Observations Of Adaptogen Research

It makes sense that researchers wishing to study adaptogens and their effects on stress would
study subjects under the influence of a stressor agent, specifically, a stressor agent to which the
study subjects was not already adapted. As Selye pointed out, to elicit the GAS you had to use a
stressor to which the organism was not adapted. However, in regards human clinical trials,
researchers often use a form of stress to which the study subjects are adapted. For example, they
select physically fit subjects, in some cases professional athletes, and use physical exercise as the
stressor agent. The following study perimeters of published adaptogen clinical trials illustrate
this point clearly. (1?2)


Eleutherococcus senticosus
Using a randomised, double blind crossover study, 9 highly trained men cycled for 120 minutes. (3)
Twenty highly trained distance runners randomly assigned in matched pairs to either an experimental or
placebo group, participated in an 8 week double blind study during which they completed five trials of a
10 min treadmill run at their 10 km race pace and a maximal treadmill test. (4)


Panax ginseng
Using a double blind protocol, 24 healthy active women were randomly assigned to a ginseng or placebo
treatment group. Before and after the trial period, each subject performed an all out effort, 30?second leg
cycle ergometry test followed by a controlled recovery under constant laboratory conditions. (5)
To determine the short term effects of Panax ginseng supplementation vs. placebo on peak aerobic exercise
performance in healthy young adults, with unrestricted diets. Twenty men and eight women were
randomly assigned to either a Panax ginseng or placebo group for a period of 3 weeks in a double blind
design. Prior to and following treatment the subjects performed a symptom limited graded exercise test on
a Schwinn airdyne ergometer. (6)
If these researchers wanted to stress professional athletes, immobility would have been a better
option because it represents stress to these individuals. Alternatively, if they were wedded to
exercise as a stressor agent, they could have selected study subjects who had not done any
physical exercise in ten years. In this case, physical exercise would have represented a stressor
agent. (7?8)
Another example of the researchers using unstressed populations can be seen with a study
involving the adaptogen Maca (Lepidium meyenii). Men under the influence of a stressor agent
have lower testosterone levels than unstressed men. In fact, stress has such an adverse effect on
testosterone production that it can lead to loss of libido, testicular atrophy, and gynecomastia
(breast growth). (8) In this example, the researchers studied to see if the Lepidium meyenii
raised testosterone levels in normal unstressed men. The study perimeters, published in the
study, were as follows: “The study aimed to test the hypothesis that Maca has no effect on serum
reproductive hormone levels in apparently healthy men when administered in doses used for aphrodisiac
and or fertility enhancing properties.” (9) Here again it would have been more appropriate to use a
group of medical students in the first year of clinical training, or a group of soldiers in combat.
The theoretical and research basis on which the work is built suggests adaptogens should be
tested out on stressed populations. One could dismiss these studies as badly designed if it were
not for the conclusions these researchers drew and published. In all five of the referenced
studies, the researchers concluded that adaptogens had no effect in stress. It would have been
more accurate to say that adaptogens had no effect in unstressed populations because the
subjects studied were not under unusual stress. In fact, in the 1960’s, Brekhman demonstrated
that adaptogens had no effect in unstressed populations and these five studies have
substantiated his finding.

Brekhman created his criterion to separate adaptogens from non?adaptogens. According to him,
traditionally used tonics that fulfilled the criterion could be designated “adaptogen”. (1?2)
Reviewing contemporary literature one will find numerous drugs labelled adaptogen. The
assumption is that these drugs fulfilled Brekhman’s criterion. However, upon closer inspection,
it becomes apparent this is not the case.
Indeed, scrutinising the drugs labelled adaptogen in the contemporary literature, one finds a
mixed bag. Some of the drugs were never used as tonics. Some of the drugs have been shown to
fulfil part of the criterion, but not all of the criterion (i.e. they are not innocuous but do raise
resistance and normalise function). Some of the drugs have been shown to fulfil part of the
criterion but part of the research is left undone (i.e. the drug has been shown to be innocuous; to
raise resistance, but normalisation has not been investigated.)
In fact, reviewing the following list illustrates this point. Searching contemporary literature for
adaptogens, one is likely to find the all drugs listed below labelled adaptogens. Upon closer
scrutiny, only the highlighted drugs have been shown to fulfil Brekhman’s criterion. The drugs
that are not highlighted only partially fulfil the criterion. Albizzia julibrissin (3)
Aralia elata (3)
Asparagus racemosus (5)
Azardirachta indica (4)
Boerhaavia diffusa (4)
Bryonia alba (3)
Centella asiatica
Cicer arietinum (3)
Codonopsis pilosula (3)
Eleutherococcus senticosus (1?2)
Emblic officinalis (5)
Glycyrrhiza sp. (4)
Hoppea dichotoma (3)
Lepidium meyenii (3)
Leuza carthamoides (3)
Ocimum sanctum (3)
Panax ginseng (3)
Panax quinquefolium (3)
Pfaffica paniculata (5)
Piper longum (5)
Rhaponticum carthamoides (1?2)
Rhodiola rosea (1?2)
Schizandra chinensis (1?2)
Smilax sp. (5)
Terminalia chebula (5)
Tinospora cordiflora (3)
Trichopus zeylanicus (3)
Withania somniferum (3)
Labelling drugs that do not fulfil the adaptogen criterion as adaptogens is a mistake. At a
minimum, it is misleading. More dangerously, it undermines the credibility of the term
adaptogen. In truth, the term should be used conservatively. To eliminate ambiguity in the
future, it would be helpful if adaptogen researchers used one of the following designations
for potential adaptogens: “The drug exhibits properties consistent with Brekhman’s
definition of an adaptogen” or “The drug exhibits properties consistent with some of
Brekhman’s definition of an adaptogen.”

