Hormesis beneficial effects

For some toxins it is possible to demonstrate an apparent improvement in functional response at levels of exposure which are below a threshold. This effect, which has been termed hormesis , is most effectively demonstrated in the consistently improved longevity of animals whose caloric intake is restricted rather than allowing them to feed ad lib (Tannenbaum, 1942). Clearly in this instance, the observed effects are the result of exposure to a complex mixture of chemicals whose metabolism determines the total amount of energy available to the organism. But it is also possible to show similar effects when single chemicals such as alcohol (Maclure, 1993), or caffeic acid (Lutz et al., 1997) are administered, as well as for more toxic chemicals such as arsenic (Pisciotto and Graziano, 1980) or even tetrachloro-p-dibenzodioxin (TCDD) ( Huff et al., 1994) when administered at very low doses. It is possible that there are toxins that effect a modest, reversible disruption in homeostasis which results in an over-compensation, and that this is the mechanism of the beneficial effect observed. These effects would not be observed in the animal bioassays since to show them it would be necessary to have at least three dose groups below the NOAEL. In addition, the strain of animal used would have to have a very low incidence of disease to show any effect. 

Hormesis the concept that at low doses of a toxicant there may be positive, beneficial effects, whereas at higher doses there will be toxic effects. 

Hormesis is the phenomenon whereby low doses of chemicals have positive, beneficial effects whereas higher doses are harmful. 

A theory that has been gaining acceptance recently is that many chemicals have beneficial effects at very low doses and may perhaps stimulate protective mechanisms, and that as the dose increases the effects become adverse. This is known as hormesis and may occur as a result of more than one exposure to a chemical (see box). ... 

The legal implications emerging from the concept of hormesis remain to be more fully explored. However, the concept of hormesis has begun to be addressed by legal scholars (74). Of particular interest has been an exploration of the potential means to incorporate the concept of pollutant-induced beneficial effects in the risk assessment and cost-benefit process. Within this general framework, the District Court forced the EPA to recognize the beneficial effects of ozone pollution on the risk of UV-induced skin cancer in its overall assessment of the health effects of ozone (75, 76). 

Among the low dose radiation-induced cellular alterations, special interest has been focused recently toward the hormesis and adaptive responses. Although these phenomena, that is, inducing stimulatory or beneficial effects are more and more targets for research, no direct evidence is available for their possible impact on human radiation protection. 

In the human diet carrots are the major dietary source of falcarinol, although it may also be supplied by many other plant food sources (Table 5.1). A recent in vitro study aiming to screen for potentially health promoting compounds from vegetables showed that falcarinol, but not -carotene, could stimulate differentiation of primary mammalian cells in concentrations between 0.004 and 0.4 p,M falcarinol. Toxic effects were found above >4p,M falcarinol (Figure 5.14), while f)-carotene had no effect even at 400 xM (Hansen et al 2003). This biphasic effect (hormesis) of falcarinol on cell proliferation is fiiUy in accordance with the hypothesis that most toxic compounds have beneficial effects... 

Except for the example of falcarinol, no systematic attempts have been made to determine the net impact of these compounds on health. Until now, almost all experiments have been one-sided designs where either toxic or beneficial effects could be assessed but not both. Another problem has been that the dose-response dependencies have often been assumed to be linear, so the range of concentrations used in the studies did not cover levels corresponding to the actual normal intake from food, since the possibility of hormesis has only recently received significant attention. A third issue, which is generally... 

Hormesis is the term used for the phenomenon of stimulatory effects at low-level exposure, and inhibition at high-level exposure. The term derives from the Greek word Hormo which means excite or set in motion, and which is also the root of the word hormone. The concept of hormesis dates back to the 1920s. A substance showing hormesis has the opposite effect in small doses compared to effects at large doses. The definition of hormesis does not imply that low-dose effects are necessarily beneficial, only that they are opposite to high-dose effects. 

Figure 1 Idealized dose-response curves for the (a) hormesis, (b) linear, and (c) threshold hypotheses. A positive toxic effect is regarded as detrimental, whereas a negative toxic effect is beneficial (hormetic).

Adverse health effects would simply be responses opposite to those established as beneficial. However, there would be a number of responses that would be difficult to resolve and classify as beneficial or adverse without more detailed assessment. Such responses could include, but not necessarily be limited to, increased organ weight, increased body weight gain, increased fecundity, and increased immune responsiveness [see (60) for a more detailed discussion of these endpoints in relation to hormesis]. 

Hormesis is a dose-response phenomenon characterized by low-dose stimulation and high-dose inhibition. The determination of whether the hormetic stimulation is beneficial or not should be decoupled from a decision as to whether the response is hormetic or not. Hormetic effects themselves can be beneficial, neutral, or harmful depending on the specific circumstances. For example, a low-level exposure to an antibiotic may stimulate the growth of harmful bacteria that could be harmful to human patients yet theoretically... 

Many researchers claim that there are several argummts for the assumption that responses from high-level and high-LET radiation may not be directly extrrqmlated to low-dose low-LET radiation. Many are of the opinion that the natural radiation background is harmless, and some even claim that it is beneficial (radiation hormesis). Thus, looking for effects at low doses can be a vain study. Walinder has pointed out that it is impossible to arrive to a reliable dose-effect relation at doses <50 mSv by epidemiological studies. 

The second hypothesis states that there is a threshold below which no harm accrues, and, further, that lower doses may even be beneficial. When a toxin at high levels is beneficial at low levels, it is called hormesis. Substances exhibiting hormesis are, for example, vitamin D, selenium, aspirin, table salt, water, and, for plants, fertilizer. There may even be a hormesis effect for low-level radiation because this might provide the stimulus for the heighteued activity of DNA repair mechanisms (Karam, 2003). 

The above examples are just a few of the many studies that have shown that radiation health effects demonstrate a hormetic effect, a characteristic of most pharmaceuticals and even to many foods. Hormesis is the concept that large doses of a substance may be detrimental to health, but small doses are beneficial. The evidence for this knowledge was effectively presented in a text published in 1980, titled Radiation Hormesis, by Dr. T.D. Luckey, and in 1991 followed by the second edition [7]. This text included over 1000 references of data on radiation hormesis. 

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