Hormesis

Last updated
A low dose of a chemical agent may trigger from an organism the opposite response to a very high dose. Hormesis dose response graph.svg
A low dose of a chemical agent may trigger from an organism the opposite response to a very high dose.

Hormesis is a two-phased dose-response relationship to an environmental agent whereby low-dose amounts have a beneficial effect and high-dose amounts are either inhibitory to function or toxic. [1] [2] Within the hormetic zone, the biological response to low-dose amounts of some stressors is generally favorable. An example is the breathing of oxygen, which is required in low amounts (in air) via respiration in living animals, but can be toxic in high amounts, even in a managed clinical setting. [3]

Contents

In toxicology, hormesis is a dose-response phenomenon to xenobiotics or other stressors. In physiology and nutrition, hormesis has regions extending from low-dose deficiencies to homeostasis, and potential toxicity at high levels. [1] Physiological concentrations of an agent above or below homeostasis may adversely affect an organism, where the hormetic zone is a region of homeostasis of balanced nutrition. [4] In pharmacology, the hormetic zone is similar to the therapeutic window.

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 Mithridatism, the practice whereby Mithridates VI of Pontus supposedly made himself immune to a variety of toxins by regular exposure to small doses. Mithridate and theriac, polypharmaceutical electuaries claiming descent from his formula and initially including flesh from poisonous animals, were consumed for centuries by emperors, kings, and queens as protection against poison and ill health. In the Renaissance, the Swiss doctor Paracelsus said, "All things are poison, and nothing is without poison; the dosage alone makes it so a thing is not a poison."

German pharmacologist Hugo Schulz first described such a phenomenon in 1888 following his own observations that the growth of yeast could be stimulated by small doses of poisons. This was coupled with the work of German physician Rudolph Arndt, who studied animals given low doses of drugs, eventually giving rise to the Arndt–Schulz rule. [5] Arndt's advocacy of homeopathy contributed to the rule's diminished credibility in the 1920s and 1930s. [5] The term "hormesis" was coined and used for the first time in a scientific paper by Chester M. Southam and J. Ehrlich in 1943 in the journal Phytopathology, volume 33, pp. 517–541.

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:

Oxygen

Many organisms maintain a hormesis relationship with oxygen, which follows a hormetic curve similar to carbon monoxide:

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. [13] Mitochondria are sometimes described as "cellular power plants" because they generate most of the cell's supply of adenosine triphosphate (ATP), a source of chemical energy. Reactive oxygen species (ROS) have been discarded as unwanted byproducts of oxidative phosphorylation in mitochondria by the proponents of the free-radical theory of aging promoted by Denham Harman. The free-radical theory states that compounds inactivating ROS would lead to a reduction of oxidative stress and thereby produce an increase in lifespan, although this theory holds only in basic research. [14] However, in over 19 clinical trials, "nutritional and genetic interventions to boost antioxidants have generally failed to increase life span." [15]

Whether this concept applies to humans remains to be shown, although a 2007 epidemiological study supports the possibility of mitohormesis, indicating that supplementation with beta-carotene, vitamin A or vitamin E may increase disease prevalence in humans. [16]

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 methylmercury, a potent neurotoxic pollutant, improved the hatching rate of mallard eggs. [23] The author of the study, Gary Heinz, who led the study for the U.S. Geological Survey at the Patuxent Wildlife Research Center in Beltsville, stated that other explanations are possible. For instance, the flock he studied might have harbored some low, subclinical infection and that mercury, well known to be antimicrobial, might have killed the infection that otherwise hurt reproduction in the untreated birds. [23]

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 radiocontaminated steel was inadvertently used in the construction of over 100 apartment buildings, causing the long-term exposure of 10,000 people. The average dose rate was 50 mSv/year and a subset of the population (1,000 people) received a total dose over 4,000 mSv over ten years. In the widely used linear no-threshold model used by regulatory bodies, the expected cancer deaths in this population would have been 302 with 70 caused by the extra ionizing radiation, with the remainder caused by natural background radiation. The observed cancer rate, though, was quite low at 7 cancer deaths when 232 would be predicted by the LNT model had they not been exposed to the radiation from the building materials. Ionizing radiation hormesis appears to be at work. [25]

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 electromagnetic wave. The resulting materials are then free to interact with any environmental elements, and the energy released can also be used as a catalyst in further ionizing radiation interactions. [26]