The work of Selye, based on the concept of homeostasis, continues to be the basis for stress and
stress related disease research. However, some researchers feel that current stress research has
several shortcomings. The first drawback, according to these researchers, is that the term stress
is vague and leaves too much room for interpretation. The second limitation is that stress
research has taken a negative direction; too often stress and adaptation to stress is seen as a
negative thing. Thirdly, stress is more complex than what the current model suggests. For
reasons such as these, some researchers feel that its time to revisit the subject of homeostasis
and offer an alternative.
Allostasis, an alternative to the homeostatic model, has been put forward recently. Allostasis
addresses the concerns of some stress researchers and is, in their opinion, an improvement over
the homeostatic model. A recent paper presents an explanation as to why a new model is
needed:
“Since the pioneering work of Hans Selye, the use of the word ‘Stress’ has become popular all over the world.
However, despite the vast amount of scientific research generated in this field the term stress has been a
stumbling block right from its first use. The term has so many different meanings that it becomes
counterproductive by inhibiting a proper application and critical interpretation of experimental results.
Stress has mostly been associated with negative events and consequences, i.e. it can take its toll on physical and
mental health. There is, however, no justification for the assumption that the expression of stress responses
always compromise health and/or welfare.
Indeed, the functional aspects of stress have been neglected too often. The paradox of stress lies in the
simultaneity of its adaptive nature and its possible maladaptive consequences.
A somewhat modified version of Marius Tausk’s metaphor of ‘water used by firemen’ can illuminate this
paradox. Firemen may use water to extinguish certain fires or to prevent them. But if much water is used it can
cause more damage than the flames. Another risk is that increased water usage can lead to a loss of water
pressure, thereby making efficient fire fighting impossible and contributing to the spread of the fire. Just like the
fireman’s water stress responses are ideally beneficial but they can impose a cost to the body, particularly when
they are either elicited too often or are inefficiently managed.”(1)
To avoid the ambiguities of the homeostatic model, researchers have modified the Allostasis
model to address its apparent limitations. Specifically:
“In this concept, Allostasis is defined as the adaptive process for actively maintaining stability through
change. The brain plays a central role in Allostasis. By controlling all the mechanisms simultaneously,
the brain can enforce its command and incorporate influential factors such as experience, memories,
anticipation, and re?evaluation of needs in anticipation of physiological requirements.
Allostasis is important during both unpredictable events, e.g. conflict in social hierarchies, competition
for resources, storms and natural disasters, and predictable events, e.g. seasonal changes that trigger
migration and hibernation.
The central idea is that cost to the body arises if mediators of Allostasis: adrenal hormones,
neurotransmitters, or immuno?cytokines, etc. are released too often or if they are inefficiently managed.
That cost is referred to as ‘Allostatic Load’ which can be described as the cumulative wear and tear.
It is well known that, dependent on the environment, some individuals are more vulnerable to stressrelated
disease than others. This implies that a certain environmental condition may differentially affect
allostatic loads in different individuals. Charles Darwin was the first to understand that animal
populations consist of individuals that differ from one another in their adaptive qualities and limitations.
Those individuals possessing a variation that confers some survival advantage in their natural habitat
and allows them to live long enough to successfully reproduce are the ones that pass on their traits more
frequently to the next generation. This process has come to be known as natural selection .
It is important to realize that natural selection exerts genetic benefits by maximizing reproductive success
of the adapted organisms even at the expense of individual happiness, health and longevity .
Thus, individual health is not necessarily the primary goal. Without doubt, the balance between
Allostasis and allostatic load has been shaped in the course of evolution by trade?offs on the basis of costs
and benefits that occur at different stages of the life cycle or that are affected by season, social status, sex,
or environmental change.
In building a new conceptual framework it is important to consider different levels of analysis that can
lead to complementary explanations .
First, we provide evolutionary explanations for the fact that different organisms adopt different
behavioural strategies in order to cope with stressful events. We discuss the evolutionary significance of
the stress response and the variation of responsiveness among individuals in their natural or ancestral
environment.
Second, we give proximate (causal) explanations for the different stress responses and we describe how
they work.
Third and fourth, we emphasise that stress research should consider a cost benefit analysis of the different
behavioural and physiological stress responses. Such an analysis forms the basis of The Darwinian
concept of stresses since the ‘benefits of Allostasis’ and the ‘costs of allostatic load’ produce trade?offs in
