Thursday, January 14, 2016

Hormesis - A Little Deeper

The primary tenet of hormesis is contained in a cardinal rule of pharmacology: The poison is in the dose. [Often stated as the dose makes the poison.]

Figure 1 gives a graphical representation of this postulate. Point A on the curve represents a "normal" amount of something - let's use, for example, Vitamin A - which results in what we might call "normal healthfulness." Less than this dose (the dashed line) will move us up into the unhealthy zone, making us prone to deficiency diseases such as night blindness. As we take more of the supplement, there is - assuming the vitamin companies aren't lying to us - an increase of health benefit ... until we reach point B.

At this inflection point, a dramatic change occurs: Up to this point, the more of the vitamin, the healthier; but from here on, the more we take, the less healthy, since we have passed the optimum dose. If we continue to take more, we reach a point at which the dose provides us the same level of health we would have had if we had not taken any additional Vitamin A: the Zero Equivalent Point (ZEP). From here on out, thought, the news gets worse: More makes us sick; still more kills us.

Hold on now. If we shift our definitions just a little bit, we can call poisons such as selenium "necessities" - since they are necessary for optimum health - and necessities such as salt "poisons." It is merely a matter of degree, is it not? Salt fits the same curve as Vitamin A and arsenic. Too little salt, unhealthiness (or possible death); too much salt, unhealthiness (and certain death). It's as if: The dose make the poison! Or maybe:

All things are poison; nothing is poison.

This illustrates one of the problems with explaining - and understanding - hormesis: It is counter-intuitive. We naturally tend to think in terms of less-poison-good, more-poison bad. Just-a-tiny-bit-of-poison-good, doesn't figure in.

Adding a bit to our confusion is the shape of the hormesis curve. Our "vitamin example" is oriented with "unhealthiness" in the upward, or positive, direction. This is done for compatibility with the convention for carcinogen-response curves. As we shall see, many other plots have the beneficial effect in the "up" direction.