Schofield’s hormetic theory of wellbeing


My first whiteboard attempt at my hormetic theory of wellbeing

I had a few things click into place in the last week or two, around how to conceptualize and manage our well-being, especially considering all the biology involved.

Without being grandiose and egotistically naming a theory after myself, I think what I have come up with has some novel concepts. I do acknowledge the inspiration from a scientific paper, which lays out the (some) diet and exercise components of the hormesis of wellbeing (see here).

So here’s a summary of the theory (or at least the bringing together of a few different ideas):

  1. Hormesis is the adaptation to a stimulus which in a bigger dose is toxic. This stress exposure is central to, and even essential for, wellbeing.
  2. Hormetic stressors come form all sorts of things; including sun exposure and our food environments (eg, fasting).
  3. Wellbeing depends on a constant ability to have neuroplasticity (rewiring of the brain). Certain biological conditions must be present for  this to occur.
  4. These conditions include high levels of BDNF (brain derived neurotropic growth factor), low insulin, increased IGF-1, and low reactive oxygen specs (ROS).
  5. Hormesis drives these conditions in a similar way across a range of different stressors – too much or too little does exactly the opposite, more or less.

It’s a cool theory I think because it offers some simplicity and parsimony when thinking about the biology of wellbeing and what drives it.

So that’s it in a nutshell and here’s a bit more detail:

What is hormesis?

Hormesis is a theoretical phenomenon of dose-response relationships in which something (as a heavy metal or ionizing radiation) that produces harmful biological effects at moderate to high doses may produce beneficial effects at low doses.

In other words, it’s the theory of general adaptation and super compensation applied across a range of stimuli. Obviously the amount of the stimulus any biological organism can take depends upon its current state (genes plus recent exposures), but also the other stimuli that organism is experiencing. The stress from the different stimuli is likely to stress that same system concurrently (important for later).

Humans need to be exposed to hormetic stimuli to maintain biological function.  With no stress, the system adapts backwards as well. If you lie in bed for weeks, or travel into space with zero gravity, your body adapts just as fast as to no stress.

Bottom line: Hormesis is adaptation to mild stress.  Stress is not just good but essential to human health and wellbeing.

Can we define wellbeing biologically?

Here’s the next important step.  The human nervous system is a complex distributed neural network. It isn’t confined to the head – its throughout your body.  Mind-brain-body=same thing.  There are around 100 billion neurons in every human. Each can synapse to up to 7000 other neurons.  Because the hardware and the software are the same thing, you must constantly rewire the system to learn anything, to experience anything and remember it, to solve problems, to experience a worthwhile life. This happens at all ages.

We call this neuroplasticity.

How does this rewiring happen? We need to produce some key biological conditions.  This is centered around production of Brain-derived Neurotropic Growth Factor (BDNF). BDNF is the protein which stimulates this rewiring.

I’m arguing that the conditions which support BDNF production are central to wellbeing.

You guessed it. Hormesis drives BNDF production.

How hormesis drives wellbeing

In the figure below, I have tried to simplify the basic logic behind a hormetic response driving neuroplasticity. What is involved (simply) to optimize the biology of rewiring is low insulin, higher insulin-like growth factor 1 (IGF-1), and absence of reactive oxygen species (ROS).

What is interesting is that a range of hormetic stimuli, sometimes through different mechanisms, achieve the same biochemistry The opposite is true when we expose ourselves to too much of the same stimulus.  Once the stress response is maladaptive rather than hormetic, we produce insulin resistance, inflammation through ROS, and (sometimes) adverse levels of IGF-1 (see Figure below).

These ROS, insulin and IGF-1 do not always perfectly covary AND importantly they are also essential for humans one way or another for living.  We need insulin, we need ROS, we need flexibility in IGF-1 production. It’s just that the systeM needs to have metabolic flexibility to respond and rebuild (especially the nervous system).

Bottom line: Neuroplasticity is essential for human wellbeing and the supporting biology may be the center of the mechanism for feeling good. There is no evidence that hormesis drives this biology.


Specific hormesis

So I’ve tried to put together a start to the broader framework of understanding how various exposures to environmental stressors are highly beneficial to us in hormetic (adaptable) doses and directly drive the BDNF and neuroplasticity mechanism and therefore well-being.

These are known mechanisms in the basic research.

Exercise is a great example of hormesis in action.  This paper ” Impact of exercise on neuroplasticity-related proteins in spinal cord injured humans” showed a five-fold increase in BDNF in athletes after a 10 minute easy stint, but a decrease in BDNF after a marathon (42 km) event.