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 Gulf War (1991) who suffered from the persistent symptoms of Gulf War Illness (GWI) were likely exposed to stresses from toxic chemicals and/or radiation. [28] The DNA damaging (genotoxic) effects of such exposures can be, at least partially, overcome by the DNA nucleotide excision repair (NER) pathway. Lymphocytes from GWI veterans exhibited a significantly elevated level of NER repair. [28] It was suggested that this increased NER capability in exposed veterans was likely a hormetic response, that is, an induced protective response resulting from battlefield exposure. [28]

Applications

Effects in aging

One of the areas where the concept of hormesis has been explored extensively with respect to its applicability is aging. [29] [30] Since the basic survival capacity of any biological system depends on its homeostatic ability, biogerontologists proposed that exposing cells and organisms to mild stress should result in the adaptive or hormetic response with various biological benefits. This idea has preliminary evidence showing that repetitive mild stress exposure may have anti-aging effects in laboratory models. [31] [32] Some mild stresses used for such studies on the application of hormesis in aging research and interventions are heat shock, irradiation, prooxidants, hypergravity, and food restriction. [31] [32] [33] Such compounds that may modulate stress responses in cells have been termed "hormetins". [31]

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 United States National Research Council (part of the National Academy of Sciences), [35] the National Council on Radiation Protection and Measurements (a body commissioned by the United States Congress) [36] and the United Nations Scientific Committee on the Effects of Ionizing Radiation all agree that radiation hormesis is not clearly shown, nor clearly the rule for radiation doses.

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 deep geological repositories for nuclear waste. [37]

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

Related Research Articles

<span class="mw-page-title-main">Carcinogen</span> Substance, radionuclide, or radiation directly involved in causing cancer

A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substances are considered carcinogens, but their carcinogenic activity is attributed to the radiation, for example gamma rays and alpha particles, which they emit. Common examples of non-radioactive carcinogens are inhaled asbestos, certain dioxins, and tobacco smoke. Although the public generally associates carcinogenicity with synthetic chemicals, it is equally likely to arise from both natural and synthetic substances. Carcinogens are not necessarily immediately toxic; thus, their effect can be insidious.

<span class="mw-page-title-main">Mutagen</span> Physical or chemical agent that increases the rate of genetic mutation

In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in animals, such mutagens can therefore be carcinogens, although not all necessarily are. All mutagens have characteristic mutational signatures with some chemicals becoming mutagenic through cellular processes.

The therapeutic index is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes toxicity to the amount that causes the therapeutic effect. The related terms therapeutic window or safety window refer to a range of doses optimized between efficacy and toxicity, achieving the greatest therapeutic benefit without resulting in unacceptable side-effects or toxicity.

<span class="mw-page-title-main">Carbon monoxide poisoning</span> Toxic effects of carbon monoxide

Carbon monoxide poisoning typically occurs from breathing in carbon monoxide (CO) at excessive levels. Symptoms are often described as "flu-like" and commonly include headache, dizziness, weakness, vomiting, chest pain, and confusion. Large exposures can result in loss of consciousness, arrhythmias, seizures, or death. The classically described "cherry red skin" rarely occurs. Long-term complications may include chronic fatigue, trouble with memory, and movement problems.

Carboxyhemoglobin is a stable complex of carbon monoxide and hemoglobin (Hb) that forms in red blood cells upon contact with carbon monoxide. Carboxyhemoglobin is often mistaken for the compound formed by the combination of carbon dioxide (carboxyl) and hemoglobin, which is actually carbaminohemoglobin. Carboxyhemoglobin terminology emerged when carbon monoxide was known by its historic name, "carbonic oxide", and evolved through Germanic and British English etymological influences; the preferred IUPAC nomenclature is carbonylhemoglobin.

<span class="mw-page-title-main">Linear no-threshold model</span> Deprecated model predicting health effects of radiation

The linear no-threshold model (LNT) is a dose-response model used in radiation protection to estimate stochastic health effects such as radiation-induced cancer, genetic mutations and teratogenic effects on the human body due to exposure to ionizing radiation. The model statistically extrapolates effects of radiation from very high doses into very low doses, where no biological effects may be observed. The LNT model lies at a foundation of a postulate that all exposure to ionizing radiation is harmful, regardless of how low the dose is, and that the effect is cumulative over lifetime.

