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Protective and damaging effects of stress mediators

Bruce S. McEwen
New England Journal of Medicine · 1998

View the original source DOI: 10.1056/NEJM199801153380307 ↗PubMed: 9428819 ↗

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THE ALLOSTASIS PROJECT

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Original paper · cite this source for the study’s findings.

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What the research tells us

Explores the dual nature of adaptation through the protective and damaging effects of stress mediators.

Scope & interpretation

The review focuses on protective and damaging mechanisms of stress mediators. Applying its account requires distinguishing mechanistic arguments, individual clinical assessment and specific intervention studies.

Study at a glance

POPULATION & SAMPLE
Review; no single trial sample
EXPOSURE / INTERVENTION / SUBJECT
Stress mediators; review
OUTCOMES
Protective and damaging actions of stress mediators
TIME FRAME
No single observation period

Cited on this site

Foundations

Allostatic Load

Foundations

Physiological Reserve

Features

Allostatic Load: The Hidden Cost of Adaptation

Editorial & review record

Record for v0.2 · Updated

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  1. Scientific review

    Not yet scientifically reviewed

Editorial note

Under the editorial responsibility of the TAP Editorial Team, this publication used AI assistance for content organization and editing. Scientific review is recorded separately on this page.

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Scope of this reading note

Bibliographic details verified; full-text verification is incomplete.

Funding & competing interests
Funding and competing-interest details have not been verified against the full text. Consult the original publication’s declarations.

Project support

Founded and supported by Resilio.

