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Adaptogens adapt to current substantiation needs

Western research is adapting its study endpoints and designs to better understand the benefits of adaptogenic herbs. 

Blake Ebersole | Mar 01, 2019

Adaptogens are an idea whose time has come, and their story has been developing for millions of years. Life on Earth has always required organisms to adapt to their environments to survive and reproduce.

It’s generally accepted that various forms of stress negatively impact health, and that reducing stress can help support a person’s well-being. In the broadest sense, stress can manifest in many ways—on physical, emotional and mental levels—down to the systemic, cellular and molecular levels. Fatigue, anxiety and depression are symptoms related to poor regulation of neurotransmitters; metabolism and related pathways all are either symptoms, causes or mitigating factors of stress and compromised health.

In a world where every nutrition and health idea draws controversy, most agree that foods can reduce stress. Not many Twitter or Facebook arguments contend that chocolate and wine don’t relieve stress.

Yet, the term “adaptogenic” is not widely accepted in the medical or scientific lexicon. The term has been hidden in the scientific literature after its coining by 1960s-era Russian researchers studying herbs including Rhodiola rosea and Eleutherococcus senticosus (eleuthero). Adaptogens were originally defined as “substances that increase resistance to a broad spectrum of harmful factors (stressors) of different physical, chemical and biological natures.”1 More recently, the definition has adapted to include “metabolic regulators, which increase the ability of an organism to adapt to environmental factors.”

One challenge to the mainstream acceptance of adaptogens in the West is their roots in Eastern philosophy. The cyclical nature of life, and the central ideas of homeostasis, often conflict with a predominant Western version of rational, reductionist thought that seeks to apply linear thinking to nonlinear problems, jamming various shapes of pegs into a specific size of square hole like a stubborn 2-year-old.

Adaptogenic activity is not confined to a single pathway, but involves subtle interactions with multiple biochemical pathways. Adaptogenic foods and herbs are not single-compound drugs, but are complex mixtures of hundreds or thousands of potentially bioactive compounds that together work in ways impossible to fully understand. Adaptogens work differently in different people at different times. As a result, the effects of adaptogens are often difficult to study and prove using typical clinical trial designs considered “gold standard” in Western-based drug research.

The Western scientific process is limited by several factors, including its objective to produce a simple pass/fail answer based on statistical probability (a.k.a., P<0.05) and the limitations of currently available measurement tools. The use and acceptance of adaptogens in the West is fraught with this conflict. It seems that the only way to make sense is to adapt and adopt the best of both East and West.

Across the spectrum of traditional use and modern scientific research, adaptogenic herbs such as rhodiola, eleuthero, ginseng (both Asian and American species), ashwagandha, astragalus, holy basil and bacopa have shown positive, repeatable effects—even in multiple forms, with effects repeated by multiple research groups. Looking broader, anti-inflammatory and antioxidant ingredients like docosahexaenoic acid (DHA), turmeric and plant polyphenols have displayed an ability to support the body’s resistance to oxidative and cellular stress, which often manifest as improving the body’s resilience to stress.

Preclinical studies have repeatedly found that treatments with adaptogenic properties (which in addition to herbs and foods, also includes many drugs like antidepressants and anti-inflammatories) alter the “tipping point” where adaptive processes turn maladaptive in the presence of stress. In the presence of stressors, adaptogens often exhibit neuroprotective, anti-fatigue, anti-depressant, immunosupportive, anxiolytic and central nervous system (CNS) stimulant activity.2 Many studies have found adaptogenic foods and herbs to exert a balancing effect on neurotransmitter receptors, including serotonin and dopamine, which may be central to their effects.1

Adaptogens are shown to support the regulation of homeostasis by acting on the hypothalamic-pituitary-adrenal (HPA) axis and regulating key mediators of stress response, such as heat shock protein, stress-activated JNK1, neuropeptide Y, antioxidant enzymes, and nitric oxide.2 Many adaptogens are associated with genetic mediating effects and longevity signaling pathways. Beyond mechanism of action, adaptogens are known to impact clinical endpoints related to cognitive function, the immune system and physical performance.

It stands to reason that natural products supported by a long history of safe and traditional use, particularly today as part of products formulated by scientists and medical experts, which are validated in well-designed, randomized, controlled human clinical trials, should be accepted within the set of options available for people to build resistance to stress.

Even the most Westernized of medical practices have begun to offer stress-relieving services like meditation and aromatherapy. It is common sense for anyone who has witnessed the efficacy of herbs to relax and recover.

In the face of the actual evidence, the “evidence-based” mongers, who disregard anything that’s not proven in the same way as a modern drug, appear as brazenly ignorant.

Luckily, research efforts have greatly accelerated in places like Europe, India and China, where thousands of peer-reviewed study publications overwhelmingly support the ability of numerous natural products and foods to support the body’s ability to adapt and resist the effects of stress.

While mainstream medicine is still reluctant about adaptogens, many peer-reviewed academic journals listed on the National Institutes of Health (NIH) database (Medline) accept the term “adaptogenic” as a primary descriptor for these types of natural products—372 published studies, based on a recent search.

Rhodiola, or “golden root,” considered by many to be the “true original” adaptogen, has been the subject of several recent studies. Two 2018 studies illustrated the effects of rhodiola on burnout3 and neuronal plasticity4 in humans.

These studies illustrate opportunities for clinical researchers to advance their design for studying adaptogens based on evolving knowledge. One of the lessons is to include enough of the right kind of subjects—including populations who are not simply selected at random, but whose medical history, lifestyles and baseline characteristics are better understood and controlled within the study.

Another lesson applied in recent research is the adoption of more sensitive and relevant clinical endpoints in real-world settings. The evolution of virtual clinical trials (VCTs) using observational study designs and modern technology (like wearables) may provide better ways to study and substantiate the effects of adaptogens.

It’s likely that future research on adaptogens will learn from past lessons. Because as science has revealed, we need to adapt to new knowledge, including the fact that there exist many other shapes of pegs than square.

Blake Ebersole has led several botanical quality initiatives and formed collaborations with dozens of universities and research centers. As president of NaturPro Scientific , Ebersole established quality compliance and product development services for supplements and ingredients such as ID Verified™. Follow him on Twitter at @NaturalBlake.

This article was first published in Natural Products Insider, March 2019

References:

1. Panossian A. “Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals.” Ann N Y Acad Sci. 2017 Aug;1401(1):49-64. DOI: 10.1111/nyas.13399.

2. Panossian A, Seo E, Efferth T. “Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology.” Phytomedicine. 2018 Nov 15;50:257-284. DOI: 10.1016/j.phymed.2018.09.204.

3. Ross S. “Burnout: A Multicenter Exploratory Clinical Trial With a Proprietary Extract of Rhodiola rosea in Patients With Burnout Syndrome.” Holist Nurs Pract. 2018 Nov/Dec;32(6):336-339. DOi: 10.1097/HNP.0000000000000299.

4. Concerto C et al. “Exploring the effect of adaptogenic Rhodiola Rosea extract on neuroplasticity in humans.” Complement Ther Med. 2018 Dec;41:141-146. DOI: 10.1016/j.ctim.2018.09.013.

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