Pipette filling sample tubes in a lab

Scientific studies behind the Sapiens diagnostics

Overview of peer-reviewed research behind the Sapiens diagnostics, including research on allostatic load, hair and saliva stress markers, as well as evidence for interventions.

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The relationship between cortisol awakening response and trait resilience in two patient cohorts and one population-based cohort

Salivary Cortisol
Cross-sectional
Medium
Read study

Across depression, cardiovascular and population-based cohorts totalling 880 participants, CAR was computed from three self-collected saliva samples and related to trait resilience. The proportion of CAR non-responders was high in all cohorts (over 50%), and no significant relationship was found between CAR response or increase and trait resilience. Sociodemographic and compliance variables were associated with CAR.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Adverse childhood experiences and diurnal cortisol patterns in older people in England

Salivary Cortisol
Cross-sectional
Medium
Read study

In 587 older adults from the English Longitudinal Study of Ageing, four saliva samples (waking, +30 min, 7pm, bedtime) yielded CAR and diurnal slope in relation to adverse childhood experiences. In men, more adverse experiences were associated with lower waking cortisol, a greater CAR and a flatter diurnal slope; in women, they related to higher 7pm cortisol. Findings suggest a lifelong association between childhood adversity and HPA-axis function.

Biomarker Studies
Saliva Stress Hormones
2015-2024

The School-Ladder Effect: Subjective Socioeconomic Status and Diurnal Cortisol Profile Among Adolescents

Salivary Cortisol
Cross-sectional
Medium
Read study

In 255 adolescents, saliva was collected four times daily across two days to derive cortisol at awakening, CAR, diurnal slope and AUCg by subjective socioeconomic status. Higher school-referenced subjective SES was associated with higher awakening cortisol, steeper diurnal slopes and higher AUCg but not CAR, while city-referenced subjective SES was unrelated to any parameter. Findings highlight the importance of reference group in subjective SES effects on stress physiology.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Diurnal cortisol secretion and health-related quality of life in healthy older people

Salivary Cortisol
Cross-sectional
Medium
Read study

In 140 healthy older adults, eight saliva samples over two days measured awakening cortisol, CAR, morning levels, wake-to-bed slope and bedtime cortisol against health-related quality of life. Higher awakening and bedtime cortisol and a greater CAR were associated with better perceived physical and mental health, and the wake-to-bed slope related positively to physical health. Awakening, bedtime and CAR indices were most relevant to quality of life.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Associations of burnout with awakening and diurnal cortisol among police officers

Salivary Cortisol
Cross-sectional
Medium
Read study

This cross-sectional study of 197 police officers examined associations of burnout with awakening and diurnal salivary cortisol parameters. Greater exhaustion and depersonalization were associated with lower diurnal AUC and a flatter diurnal slope.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Socioeconomic status disparities affect children's anxiety and stress-sensitive cortisol awakening response through parental anxiety

Salivary Cortisol
Cross-sectional
Medium
Read study

Across two studies totalling over 1300 children, family socioeconomic status, parental anxiety, child anxiety and cortisol were examined. Low-SES children showed increased pre-bedtime basal cortisol but a decreased cortisol awakening response, mediated by increased parental and child anxiety. Findings suggest low SES alters children's HPA-axis integrity through parental anxiety.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Overall cortisol, diurnal slope, and stress reactivity in psychosis: An experience sampling approach

Salivary Cortisol
Cross-sectional
Medium
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This experience sampling study measured salivary cortisol over six days in psychotic patients, relatives, and healthy volunteers to assess overall cortisol, diurnal slope, and stress reactivity. There were no group differences in overall cortisol, but relatives showed a steeper diurnal slope and both patient groups showed attenuated cortisol stress reactivity.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Sleep quality and the cortisol awakening response (CAR) among law enforcement officers: The moderating role of leisure time physical activity

Salivary Cortisol
Cross-sectional
Medium
Read study

In 275 police officers, saliva was collected at awakening and 15, 30 and 45 minutes later to assess CAR by sleep quality and leisure-time physical activity. Among insufficiently active officers, poor sleep quality was associated with reduced total awakening cortisol and a blunted post-awakening rise, while no such difference appeared in sufficiently active officers. Physical activity appeared to protect against sleep-related CAR dysregulation.

