Hormesis
This article needs to be updated. The reason given is: seems relatively widely accepted concept now.(December 2023) |
Hormesis is a two-phased
In toxicology, hormesis is a dose-response phenomenon to xenobiotics or other stressors. In
In the context of toxicology, the hormesis model of dose response is vigorously debated.[5] The biochemical mechanisms by which hormesis works (particularly in applied cases pertaining to behavior and toxins) remain under early laboratory research and are not well understood.[1]
Etymology
The term "hormesis" derives from Greek hórmēsis for "rapid motion, eagerness", itself from ancient Greek hormáein to excite.[2] The same Greek root provides the word hormone. The term "hormetics" is used in the study of hormesis.[1] The word hormesis was first reported in English in 1943.[2]
History
A form of hormesis famous in antiquity was
German
In 2004, Edward Calabrese evaluated the concept of hormesis.[6][7] Over 600 substances show a U-shaped dose–response relationship; Calabrese and Baldwin wrote: "One percent (195 out of 20,285) of the published articles contained 668 dose-response relationships that met the entry criteria [of a U-shaped response indicative of hormesis]"[8]
Examples
Carbon monoxide
Carbon monoxide is produced in small quantities across phylogenetic kingdoms, where it has essential roles as a neurotransmitter (subcategorized as a gasotransmitter). The majority of endogenous carbon monoxide is produced by heme oxygenase; the loss of heme oxygenase and subsequent loss of carbon monoxide signaling has catastrophic implications for an organism.[9] In addition to physiological roles, small amounts of carbon monoxide can be inhaled or administered in the form of carbon monoxide-releasing molecules as a therapeutic agent.[10]
Regarding the hormetic curve graph:
- Deficiency zone: an absence of carbon monoxide signaling has toxic implications
- Hormetic zone / region of homeostasis: small amount of carbon monoxide has a positive effect:
- essential as a neurotransmitter
- beneficial as a pharmaceutical
- Toxicity zone: excessive exposure results in carbon monoxide poisoning[11]
Oxygen
Many organisms maintain a hormesis relationship with oxygen, which follows a hormetic curve similar to carbon monoxide:
- Deficiency zone: hypoxia / asphyxia
- Hormetic zone / region of homeostasis
- Toxicity zone: oxidative stress[3]
Physical exercise
Physical exercise intensity may exhibit a hormetic curve. Individuals with low levels of physical activity are at risk for some diseases; however, individuals engaged in moderate, regular exercise may experience less disease risk.[12]
Mitohormesis
The possible effect of small amounts of oxidative stress is under laboratory research.
Whether this concept applies to humans remains to be shown, although a 2007
Alcohol
Alcohol is believed to be hormetic in preventing heart disease and stroke,[17] although the benefits of light drinking may have been exaggerated.[18][19] The gut microbiome of a typical healthy individual naturally ferments small amounts of ethanol, and in rare cases dysbiosis leads to auto-brewery syndrome, therefore whether benefits of alcohol are derived from the behavior of consuming alcoholic drinks or as a homeostasis factor in normal physiology via metabolites from commensal microbiota remains unclear.[20][21]
In 2012, researchers at UCLA found that tiny amounts (1 mM, or 0.005%) of ethanol doubled the lifespan of Caenorhabditis elegans, a roundworm frequently used in biological studies, that were starved of other nutrients. Higher doses of 0.4% provided no longevity benefit.[22] However, worms exposed to 0.005% did not develop normally (their development was arrested). The authors argue that the worms were using ethanol as an alternative energy source in the absence of other nutrition, or had initiated a stress response. They did not test the effect of ethanol on worms fed a normal diet.
Methylmercury
In 2010, a paper in the journal Environmental Toxicology & Chemistry showed that low doses of
Radiation
Ionizing radiation
Hormesis has been observed in a number of cases in humans and animals exposed to chronic low doses of ionizing radiation. A-bomb survivors who received high doses exhibited shortened lifespan and increased cancer mortality, but those who received low doses had lower cancer mortality than the Japanese average.[24]
In Taiwan, recycled
Chemical and ionizing radiation combined
No experiment can be performed in perfect isolation. Thick lead shielding around a chemical dose experiment to rule out the effects of ionizing radiation is built and rigorously controlled for in the laboratory, and certainly not the field. Likewise the same applies for ionizing radiation studies. Ionizing radiation is released when an unstable particle releases radiation, creating two new substances and energy in the form of an
The resulting confusion in the low-dose exposure field (radiation and chemical) arise from lack of consideration of this concept as described by Mothersill and Seymory.[27]
Nucleotide excision repair
Veterans of the
Applications
Effects in aging
One of the areas where the concept of hormesis has been explored extensively with respect to its applicability is aging.
Controversy
Hormesis suggests dangerous substances have benefits. Concerns exist that the concept has been leveraged by lobbyists to weaken environmental regulations of some well-known toxic substances in the US.[34]
Radiation controversy
The hypothesis of hormesis has generated the most controversy when applied to ionizing radiation. This hypothesis is called radiation hormesis. For policy-making purposes, the commonly accepted model of dose response in radiobiology is the linear no-threshold model (LNT), which assumes a strictly linear dependence between the risk of radiation-induced adverse health effects and radiation dose, implying that there is no safe dose of radiation for humans.
Nonetheless, many countries including the Czech Republic, Germany, Austria, Poland, and the United States have radon therapy centers whose whole primary operating principle is the assumption of radiation hormesis, or beneficial impact of small doses of radiation on human health. Countries such as Germany and Austria at the same time have imposed very strict antinuclear regulations, which have been described as radiophobic inconsistency.
The
A United States-based National Council on Radiation Protection and Measurements stated in 2001 that evidence for radiation hormesis is insufficient and radiation protection authorities should continue to apply the LNT model for purposes of risk estimation.[36]
A 2005 report commissioned by the French National Academy concluded that evidence for hormesis occurring at low doses is sufficient and LNT should be reconsidered as the methodology used to estimate risks from low-level sources of radiation, such as
Policy consequences
Hormesis remains largely unknown to the public, requiring a policy change for a possible toxin to consider exposure risk of small doses.[38]
See also
- Calorie restriction
- Michael Ristow
- Petkau effect
- Radiation hormesis
- Stochastic resonance
- Mithridatism
- Antifragility
- Xenohormesis
References
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- ^ Poumadere, M. (2003). Hormesis: public health policy, organizational safety and risk communication. Human & experimental toxicology, 22(1), 39-41