So exercise which we can easily accommodate and then adapt to drives the physiology of neuroplasticity and wellbeing. This is the hormetic response.  The stimulus (exercise) eventually becomes toxic at high and more intense doses.

So my theory is that there is a straight biological and hormetic connection to wellbeing through neuroplasticity for several (and there are likely more than I have identified here) important health and lifestyle behaviors.

I’ll get to the indirect effect later in this piece.

Some factors, like psychological stress, simply drive adrenal axis responses which would be appropriate for an acute “fight or flight” short lifesaving sprint, but are entirely inappropriate and toxic applied chronically. Chronic psychological stress is known to drive reduced insulin sensitivity and increased ROS.

Others, like exercise, offers a balance. You need the stress, but too much is toxic.  Sunlight exposure is like this.  Some exposure drives Vitamin D production.  There is good evidence to show the antioxidant (ROS defeating) effects of Vitamin D, as well as the vascular effects and increased insulin sensitivity through nitrate availability, but if you go and get sunburned then you will see the opposite effect.

Food is a really interesting stimulus. I think what we want is both the hormetic effect of the occasional fast, which is known to promote a catabolic (repair) effect and reduce ROS, IGF-1 increases, and low insulin. Obviously fasting for too long might have the opposite effect through probably high cortisol production. Equally, we need the anabolic effect of eating and the nutrients supplied by food. Too much food, especially junk processed carbs, bangs up insulin and ROS. So I think the intermittent fasting people are onto something when they cycle in and out of food availability.

Metabolic flexibility is an overriding theme here too.

By that I think that when you become metabolically dysfunctional and are constantly hyperinsulinemic and have high ROS, you really have the least effective system for neuroplasticity and cognitive rewiring.

Another factor is the health of your gut microbiome.  Again, when not in its usual human supporting and symbiotic form, this is inflammatory.  It helps create insulin resistance, ROS everywhere, and general metabolic dysfunction.

You’ll see below several ideas and mechanisms I propose. If you think of more then let me know.

Actually I just thought of another – brief ice baths.  Short exposure-reduced ROS and increased insulin sensitivity.  Too long=severe stress and probably increased ROS?

Hormesis 1.002 Hormesis 2.003

Indirect effects and wellbeing

Where positive psychology fits in here is something I have been thinking carefully about.  I, along with others, have been into that field for a while now and we talk about creating social networks, being nice to others, giving your time and resources to others, and many other things. Have a look at our Sovereign NZ wellbeing index for the full meal deal.

So indeed these are important, but because many create the resources you need to buffer stress and control the exposure to the potentially toxic stimuli. Having a social network for example means you will less easily be overwhelmed by stress and more in control of your life.

A more distant indirect effect is money.  Money by itself clearly has no direct effect on your BDNF, insulin, ROS and so forth. I’m pretty sure no one has done this study, but I predict that sitting and staring at a large pile of cash has very little effect on these!

But money gives you the resources.  The time and space to create the networks, to give to others, and to control the exposures to the life stresses you want and thrive on.

Bottom line: Hormetic stress is the biological basis of wellbeing.  We see good evidence across a range of environmental stressors how this all works. This brings the “Primal” type approach right into mainstream science where it belongs.  I know the primal/paleo guys have been saying this for years, but we do need to convincingly bring the biology and the practice together which is what I’m trying to do.


This is a theory of stress, but in a controlled and balanced way.

I am critical of much of the work in public health, quite a bit of which I have done myself.  We often try to understand how a single factor (e.g., exercise) is related to wellbeing. We assume a linear model where more is better and the dose applies across the population.

Clearly, in this hormetic, model that is just rubbish.  Everyone can take a different amount of a particular stress (say exercise).  What they can take and probably adapt to (hormesis) depends on:

  • Their genes
  • Their exposure to exercise in their lifetime, weighted more heavily recently
  • The sum of all the other stressors they are currently being exposed to – obviously there’s less chance of adapting to an exercise session if you are sunburned and had a poor night’s sleep and an argument with your wife.

So what this all means is that what you need to optimize your potential at anytime is highly dynamic and different for you now than it was yesterday.  And you almost certainly won’t resemble the same profile as others around you.

Last bottom line…

Moderation and stress that you can adapt to is crucial for well-being.


  1. Great article Grant – sums it all up rather nicely. I would like to add that some plant botanicals are also hormetic, containing small amounts of toxins that persuade an insect not to eat it, but cause just the right amount of metabolic stress in us, with upregulation of protective genes (just like exercise does) such as ppar-gamma (increases insulin sensitivity), catalayse and super-oxide dismatuse – the ‘special forces’ of our ROS defence mechanism.

