What is “Hormesis”?

hormesisJust about every textbook of toxicology pays homage to Paracelsus, the sixteenth century alchemist. Why? Because he introduced the idea that “only the dose makes the poison.” It makes no sense to talk about the toxicity of a substance, Paracelsus said, without talking about the extent of exposure. A high dose can be lethal, but minute amounts of the same substance may be perfectly safe. This really is the approach authorities take today to determine the toxicity of substances to which we are likely to be exposed. Animals are given increasing doses until they show some adverse effect and the maximum dose per kilogram of body weight at which no effect is seen is determined. This dose is then divided by an additional safety factor of a hundred to come up with a safe dose for humans. Toxicity data for things like food additives, pesticides and caffeine are arrived at in this fashion. Substances that cause cancer in test animals are more controversial with many experts believing that the only safe level of exposure is zero exposure.

Would you believe that these ideas about toxicity may have to be modified? The scientific community is excited about a relatively new area of research known as “hormesis.” The term, appropriately enough, comes from the Greek word meaning “to excite.” According to the proponents of the theory of hormesis, tiny doses of toxins in the body act in a completely different fashion from large doses and may even be beneficial! They “excite” the body’s immune system and repair mechanisms allowing for a better response to chemical insults. Hormesis was first noted with respect to radiation. While it was clear that radiation could cause cancer, researchers also learned that extremely low doses could stimulate DNA repair and delay cancer in mice. There is even some human epidemiological data suggesting that people exposed to low dose radiation have a reduced risk of developing cancer .

Although, at first the idea that small doses of toxins may be good for us sounds bizarre, there is actually evidence for it. Exercise, for example, certainly puts stress on our cells. The increase in metabolism generates free radicals which can be very damaging. But we know that the body adapts and eventually develops a more efficient defense system. And so it may be with some chemical exposure as well. Believe it or not, dioxins, perhaps the most notorious toxins of them all, have been shown in animal experiments to have possible advantageous effects at low doses. Animals fed low doses of dioxins actually developed fewer liver tumors than those that had no exposure at all. Of course that doesn’t mean that we should be thinking about taking low-dose dioxin pills because cancer is not the only issue with dioxins. The tiny amounts that have an anti-cancer effect may still lead to developmental and reproductive effects.

If it turns out that there really is something to the theory of hormesis, we may have to reevaluate how we evaluate toxicity. It may turn out that at least for some substances which are dangerous at high doses, total elimination is not the most desirable route to take. Who knows? One day we may be popping low-dose arsenic tablets to ward off disease! Stranger things have happened. After all, don’t researchers now suggest that a yeast metabolite which is obviously toxic at high doses actually may make us live longer when consumed in small amounts? That yeast metabolite of course is alcohol.

 Joe Schwarcz

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