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This is part four of a five-part article series on adaptogens: Miracle Plant or Myth. If you haven’t read parts 1-3 you can find them here. An introduction to adaptogens (part 1), Adaptogens and stress (part 2 & Adaptogens and scientific research (part 3)

In this part, I review clinical studies on Ashwagandha, Eleuthero, Rhodiola, Panax ginseng, and Schisandra. Many studies confirm their adaptogenic properties but most of them were performed in vitro (outside the body) or using animal models.

This review only includes studies performed in human subjects. Specifically, placebo-controlled double-blinded studies, meta-analysis, and systemic reviews. Although they are other indications, this review highlights their use for stress, mood, fatigue, and cognitive enhancement.

Ashwagandha

Ashwagandha (Withania somnifera) is an evergreen shrub that grows in dry regions of South Asia, Central Asia, and Africa. It has been used for over 3,000 years in Ayurvedic (the traditional medicine of India) medicine. Various parts of the plant are used, but the most common is the root extract. Ashwagandha has been traditionally used to enhance mood and cognitive function, relieve stress and improve general health. It has been studied scientifically for its immunomodulatory, anti-inflammatory, and adaptogenic properties.

Key Constituents

The withanolides are the major chemical constituents of ashwagandha. To date, about 35 withanolides have been extracted from the root of the plant.

Clinical Studies

In a study from 2008, performed on 130 participants with anxiety disorder, the ashwagandha group (compared to placebo) experienced an improvement in stress/anxiety, fatigue, and other clinical parameters. Another study published in 2012, with 64 participants diagnosed with chronic mental stress, ashwagandha improved all tested parameters and reduced serum cortisol by 27.9%. Finally, in this randomized, double-blind, placebo-controlled study from 2019, in 60 participants with high levels of stress, the authors found a modest reduction in the Perceived Stress Scale score in the ashwagandha group vs. placebo. The ashwagandha group also saw an improvement in cortisol level, Hamilton Anxiety Rating Scale, and sleep.

Conclusion

These studies suggest that ashwagandha reduces anxiety, stress, fatigue, and cortisol levels. However, more research is needed to increase the certainty of its effectiveness, due to the study limitations such as sample size, outcome measure variability, conflicts of interest, and study methodology. Nonetheless, these studies, coupled with centuries of use in traditional medicine and good safety profile prove that ashwagandha might have a role in improving well-being.

Eleuthero

Eleutherococcus senticosus, (formerly known as Siberian ginseng), is a herb used in traditional medicine to combat fatigue for many decades in France, Germany, United Kingdom, China, and Russia. In traditional Chinese medicine, it is used as an anti-fatigue, pro-vitality, and longevity tonic. Eleutherococcus senticosus is marketed as ADAPT-232, a blend of (Eleutherococcus senticosus, Schisandra chinensis, and Rhodiola rosea).

Key constituents

Eleuthero contains both saponins and lignans, and many other molecules (aglycones or glycosides). The main bioactive appears to be the lignans Eleutheroside B and Eleuetheroside E.

Clinical Studies

In a randomized controlled trial published in 2004, on 96 participants with chronic fatigue, the authors concluded that efficacy was not demonstrated. Similarly, another study from 2005 concluded that Eleutherococcus senticosus supplementation offers no advantage during exercise. However, this study published in 2010 shows that an 8-week Eleutherococcus senticosus supplementation in 9 participants enhanced endurance capacity. Finally, this relatively larger study from 2013, with 144 participants suffering from chronic stress, found no benefit from adding Eleutherococcus senticosus to stress management training in stress-related fatigue/weakness, impaired work, or concentration.

Conclusion

Even though non-clinical research suggests Eleutherococcus senticosus has adaptogenic properties, available clinical studies do not confirm these effects. The few studies that show benefit, unfortunately, lack reliable method. None of the studies would be sufficient to substantiate the efficacy of Eleutherococcus for stress and/or fatigue reduction. The European Medicines Agency (EMA), in their assessment report from 2014, states that “Eleutherococcus root preparations do not reach the level of scientific evidence that would be sufficient to grant a marketing authorization. However, the studies provide a solid basis for the plausibility of the traditional use”

Rhodiola Rosea

Rhodiola rosea is a plant that grows in the wild arctic regions of Europe, Asia, and North America. The herbal substance used consists of the dried roots and rhizomes of the plant. Rhodiola is traditionally accepted as an anti-fatigue agent that enhances mental and physical performance. It has also been used to treat anxiety and a depressed mood. Rhodiola is marketed comercially as ADAPT-232, a blend of (Eleutherococcus senticosus, Schisandra chinensis, and Rhodiola rosea)

Key constituents

The root of Rhodiola contains tyrosol, salidroside, and rosavins. The main active ingredients appear to be tyrosol and salidroside.