    I also have an interesting paper showing that BDNF is greatly increased around lactate threshold – possibly an adaptive response to being chased by things that want to eat you! (don’t come back to this watering hole, and remember where it is!!!).

    In short, hormesis allows us to move beyond resilience – to stress adapted…

  2. Good analysis.

    How does pain (chronic or acute) fit
    into the picture?

    What are some time frames for hormesis?

    1. Good point, not sure about acute pain being hormesis – I guess it drives short term adaptation. Chronic pain is likely to be inflammatory and stressful, non adaptive. I’ll welcome any ideas

  3. Nice diagrams.
    Bill, self inflicted pain, exercise pain, these types of controlled and intended pain might be hormetic. Broken leg pain is just adaptive.
    Here’s a suggested mechanism for phytochemical hormesis;
    Imagine a toxin that damages cells in human ancestors – as onions and other allium sp. do, via Heinz body effect, in cats and dogs.
    An easy adaptation is to make cells stronger, or make more stem cells.
    Now imagine time passes with onions in diet. Humans now detoxify onions efficiently, but the original adaptation is still in effect, slowly fading perhaps.
    Allium now has hormetic benefits at minimal risk.

  4. John Ratey talks about this in his book Spark. 2 things spring to mind from this book. The theory of hormesis seemed apparent in exposure to low levels of radiation at a nuclear plant. I wonder how our current exposure to all the many types of electromagnetic radiation fits in to this.

    In relation to exercise and BDNF he also mentions how increasing complexity of movement can increase its production. Something that often gets missed in health and fitness programming.

    1. Yes agreed complex movements can be god. Radiation, perhaps but that might be a bit to get into public health!

      1. I agree about the radiation. I was thinking more about how much wi-fi, mobile phone masts etc etc maybe placing a mal-adaptive stress on us

    2. Great comment Mike. I have read an excellent journal article that reports that complex, but not simple, motor skill training creates neurogenesis in the cerebellum. Certain aspects of the fitness industry are (slowly) catching on to this, as well as the benefits of high-intensity intermittent training.

      1. Hi Paul – thanks. Scott Sonnon is one who pushes increasing complexity. Do you have a reference for the article you mention?

  5. Juggling makes me happy.

  6. Hi Grant, I enjoy reading your blog. As a nutritionist, it provides a different persepective from what you hear generally in the nutrition world and provides food for thought!
    Just a question, not related to this post. There’s a lot of research on the benefits of a Meditteranian type diet, what are your thoughts on this and what are they benefits of a LCHF diet like you follow over a Medditteranian type diet in terms of the research?

    Another question, thinking of some of the people I work with, would you still reccomend saturated fats over say something like olive oil, if they were still eating refined carbohydrates in their diet (doesn’t matter how much advice and guidance you give someone, sometimes they just won’t stop eating those refined carbs…).


    1. I think that a stricter LCHF approach is needed for sure when you become insulin resistant. You will need to restrict carbs when you have trouble getting the into your cells. Extra CHO load isn’t helpful and hyperinsulinemia which has directly damaging pathology. Other Mediterranean diets are fine for people and obviously people do better on this than the standard american diet, and probably just as well as the LCHF for the metabolically healthy.

      Also for athletes in ultra endurance my experience isn’t so much carb restriction, but at least a strict adaptation phase which is ketogenic to get the system optimized for fat burning.

      Others can take their pick. I don’t think there’s anything bad likely to happen from an LCHF and many people like the cognitive improvements. Others find it hard to maintain (I don’t and plenty of others don’t). In any case, eating whole foods is the best approach. If you are metabolically healthy that is likely to keep you healthy. If you aremetabolically dysfuncitonal through insulin resistance, then you should, in my opinion, restrict carbs.

      Last you asked about substituting saturated fat and olive oil and lighter oils when people remain eating refined carbs. INteresting idea, I just don’t advise people to eat refined carbs o matter what. Fat and refined carbs are a bad mix. As well, olive oil and animal fats typically are in very different foods. I am all for eating healthy animals and the fat that happens to come with them. That could be salmon with MUFAs, cows with saturated fats.

  7. interesting article, like the analogy of it.

  8. […] as I have written about previously, is about the application of stress and your adaptation to it. Too much stress is toxic. My opinion […]

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Richard David Feinman

Richard Feinman, the Other

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