Biomarker Studies
Saliva Stress Hormones
2015-2024

The cross-sectional relation between medically unexplained physical symptoms (MUPS) and the Cortisol Awakening Response

Salivary Cortisol
Cross-sectional
Medium
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In 296 patients with medically unexplained physical symptoms, salivary CAR was related to symptom clusters, severity and duration. No significant relation was found between CAR and any symptom cluster, severity or duration. The authors conclude CAR is not associated with symptomatology in this heterogeneous population.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Stress management skills, cortisol awakening response, and post-exertional malaise in Chronic Fatigue Syndrome

Salivary Cortisol
Cross-sectional
Medium
Read study

In 117 adults with Chronic Fatigue Syndrome, salivary cortisol at waking and 30 minutes post-waking was used to compute CAR alongside self-reported stress management skills and post-exertional malaise. Greater perceived stress management skills related to a greater CAR, and a greater CAR related to less post-exertional malaise severity. An indirect effect linked stress management skills to reduced malaise via a greater CAR.

Biomarker Studies
Saliva Stress Hormones
Before 2015

Infant hair cortisol: associations with salivary cortisol and environmental context

Salivary Cortisol
Longitudinal
Medium
Read study

In 111 infants assessed at 6 and 12 months, hair cortisol was related to basal salivary cortisol (waking, evening, AUC, diurnal slope) and environmental context. At 12 months, infant hair cortisol was positively associated with waking and evening salivary cortisol and AUC but independent of diurnal slope, while sleep disruption and reduced nighttime sleep related to a flatter slope. Results support hair cortisol as a marker of cumulative exposure alongside diurnal salivary measures.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Alterations of Stress-Related Glucocorticoids and Endocannabinoids in Hair of Chronic Cocaine Users

Hair Endocannabinoids
Case-control
Medium
Read study

Hair concentrations of glucocorticoids and endocannabinoids (2-AG, AEA, OEA, PEA) were compared between recreational cocaine users, dependent cocaine users, and stimulant-naive controls. Dependent users showed lower hair OEA and PEA, and elevated cocaine hair levels predicted increased glucocorticoids and decreased OEA.

Biomarker Studies
Hair Stress Hormones
2015-2024

Childhood Adversity, Self-Esteem, and Diurnal Cortisol Profiles Across the Life Span

Salivary Cortisol
Cross-sectional
Medium
Read study

This study of adults and youths examined whether childhood adversity relates to diurnal salivary cortisol parameters and whether self-esteem explains the link. Childhood adversity was associated with lower awakening cortisol and, via low self-esteem, with flatter cortisol slopes.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Socioeconomic status, perceived control, diurnal cortisol, and physical symptoms: A moderated mediation model

Salivary Cortisol
Cross-sectional
Medium
Read study

Using the MIDUS national sample, morning cortisol and diurnal cortisol slope were examined in relation to socioeconomic status, perceived control and physical symptoms. SES interacted with perceived control to predict cortisol slopes, and a flatter slope mediated the link between lower SES and greater physical symptoms only among those with low perceived control. Perceived control appeared to buffer SES effects on cortisol and health.

Biomarker Studies
Saliva Stress Hormones
2015-2024

The cortisol awakening response: a pilot study on the effects of shift work, morningness and sleep duration

Salivary Cortisol
Cross-sectional
Medium
Read study

Sixteen young men (eight morning-type, eight evening-type) provided saliva on awakening and 30 minutes later after simulated day and night shifts in the laboratory. The CAR was significantly smaller after day sleep than night sleep and increased with total sleep time in evening types. Morning types had higher awakening cortisol, likely reflecting a later circadian waking phase.

Biomarker Studies
Saliva Stress Hormones
Before 2015

Life course predictors of allostatic load among sexual and gender minority (SGM) midlife & older adults

Allostatic Load
Cross-sectional
Medium
Read study

Using NHAS data on 284 sexual and gender minority adults aged 50-97, hierarchical Poisson regressions examined life-course predictors of allostatic load. Lower current assets, adult physical abuse, ever being in an opposite-sex marriage, and older age at first SGM identity disclosure predicted higher AL, whereas childhood SES, lifetime discrimination and identity stigma were not significant.

Allostatic Load Studies
Since 2024

Heart Rate Fragmentation: A Novel Analytic Approach to Detect Allostatic Load Among Healthy Adults

Allostatic Load
Cross-sectional
Medium
Read study

In 156 undergraduates, the nonlinear HRV metric heart rate fragmentation (HRF) was tested as an allostatic load biomarker under a rest-reactivity-recovery paradigm. HRF significantly differentiated the three conditions (p<.001); healthy individuals showed significantly greater HRF reactivity between conditions than those with probable mental health symptoms, who displayed a blunted pattern.

Allostatic Load Studies
Since 2024

Race, Lifetime SES, and Allostatic Load Among Older Adults

Allostatic Load
Cross-sectional
Medium
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Among 518 Black and White adults aged 50+ in the Nashville Stress and Health Study, stable high socioeconomic status was associated with greater odds of high allostatic load. Significant Black-White disparities in AL were observed only among upwardly mobile (OR 1.76) and high-SES (OR 2.22) groups, indicating older Black Americans receive fewer health benefits from higher SES.

Allostatic Load Studies
2015-2024

Hair cortisol and cortisone as markers of stress in Indigenous and non-Indigenous young adults

Hair Steroids
Cross-sectional
Medium
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This cross-sectional analysis of two Australian cohorts (N=325 young adults) assessed hair cortisol and cortisone in relation to sociodemographics, substance use and emotional wellbeing. Indigenous women had higher cortisone than non-Indigenous women, and hair cortisol and cortisone increased with age in Indigenous young adults; no association was found with substance use or emotional wellbeing.

Biomarker Studies
Hair Stress Hormones
2015-2024

Allostatic load and stress biomarkers in a sample of community-dwelling older adults

Allostatic Load
Cross-sectional
Medium
Read study

Among 256 community-dwelling adults aged 65+, the mean allostatic load index (10 biomarkers) was 2.30 with no significant gender difference. AL was associated with number of chronic conditions (beta 0.24), mobility disability (beta 0.58) and handgrip strength (beta 0.06).

Allostatic Load Studies
2015-2024

Discrimination and anger control as pathways linking socioeconomic disadvantage to allostatic load in midlife

Allostatic Load
Cross-sectional
Medium
Read study

Among 909 adults in the MIDUS biomarkers subproject, perceived discrimination was associated with higher allostatic load, and perceived discrimination and anger control sequentially explained the link between socioeconomic disadvantage and AL. Greater discrimination was associated with lower anger control, which accounted for discrimination's effect on AL.

Allostatic Load Studies
2015-2024

Mediators of the relationship between race and allostatic load in African and White Americans

Allostatic Load
Cross-sectional
Medium
Read study

Among 176 healthy middle-aged adults, African Americans had higher allostatic load (11 biomarkers) than White Americans, and a serial pathway of discrimination, experience of anger and poor subjective sleep quality fully mediated the race-AL relationship. Discrimination played an important role in explaining racial differences in AL.

Allostatic Load Studies
2015-2024

The impact of prior day sleep and physical activity on the cortisol awakening response

Salivary Cortisol
Longitudinal
Medium
Read study

In 85 young adults, saliva was collected at waking and 30 minutes later across two consecutive days while accelerometers objectively measured sleep and physical activity. A significant interaction showed that short sleep combined with high physical activity produced an augmented CAR. Both sleep duration and prior-day physical activity should be considered when assessing the CAR.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Dissecting the impact of sleep and stress on the cortisol awakening response in young adults

Salivary Cortisol
Longitudinal
Medium
Read study

Fifty-eight college students provided salivary cortisol during the first hour after awakening across two days, with self-reported stress and sleep. Total sleep time predicted CAR magnitude, while daily hassles and anticipatory stress did not after accounting for sleep. Lower total sleep time was associated with lower awakening cortisol but a greater CAR.

Biomarker Studies
Saliva Stress Hormones
Before 2015

Endocannabinoid concentrations in hair are associated with PTSD symptom severity

Hair Endocannabinoids
Case-control
Medium
Read study

Hair N-acylethanolamide concentrations (PEA, OEA, SEA) were measured in 38 rebel war survivors with PTSD and 38 without in Northern Uganda. PTSD patients showed reduced hair OEA, and all N-acylethanolamides were negatively related to PTSD symptom severity.