<span class="mw-page-title-main">Radiation hormesis</span> Hypothesis regarding low doses of ionizing radiation on health

Radiation hormesis is the hypothesis that low doses of ionizing radiation are beneficial, stimulating the activation of repair mechanisms that protect against disease, that are not activated in absence of ionizing radiation. The reserve repair mechanisms are hypothesized to be sufficiently effective when stimulated as to not only cancel the detrimental effects of ionizing radiation but also inhibit disease not related to radiation exposure. It has been a mainstream concept since at least 2009.

Bernard Leonard Cohen was born in Pittsburgh, and was Professor Emeritus of Physics at the University of Pittsburgh. Professor Cohen was a staunch opponent of the so-called Linear no-threshold model (LNT) which postulates there exists no safe threshold for radiation exposure. His view which has support from a minority. He died in March 2012.

<span class="mw-page-title-main">Dose–response relationship</span> Measure of organism response to stimulus

The dose–response relationship, or exposure–response relationship, describes the magnitude of the response of an organism, as a function of exposure to a stimulus or stressor after a certain exposure time. Dose–response relationships can be described by dose–response curves. This is explained further in the following sections. A stimulus response function or stimulus response curve is defined more broadly as the response from any type of stimulus, not limited to chemicals.

Exposure science is the study of the contact between humans and harmful agents within their environment – whether it be chemical, physical, biological, behavioural or mental stressors – with the aim of identifying the causes and preventions of the adverse health effects they result in. This can include exposure within the home, workplace, outdoors or any other environment an individual may encounter. The term ‘exposure’ is the umbrella term for many different types, ranging from ultraviolet exposure, exposure to the chemicals in the food we eat, to exposure to long working hours being the occupational factor most attributable to the burden of disease.

Nanotoxicology is the study of the toxicity of nanomaterials. Because of quantum size effects and large surface area to volume ratio, nanomaterials have unique properties compared with their larger counterparts that affect their toxicity. Of the possible hazards, inhalation exposure appears to present the most concern, with animal studies showing pulmonary effects such as inflammation, fibrosis, and carcinogenicity for some nanomaterials. Skin contact and ingestion exposure are also a concern.

The collective effective dose, dose quantity S, is calculated as the sum of all individual effective doses over the time period or during the operation being considered due to ionizing radiation. It can be used to estimate the total health effects of a process or accidental release involving ionizing radiation to an exposed population. The total collective dose is the dose to the exposed human population between the time of release until its elimination from the environment, perhaps integrating to time equals infinity. However, doses are generally reported for specific populations and a stated time interval. The International Commission on Radiological Protection (ICRP) states: "To avoid aggregation of low individual doses over extended time periods and wide geographical regions the range in effective dose and the time period should be limited and specified.

<span class="mw-page-title-main">Christopher Busby</span> British scientist

Christopher Busby is a British scientist primarily studying the health effects of internal ionising radiation. Busby is a director of Green Audit Limited, a private company, and scientific advisor to the Low Level Radiation Campaign (LLRC).

<span class="mw-page-title-main">Dioxins and dioxin-like compounds</span> Class of chemical compounds

Dioxins and dioxin-like compounds (DLCs) are a group of chemical compounds that are persistent organic pollutants (POPs) in the environment. They are mostly by-products of burning or various industrial processes or, in the case of dioxin-like PCBs and PBBs, unwanted minor components of intentionally produced mixtures.

<span class="mw-page-title-main">2,3,7,8-Tetrachlorodibenzodioxin</span> Polychlorinated dibenzo-p-dioxin, chemical compound

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a polychlorinated dibenzo-p-dioxin (sometimes shortened, though inaccurately, to simply 'dioxin') with the chemical formula C12H4Cl4O2. Pure TCDD is a colorless solid with no distinguishable odor at room temperature. It is usually formed as an unwanted product in burning processes of organic materials or as a side product in organic synthesis.

Exposure to ionizing radiation is known to increase the future incidence of cancer, particularly leukemia. The mechanism by which this occurs is well understood, but quantitative models predicting the level of risk remain controversial. The most widely accepted model posits that the incidence of cancers due to ionizing radiation increases linearly with effective radiation dose at a rate of 5.5% per sievert; if correct, natural background radiation is the most hazardous source of radiation to general public health, followed by medical imaging as a close second. Additionally, the vast majority of non-invasive cancers are non-melanoma skin cancers caused by ultraviolet radiation. Non-ionizing radio frequency radiation from mobile phones, electric power transmission, and other similar sources have been investigated as a possible carcinogen by the WHO's International Agency for Research on Cancer, but to date, no evidence of this has been observed.

