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Dr. Wissink is Assistant Director of Integrative Medicine, Department of Family Medicine, Maine Medical Center, Portland; Dr. Lamoreau is a physician with Maine Medical Partners, Falmouth; and Dr. Schneider is Director of Integrative Medicine, Department of Family Medicine, Maine Medical Center, Portland.
Dr. Wissink, Dr. Lamoreau, and Dr. Schneider report no financial relationships relevant to this field of study.
The term “adaptogen” appears to have been coined by Russian researchers in the 1950s to describe medicinal botanicals with the potential to increase stamina and survival in stressful environments.1 The concept appears to have been inspired by the use of stimulants to enhance mental and physical performance among Russian fighter pilots and submarine crews during World War II.2 Among the first adaptogen studies published in Soviet Union World War II military journals was Schisandra chinensis. Initial interest in S. chinensis arose from ethnopharmacological research from the late 19th and early 20th century noting that these berries and seeds were used by Nanai hunters as a tonic to reduce thirst, hunger, and exhaustion and to improve night vision.1
After World War II, Russian interest in gaining a competitive advantage for its military extended to its athletes and cosmonauts, fueling further research into other adaptogens. In the 1960s, a scientist named Israel Brekhman began his search to develop drugs from natural substances to stimulate the intrinsic adaptive mechanisms of an organism to help survival in situations of intense and prolonged stress, while maintaining capability for physical and mental work.3 Brekhman began by investigating Asian ginseng (aka Panax ginseng), long regarded as the “longevity herb” in traditional Chinese medicine. However, Asian ginseng did not grow in the Soviet Union and was costly to import. This led him to expand his search to Eleutherococcus senticosus, which he termed Siberian ginseng.3 Eventually Brekhman and his colleague Nicolai Lazarev built a team of researchers who conducted nearly 3,000 clinical trials and experiments on adaptogens. After the collapse of the Soviet Union, clinical studies on adaptogens continued but at a slower pace as funding became more scarce.
This article summarizes the results from a literature search on more recent clinical studies on several adaptogens. The most clinical research in the area surrounded athletic performance, so the review will focus on that outcome.
Siberian ginseng or eleuthero (E. senticosus) is a thin, thorny shrub native to the forests of southeastern Russia, northern China, Japan, and Korea.4 Eleutherosides are the group of active chemicals derived from the root and rhizome of eleuthero.5 Siberian ginseng root extract has been used safely in clinical trials lasting up to three months, with the most commonly reported side effects being diarrhea and insomnia.6 When used orally and appropriately long term, Siberian ginseng has been used in combination with low-dose calcium plus vitamin D3 for up to one year with no significant side effects.7 Anecdotal reports suggest that taking Siberian ginseng for longer than two months without a two- to three-week break is not recommended.8
Early studies concluding eleuthero improves endurance exercise, oxygen uptake, and overall performance in athletes were methodologically flawed. The authors of these studies only used a single-blind protocol with no crossover design.9,10 In a review article of five studies with good methodology, researchers found no effect of eleuthero raw herb 800 to 1,200 mg/day for one to six weeks on cardiorespiratory fitness, fat metabolism, and endurance performance.11
In 2010, Kuo et al published a double-blind, placebo-controlled, crossover study of nine recreationally trained male college students using 800 mg/day of raw dried root and rhizome of eleuthero.12 The participants already were engaged in a school tennis team, were training 15-16 hours per week, and were not consuming eleuthero or any other nutritional supplement. Baseline assessments determined peak oxygen uptake (VO2 peak) during a high-intensity endurance workout on a stationary bicycle. VO2 peak was determined with the following criteria: 1) participant perceived exertion (RPE) using a Borg’s 20-point rating scale when > 19; 2) respiratory exchange ratio (RER) > 1.1; and 3) reaching age-predicted maximum heart rate. Then, participants were given either eleuthero or a placebo 800 mg/day for eight weeks, followed by a four-week washout period, after which participants received the other intervention for eight weeks. Participants were asked to maintain their normal training pattern and diet habits during the 20 weeks of the study. For the 24 hours prior to each exhaustion ride, participants were asked to refrain from exercise, caffeine, and alcohol consumption, and to consume the same meal one hour before the task. Testing occurred at the same time of day. During exercise, blood sampling was done at rest, at 15 minutes of exercise, at 30 minutes of exercise, and at exhaustion. Glucose and plasma free fatty acid (FFA) concentrations were measured each time.