Biomarker Studies
Hair Stress Hormones
2015-2024

Fear conditioning depends on the nature of the unconditional stimulus and may be related to hair levels of endocannabinoids

Hair Endocannabinoids
Cross-sectional
Medium
Read study

Study comparing scream, shock, and unpredictable unconditional stimuli on fear conditioning in 109 healthy participants, with hair samples analyzed for endocannabinoids. Exploratory analyses showed hair endocannabinoids were associated with overall physiological arousal during fear conditioning and higher return of fear to the threat cue. This provides first evidence linking hair endocannabinoids to human fear conditioning.

Biomarker Studies
Hair Stress Hormones
2015-2024

Altered hair endocannabinoid levels in mothers with childhood maltreatment and their newborns

Hair Endocannabinoids
Cross-sectional
Medium
Read study

Hair samples from mothers and newborns were analyzed for endocannabinoids to assess intergenerational effects of maternal childhood maltreatment during the last trimester. Mothers with maltreatment showed higher 1-AG and lower SEA, and their newborns exhibited higher 1-AG and OEA.

Biomarker Studies
Hair Stress Hormones
2015-2024

Testosterone but not cortisol concentrations in hair correlate between mothers and their prepubertal children under real-life stress conditions

Hair Steroids
Cross-sectional
Medium
Read study

This study measured hair testosterone and cortisol in 45 healthy mothers and their prepubertal children during COVID-19 stress conditions. Hair testosterone concentrations correlated positively between mothers and children (particularly strong in women with intense anger), whereas hair cortisol did not correlate between mothers and children.

Biomarker Studies
Hair Stress Hormones
2015-2024

Trauma film viewing and intrusive memories: Relationship between salivary alpha amylase, endocannabinoids, and cortisol

Hair Endocannabinoids
Cross-sectional
Medium
Read study

Adapted trauma film paradigm collecting saliva and hair samples tested for endocannabinoids, cortisol, and salivary alpha amylase. Salivary alpha amylase activity was positively correlated with salivary endocannabinoids, particularly 2-AG. Decreases in AEA post-stress were associated with more intrusive memories in cortisol non-responders.

Biomarker Studies
Hair Stress Hormones
Since 2024

Hair endocannabinoids predict physiological fear conditioning and salivary endocannabinoids predict subjective stress reactivity in humans

Hair Endocannabinoids
Cross-sectional
Medium
Read study

Study collecting hair and saliva samples from 99 healthy participants completing a fear conditioning and intrusive memory task. Hair 2-arachidonoylglycerol was associated with better retention of safety learning during extinction and renewal, while hair OEA and PEA were associated with overall physiological arousal. Salivary ECs predicted subjective stress responses.

Biomarker Studies
Hair Stress Hormones
2015-2024

Endocannabinoid concentrations in hair and mental health of unaccompanied refugee minors

Hair Endocannabinoids
Cross-sectional
Medium
Read study

Cross-sectional study quantifying AEA, 2-AG, OEA, SEA, and PEA in 3-cm scalp hair segments of 91 male unaccompanied refugee minors using LC-MS/MS. Associations of hair ECs with psychological symptoms were weak and inconsistent, with only 2-AG positively correlated with depression. OEA, SEA, and PEA were positively related to prosocial behavior and self-efficacy.

Biomarker Studies
Hair Stress Hormones
2015-2024

Endocannabinoid and steroid hormone levels during and after pregnancy in fingernail samples from mothers and their infants

Hair Endocannabinoids
Longitudinal
Medium
Read study

Longitudinal pilot study quantifying four endocannabinoids (2-AG, AEA, OEA, PEA) and five steroid hormones in fingernail samples from five mothers and four infants across pregnancy and postpartum via LC-MS/MS. Endocannabinoid concentrations were lower in the third trimester than the second, while progesterone and cortisol rose toward delivery. Demonstrates feasibility of fingernails as a keratinized matrix for retrospective EC assessment.

