Hormesis

Hormesis is a dose response phenomenon characterized by a low dose stimulation, high dose inhibition, resulting in either a J-shaped or an inverted U-shaped dose response.

It directly challenges the long held beliefs by the field of toxicology and the risk assessment practices of regulatory agencies such as EPA and FDA that use the threshold model (for non-carcinogens) and the linear model (for carcinogens).

Table of contents

1 How hormesis changes everything
2 Does hormesis conclude that low doses of toxins are beneficial?
3 Could low doses of toxins be beneficial?
4 How strong is the evidence to support hormesis
5 How does hormesis compare with other models
6 Why has it been ignored
7 Does hormesis impact the field of medicine?

How hormesis changes everything

How government agencies assess risk would profoundly change, especially for carcinogens. Exposure standards for toxins in air, water, food and soil would likely markedly change.
It would greatly affect the costs of environmental regulations and cleanup/remediation activities.
It would affect how scientists design and conduct studies and the selection of statistical models that estimate risk.
It would change how society perceives environmental hazards.

Does hormesis conclude that low doses of toxins are beneficial?

No. Hormesis is a dose-response phenomenon and does not include within its definition the determination of whether the low dose stimulation is beneficial or harmful.

Could low doses of toxins be beneficial?

It depends on the definition of beneficial. In many experimental studies low doses of toxins acting in an hormetic dose response fashion have increased lifespan, reduced diseases such as heart disease and cancer and increased cognitive function. At the level of the individual these responses would most likely be considered beneficial.

However, low dose stimulation by some agents have increased various organ sizes such as the prostate which could be an unwelcomed or harmful response. Thus, the low dose stimulatory effects could be beneficial or harmful and must be judged on a case-by-case basis.

How strong is the evidence to support hormesis

The evidence in the peer-reviewed toxicological and biomedical literature is overwhelming and convincing. The results of thousands of experiments have reliably demonstrated hormesis. Not only is the evidence convincing but it also occurs for essentially all biological models, endpoints and chemical classes.

How does hormesis compare with other models

In head-to-head published comparison the hormetic model was far more common in the toxicological literature than the threshold model which has long been believed to be the most likely model. Thus, it can be argued that the most fundamental dose-response model is neither threshold or linearity but rather the hormetic model.

Why has it been ignored

Many reasons:

Toxicology experiments have typically used very few doses and emphasized high doses, thus missing the hormetic phenomenon.
Hormesis was associated with the medical practice of homeopathy in its early years and was a victim of the long battle between traditional medicine and hormesis.
Hormesis is hard to assess. To prove the occurrence of hormesis one needs more doses, more subjects, and more time points to measure than the typical toxicology experiment; it is also harder to discern because the response is modest and could easily be thought of as variability and not a real biological effect.

Does hormesis impact the field of medicine?

It already has. For example, the concept of hormesis is now being used to enhance cognitive function in patients with neurodegradative diseases such as AD, in boosting immune function to prevent diseases in people and in commercial fisheries, and in avoiding harmful tumor-promoting effects of anti-cancer drugs.

This is a slightly edited and wikified copy of a press handout: "Hormesis: Principal Concepts and Take Home Message", by Edward J. Calabrese, Ph.D., University of Massachusetts, from a hormesis panel discussion, Feb 25, 2004, Washington, DC [1]