Hormesis - Do Toxins Make You Stronger? Part 1

“That which does not kill us makes us stronger” is a well known maxim attributed to Friedrich Nietzsche. But is it true?

Some toxins and stressors can indeed make you stronger by a process known as hormesis. In this two part series I explain when toxins or other stressors are beneficial and when they become harmful.

What is hormesis?

The term ‘hormesis’ refers to the process by which a short-term mild stressor or a low dose of toxin provides health benefits by causing you to mount an adaptive protective response which can slow down ageing and prolong your lifespan (1, 2). A higher dose of the toxin or stressor, on the other hand, will harm you (3).

In The Dangers Of Over Exercising I described how the right level of exercise causes some oxidative stress which increases your anti-oxidant production and thus benefits you (4 , 5). Excessive exercise, on the other hand, will simply overwhelm your anti-oxidant defences and this dose-dependant response is one of the hallmarks of hormesis (6). The fact that the health benefits are initiated by oxidative stress may explain why some studies show that anti-oxidants like vitamin C and vitamin E reduce the benefits of exercise (7).

I also described how toxins like polyphenols that plants produce to protect themselves from pathogens and other stressors like ultraviolet light and temperature extremes can stimulate protective mechanisms in the human body and thus confer benefits (8)

How does hormesis work?

So how does hormesis work?

One way is that plant toxins such as curcumin from turmeric or glucosinolates from cruciferous vegetables have a pro-oxidant effect that activates transcription factors such as Nrf2 (9) and these transcription factors then switch genes on that stimulate detoxification pathways and anti-oxidant production and that also produce other proteins such as growth factors and heat shock proteins that help protect the body from stressors. By activating various genes Nrf2, for example, will increase the production of your main intracellular anti-oxidant glutathione, of anti-oxidant enzymes that use glutathione such as glutathione peroxidase and glutathione-S-transferase, of other anti-oxidant enzymes superoxide dismutase and catalase as well as detoxification enzymes (10), heat shock proteins (11), enzymes to protect from the damaging effects of sugar binding to proteins (12, 13) , and ferritin (14) to bind with iron to prevent the oxidative cascade that results when unbound iron is exposed to oxidative stress.

Polyphenols also stimulate Sirtuin-1 enzymes that promote longevity (15) and this is also one of the hormetic mechanisms stimulated by caloric restriction (16).

Xenohormesis

‘Xenohormesis’ is the idea that by consuming these plants that are rich in polyphenols we receive the information that difficult environmental conditions or a shortage of food may lie ahead, since the plants produce the polyphenols in response to environmental stressors. This causes a protective response in the human body that promotes longevity (17, 18). So now you can see why it is called xenohormesis (‘xeno’ meaning ‘foreign’ or ‘other’) because it is not us but the plants in which the initial response to a stressor happens that we then benefit from.

How your survival instinct is killing you

Intermittent fasting also has a hormetic effect (19) and the ketogenic diet could also be thought of as a stressor which activates Nrf2 (20, 21). For weight loss, longevity, and to reduce the risk of neurodegenerative conditions such as Alzheimer’s disease and Parkinsons’s disease I recommend to at least fast overnight every night for 12-13 hours beginning the fast at least 3 hours before bedtime.

We evolved in conditions in which we would have to go hungry at times and we would have to move our bodies and exert ourselves physically in order to survive. It has been hypothesised that one of the reasons for the current epidemic of chronic disease and especially why the prevalence of type 2 diabetes, obesity and metabolic syndrome has increased is because of the abundance of food 24 hours a day (22) as well as the lack of the need to exert ourselves physically in order to obtain that food (23).

There are a few interesting paradoxes here. To maximise our chances of survival in times of food shortage we evolved to crave these high reward high calorie foods that are now so readily available and we evolved to store the excess calories for times of greater need. So it could be argued that our survival instinct is actually killing us, given the environment of 24/7 caloric abundance. Perhaps life is difficult in terms of health precisely because by setting up convenience stores we have made it so easy. And yet if convenience or the avoidance of stressors has become the golden goal of modern life we plunge headlong into stressful careers to provide these conveniences. We stress out in order to avoid stressors! That running away from pain or inconvenience causes more suffering is one of the tenets of Buddhism, so it’s interesting that it applies at this more crude biochemical or biophysical level that I am focusing on here.

The wrong kind of stress and the right kind of stress

We could say that there are two factors causing poor health:

Firstly, too little of the stressors that in small doses would benefit us because we evolved to deal with them, such as exercise, hunger or fasting and the toxins found in cruciferous vegetables such as broccoli, cabbage, cauliflower and Brussel sprouts.

