My Take on Hormesis, it’s good or bad, depending on the dose!


Today, I want to chat briefly about the concept of Hormesis.

Hormesis is a biological phenomenon likely best known from Toxicology in which a beneficial effect results from a low dose exposure to an agent (or a practice) that can become otherwise toxic or lethal when given at higher doses.  You will often see Hormesis denoted by a U or J shaped curve (often inverted).  Here is a nice image that I think illustrates Hormesis well.  You can clearly see that there is a range of dosing that produces beneficial (healthy) results, and then either too little or too much produces negative outcomes.  This, in a nutshell is Hormesis.

To clarify, let’s examine a couple examples.

1) Exercise.  It is widely known that exercise can have a plethora of benefits to human health & longevity, including altering gene expression over the long run to make humans more efficient at partition energy for expenditure and hence improving overall health.  However the dosing is key, and everyone’s tolerances and genetic propensities are different.  Take running and cardiovascular disease prevention.  This has been a long-standing recommendation, and often dosing specific recommendations are avoided in Medicine, because “not enough is known”.  If we explore the literature on this topic we see that mild endurance activity seems to be protective against cardiovascular disease, but higher doses of endurance training actually increase risk for cardiovascular disease.  A working theory of the benefits obtained from exercise is that exercise stresses our system through oxidative stress and our body has to mount a response to this.  As long as we can respond adequately, we gain benefit from exercise.  If the stress load is too great to mount a response (i.e. too high exercise volume) then it ceases to be beneficial and become toxic.

2) Antioxidants.  We see another example of hormesis from studies showing that high dose antioxidant supplementation (i.e. >1 g Vit C/day) while exercising actually blunts the beneficial gains from that exercise by blocking adaptation to the exercise conditions.  This is another example of hormesis, because lower antioxidant supplementation helps to speed recovery and even contribute additive health benefits to the exercise, however, when the dose is too great, then the adaptation goes away and it becomes toxic.  Additionally, high level supplementation with many antioxidants has been shown to be pro-oxdiative, again because our bodies respond to mild oxdiative stressors within compounds we call antioxidants by producing increased levels of antioxidants.  If the load of the stress is too great then we can’t respond adequately and the result is increased oxdiative stress and negative health consequences.

3) Ketosis.  This is one of my favorite examples and I was first made aware of it from the Robb Wolf Paleo solution podcast in which he and Greg Everett interviewed Dr. Kurt Harris.  Be sure to check out their blogs and podcasts for a ton more info on cutting edge nutrition research! The concept of the benefits of ketosis has been bounced around for some time, especially revolving around fat loss.  Certainly, most conventional health circles avoid it or chastise it due to confusion with the potentially life-threatening ketoacidosis that can occur in diabetes.  However, in and of itself ketosis can be extremely beneficial in that it facilitates adaptation by the human body to a fuel source other than glucose, specifically ketone bodies produced by breakdown of fatty acids.  There’s more to this and perhaps I will discuss more details in a later post, but I think this is adequate to briefly introduce the concept of Ketosis for the purposes of this discussion.  Anyway, this is also an example of hormesis, as there is literature supporting ketosis for fat loss, stimulating autophagy, starvation of tumors in cancer and reversal of the symptoms of the metabolic syndrome (insulin resistance, low HDL, elevated triglycerides, central adiposity and high blood pressure).  As a Dietitian, I’ve counseled many people who were staying in ketosis for various reasons and what was interesting, was that once people corrected a metabolic derangement or achieved a fat loss goal, if they persisted with ketosis year round, with no increase in (good quality) carbohydrate intake above 50 g per day, then they started to face some issues counter productive to health, performance and longevity.  Most often, this would arise in individuals who perform a glycolytically demanding activity (i.e. crossfit or high intensity training or other sport) in which the lack of carbohydrates causes them to crash during their activity due to failure to replenish muscle stores of glycogen for the next bout.

Please feel free to comment with your questions or any topics you would like to see in future posts.

Great blogs that define Hormesis. 
Figure represented from: