Allostasis proposes that efficient regulation requires anticipating needs and preparing to satisfy them before they arise,[1] as opposed to homeostasis, in which the goal is a steady state. Allostasis, stability through variation, was proposed by Sterling and Eyer in 1988 as a new model of physiological regulation. It differs in several respects from the standard model of homeostasis that is stability through constancy.[2][3]


Allostasis /ˌɑːlˈstsɪs/ from the Greek prefix ἄλλος, állos, "other," "different" + the suffix στάσις, stasis, "standing still". The concept was named by Sterling and Eyer in 1988. Allostasis was coined from the Greek allo, which means "variable;" thus, "remaining stable by being variable".[4][5]

Nature of conceptEdit

Allostasis proposes a broader hypothesis than homeostasis: The key goal of physiological regulation is not rigid constancy; rather, it is flexible variation that anticipates the organism's needs and promptly meets them.[6] Rather than simply responding to the environment, allostasis utilizes predictive regulation, which has a more complex goal in evolution of adaptation by changing based on what it anticipates, rather than by staying the same or "in balance" in response to environmental changes, as homeostasis suggests. This places homeostasis as a function within allostasis; however, some argue it is a larger paradigm altogether.[7] Allostasis redefines health and disease beyond the stable measures from lab tests or blood pressure, for example; and expands it to define health as the flexibility of these values. Blood pressure is one of Sterling's prime examples of a health measure that is best when it can fluctuate in anticipation of the brain-body's expected demands, so it can match this demand. The alternative, or a less healthy state on the health-disease continuum, would be for blood pressure to remain the same, or "stable," and not meet the new demand.[4]

Sung Lee (2019)[7] introduced the paradigm of allostatic orchestration (PAO) extending the principle of allostasis (as originally put forth by Peter Sterling) stating, “The PAO originates from an evolutionary perspective and recognizes that biological set points change in anticipation of changing environments.”

The brain is the organ of central command, orchestrating cross-system operations to support optimal behavior at the level of the whole organism. The PAO describes differences between homeostasis and allostasis paradigms and conciliation of the paradigms illustrated with alternative views of posttraumatic stress disorder (PTSD). Lee states:

The allostatic state represents the integrated totality of brain-body interactions. Health itself is an allostatic state of optimal anticipatory oscillation, hypothesized to relate to the state of criticality…Diseases are allostatic states of impaired anticipatory oscillations, demonstrated as rigidifications of set points across the brain and body (disease comorbidity).

The PAO implications for health extend beyond blood pressure and diabetes to include addiction, depression, and deaths of despair (from alcohol, drugs, and suicide) that have been increasing since 2000,[8] emphasizing that an integrated view of health includes environmental context. Allostasis encourages increased attention to new solutions at the level of society, as well as the individual and immediate community.[6][7]

Allostatic regulation reflects, at least partly, cephalic involvement in primary regulatory events, in that it is anticipatory to systemic physiological regulation.[4][9] This is different from homeostasis, which occurs in response to subtle ebb and flow. Both homeostasis and allostasis are endogenous systems responsible for maintaining the internal stability of an organism. Homeostasis is formed from the Greek adjective homoios, meaning "similar," and the noun stasis, meaning "standing;" thus, "standing at about the same level."[4]

Wingfield states:

The concept of allostasis, maintaining stability through change, is a fundamental process through which organisms actively adjust to both predictable and unpredictable events... Allostatic load refers to the cumulative cost to the body of allostasis, with allostatic overload... being a state in which serious pathophysiology can occur... Using the balance between energy input and expenditure as the basis for applying the concept of allostasis, two types of allostatic overload have been proposed.[10]

Sterling (2020) proposed several interrelated points that belong the allostasis model:[6]

  1. Animals are designed to be efficient.
  2. Efficiency requires a brain to predict what will be needed and avoid costly errors.
  3. The brain further enhances efficiency by prioritizing needs and enforcing trade-offs.
  4. All systems, including the brain, organ systems, and single cells are designed for a particular operating range. (Example, cone photoreceptors adapt for daylight, and rod photoreceptors adapt for moonlight and starlight).
  5. A system's parameters vary according to predicted demand and adapt their sensitivities.  
  6. While a wide range denotes a flexible and healthy system, when their evolved operating ranges are chronically exceeded, systems at all levels break down.

Sterling (2004) proposed six interrelated principles that underlie allostasis:[11]

  1. Organisms are designed to be efficient
  2. Efficiency requires reciprocal trade-offs
  3. Efficiency also requires being able to predict future needs
  4. Such prediction requires each sensor to adapt to the expected range of input
  5. Prediction also demands that each effector adapt its output to the expected range of demand
  6. Predictive regulation depends on behavior whilst neural mechanisms also adapt.


Allostasis emphasizes that regulation must be efficient, whereas homeostasis makes no reference to efficiency. In addition, allostasis recognizes that efficiency requires predicting bodily needs to prevent errors, whereas homeostasis emphasizes detecting errors and correcting them–– responding like a thermostat. Prediction requires the brain to: (i) collect information across all spatial and temporal scales; (ii) analyze, integrate, and decide what will be needed; (iii) exert feedforward control of all parameters. Naturally, many needs are somewhat unpredictable, so errors are inevitable; and for those errors, homeostatic mechanisms––feedback control––are available to correct them.[12][13]  

Allostatic (predictive) regulation allows the brain to prioritize needs, for example, by sending more oxygen and nutrients to organs that need it most. For this example, during peak exercise muscle requires an 18-fold increase in oxygenated blood, but the heart can increase its capacity only 3.5-fold. Therefore, the brain temporarily borrows blood from the digestive system and kidney rerouting it to muscle. It later repays the debt when muscle's increased need subsides. Without the ability to prioritize trade-offs between organ systems, the heart and lungs would need to be far larger while much of this costly extra capacity would go unused.[14][15]

Predictive regulation also occurs at the cellular and systems levels. When humans are chronically stressed, the brain chronically raises blood pressure; then arterial muscles predict higher pressure and respond with hypertrophy (like skeletal muscles when we lift weights). Gradually the whole cardiovascular system adapts to life at an elevated pressure level. This is known as chronic hypertension, which elevates mortality from cardiovascular disease and stroke. Similarly, a chronically high carbohydrate diet requires chronically high blood glucose and leads to chronically high levels of insulin that increase in anticipation of the need to manage the high level of carbohydrates. Cells that express insulin receptors, predicting high insulin, adapt by reducing their sensitivity (like photoreceptors in bright light). This leads to type 2 diabetes and elevated mortality from many causes. Although physicians term this response insulin resistance, it can be better understood as consequent to predictive regulation.[6]

Every system evolves to operate over a particular range. For example, cone photoreceptors evolved to sense daylight over a 10,000-fold range of intensities, whereas rod photoreceptors evolved a different design to sense moonlight and starlight down to detection of single photons. To function optimally across their wide operating ranges, all systems adapt their sensitivities. A rod photoreceptor adapts to bright moonlight and requires minutes to increase its sensitivity to starlight.[15] When a system is chronically forced beyond its intended operating range – as by chronic high carbohydrate diet or other stress – the limits of adaptation are exceeded, and systems break down. This condition was termed by Bruce McEwen as allostatic load.[16] The health of an organism is maintained when operating within certain parameters, but having dynamic variability of range.[7]

Allostasis can be carried out by means of alteration in HPA axis hormones, the autonomic nervous system, cytokines, or a number of other systems, and is generally adaptive in the short term.[17] Allostasis is essential in order to maintain internal viability amid changing conditions.[4][18][16][9]

Allostasis provides compensation for various problems, such as in compensated heart failure, compensated kidney failure, and compensated liver failure. However, such allostatic states are inherently fragile, and decompensation can occur quickly, as in acute decompensated heart failure.