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Project informationPrivacy PolicyProject informationContactAssessmentTAP Load & Recovery ProfileMethodsLoad & Recovery Profile: Methods & DevelopmentExploreQuestions about Human AdaptationExploreMeasurement & InterpretationReading guide · Essential 35Load & Recovery: Six Research DirectionsReading guide · Essential 5Allostatic LoadReading guide · Essential 5Recovery ScienceReading guide · Essential 5Reserve & ResilienceReading guide · Essential 5MeasurementFoundationsLoadFoundationsAllostasisFoundationsRecoveryFoundationsAllostatic LoadFoundationsPhysiological ReserveFoundationsResilienceFeaturesAllostatic Load: The Hidden Cost of AdaptationFeaturesRecovery Is Not RestFeaturesWhat Is Resilience Nutrition?FeaturesModels of Adaptation: What Different Frameworks ExplainFeaturesTAP Human Adaptation FrameworkFeaturesAre Recovery and Resilience the Same Thing?FeaturesCan Underfueling Affect Recovery?FeaturesCan Weekend Catch-Up Sleep Make Up for a Week of Short Sleep?FeaturesDoes Recovery Always Mean Returning to the Same Baseline?FeaturesHow Are Physiological Reserve and Resilience Related?FeaturesWhat Can HRV Tell Us About Recovery?FeaturesWhat Counts as Evidence That Nutrition Supports Recovery?FeaturesWhat Does Your Wearable’s Recovery Score Actually Tell You?FeaturesWhen HRV Drops: Normal Variation or a Change in Recovery?FeaturesWhy Can Stress Responses Continue After Work Ends?FeaturesWhy Feeling Better Doesn’t Always Mean Fully RecoveredMethods & projectEvidence grading & methodsMethods & projectEditorial & scientific standardsMethods & projectAbout the projectResearch · 1993Stress and the individual. Mechanisms leading to diseaseResearch · 1998Protective and damaging effects of stress mediatorsResearch · 2001Frailty in older adults: evidence for a phenotypeResearch · 2003The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivationResearch · 2004Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory researchResearch · 2006The perseverative cognition hypothesis: a review of worry, prolonged stress-related physiological activation, and healthResearch · 2007The Recovery Experience Questionnaire: development and validation of a measure for assessing recuperation and unwinding from workResearch · 2009The Reactive Scope Model — A new model integrating homeostasis, allostasis, and stressResearch · 2010Neurobehavioral dynamics following chronic sleep restriction: dose-response effects of one night for recoveryResearch · 2010Greater cardiovascular responses to laboratory mental stress are associated with poor subsequent cardiovascular risk status: a meta-analysis of prospective evidenceResearch · 2010Allostatic load biomarkers of chronic stress and impact on health and cognitionResearch · 2011Stress- and Allostasis-Induced Brain PlasticityResearch · 2012Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant dataResearch · 2012Allostasis: a model of predictive regulationResearch · 2012A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and healthResearch · 2012Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trialResearch · 2013Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesisResearch · 2013The LF/HF ratio does not accurately measure cardiac sympatho-vagal balanceResearch · 2013Effects of recovery sleep after one work week of mild sleep restriction on interleukin-6 and cortisol secretion and daytime sleepiness and performanceResearch · 2013Sleep drives metabolite clearance from the adult brainResearch · 2014Monitoring training status with HR measures: do all roads lead to Rome?Research · 2014Clarifying the roles of homeostasis and allostasis in physiological regulationResearch · 2014Resilience definitions, theory, and challenges: interdisciplinary perspectivesResearch · 2015Recovery from job stress: The stressor-detachment model as an integrative frameworkResearch · 2016Physiological concomitants of perseverative cognition: A systematic review and meta-analysisResearch · 2016Successfully leaving work at work: The self-regulatory underpinnings of psychological detachmentResearch · 2016Physical Resilience in Older Adults: Systematic Review and Development of an Emerging ConstructResearch · 2017Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysisResearch · 2017Evidence for a Large-Scale Brain System Supporting Allostasis and Interoception in HumansResearch · 2017Heart Rate Variability and Cardiac Vagal Tone in Psychophysiological Research - Recommendations for Experiment Planning, Data Analysis, and Data ReportingResearch · 2017The impact of reduced worktime on sleep and perceived stress - a group randomized intervention study using diary dataResearch · 2017A Meta-Analysis on Antecedents and Outcomes of Detachment from WorkResearch · 2017Multi-parameter comparison of a standardized mixed meal tolerance test in healthy and type 2 diabetic subjects: the PhenFlex challengeResearch · 2018Recovery