health and disease. We discuss how different personalities, each with associated differences in underlying
physiology and behaviour, vary in their vulnerability to stress?related diseases.” (1)
One of the quandaries of stress research has been that individuals do respond to stress
differently. When chronically stressed, the syndrome described by Selye will occur. However,
it will not necessarily present identically in all individuals. The Allostasis researchers address
this fact and offer the explanation that this difference can be explained by Darwin’s ideas of
evolution and survival of the fittest. According to Darwin, some individuals are more adaptive
than others. Simply put, these researchers assert there is an evolutionary component to the
adaptive reaction.
Looking at another recent paper, we find a comparison of Homeostasis and Allostasis from the
perspective of the proponents of Allostasis.
Homeostasis
“Homeostasis is the stability of physiological systems that maintain life, used here to apply strictly to a
limited number of systems such as pH, body temperature, glucose levels, and oxygen tension that are truly
essential for life and are therefore maintained within a range optimal for the current life history stage.” (2)
Allostasis
“Allostasis is achieving stability through change. This is a process that supports homeostasis, i.e., those
physiological parameters essential for life defined above, as environments and/or life history stages change.
This means that the ?set?points? and other boundaries of control must also change. There are primary
mediators of Allostasis such as, but not confined to, hormones of the hypothalamo–pituitary–adrenal (HPA)
axis, catecholamines, and cytokines. Allostasis also clarifies an inherent ambiguity in the term ?homeostasis?
and distinguishes between the systems that are essential for life (?homeostasis?) and those that maintain these
systems in balance (?Allostasis?) as environment and life history stage change.
We note, however, that another view of homeostasis is the operation of coordinated physiological processes that
maintain most of the steady states of the organism. In this interpretation, homeostasis and Allostasis might
seem to mean almost the same thing. The reason they do not is that the notion of ?steady state? is itself vague
and does not distinguish between those systems essential for life and those that maintain them. It also does
not differentiate changes in state to enable reproduction (and other life cycle processes) that are not required
for immediate survival.”(2)
Allostatic state
“The allostatic state refers to altered and sustained activity levels of the primary mediators, e.g.,
glucocorticosteroids, that integrate physiology and associated behaviors in response to changing
environments and challenges such as social interactions, weather, disease, predators, pollution, etc. Originally
proposed for understanding physiological aspects of drug abuse, an allostatic state results in an imbalance of
the primary mediators, reflecting excessive production of some and inadequate production of others. Examples
are hypertension, a perturbed cortisol rhythm in major depression or after chronic sleep deprivation, chronic
elevation of inflammatory cytokines and low cortisol in Chronic Fatigue Syndrome, and imbalance of cortisol,
CRF, and cytokines in the Lewis rat that increases risk for autoimmune and inflammatory disorders.
Allostatic states can be sustained for limited periods if food intake and/or stored energy such as fat can fuel
homeostatic mechanisms. For example, bears and other hibernating animals preparing for the winter become
hyperphagic as part of the normal life cycle and at a time (summer and early autumn) when food resources
can sustain it. In contrast, facultative hyperphagia in response to environmental perturbations (impending
storms or increased predator pressure) may not always be supported by local resources. If imbalance continues
for longer periods, and becomes independent of maintaining adequate energy reserves, then symptoms of
allostatic overload appear.” (2)
Allostatic load and allostatic overload
“The cumulative result of an allostatic state (e.g., facultative fat deposition in an animal responding to
unexpected environmental change) is allostatic load. It can be considered the result of the daily and seasonal
routines organisms have to obtain food and survive and extra energy needed to migrate, molt, breed, etc.
Within limits, they are adaptive responses to seasonal and other demands. However, if one superimposes
additional loads of unpredictable events in the environment such as disease, human disturbance, and social
interactions, then allostatic load can increase dramatically.
We envision two distinctly different outcomes. First, if energy demands exceed energy income, and what can be
mobilized from stores, then Type 1 allostatic overload occurs. For example, breeding birds use increasing food
abundance in spring to raise young. If inclement weather then increases the cost of maintaining homeostasis in
addition to the demands of breeding, and at the same time reduces food available to fuel this allostatic load, then
negative energy balance results in loss of body mass and suppression of reproduction. Another example is the
mass movement of seabirds to islands in the face of a severe storm that limited access to food. The increased
allostatic load of dealing with the storm in the face of reduced energy income resulted in Type 1 allostatic
overload.
Second, Type 2 allostatic overload occurs if energy demands are not exceeded and the organism continues to
take in or store as much or even more energy than it needs. This may be a result of stress?related food