Clinical Studies

Starting with this study published 2000, the authors examined Rhodiola’s effects on mental performance in 56 night-duty physicians. They found an improvement in these tests of the Rhodiola group vs. placebo. This randomized, double-blind, placebo-controlled study from 2009 in 60 subjects showed that repeated administration of Rhodiola extract exerts an anti-fatigue effect that increases mental performance, and decreases cortisol in patients with fatigue syndrome. Surprisingly, this randomized, double-blinded, placebo-controlled study from 2014 found that Rhodiola worsened fatigue. Finally, a meta-analysis from 2011, concluded that Rhodiola may have beneficial effects on physical and mental performance, and other mental health conditions. However, there is a lack of independent replications of the single different studies reviewed.

Conclusion

Research regarding Rhodiola’s effects are contradictory. While some evidence suggests that the herb may help enhance physical performance and alleviate mental fatigue, methodological flaws limit accurate assessment of overall efficacy. The EMA’s assessment report on Rhodiola states that the traditional use is appropriate for traditional herbal medicinal products. “However, the published clinical trials exhibit considerable deficiencies in their quality. Therefore, ‘well-established use’ cannot be accepted”

Panax ginseng C.A. Meyer

Panax ginseng C.A. Meyer herbal preparations have been used worldwide for centuries, especially in traditional medicine systems of Eastern Asia. Herbal preparations have been marketed as a tonic for tiredness, to improve mental and physical capacity, and concentration. It is commonly referred to as the ‘True Ginseng’ and is the most researched in the ginseng family. It has also been researched for improvement in mood, immunity, testosterone levels, and exercise.

Key Constituents

The key constituents of Panax ginseng root include a complex mixture of saponins called ginsenosides

Clinical Studies

Starting with this study published 2002 with 30 participants, Panax ginseng improved cognition, social function, and mood after 4 weeks vs. placebo. However, these differences attenuated with continued use. Another double-blind, placebo-controlled study from 2005, also with 30 participants found that Panax ginseng improved performance and subjective feelings of mental fatigue during sustained mental activity. On the contrary, this study from 2010 found that single doses of Panax ginseng (day 1 & day 8) impoved cognitive function and mood but subsequent ingestion had no effect on mood or cognitive performance.

Conclusion

Although some studies show beneficial effects in some aspects of cognitive function and fatigue but due to study limitations (study heterogeneity, preparations used, poor methodological quality, and small size) there is no strong evidence for clinical efficacy as an adaptogen. The extensive report from the EMA concludes that “Even though numerous clinical studies investigating the pharmacological properties of Panax ginseng have been conducted since the 1980s, several systematic reviews reveal that data is still inconclusive and strong evidence for clinical efficacy cannot be deduced.” However, The plausibility of traditional use in the proposed indication are supported by the long-standing use and the outcome of many preclinical and clinical investigations.

Schisandra chinensis

Schisandra chinensis is a perennial plant distributed in north-eastern regions of Korea, China, Japan, and Russia. Schisandra berries and seeds were used by Nanai hunters as a tonic to improve night vision, to reduce hunger, thirst, and exhaustion. Russian scientists have studied the activity of Schisandra extensively, but access to those study results are limited. Schisandra chinensis is marketed as ADAPT-232, a blend of (Eleutherococcus senticosus, Schisandra chinensis, and Rhodiola rosea).

Key Constituents

The lignans (Schisandrin A, Schisandrin B, and Schisandrin C) are the major bioactive components that have been isolated.

