.5L/minute and 2.7 L/minute for female athletes.

Statistical Analysis
Data are presented as mean±SD, paired student t test was used to identify the significance of the differences before and after drug intake in each treated group, while the ANOVA test was used for detection the inter-groups differences regarding p value less than 0.05 as the significance.

RESULTS
Regarding the placebo effects as evaluated by the bicycle Ergometer, the ergogenic effects of placebo effects were insignificant following two consecutive weeks of treatment p>0.05 [1].
While, Ginseng showed more significant effects on the most of ergogenic parameters including pulse, time and distance, Ginseng therapy leads to increase of the pulse from (83.73±13.97) beats/min to (91.46±7.37) beat/min significantly p=0.0182, time increased from (4.52±2.50) min to (6.72±3.31) min significantly p=0.0323 and the distance was increased from (1.45±.027) meter to (1.68±0.32) meter significantly p=0.0112. While Ginseng has a more significant effect on calorie consumption, it increased the calorie consumption from 30.26±10.98 Kcal to 48.00±15.22 Kcal p < 0.0001, but Ginseng showed insignificant effects on speed of exercise and maximal oxygen consumption (Vo2max) variables (p>0.05) Table 2.
Concerning, the inter-group differences in the ergogenic effects between placebo and Ginseng on all of the ergogenic variables at pre and post treatment period. At the pre -treatment period the Ergometer measures involving time, speed, calorie and distance were significantly differ among the groups p<0.05 except for a pulse and Vo2max that were insignificantly affected p>0.05, Table 3.

DISCUSSION
In this study placebo does not produce any significant effects on ergogenic variables, including distance, speed, heart rate, calories consumption and maximal oxygen consumption after receiving placebo for two weeks on healthy volunteer. These results are in agreement with several studies that deal with the expected ergogenic effect of salbutamol that received by nonasthmatic athletes that found an insignificant effect on ergogenic parameters compared to the placebo for three weeks duration of therapy [14]. Al-kuraishy et al. [15,16]  On the other hand, Tallis et al. [18] single-blind experimental trial reported a positive effect of placebo that depending on the subject expectancy; ergogenic performances were low in subjects preoccupied that caffeine has a higher effect on ergogenic performance even when treated with caffeine, also significant effects were produced in subjects preoccupied that caffeine has higher effects on ergogenic performance even when treated by placebo [18]. The possible explanation of placebo effect may due to modulation of dopamine and noradrenalin neurotransmitters at mesocortical tract that improve alertness during physical performance [19].   On the other hand, the present study showed Ginseng acts as an ergogenic agent and has beneficial effects in the amelioration of physical performance through enhancing the ergogenic parameters noticeably. The result showed significant changes on the most of ergogenic parameters including pulse, time and distance, as well as a highly significant effect on calorie consumption, but maximal oxygen consumption (Vo 2max ) and speed were not affected by Ginseng therapy which may be due to small sample size, low dose of Ginseng or poor volunteer complains, these finding are in agreement with previous clinical trial studies that showed an improvement in the physical activity of the younger athletes and healthy elderly persons after treatment with Ginseng due to anti-stress properties with highly safety effect of Ginseng which may due to improvement of post-exercise skeletal muscle glycogen storage and citrate synthase activity as well as reduction of inflammatory markers such as tumor necrosis factor (TNF) and interleukin 10(IL-10), also Vo 2max was not augmented thus; Ginseng therapy improves physical performance with significant attenuation of exercise-induced inflammatory changes [20].
Recently, Lee et al. [21] animal model study demonstrated that gintonin which is an active ingredient of Ginseng has powerful ergogenic effect through activation of lysophosphotic acid receptors causing dose dependent effect increasing in the blood glucose after thirty minute of Ginseng administration, also gintonin enhance adrenaline and noradrenalin serum levels in addition to the stimulation of β-adrenergic receptors, these leading to sympathetic activation and preservation of skeletal muscle glucose uptake. This study is certainly corresponded with our ergogenic results of Ginseng but we have not measured the catecholamine serum levels during cycling Ergometer.
On the other hand, Biondo et al. [22] showed insignificant effects of Ginseng therapy on cortisol, lactate, insulin and growth hormone serum levels as well as exercise induced immune response following five weeks duration of therapy [22]. Moreover, Panax ginseng produced different pharmacological actions, on the reduction of stress capacity via ginsenosides active constituent that potentiates the ergogenic effect of Ginseng through its effect on the hypothalamus-pituitary-adrenal cortex axis that affecting metabolic and cardiovascular functions as well ameliorate and boost the energy expenditure through stimulation of sympathetic nervous system [23]. Therefore, most of these studies supporting our findings regarding the positive ergogenic effects of Ginseng regardless of Vo2max.
The possible explanation and elucidation of ergogenic effect of Ginseng was reported by Hwang et al. [24] research on mice treated with Ginseng for two weeks, founded that Ginseng led to significant promotion in fat oxidation and glucose homeostasis that delay the peripheral fatigue during acute exercise performance since; peripheral exhaustion and fatigue are chiefly caused by diminution of body stored energy thus; in order to improve the body efficiency it is essential to increase muscle glycogen, encourage oxidation and advance muscle circulation which done by Ginseng that modulates peroxisome proliferator-activated receptor α (PPAR-α) function that play an essential role in lipid metabolism causing lowering in plasma free fatty acids and elevating blood glucose as well as hepatic glycogen store due to augmentation of insulin signaling pathway mediated by up-regulation of skeletal muscle glucose transporter (GLUT4). In addition, ginsenosides and saponins are able to modulating glucagon-like peptide (GLP-1) that induced 3 mRNA expression leading to significant attenuation in insulin resistance with promotion of glucose uptake during physical performance which per se explains the antifatigue effect of Ginseng [25]. Therefore, Ginseng leads to significant ergogenic effects on normal healthy volunteers compared to placebo.

CONCLUSIONS
Ginseng leads to significant ergogenic effect on normal healthy volunteers compared to placebo.

ETHICAL APPROVAL
All authors declare that all experimental steps are approved by Ethics Committee in college of Medicine, Al-Mustansiriyia University, Baghdad-Iraq.