consumption, choice of a fat?rich diet, or metabolic imbalances (prediabetic state) that favors fat deposition.
There are other cumulative changes in other systems, e.g., neuronal remodeling or loss in hippocampus,
atherosclerotic plaques, left ventricular hypertrophy of the heart, glycosylated hemoglobin, and other proteins
by advanced glycosylation end products as a measure of sustained hyperglycemia. High cholesterol with low
HDL may also occur, and chronic pain and fatigue, e.g., in arthritis or psoriasis, associated with imbalance of
immune mediators. Thus it may be possible to distinguish between allostatic load in the normal life cycle
(incorporating unpredictable events in the environment) and allostatic overload that exceeds the capacity of the
individual to cope, albeit in the two distinctive directions described above. This is particularly severe if the
overload is permanent such as with injury, disease, and some lifestyles. These are all secondary outcomes that
can be measured and are associated with increased risk for a disease.” (2)
This group of researchers again offer reasons as to why Allostasis represents an improvement upon
the homeostasis model. To wit:
“Using these definitions as a starting point, we now discuss the overused term ?stress? and how, in its place,
the concept of allostasis may allow us to consider the life cycle in general as a continuum from daily routines to
allostatic overload and the accompanying pathologies. Within the framework of allostasis, a narrower and more
precise definition of stress has an important place. This is particularly heuristic because it allows us to include
individual variation due to experience, genetics, and social status. It incorporates thresholds and transitions
among physiological and behavioral states that also vary from individual to individual. Despite this
complexity, the framework illustrates that similar hormone systems may be involved. Furthermore, the
framework allows formulation of clear predictions that can be tested experimentally.” (2)
It would be fair to say the allostatic model does take a more holistic view of stress than does the
former homeostatic research model. As these researchers state, Allostasis takes into
consideration individual variation due to experience, genetics, and social status. Clearly adding
these variables into a study project would result in a much more refined data yield.
It could be argued, though, that as a consequence of its complexity, the allostatic model would
make studying a stressed population so complicated as to be unwieldy. How Allostasis plays
out functionally in research is unknown. The concept is relatively new and has yet to see the test
of practical experience. The notion that stress is an extremely complex subject, and that better
stress research will occur when the totality of its complexity can be embraced, cannot be argued.
Regarding the role of adaptogens in this more complex system of studying stress, there seems to
be little incompatibility. Indeed, Selye stated that organisms could withstand stress (State of
Resistance). When stress went on too long, or was compounded with additional stressors, the
organism was no longer able to withstand the stress (State of Exhaustion). Once State of
Exhaustion occurred, the individual was prone to disease. The proponents of Allostasis suggest
that stress is not a bad thing (Allostatic Load), unless it goes on for too long or is complicated
with additional stressors (Allostatic Overload). That is, both models suggest the human body
can handle a certain amount of stress and no more.
Indeed, in the Homeostatic model and the Allostatic model, the same question arises: are there
substances that will increase organisms’ ability to withstand stress? Both models acknowledge
that adaptation to stress is mediated at least in part by chemicals produced by the body. If the
body could be provided with more of these substances, could it not withstand more stress or
stress for a longer period of time? Clearly, both models raise the possibility of substances that
increase human resistance to stress and thereby prevent disease.
The fact is the adaptogen concept fits well within either model – homeostatic or allostatic. If
Allostasis develops and results in a more sophisticated and refined ability to study stress, it can
only result in an improved means of studying the adaptogen.

Adaptogen research has become aimless. When the research community refocuses its attention
on the concepts put forward by the original workers, research can proceed like never before.
We now have greater access to data on the herbal adaptogens, the chemicals they contain, and
the activity of those chemicals. Indeed, there has been an incredible amount of research done on
the medicinal plants of the world and the chemicals that make them active. The amount of data
on herbal remedies, created most usually for drug research, opens up tremendous research
possibilities for the researcher interested in adaptogens.
Moreover, the world of clinical testing has made enormous progress since the days of Selye and
Brekhman. Once incredibly expensive and time consuming, there are machines and
technologies available today that can monitor stress markers for a pittance. Adaptogens that
make it through the identification process can be studied and monitored more easily and more
precisely.
In fact, the modern age offers incredible opportunities for the adaptogen researcher. Raw data
compiled for other purposes is abundant and new technology makes an even more thorough
look possible. An adaptogen researcher, on track and using the tools to hand, can readily
further our knowledge of this useful class of drug.

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