Related TermsEdit

The term heterostasis is also used in place of allostasis, particularly where state changes are finite in number and therefore discrete (e.g. computational processes).[19]


McEwen and Wingfield propose two types of allostatic overload which result in different responses:

Type 1 allostatic overload occurs when energy demand exceeds supply, resulting in activation of the emergency life history stage. This serves to direct the animal away from normal life history stages into a survival mode that decreases allostatic load and regains positive energy balance. The normal life cycle can be resumed when the perturbation passes.

Type 2 allostatic overload begins when there is sufficient or even excess energy consumption accompanied by social conflict and other types of social dysfunction. The latter is the case in human society and certain situations affecting animals in captivity. In all cases, secretion of glucocorticosteroids and activity of other mediators of allostasis such as the autonomic nervous system, CNS neurotransmitters, and inflammatory cytokines wax and wane with allostatic load. If allostatic load is chronically high, then pathologies develop. Type 2 allostatic overload does not trigger an escape response, and can only be counteracted through learning and changes in the social structure.[17][4]

Whereas both types of allostasis are associated with increased release of cortisol and catecholamines, they differentially affect thyroid homeostasis: Concentrations of the thyroid hormone triiodothyronine are decreased in type 1 allostasis, but elevated in type 2 allostasis.[20] This may result from type 2 allostatic load increasing the set point of pituitary-thyroid feedback control.[21]

Allostatic loadEdit

In the long run, the maintenance of allostatic changes over a long period may result in wear and tear, the so-called allostatic load. If a dehydrated individual is helped but continues to be stressed and hence does not reinstate normal body function, the individual's body systems will wear out.[citation needed]


In 2005, Trevor A. Day has argued that the concept of allostasis is no more than a renaming of the original concept of homeostasis.[22]