After eight weeks of supplementation, VO2 peak of the eleuthero group was significantly higher than the placebo group. RPE increased slightly for both placebo and eleuthero groups, but the eleuthero RPE was significantly higher than placebo. Resting heart rate showed no difference, but maximal heart rate increased significantly (P < 0.05) in the eleuthero group (E = 190 vs. P = 182). Significant differences also were found in the RER at 30 minutes. The blood parameter analysis showed FFA levels were higher at 30 minutes (E = 298 µM vs. P = 265 µM) and at exhaustion (E = 343 µM vs. P = 287 µM) in the eleuthero group and were significantly higher than placebo. Significant differences (P < 0.05) were found with the RER at 30 minutes (E = 0.90 vs. P = 0.96). Glucose levels were decreased significantly at 30 minutes (E = 82.4 mg/dL vs. P = 88.6 mg/dL) and exhaustion (E = 86.6 mg/dL vs. P = 92.8 mg/dL).
Based on these results, eleuthero supplementation enhanced endurance time, elevated cardiovascular functions, and altered metabolism of plasma FFA and glucose during the 75% VO2 peak exercise to exhaustion on a stationary bicycle. The authors theorized that duration of treatment was the important factor to explain the positive results in this study (eight weeks) compared to negative results in prior studies (less than six weeks). Eleuthero supplementation also seemed to increase FFA availability by increasing fat oxidation, sparing muscle glycogen. They concluded eleuthero may be an effective nutritional supplement for endurance athletes, but the exact mechanisms involved need further investigation.
The only side effect reported was mild insomnia in one participant for the first day of eleuthero supplementation. The authors reported no financial interest in eleuthero as a supplement.
Cordyceps sinensis is a naturally occurring parasitic fungus native to the Tibetan Plateau. It is also known as the caterpillar fungus or “DongChongXiaCao” (Summer-plant, Winter-worm), which colonizes the larvae of Hepialidae moths, filling their bodies with mycelium. Traditional Tibetan and Chinese medicine practitioners used it for its ability to invigorate the body and reduce fatigue13 by its function to “replenish the kidney and soothe the lung.”14
Although wild Cordyceps increasingly is rare in its natural habitat and thus very expensive, a refined standardized fermentation product, Cs-4, is produced from mycelial strains isolated from wild Cordyceps and contains similar chemical constituents (0.14% adenosine, 5% mannitol; Cs-4, CordyMax).
Researchers from UCLA conducted a double-blind, placebo-controlled, prospective study of the commercially available Cs-4 product on 20 men and women between 50 and 75 years of age. Subjects were randomized to Cs-4 or placebo (starch) capsules, taken three times a day with water or food for 12 weeks. Exercise performance was evaluated on a cycle ergometer, while physical fitness was assessed through measurements of VO2max and gas exchange metabolic threshold. Dropouts in each group were similar at study completion, with eight in the Cs-4 group and seven in the placebo group. From baseline, the Cs-4 group had an increase in metabolic threshold of 10.5% (P = 0.022), while the placebo group decreased by 3.9% (P = 0.182), with similar results occurring in ventilatory threshold. There were no other significant differences in VO2max, heart rate, maximum work rate or maximum ventilation, blood pressure, lactic acid peak level, recovery, or heart rate recovery. The authors believed this small but consistent improvement in aerobic performance of subjects receiving Cs-4 would translate to meaningful improvements in activities of daily living in older adults if it could be reproduced in larger studies.15
Like cordyceps, Rhodiola crenulata, which is closely related to Rhodiola rosea and grows mostly in the Tibetan region, is another botanical native to cold, mountainous regions of Asia, Europe, and high altitudes in the Arctic. It also has a long history of use in traditional Asian medical systems for a wide variety of conditions, including improved physical endurance and work performance, resistance to high-altitude sickness, mental capacity, and longevity. Today, rhodiola most commonly is used for increasing energy, endurance, strength, and mental capacity.16
Chen et al conducted a double-blind, placebo-controlled trial on 18 male long-distance track and field athletes during high-altitude training (2,200 meters).17 One group received a placebo (starch) and the other group received R. crenulata plus C. sinensis (RC, 1,000 mg capsule) twice daily with breakfast and dinner. The groups participated in intensive exercise training, which included distance, speed, endurance, and strength workouts. Measurements conducted at sea level post-intervention showed that the RC group run time to exhaustion was prolonged significantly compared to placebo (placebo: +2.2% vs. RC: +5.7%; P < 0.05). Additionally, the decline in parasympathetic activity in the RC group was attenuated (placebo: -51% vs. RC: -41%; P < 0.05), and endogenous EPO production was lower compared to the placebo group (placebo: ~48% higher than RC values; P < 0.05.) There were no differences in VO2max, red blood cell, hemoglobin, testosterone, or cortisol levels. The authors concluded that RC improves aerobic exercise capacity and produces anti-stress reactions that may increase adaptations to exercise training at high altitude.17 The authors of these human trials disclosed no competing financial interests.