The second cause of poor health is having too high doses of other stressors such as psychological stress, exercise when we chronically overdo it, overuse of addictive substances such as alcohol and ultra-processed foods, and too high levels of the environmental toxins that are the by-products of trying to make our lives so convenient and pain-free.

Now it is worth mentioning here that some degree of work stress may actually have positive health outcomes if your work serves a deeper purpose that you believe in, as explained by Kelly McGonigal in her fascinating TED talk How To Make Stress Your Friend.

Thinking as a hormetic stressor

There is some epidemiological evidence that regular intellectual activity can help to protect the brain from Alzheimer’s disease (24). Neurons need a lot of energy and are therefore rich in mitochondria which generate ATP which your body uses to store energy in a directly usable form. However, the process of making ATP constantly generates free radicals (25). The resulting oxidative stress is one of the stressors undergone by neurons that are being used in mentally challenging activity, repeated calcium influx into the neuron being another stressor. As a result of such stressors the production of protective proteins such as heat shock protein and neurotrophic factors are increased and this seems to be another example of hormesis (26) that would account for the association between challenging intellectual activity and reduced risk of Alzheimer’s disease.

Temperature as a hormetic stressor

Temperature extremes can also have a hormetic effect. Saunas benefit not only by reduction of excess environmental toxin stress but by activating Nrf-2 and increasing the production of heat shock protein (27) which promotes longevity. Regular brief exposure to cold water will promote anti-oxidant production in winter swimmers (28), and all boost the T-cells and natural killer cells of your immune system (29). One study showed a 29% reduction in sick leave when study participants were asked to turn the temperature to cold at the end of their daily shower (30). If you shiver as a result will also promote the production of beneficial brown fat (31) which will burn more calories (32) .

Is alcohol good for you?

So the big question for some people is whether alcohol is hormetic or not and whether the benefit is rather from the polyphenols such as resveratrol and other phytochemicals in wine and to a lesser extent in beer. At first it seems that the short answer is that a small glass of red wine per day may confer some benefit coming more from the antioxidant effect of the polyphenols than the alcohol (33), and may reduce mortality, but firstly the data is unclear due to confounding factors such as diet and smoking, secondly any benefits would probably need to be in the context of a diet with a wide range of polyphenols for synergistic effect (34), thirdly many chronically ill people such as people with Chronic Fatigue Syndrome or ME cannot tolerate alcohol even in small quantities (35), and finally women at higher risk of breast cancer could reduce their risk by avoiding alcohol altogether (36, 37). It has been argued that perhaps the alcohol increases the absorption of the polyphenols such as resveratrol, but the benefits are also apparent from eating red grapes and unfermented red grape products (38). Another problem with the research on alcohol is its reliance on notoriously unreliable intake questionnaires, and I would imagine that since many researchers enjoy alcohol there could well be some measure of unconscious bias in exaggerating any benefits of alcohol. However a study in 2014 looked at cardiovascular disease rates in participants with a genetic variant that results in reduced desirability of alcohol due to facial flushing and nausea as a result of alcohol consumption. This bypassed the need for the unreliable intake questionnaires used in observational studies, to give more objective results which suggested that “reduction of alcohol consumption, even for light or moderate drinkers, is beneficial for cardiovascular health” (39). Since studies look at averages across a population it is possible that alcohol can reduce heart disease risk in individuals who are at higher risk due to poor dietary and lifestyle choices, but may turn out to shorten lifespan in those who make otherwise health-promoting dietary and lifestyle choices. After all, even moderate alcohol intake reduces brain size (40) and alcohol is converted in your body to the carcinogenic (41) and neurotoxic (42) acetaldehyde, which also binds with the motivating neurotransmitter dopamine to form the neurotoxic compound salsonilol (43) and seems to be behind the increased reproductive issues in women who drink (44).

Is cannabis a hormetic stressor?

Interestingly however, THC, tetrahydrocannabinol, the main psychotropic component of cannabis, which is known to adversely effect short-term memory, can actually protect the brain at very low doses, thus qualifying it as a hormetic agent (45). However the amount that would actually benefit you would probably be much less that what is typically used recreationally. It seems that a very minute dose over a longer period confers the benefits.

More on hormesis

In the next post I will give some more practical advice on how to maximise your benefits from hormesis.

Many of the ways in which you may have been taking care of your health could come under the umbrella of hormesis. Does an understanding of this concept support and motivate you to allow a bit of discomfort in your life for greater enjoyment of life in the long term? Let me know in the comments below.

Read Part 2, learn more about my work in London and Totnes, or find out about online consultations.

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The Dangers of Over Exercising

The Colours That Heal You – Eating The Rainbow

Related TED talk:

How to Make Stress Your Friend – Kelly McGonigal