Travel outside the Earth's protective atmosphere, magnetosphere, and in free fall can harm human health, and understanding such harm is essential for successful crewed spaceflight. Potential effects on the central nervous system (CNS) are particularly important. A vigorous ground-based cellular and animal model research program will help quantify the risk to the CNS from space radiation exposure on future long distance space missions and promote the development of optimized countermeasures.

<span class="mw-page-title-main">Carbon monoxide-releasing molecules</span> Substances delivering CO within the body

Carbon monoxide-releasing molecules (CORMs) are chemical compounds designed to release controlled amounts of carbon monoxide (CO). CORMs are being developed as potential therapeutic agents to locally deliver CO to cells and tissues, thus overcoming limitations of CO gas inhalation protocols.

<span class="mw-page-title-main">Radiation exposure</span> Measure of ionization of air by ionizing radiation

Radiation exposure is a measure of the ionization of air due to ionizing radiation from photons. It is defined as the electric charge freed by such radiation in a specified volume of air divided by the mass of that air. As of 2007, "medical radiation exposure" was defined by the International Commission on Radiological Protection as exposure incurred by people as part of their own medical or dental diagnosis or treatment; by persons, other than those occupationally exposed, knowingly, while voluntarily helping in the support and comfort of patients; and by volunteers in a programme of biomedical research involving their exposure. Common medical tests and treatments involving radiation include X-rays, CT scans, mammography, lung ventilation and perfusion scans, bone scans, cardiac perfusion scan, angiography, radiation therapy, and more. Each type of test carries its own amount of radiation exposure. There are two general categories of adverse health effects caused by radiation exposure: deterministic effects and stochastic effects. Deterministic effects are due to the killing/malfunction of cells following high doses; and stochastic effects involve either cancer development in exposed individuals caused by mutation of somatic cells, or heritable disease in their offspring from mutation of reproductive (germ) cells.

Ionizing radiation can cause biological effects which are passed on to offspring through the epigenome. The effects of radiation on cells has been found to be dependent on the dosage of the radiation, the location of the cell in regards to tissue, and whether the cell is a somatic or germ line cell. Generally, ionizing radiation appears to reduce methylation of DNA in cells.