See alsoEdit


  1. ^ Sterling, Peter (April 2012). "Allostasis: A model of predictive regulation". Physiology & Behavior. 106 (1): 5–15. doi:10.1016/j.physbeh.2011.06.004. PMID 21684297. S2CID 27164469.
  2. ^ Cannon, Walter B. (c. 1932). Wisdom of the body. W.W. Norton & Co. OCLC 249738801.
  3. ^ Bernard (2008-09-11). Introduction à l'étude de la médecine expérimentale. doi:10.14375/np.9782081307582. hdl:2027/uc1.b5585311. ISBN 9782081307582. S2CID 31696047.
  4. ^ a b c d e f Sterling, P.; Eyer, J. (1988). "Allostasis: A new paradigm to explain arousal pathology". In Fisher, S.; Reason, J. T. (eds.). Handbook of life stress, cognition, and health. Chicester, NY: Wiley. ISBN 9780471912699. OCLC 17234042.
  5. ^ Klein, Robyn (2004). "Chapter 3" (PDF). Phylogenetic and phytochemical characteristics of plant species with adaptogenic properties (MS). Montana State University. Archived from the original (PDF) on October 17, 2006. 
  6. ^ a b c d Sterling, Peter (2020). What Is Health?. The MIT Press. doi:10.7551/mitpress/11472.001.0001. ISBN 978-0-262-35629-9. S2CID 241512181.
  7. ^ a b c d Lee, Sung W. (2019-04-26). "A Copernican Approach to Brain Advancement: The Paradigm of Allostatic Orchestration". Frontiers in Human Neuroscience. 13: 129. doi:10.3389/fnhum.2019.00129. ISSN 1662-5161. PMC 6499026. PMID 31105539.
  8. ^ Case, Anne; Deaton, Angus (2017). "Mortality and Morbidity in the 21st Century". Brookings Papers on Economic Activity. 2017 (1): 397–476. doi:10.1353/eca.2017.0005. ISSN 1533-4465. PMC 5640267. PMID 29033460.
  9. ^ a b Schulkin, Jay (2003). Rethinking homeostasis : allostatic regulation in physiology and pathophysiology. Cambridge, MA: MIT Press. ISBN 9780262194808. OCLC 49936130.
  10. ^ Wingfield, John C. (2003). "Control of behavioural strategies for capricious environments". Anniversary Essays. Anim. Behav. 66 (5): 807–16. doi:10.1006/anbe.2003.2298. S2CID 53156304. 
  11. ^ Sterling, Peter (2004). "Chapter 1. Principles of Allostasis". In Schulkin, Jay (ed.). Allostasis, homeostasis, and the costs of physiological adaptation. New York, NY: Cambridge University Press. ISBN 9780521811415. OCLC 53331074.
  12. ^ Sterling, Peter (2018-06-29). "Predictive regulation and human design". eLife. 7: e36133. doi:10.7554/eLife.36133. ISSN 2050-084X. PMC 6025954. PMID 29957178.
  13. ^ Schulkin, Jay; Sterling, Peter (October 2019). "Allostasis: A Brain-Centered, Predictive Mode of Physiological Regulation". Trends in Neurosciences. 42 (10): 740–752. doi:10.1016/j.tins.2019.07.010. PMID 31488322. S2CID 201742508.
  14. ^ Weibel, E. R.; Taylor, C. R.; Hoppeler, H. (1991-11-15). "The concept of symmorphosis: a testable hypothesis of structure-function relationship". Proceedings of the National Academy of Sciences. 88 (22): 10357–10361. Bibcode:1991PNAS...8810357W. doi:10.1073/pnas.88.22.10357. ISSN 0027-8424. PMC 52927. PMID 1946456.
  15. ^ a b Sterling, Peter (2015). Principles of neural design. Simon Laughlin. Cambridge, Massachusetts. ISBN 978-0-262-32731-2. OCLC 910237745.
  16. ^ a b McEwen, Bruce S. (1998). "Stress, Adaptation, and Disease: Allostasis and Allostatic Load". Ann. N. Y. Acad. Sci. 840 (1): 33–44. Bibcode:1998NYASA.840...33M. doi:10.1111/j.1749-6632.1998.tb09546.x. PMID 9629234. S2CID 20043016. 
  17. ^ a b McEwen, Bruce S.; Wingfield, John C. (2003). "The concept of allostasis in biology and biomedicine". Horm. Behav. 43 (1): 2–15. doi:10.1016/S0018-506X(02)00024-7. ISSN 0018-506X. PMID 12614627. S2CID 11329342. 
  18. ^ McEwen, Bruce S. (1998). "Protective and Damaging Effects of Stress Mediators". Seminars in Medicine of the Beth Israel Deaconess Medical Center. N. Engl. J. Med. 338 (3): 171–9. CiteSeerX doi:10.1056/NEJM199801153380307. PMID 9428819. 
  19. ^ Selye, H. (1973). "Homeostasis and Heterostasis". Perspectives in Biology and Medicine. 16 (3): 441–445. doi:10.1353/pbm.1973.0056. PMID 4705073. S2CID 13128548.
  20. ^ Chatzitomaris, Apostolos; Hoermann, Rudolf; Midgley, John E.; Hering, Steffen; Urban, Aline; Dietrich, Barbara; Abood, Assjana; Klein, Harald H.; Dietrich, Johannes W. (20 July 2017). "Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming". Frontiers in Endocrinology. 8: 163. doi:10.3389/fendo.2017.00163. PMC 5517413. PMID 28775711.
  21. ^ Dietrich, Johannes Wolfgang; Hoermann, Rudolf; Midgley, John E. M.; Bergen, Friederike; Müller, Patrick (26 October 2020). "The Two Faces of Janus: Why Thyrotropin as a Cardiovascular Risk Factor May Be an Ambiguous Target". Frontiers in Endocrinology. 11: 542710. doi:10.3389/fendo.2020.542710. PMC 7649136. PMID 33193077.
  22. ^ Day, Trevor A. (2005). "Defining stress as a prelude to mapping its neurocircuitry: No help from allostasis". Prog. Neuropsychopharmacol. Biol. Psychiatry. 29 (8): 1195–1200. doi:10.1016/j.pnpbp.2005.08.005. ISSN 0278-5846. PMID 16213079. S2CID 43073227. 

Further readingEdit