and Performance in Sport: Consensus StatementResearch · 2018Quantifying resilience of humans and other animalsResearch · 2019Ad libitum Weekend Recovery Sleep Fails to Prevent Metabolic Dysregulation during a Repeating Pattern of Insufficient Sleep and Weekend Recovery SleepResearch · 2019Resilience in Clinical Care: Getting a Grip on the Recovery Potential of Older AdultsResearch · 2019Protein supplementation improves lean body mass in physically active older adults: a randomized placebo-controlled trialResearch · 2020Effect of Multimodal Prehabilitation vs Postoperative Rehabilitation on 30-Day Postoperative Complications for Frail Patients Undergoing Resection of Colorectal Cancer: A Randomized Clinical TrialResearch · 2020Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenanceResearch · 2021Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts human lifespan limitResearch · 2021Leaving Work at Work: A Meta-Analysis on Employee Recovery From WorkResearch · 2022"Give me a break!" A systematic review and meta-analysis on the efficacy of micro-breaks for increasing well-being and performanceResearch · 2022Allostatic Load Measurement: A Systematic Review of Reviews, Database Inventory, and Considerations for Neighborhood ResearchResearch · 2022Allostatic Load and Mortality: A Systematic Review and Meta-AnalysisResearch · 2022Recovery from Work: Advancing the Field Toward the FutureResearch · 2023Brief structured respiration practices enhance mood and reduce physiological arousalResearch · 2023Conceptualizing a resilience research framework at The National Institutes of HealthResearch · 2023Towards a consensus definition of allostatic load: a multi-cohort, multi-system, multi-biomarker individual participant data (IPD) meta-analysisResearch · 2023Effect of Multimodal Prehabilitation on Reducing Postoperative Complications and Enhancing Functional Capacity Following Colorectal Cancer Surgery: The PREHAB Randomized Clinical TrialResearch · 20232023 International Olympic Committee’s (IOC) consensus statement on Relative Energy Deficiency in Sport (REDs)Research · 2023Low energy availability reduces myofibrillar and sarcoplasmic muscle protein synthesis in trained femalesResearch · 2024Low energy availability increases immune cell formation of reactive oxygen species and impairs exercise performance in female endurance athletesResearch · 2024Impact of baseline and longitudinal allostatic load changes on incident cardiovascular disease and all-cause mortality: A 7-year population-based cohort study in ChinaResearch · 2024Brain clearance is reduced during sleep and anesthesiaResearch · 2024Sleep regularity is a stronger predictor of mortality risk than sleep duration: A prospective cohort studyResearch · 2025Allostatic (over)Load Measurement: Workflow and repositoryResearch · 2025Validation of nocturnal resting heart rate and heart rate variability in consumer wearablesResearch · 2025Readiness, recovery, and strain: an evaluation of composite health scores in consumer wearablesResearch · 2025Resilience phenotypes derived from an active inference account of allostasisResearch · 2025A meta-analysis of the influence of work connectivity behavior after-hours on employees: The mediating role of work autonomy and psychological detachmentResearch · 2025Inter- and Intrapersonal Associations Between Physiology and Mental Health: A Longitudinal Study Using Wearables and Mental Health SurveysResearch · 2026Allostatic (over) load measurement: Workflow and repositoryResearch · 2026A reporting checklist for human and animal heart rate variability researchResearch · 2026Acute sleep rebound following sleep restriction is associated with reduced mortality riskResearch · 2026Building an ontology of resilience: Insights from the physical resilience literatureResearch · 2026Pilot study of the impact of weekend sleep restriction and recovery sleep on metabolic and cardiovascular risk indicators: Results from a randomized crossover clinical trialTAP Record · TAP-CON-0001LoadTAP Record · TAP-CON-0002AllostasisTAP Record · TAP-CON-0003RecoveryTAP Record · TAP-CON-0004Allostatic LoadTAP Record · TAP-CON-0005Physiological ReserveTAP Record · TAP-CON-0006ResilienceTAP Record · TAP-FTR-0001Allostatic Load: The Hidden Cost of AdaptationTAP Record · TAP-FTR-0002Recovery Is Not RestTAP Record · TAP-FTR-0009What Is Resilience Nutrition?TAP Record · TAP-FTR-0008Models of Adaptation: What Different Frameworks ExplainTAP Record · TAP-MDL-0001TAP Human Adaptation FrameworkTAP Record · TAP-FTR-0006Are Recovery and Resilience the Same Thing?TAP Record · TAP-FTR-0015Can Underfueling Affect Recovery?TAP Record · TAP-FTR-0013Can Weekend Catch-Up Sleep Make Up for a Week of Short Sleep?TAP Record · TAP-FTR-0007Does Recovery Always Mean Returning to the Same Baseline?TAP Record · TAP-FTR-0004How Are Physiological Reserve and Resilience Related?TAP Record · TAP-FTR-0005What Can HRV Tell Us About Recovery?TAP Record · TAP-FTR-0012What Counts as Evidence That Nutrition Supports Recovery?TAP Record · TAP-FTR-0011What Does Your Wearable’s Recovery Score Actually Tell You?TAP Record · TAP-FTR-0014When HRV Drops: Normal Variation or a Change in Recovery?TAP Record · TAP-FTR-0010Why Can Stress Responses Continue After Work Ends?TAP Record · TAP-FTR-0003Why Feeling Better Doesn’t Always Mean Fully RecoveredTAP Record · TAP-RDN-0001TAP reading note: Stress and the individual. Mechanisms leading to diseaseTAP Record · TAP-RDN-0002TAP reading note: Protective and damaging effects of stress mediatorsTAP Record · TAP-RDN-0067TAP reading note: Frailty in older adults: evidence for a phenotypeTAP Record · TAP-RDN-0003TAP reading note: The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivationTAP Record · TAP-RDN-0050TAP reading note: Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory researchTAP Record · TAP-RDN-0016TAP reading note: The perseverative cognition hypothesis: a review of worry, prolonged stress-related physiological activation, and healthTAP Record · TAP-RDN-0020TAP reading note: The Recovery Experience Questionnaire: development and validation of a measure for assessing recuperation and unwinding from workTAP Record · TAP-RDN-0032TAP reading note: The Reactive Scope Model — A new model integrating homeostasis, allostasis, and stressTAP Record · TAP-RDN-0024TAP reading note: Neurobehavioral dynamics following chronic sleep restriction: dose-response effects of one night for recoveryTAP Record · TAP-RDN-0004TAP reading note: Greater cardiovascular responses to laboratory mental stress are associated with poor subsequent cardiovascular risk status: a meta-analysis of prospective evidenceTAP Record · TAP-RDN-0013TAP reading note: Allostatic load biomarkers of chronic stress and impact on health and cognitionTAP Record · TAP-RDN-0005TAP reading note: Stress- and Allostasis-Induced Brain PlasticityTAP Record · TAP-RDN-0060TAP reading note: Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant dataTAP Record · TAP-RDN-0006TAP reading note: Allostasis: a model of predictive regulationTAP Record · TAP-RDN-0053TAP reading note: A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and healthTAP Record · TAP-RDN-0038TAP reading note: Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trialTAP Record · TAP-RDN-0037TAP reading note: Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesisTAP Record · TAP-RDN-0018TAP reading note: The LF/HF ratio does not accurately measure cardiac sympatho-vagal balanceTAP Record · TAP-RDN-0026TAP reading note: Effects of recovery sleep after one work week of mild sleep restriction on interleukin-6 and cortisol secretion and daytime sleepiness and performanceTAP Record · TAP-RDN-0062TAP reading note: Sleep drives metabolite clearance from the adult brainTAP Record · TAP-RDN-0044TAP reading note: Monitoring training status with HR measures: do all roads lead to Rome?TAP Record · TAP-RDN-0012TAP reading note: Clarifying the roles of homeostasis and allostasis in physiological regulationTAP Record · TAP-RDN-0029TAP reading note: Resilience definitions, theory, and challenges: interdisciplinary perspectivesTAP Record · TAP-RDN-0007TAP reading note: Recovery from job stress: The stressor-detachment model as an integrative frameworkTAP Record · TAP-RDN-0017TAP reading note: Physiological concomitants of perseverative cognition: A systematic review and meta-analysisTAP Record · TAP-RDN-0040TAP reading note: Successfully leaving work at work: The self-regulatory underpinnings of psychological detachmentTAP Record · TAP-RDN-0008TAP reading note: Physical Resilience in Older Adults: Systematic Review and Development of an Emerging ConstructTAP Record · TAP-RDN-0051TAP reading note: Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysisTAP Record · TAP-RDN-0049TAP reading note: Evidence for a Large-Scale Brain System Supporting Allostasis and Interoception in HumansTAP Record · TAP-RDN-0019TAP reading note: Heart Rate Variability and Cardiac Vagal Tone in Psychophysiological Research - Recommendations for Experiment Planning, Data Analysis, and Data ReportingTAP Record · TAP-RDN-0059TAP reading note: The impact of reduced worktime on sleep and perceived stress - a group randomized intervention study using diary dataTAP Record · TAP-RDN-0009TAP reading note: A Meta-Analysis on Antecedents and Outcomes of Detachment from WorkTAP Record · TAP-RDN-0036TAP reading note: Multi-parameter comparison of a standardized mixed meal tolerance test in healthy and type 2 diabetic subjects: the PhenFlex challengeTAP Record · TAP-RDN-0010TAP reading note: Recovery and Performance in Sport: Consensus StatementTAP Record · TAP-RDN-0064TAP reading note: Quantifying resilience of humans and other animalsTAP Record · TAP-RDN-0025TAP reading note: Ad libitum Weekend Recovery Sleep Fails to Prevent Metabolic Dysregulation during a Repeating Pattern