Ashwagandha (Withania somnifera), also known as Indian ginseng or winter cherry, is a dense shrub with roots that have been used extensively in Ayurvedic medicine for 3,000 years as a general tonic to help the body adapt to stress. The root contains a number of antioxidants as well as flavonoids, alkaloids, and steroidal lactones, which are thought to confer the beneficial effects in the body.18 Recent advances have been made to elucidate the biological properties of W. somnifera and its potential role in health benefits.
A randomized, double-blind, prospective clinical study of 57 male subjects 18 to 50 years of age with minimal experience in resistance training were divided into treatment and placebo groups. Participants agreed to refrain from tobacco, alcohol, and anti-inflammatory agents during the study and had to be cleared for participation by their physician. The treatment group reviewed 300 mg Ashwagandha root twice daily, while the control received a starch placebo. Muscle strength, muscle size, body composition, serum testosterone level, and muscle recovery was measured at baseline and then again after eight weeks of a resistance training program. The three-days-weekly training program targeted large muscle groups with instruction on proper technique. Muscle strength was measured using the one repetition maximum for bench press and leg extension exercise. Serum creatine kinase was used as a marker of muscle injury to evaluate recovery. The treatment group had significantly greater improvement in muscle strength in both exercises (26.4 kg vs. 46.0 kg on the bench press [P = 0.001]; 14.5 kg vs. 19.8 kg, [P = 0.04]), increase in size of the chest (1.4 cm vs. 3.3 cm; P = 0.001) and arms (5.3 cm vs. 8.6 cm; P = 0.01), lower creatine kinase (1,307.5 U/L decrease vs. Ashwagandha 1,462.6 U/L; P = 0.03), a greater increase in testosterone levels (18.0 ng/dL vs. Ashwagandha: 96.2 ng/dL; P = 0.004), and a greater decrease in body fat percentage (1.5% vs. 3.5%; P = 0.03). The authors concluded that Ashwagandha may be useful to take in a resistance training program.19
Shenoy et al studied supplementation of Ashwagandha in 40 elite cyclists (20 of each gender), defined as participation of the athlete in at least state-level events.20 Participant ages ranged from 18-27 years and they took no other supplements or performance aides. They were divided into treatment (500 mg capsules of standardized Ashwagandha root extract twice daily) and placebo (starch tablets). A baseline graded-exercise test (GXT) was performed on a treadmill with electronic heart rate monitor and full nose-mouth piece to measure VO2max, respiratory exchange ratio (RER), and total time for the athlete to reach their volitional point of exhaustion. After eight weeks of supplementation, the same testing was performed. The Ashwagandha group but not the placebo group experienced significant improvement in several parameters. Specifically, VO2max increased 13% (P = 0.001), and time to exhaustion improved by over full minute (P = 0.0010). A subanalysis showed that males were more responsive to the treatment than females. The authors concluded that Ashwagandha significantly improved aerobic performance in well-trained athletes, a group in which it usually is quite difficult to detect minor changes.20
Sandhu et al measured a number of variables, including VO2max, velocity, power, and blood pressure, in a single-blind, randomized study of 40 healthy young college students, 22 female and 18 males, mean age 20.6 years, and mean body mass index (BMI) 21.9 kg/m2.21 Ten participants received Ashwagandha alone (500 mg standardized aqueous root extract), while another 10 received Terminalia arjuna alone (500 mg aqueous bark extract of this botanical commonly used in Ayurvedic medicine for heart conditions). Ten received both Ashwagandha and T. arjuna, and 10 received a placebo capsule (flour). Although generally healthy, none of the participants had participated in regular exercise for the prior six months. Velocity was measured using a multiple camera program called Kinematic Measuring System (KMS) during a sprint. Power of the lower limbs during vertical jumps also was measured using KMS. Balance was measured with a wobble board program called Kinematic. Peak oxygen consumption was measured with a computer controlled Vista Turbo Trainer machine. The researchers measured systolic and diastolic blood pressure and monitored subjects’ BMI. All variables were collected at baseline and at eight weeks. Compliance with medications was ensured by daily administration after a meal.