References

  1. 1 2 3 4 Mattson, M. P (2007). "Hormesis defined". Ageing Research Reviews. 7 (1): 1–7. doi:10.1016/j.arr.2007.08.007. PMC   2248601 . PMID   18162444.
  2. 1 2 3 Calabrese EJ (2014). "Hormesis: a fundamental concept in biology". Microbial Cell. 1 (5): 145–9. doi:10.15698/mic2014.05.145. PMC   5354598 . PMID   28357236.
  3. 1 2 Hochberg CH, Semler MW, Brower RG (September 2021). "Oxygen toxicity in critically ill adults". American Journal of Respiratory and Critical Care Medicine. 204 (6): 632–641. doi:10.1164/rccm.202102-0417CI. PMC   8521700 . PMID   34086536.
  4. ↑ Hayes, D. P. (2007). "Nutritional hormesis". European Journal of Clinical Nutrition. 61 (2): 147–159. doi: 10.1038/sj.ejcn.1602507 . ISSN   1476-5640. PMID   16885926.
  5. 1 2 3 Kaiser, Jocelyn (2003). "Sipping from a Poisoned Chalice". Science. 302 (5644): 376–9. doi:10.1126/science.302.5644.376. PMID   14563981. S2CID   58523840.
  6. ↑ Calabrese, Edward J. (2004). "Hormesis: A revolution in toxicology, risk assessment and medicine". EMBO Reports. 5 (Suppl 1): S37–40. doi:10.1038/sj.embor.7400222. PMC   1299203 . PMID   15459733.
  7. ↑ Bethell, Tom (2005). The Politically Incorrect Guide to Science . USA: Regnery Publishing. pp.  58–61. ISBN   978-0-89526-031-4.
  8. ↑ Calabrese EJ, Baldwin LA (2001). "The frequency of U-shaped dose responses in the toxicological literature". Toxicological Sciences. 62 (2): 330–8. doi: 10.1093/toxsci/62.2.330 . PMID   11452146.
  9. ↑ Hopper, Christopher P.; De La Cruz, Ladie Kimberly; Lyles, Kristin V.; Wareham, Lauren K.; Gilbert, Jack A.; Eichenbaum, Zehava; Magierowski, Marcin; Poole, Robert K.; Wollborn, Jakob; Wang, Binghe (2020-12-23). "Role of Carbon Monoxide in Host–Gut Microbiome Communication". Chemical Reviews. 120 (24): 13273–13311. doi:10.1021/acs.chemrev.0c00586. ISSN   0009-2665. PMID   33089988. S2CID   224824871.
  10. ↑ Motterlini, Roberto; Otterbein, Leo E. (2010). "The therapeutic potential of carbon monoxide". Nature Reviews Drug Discovery. 9 (9): 728–743. doi:10.1038/nrd3228. ISSN   1474-1784. PMID   20811383. S2CID   205477130.
  11. ↑ Hopper, Christopher P.; Zambrana, Paige N.; Goebel, Ulrich; Wollborn, Jakob (June 2021). "A brief history of carbon monoxide and its therapeutic origins". Nitric Oxide. 111–112: 45–63. doi:10.1016/j.niox.2021.04.001. PMID   33838343. S2CID   233205099.
  12. ↑ Radak, Zsolt; Chung, Hae Y.; Koltai, Erika; Taylor, Albert W.; Goto, Sataro (2008). "Exercise, oxidative stress and hormesis". Ageing Research Reviews. 7 (1): 34–42. doi:10.1016/j.arr.2007.04.004. PMID   17869589. S2CID   20964603.
  13. ↑ Bárcena, Clea; Mayoral, Pablo; Quirós, Pedro M. (1 January 2018). "Chapter Two - Mitohormesis, an Antiaging Paradigm" (Book series). In López-Otín, Carlos; Galluzzi, Lorenzo (eds.). International Review of Cell and Molecular Biology: Mitochondria and Longevity. Elsevier. pp. 35–77. ISBN   9780128157367 . Retrieved 11 October 2021.
  14. ↑ Sanz, Alberto; Stefanatos, Rhoda K.A. (1 March 2008). "The Mitochondrial Free Radical Theory of Aging: A Critical View". Current Aging Science. 1 (1): 10–21. doi:10.2174/1874609810801010010. PMID   20021368.
  15. ↑ Brewer, Gregory J. (March 2010). "Epigenetic oxidative redox shift (EORS) theory of aging unifies the free radical and insulin signaling theories". Experimental Gerontology. 45 (3): 173–179. doi:10.1016/j.exger.2009.11.007. PMC   2826600 . PMID   19945522.
  16. ↑ Bjelakovic, Goran; Nikolova, Dimitrinka; Gluud, Lise Lotte; Simonetti, Rosa G.; Gluud, Christian (28 February 2007). "Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis". JAMA. 297 (8): 842–857. doi:10.1001/jama.297.8.842. PMID   17327526 . Retrieved 11 October 2021.
  17. ↑ Calabrese, Edward J.; Cook, Ralph (2006). "The Importance of Hormesis to Public Health". Environmental Health Perspectives. 114 (11): 1631–5. doi:10.1289/ehp.8606. JSTOR   4091789. PMC   1665397 . PMID   17107845.
  18. ↑ Fillmore, Kaye Middleton; Kerr, William C.; Stockwell, Tim; Chikritzhs, Tanya; Bostrom, Alan (2006). "Moderate alcohol use and reduced mortality risk: Systematic error in prospective studies". Addiction Research & Theory. 14 (2): 101–32. doi:10.1080/16066350500497983. S2CID   72709357.