of Insufficient Sleep and Weekend Recovery SleepTAP Record · TAP-RDN-0027TAP reading note: Resilience in Clinical Care: Getting a Grip on the Recovery Potential of Older AdultsTAP Record · TAP-RDN-0039TAP reading note: Protein supplementation improves lean body mass in physically active older adults: a randomized placebo-controlled trialTAP Record · TAP-RDN-0066TAP reading note: Effect of Multimodal Prehabilitation vs Postoperative Rehabilitation on 30-Day Postoperative Complications for Frail Patients Undergoing Resection of Colorectal Cancer: A Randomized Clinical TrialTAP Record · TAP-RDN-0028TAP reading note: Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenanceTAP Record · TAP-RDN-0052TAP reading note: Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts human lifespan limitTAP Record · TAP-RDN-0022TAP reading note: Leaving Work at Work: A Meta-Analysis on Employee Recovery From WorkTAP Record · TAP-RDN-0023TAP reading note: "Give me a break!" A systematic review and meta-analysis on the efficacy of micro-breaks for increasing well-being and performanceTAP Record · TAP-RDN-0011TAP reading note: Allostatic Load Measurement: A Systematic Review of Reviews, Database Inventory, and Considerations for Neighborhood ResearchTAP Record · TAP-RDN-0015TAP reading note: Allostatic Load and Mortality: A Systematic Review and Meta-AnalysisTAP Record · TAP-RDN-0021TAP reading note: Recovery from Work: Advancing the Field Toward the FutureTAP Record · TAP-RDN-0057TAP reading note: Brief structured respiration practices enhance mood and reduce physiological arousalTAP Record · TAP-RDN-0033TAP reading note: Conceptualizing a resilience research framework at The National Institutes of HealthTAP Record · TAP-RDN-0014TAP reading note: Towards a consensus definition of allostatic load: a multi-cohort, multi-system, multi-biomarker individual participant data (IPD) meta-analysisTAP Record · TAP-RDN-0065TAP reading note: Effect of Multimodal Prehabilitation on Reducing Postoperative Complications and Enhancing Functional Capacity Following Colorectal Cancer Surgery: The PREHAB Randomized Clinical TrialTAP Record · TAP-RDN-0047TAP reading note: 2023 International Olympic Committee’s (IOC) consensus statement on Relative Energy Deficiency in Sport (REDs)TAP Record · TAP-RDN-0045TAP reading note: Low energy availability reduces myofibrillar and sarcoplasmic muscle protein synthesis in trained femalesTAP Record · TAP-RDN-0046TAP reading note: Low energy availability increases immune cell formation of reactive oxygen species and impairs exercise performance in female endurance athletesTAP Record · TAP-RDN-0031TAP reading note: Impact of baseline and longitudinal allostatic load changes on incident cardiovascular disease and all-cause mortality: A 7-year population-based cohort study in ChinaTAP Record · TAP-RDN-0063TAP reading note: Brain clearance is reduced during sleep and anesthesiaTAP Record · TAP-RDN-0061TAP reading note: Sleep regularity is a stronger predictor of mortality risk than sleep duration: A prospective cohort studyTAP Record · TAP-RDN-0035TAP reading note: Allostatic (over)Load Measurement: Workflow and repositoryTAP Record · TAP-RDN-0055TAP reading note: Validation of nocturnal resting heart rate and heart rate variability in consumer wearablesTAP Record · TAP-RDN-0041TAP reading note: Readiness, recovery, and strain: an evaluation of composite health scores in consumer wearablesTAP Record · TAP-RDN-0034TAP reading note: Resilience phenotypes derived from an active inference account of allostasisTAP Record · TAP-RDN-0058TAP reading note: A meta-analysis of the influence of work connectivity behavior after-hours on employees: The mediating role of work autonomy and psychological detachmentTAP Record · TAP-RDN-0056TAP reading note: Inter- and Intrapersonal Associations Between Physiology and Mental Health: A Longitudinal Study Using Wearables and Mental Health SurveysTAP Record · TAP-RDN-0048TAP reading note: Allostatic (over) load measurement: Workflow and repositoryTAP Record · TAP-RDN-0054TAP reading note: A reporting checklist for human and animal heart rate variability researchTAP Record · TAP-RDN-0043TAP reading note: Acute sleep rebound following sleep restriction is associated with reduced mortality riskTAP Record · TAP-RDN-0030TAP reading note: Building an ontology of resilience: Insights from the physical resilience literatureTAP Record · TAP-RDN-0042TAP reading note: Pilot study of the impact of weekend sleep restriction and recovery sleep on metabolic and cardiovascular risk indicators: Results from a randomized crossover clinical trialTAP Record · TAP-MTH-0002Same Biomarkers, Different ScoresTAP Record · TAP-ASM-0001TAP Load & Recovery ProfileTAP Record · TAP-MTH-0001Load & Recovery Profile: Methods & DevelopmentTAP Record · TAP-FIG-0001Human Adaptation MapTAP Record · TAP-FIG-0002Recovery trajectoriesTAP Record · TAP-STD-0001Citation & Reuse