Ashwagandha significantly increased velocity (P = 0.005), power (P = 0.002), and VO2max (P = 0.005). There was no improvement in balance or blood pressure. T. arjuna significantly increased VO2max and lowered resting systolic blood pressure. The combination also resulted in significantly increased VO2max, velocity, and power, as well as improved systolic blood pressure, but not significantly beyond either herb alone. There were no changes in any variables for the placebo group. No side effects were reported, but authors noted that future studies are needed that are longer in duration.21
Choudhary et al conducted a randomized, double-blind, placebo-controlled study on 50 young healthy male and female adults aged 20-45 years with a BMI range of 18.5-24.9 kg/m2.22 Participants were randomized to placebo (sucrose) or Ashwagandha (KSM-66 by Ixoreal Biomed, containing 300 mg of standardized root extract) capsules twice daily for 12 weeks. Cardiorespiratory endurance was evaluated with a 20-meter shuttle run test, which is used commonly as a more feasible, but still reliable, means of calculating VO2max. The researchers also administered the World Health Organization Quality of Life (WHO-QOL) self-reported questionnaire, which includes a subdomain for physical health. These were evaluated at baseline, four, eight, and 12 weeks. Treatment with the Ashwagandha (n = 24, one subject dropped out) compared to placebo (n = 25) resulted in a significant improvement in VO2max from baseline (P < 0.0001) at week 8 (4.91 and 1.42, respectively) and at week 12 (5.67 and 1.86, respectively). The WHO-QOL scores also improved for all domains including physical health in the Ashwagandha group by week 12 (P < 0.05). The authors concluded that Ashwagandha enhanced cardiorespiratory endurance and improved quality of life in healthy adults, but more studies are needed to see if this generalizes to all populations.22
These four adaptogens are the most cited in the literature for athletic endpoints, and seem to be the main components in many herbal combination dietary supplements marketed to athletes for performance improvement. Caution should be used in interpreting these studies, since the literature search found no recent negative studies on these adaptogens and publication bias may be present. Also, the populations studied generally consisted of healthy adults, including high-level athletes; thus, the generalizability of these findings remains unclear.
For the average patient seeking advice on athletic performance-enhancing combination products, there is little in the literature to suggest additive or synergistic effects of these adaptogens, and patients should be advised caution. In reviewing the labels on several of these products, it is evident that dosing of the herbs in combination products often is lower than that used in the studies. Several products also included stimulants like caffeine, presumably as an attempt to give the user a perceived increase in energy directly after taking the product.
Instead, for interested athletes, we suggest recommending a single adaptogen in appropriate dosing based on the studies reviewed. Eleuthero (800-1,200 mg dried raw herb daily) and Ashwagandha (300-500 mg standardized root extract BID) have the strongest evidence base in the literature. Given that the studies did not extend beyond two to three months, it would be best to encourage a holiday of several weeks after that time. It also would be advisable to review common side effects and run an interaction check with all of a patient’s prescription medications. Because of their proposed immunologic mechanism of action, adaptogens may best be paused during bacterial infections as well; otherwise, there are no clear contraindications. As is often the case in medicine, statistical significance does not always mean clinical relevance, and expectations should be realistic. As important as the modest benefits observed in measures of endurance and recovery, the improvements in ratings of perceived exertion and quality of life may be even more relevant.
Financial Disclosure: Integrative Medicine Alert’s Executive Editor David Kiefer, MD; Peer Reviewer Suhani Bora, MD; Relias Media Executive Editor Leslie Coplin; Editor Jonathan Springston; and Editorial Group Manager Terrey L. Hatcher report no financial relationships relevant to this field of study.