Clinical Studies

Starting with this placebo-controlled double-blind study published in 1999 with 71 athletes, they found that Schisandra increased circulating levels of Nitric Oxide (NO) in athletes when taken before exercise, but the effect was not cumulative. A review article published in 2019 concluded that Schisandra displays a variety of beneficial health effects, with no side effects but further research is needed to determine the molecular mechanism of action. A recent study published in 2020 found that quadriceps muscle strength (QMS) was increased and lactate level at rest was decreased with Schisandra vs. placebo. Finally, this double-blind, placebo-controlled, randomized study, reviewed the effect of a single dose of ADAPT-232 (a blend of Eleutherococcus senticosus, Schisandra chinensis, and Rhodiola rosea) on mental performance. The study found that ADAPT-232 did improve mental performance under stressful conditions. However, this finding is confounded by the fact that ADAPT 232 is a blend with other compounds with adaptogenic properties.

Conclusion

Older human studies performed in Russia are difficult to gain access to and the available human studies don’t provide a high level of confidence in their effects as adaptogens.

Adaptogen Studies Conclusion

In a review article published in Yale Journal of Biology and Medicine in 2020, the authors correctly affirm that important gaps exist between the traditional use of adaptogens and the clinical evidence currently available. 

In their review of the published adaptogen studies, their findings highlight the need to develop consistent study methods to help bridge that gap. 

The EMA, in their 2008 reflection paper on the adaptogenic concept, concluded that none of the available studies (reviewed at the time of the publication) would be enough to substantiate the efficacy of adaptogen preparations in a clearly defined clinical condition, although, in total, the data available are enough to justify further research. 

The concept of adaptogens and their role in modulating stress, fatigue, and mood in humans cannot be completely dismissed. But, we are far from making substantial and/or definitive claims about their effectiveness.  However, their long-standing use, coupled with their relatively safe profile allows for traditional herbal use, pending results of more robust studies that establish their definitive role.

Summary of Key Points

  • There isn’t enough evidence from the currently available human studies to show that all adaptogens conclusively and consistently modulate the stress response.
  • Adaptogens have been successfully used in traditional medical systems but the current scientific studies might lack appropriate measurement tools in their study design, possibly explaining the outcome variability seen.
  • Unlike definitive disease states with specific markers (blood pressure, blood sugar, cholesterol levels, etc) there isn’t a universally standardized measure for stress, fatigue, or cognition. This increases study heterogeneity and decreases the generalizability of study results.
  • Even with some studies demonstrating their effectiveness, one cannot automatically assume that any product labeled as an adaptogen or containing one will be effective against stress and fatigue. This is due to key constituent variability (parts used, extract concentration, etc) that exist between the studies and the products marketed.
  • Due to its relatively safe profile, (under the direction of a qualified practitioner) select adaptogens might be used to decrease stress, in combination with other stress reduction strategies, as we await results of more robust studies to confirm their role.

References:

  • Winston, David, and Steven Maimes. Adaptogens: Herbs for Strength, Stamina, and Stress Relief. Healing Arts Press, 2019.
  • Liao, Lian-Ying, et al. “A Preliminary Review of Studies on Adaptogens: Comparison of Their Bioactivity in TCM with That of Ginseng-like Herbs Used Worldwide.” Chinese Medicine, vol. 13, no. 1, 2018, doi:10.1186/s13020-018-0214-9.
  • Panossian, Alexander, and Georg Wikman. “Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress-Protective Activity.” Pharmaceuticals (Basel, Switzerland) vol. 3,1 188-224. 19 Jan. 2010, doi:10.3390/ph3010188
  • Yance, Donald R. Adaptogens in Medical Herbalism: Elite Herbs and Natural Compounds for Mastering Stress, Aging, and Chronic Disease. Healing Arts Press, 2013.
  • Gerontakos SE, Casteleijn D, Shikov AN, Wardle J. A Critical Review to Identify the Domains Used to Measure the Effect and Outcome of Adaptogenic Herbal Medicines. The Yale Journal of Biology and Medicine. 2020 Jun;93(2):327-346.
  • Gerontakos S, Casteleijn D, Wardle J. Clinician perspectives and understanding of the adaptogenic concept: A focus group study with Naturopaths and Western Herbalists Integrative Medicine Research. 2020 May;10(1).
  • An independent and unbiased encyclopedia on supplementation and nutrition. www.examine.com. Last accessed Sept 4th, 2020

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