| Chemical Hormesis |
In a series of articles,
BELLE Newsletter Vol. 6, No. 2, Vol 6, No. 3, and Vol. 7, No. 1, published by the Northeast Regional Environmental Public Health Center, School of Public Health, University of Massachusetts, Amherst, MA 01003, explores the phenomenon of chemical hormesis in biological systems. This phenomenon parallels radiation hormesis, which has been discussed many times in Access to Energy, especially with respect to the work of Bernard Cohen. Cohen has shown that low-level radiation from radon actually decreases the death rate from lung cancer by a very significant amount.
Figure 1 summarizes chemical hormesis in a variety of toxicological systems. The general finding is that toxins often have a positive effect on the health of organisms at low doses. This has serious implications for Environmental Protection Agency regulations based on linear extrapolations to zero dose - that condemn even the slightest trace of a toxin in the environment. In many (possibly most) cases, the EPA actually damages overall human health by these regulations.
As shown in Figure 1, the beneficial effect of a chemical toxin usually rises to about 150% of control and extends over a ten-fold dose before falling to the NOAEL (No Observed Adverse Effect Level).
A famous case in point is that of Linus Pauling (an outstanding chemist) who, after adopting in 1968 the recommendations of health food advocates that he take Vitamin C and parlaying this interest into some valuable theoretical work on nutrition, ended his days (which were extended to the age of 92 - probably, in part, by hormesis) in partial personal and professional disgrace and disrepute.
Ironically, Pauling rose to public prominence during the Teller-Pauling debates and the controversy over atomic testing in the atmosphere. Using a linear extrapolation to zero of the harmful effects of radiation, Pauling demonized Teller (who was working to build America's nuclear deterrent to Communism) as a murderer - on the basis that the tiny increases in low-level background radiation from nuclear weapons tests were killing people - especially "the children.'' We now know that, due to radiation hormesis, Teller's weapons tests were probably extending human life spans rather than shortening them.
Even then, however, Pauling was practicing life-extension by chemical hormesis. He consumed one to two alcoholic drinks per day on the basis of studies showing that this practice extends lifespan. The NOAEL for alcohol seems to be at about one ounce of ethanol per day - but one must always remember individual biological variation.
When Pauling became interested in Vitamin C, he adopted the health food industry view that Vitamin C supplements strengthen the immune system. He refused, however, to accept hormesis. For example, he convinced George Fegan, a famous Stanford pathologist and immunologist, to undertake a study of immune system stimulation in rabbits by Vitamin C. Fegan did observe an increase in immune system activity. He concluded, however, that this effect was the result of oxidative destruction of biological macromolecules by Vitamin C and the resulting stimulation of the immune system by biochemical breakdown products - chemical hormesis by a substance with (at higher doses) a toxic effect. Unwilling to accept the idea that Vitamin C was a toxin, Pauling rejected Fegan's conclusion. Pauling was so upset by the data showing that Vitamin C oxidation products attacked macromolecules (proteins and DNA) that he deliberately destroyed the career of a young graduate student whose thesis work had demonstrated this and had examined the reactions carefully.
Later, when my coworkers and I (See "Suppression of Squamous Cell Carcinoma in Hairless Mice by Dietary Nutrient Variation,''
Mechanism of Ageing and Development 76, pp 201-214 (1994)) showed that the growth rate of cancer in mice was increased by moderate doses of Vitamin C and then decreased at higher, toxic dose levels, Pauling became so angry that (even though we had worked together for 15 years and I was then President and Research Director of the Pauling Institute) he ultimately spent over one million dollars of the cancer research funds of that Institute to hire lawyers instructed to carry out his response to my experiments on Vitamin C and cancer -"I will see that you never work in science again.'' (He and they lost.)In general, better nutrition probably decreases the incidence of cancer by strengthening immune response, but - after cancer has established itself - better nutrition increases cancer growth rate by providing a richer mixture of essential nutrients.
Vitamin C is a toxin at high doses - to cancer cells and to normal cells. At lower doses, however, it apparently has a hormetic effect -suppressing cancer incidence, but stimulating its growth rate after cancer becomes a part of the organism. Humans eat about one kilogram of food per day, so the doses in Figure 2 roughly correspond to daily human intakes of 3 to 192 grams per day. The lethal dose of Vitamin C for mice is a little over 200 grams per kilogram of food.
Notice the close similarity of Figure 2, which displays the growth rate of squamous cell carcinoma in mice during our experiments, and Figure 1, which summarizes the general hormetic effect of toxic chemicals on the health of biological systems. Both qualitatively and quantitatively, this Vitamin C experiment fits the hormesis hypothesis.
Pauling drank one or two drinks of hard liquor (usually gin) per day, did not smoke, and increased his Vitamin C intake from 3 grams per day at the age of 67 to 18 grams per day at the age of 92. By ignoring the possibility of radiation hormesis and falsely demonizing Teller, he managed to obtain a Nobel Prize for Peace. By practicing chemical hormesis, however, (whether he recognized it or not) he increased his chances of living in good health for many years.
Edward Teller told me ten years ago that he was taking Vitamin C, so that there would be one thing that Linus and he agreed about.