  19. ↑ Fillmore, Kaye Middleton; Stockwell, Tim; Chikritzhs, Tanya; Bostrom, Alan; Kerr, William (2007). "Moderate Alcohol Use and Reduced Mortality Risk: Systematic Error in Prospective Studies and New Hypotheses". Annals of Epidemiology. 17 (5): S16–23. doi:10.1016/j.annepidem.2007.01.005. PMID   17478320.
  20. ↑ Painter, Kelly; Cordell, Barbara J.; Sticco, Kristin L. (2021), "Auto-brewery Syndrome", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   30020718 , retrieved 2021-05-04
  21. ↑ Yong, Ed (2019-09-20). "The Real Danger of Booze-Making Gut Bacteria". The Atlantic. Retrieved 2021-05-04.
  22. ↑ Castro, Paola V.; Khare, Shilpi; Young, Brian D.; Clarke, Steven G. (2012). Singh, Shree Ram (ed.). "Caenorhabditis elegans Battling Starvation Stress: Low Levels of Ethanol Prolong Lifespan in L1 Larvae". PLOS ONE. 7 (1): e29984. doi: 10.1371/journal.pone.0029984 . PMC   3261173 . PMID   22279556.
  23. 1 2 Heinz, Gary H.; Hoffman, David J.; Klimstra, Jon D.; Stebbins, Katherine R. (2010). "Enhanced reproduction in mallards fed a low level of methylmercury: An apparent case of hormesis". Environmental Toxicology and Chemistry. 29 (3): 650–3. doi:10.1002/etc.64. PMID   20821490. S2CID   34149560.
  24. ↑ Sutou, S. (2018). Low-dose radiation from A-bombs elongated lifespan and reduced cancer mortality relative to un-irradiated individuals. Genes and Environment, 40(1), 26. https://doi.org/10.1186/s41021-018-0114-3
  25. ↑ Sanders, Charles (2010). Sanders, Charles L. (ed.). Radiation Hormesis and the Linear-No-Threshold Assumption. Berlin: Springer. Bibcode:2010rhln.book.....S. doi:10.1007/978-3-642-03720-7. ISBN   978-3-642-42566-0.
  26. ↑ "Ionizing radiation, health effects and protective measures". World Health Organization. Retrieved 2017-02-16.
  27. ↑ Mothersill C, Seymour C (2009). "Implications for environmental health of multiple stressors". Journal of Radiological Protection. 29 (2A): A21–8. Bibcode:2009JRP....29...21M. doi:10.1088/0952-4746/29/2A/S02. PMID   19454807. S2CID   32270666.
  28. 1 2 3 Latimer JJ, Alhamed A, Sveiven S, Almutairy A, Klimas NG, Abreu M, Sullivan K, Grant SG. Preliminary Evidence for a Hormetic Effect on DNA Nucleotide Excision Repair in Veterans with Gulf War Illness. Mil Med. 2020 Feb 13; 185(1–2):e47–e52. doi : 10.1093/milmed/usz177. PMID   31334811; PMC   PMC7353836.
  29. ↑ Le Bourg, Eric; Rattan, Suresh, eds. (2008). Mild Stress and Healthy Aging: Applying hormesis in aging research and interventions. Springer. ISBN   978-1-4020-6868-3.[ page needed ]
  30. ↑ Rattan, S. I. (2008). "Principles and practice of hormetic treatment of aging and age-related diseases". Human & Experimental Toxicology. 27 (2): 151–4. doi:10.1177/0960327107083409. PMID   18480141. S2CID   504736.
  31. 1 2 3 Rattan, Suresh I.S. (2008). "Hormesis in aging". Ageing Research Reviews. 7 (1): 63–78. doi:10.1016/j.arr.2007.03.002. PMID   17964227. S2CID   29221523.
  32. 1 2 Gems, David; Partridge, Linda (2008). "Stress-Response Hormesis and Aging: "That which Does Not Kill Us Makes Us Stronger"". Cell Metabolism. 7 (3): 200–3. doi: 10.1016/j.cmet.2008.01.001 . PMID   18316025.
  33. ↑ Le Bourg; Rattan, eds. (2008). Mild Stress and Healthy Aging: Applying hormesis in aging research and interventions. Springer. ISBN   978-1-4020-6868-3.[ page needed ]
  34. ↑ "Scientist says some pollution is good for you — a disputed claim Trump's EPA has embraced". Los Angeles Times. 2019-02-19. Retrieved 2020-08-11.
  35. ↑ Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation, National Research Council (2005). Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2. National Academies Press. ISBN   978-0-309-09156-5.[ page needed ]
  36. 1 2 Evaluation of the Linear-Nonthreshold Dose-Response Model for Ionizing Radiation . National Council on Radiation Protection and Measurements. 2001. ISBN   978-0-929600-69-7.[ page needed ]
  37. ↑ Tubiana, Maurice (2005). "Dose–effect relationship and estimation of the carcinogenic effects of low doses of ionizing radiation: The joint report of the Académie des Sciences (Paris) and of the Académie Nationale de Médecine". International Journal of Radiation Oncology, Biology, Physics. 63 (2): 317–9. doi: 10.1016/j.ijrobp.2005.06.013 . PMID   16168825.
  38. ↑ Poumadere, M. (2003). Hormesis: public health policy, organizational safety and risk communication. Human & experimental toxicology, 22(1), 39-41
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.