In toxicology, 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. A pollutant or toxin showing hormesis thus has the opposite effect in small doses than in large doses.

As an example, challenging mice with small doses of gamma ray radiation shortly before irriadating them with very high levels of gamma rays actually decreases the likelihood of cancer. There is a similar effect when dioxin is given to rats. The hormesis model has been shown to hold for several other substances.

Contents

1 Possible explanation 2 Policy consequences 3 Low doses beneficial? 4 Medical uses 5 Slow acceptance

Possible explanation

The reason for the hormesis phenomenon is not completely understood. It is conjectured that a low dose challenge with a toxin may jump start certain repair mechanisms in the body, and these mechanisms are efficient enough that they not only neutralize the toxin's effect, but even repair other defects not caused by the toxin. This is similar in principle to viral vector vaccines under development for diseases such as cancer and AIDS.

Policy consequences

Traditionally, regulatory agencies such as the EPA, the FDA, and the NRC use a threshold model for non-carcinogens and a linear no-threshold model for carcinogens (including radioactive substances). In the threshold model, anything above a certain dose is considered dangerous, and anything below it safe. In the linear model, there is no safe dosage. Changing to a hormesis model for some of these toxins would likely change exposure standards for these toxins in air, water, food and soil. As a result, costs of environmental regulations and cleanup/remediation activities could be lowered.

Wider use of the hormesis model would affect how scientists design and conduct studies and the selection of statistical models that estimate risk.

The study of hormesis has been best developed, perhaps, in the field of ionizing radiation.

The United States based National Council on Radiation Protection and Measurements (NCRP), a body commissioned by U.S. Congress, recently released report written by the national experts in the field which states that, for the sake of caution, radiation's effects should be considered to be proportional to the dose an individual receives, regardless of how small that dose is. However, it is not possible to prove or disprove this conclusion. The number of people required for such a study would have to include the entire population of the Earth.

In the absence of conclusive data, and with significant amounts of money at stake as well as a number of people's livelihoods, the controversy is very active.

Low doses beneficial?

While the most prominent cases of hormesis show low doses of toxins showing beneficial effects, this is not part of the definition of hormesis. The key is that low doses show the opposite effect of high doses. There are substances where low doses show detrimental effects not seen in high doses.

Medical uses

The concept of hormesis is now being used to:

• enhance cognitive function in patients with neurodegradative diseases such as Alzheimer's disease.

• boost immune function to prevent diseases in people and in commercial fisheries.

• avoid harmful tumor-promoting effects of anti-cancer drugs.

Slow acceptance

The acceptance of the hormesis model of dosage response has been slow. Reasons may include:

• Unproveable in an ethical study of humans.

• Counterintuitive result.

• 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 homeopathy.

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An early version of this article was based on the 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]