Biomarker Studies
Hair Stress Hormones
Since 2024

Age-related changes in endogenous glucocorticoids, gonadal steroids, endocannabinoids and their ratios in plasma and hair from the male C57BL/6 mice

Hair Endocannabinoids
Longitudinal
Medium
Read study

Longitudinal animal study developing an LC-MS/MS framework to measure ten hormones and two endocannabinoids (AEA, 1-AG) in both plasma and hair of male C57BL/6 mice from 21 days to 10 months. Endocannabinoids showed nadir and zenith values at 2.7 and 3.4 months, respectively, and age-related patterns in hair mirrored those in plasma. Absolute levels differed markedly between the two matrices.

Biomarker Studies
Hair Stress Hormones
2015-2024

Awakening not associated with an increased rate of cortisol secretion

Salivary Cortisol
Cross-sectional
Medium
Read study

Using ambulatory microdialysis to measure tissue-free cortisol before and after awakening in 201 healthy volunteers at home, the authors found no change in the rate of cortisol increase in the hour after waking versus the hour before. Substantial interindividual variability was observed, partly attributable to sleep duration and timing. The findings question whether awakening itself drives the cortisol awakening response.

Biomarker Studies
Saliva Stress Hormones
Since 2024

Morning and evening type: The cortisol awakening response in a sleep laboratory

Salivary Cortisol
Cross-sectional
Medium
Read study

In 103 young men studied under supervised sleep-laboratory conditions, saliva was collected at 0, 15 and 30 minutes post-awakening to assess CAR by chronotype. Greater morningness was associated with higher awakening cortisol and greater overall cortisol output but not with the CAR increase itself. Results held under objectively controlled compliance conditions.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Hair levels of steroid, endocannabinoid, and the ratio biomarkers predict viral suppression among people living with HIV/AIDS in China

Hair Endocannabinoids
Cross-sectional
Medium
Read study

Cross-sectional study measuring steroids and endocannabinoids (AEA, 1-AG) in hair of 1198 people living with HIV/AIDS on antiretroviral therapy via LC-APCI-MS/MS. Hair AEA, DHEA, and the cortisol-to-DHEA ratio differed by viral suppression status and correlated with viral load. Hair AEA of 2.4 pg/mg predicted viral suppression with modest classification performance.

Biomarker Studies
Hair Stress Hormones
2015-2024

Determinants of cortisol awakening responses to naps and nighttime sleep

Salivary Cortisol
Cross-sectional
Medium
Read study

Across EEG-monitored nap and nighttime sleep conditions, saliva was collected at 0, 30, 45 and 60 minutes post-awakening to assess CAR determinants. Cortisol increases were observed after all conditions except a 50-minute afternoon nap, and were predicted by Stage 2 sleep after nighttime sleep and Stage 1 sleep after morning naps. Sleep duration and architecture contribute to CAR generation.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Network analysis of the hair-based nine hormones from four neuroendocrine systems

Hair Endocannabinoids
Cross-sectional
Medium
Read study

Cross-sectional study measuring nine hair hormones from four neuroendocrine systems, including endocannabinoids, in 252 healthy students via LC/MS, then constructing a hormonal network. The HPA axis (cortisol, cortisone) formed the central hub with melatonin as bridge hormone, while endocannabinoids integrated into a sparse, stable network. Demographic variables affected only local network features.

Biomarker Studies
Hair Stress Hormones
Since 2024

Health risk behaviours and allostatic load: A systematic review

Allostatic Load
Systematic review
High
Read study

A systematic review of 26 human studies examining how health-risk behaviours (obesity, alcohol, smoking, drug use, physical inactivity, sleep impairment) relate to allostatic load, a multisystem index of cumulative physiological burden.

Allostatic Load Studies
2015-2024

Salivary cortisol in post-traumatic stress disorder: a systematic review and meta-analysis

Salivary Cortisol
Meta-analysis
High
Read study

A systematic review and meta-analysis pooling published data to compare salivary cortisol concentrations between PTSD patients and controls, motivated by inconsistent prior findings on cortisol as a PTSD susceptibility marker.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Effects of physical exercise on anxiety depression and emotion regulation in children with attention deficit hyperactivity disorder: a systematic review and meta-analysis

Intervention
Meta-analysis
High
Read study

A systematic review and meta-analysis of 18 RCTs (830 children) evaluating physical-exercise interventions for anxiety, depression, and emotional regulation in children with ADHD, using standardized mean differences with GRADE and risk-of-bias assessment.

Intervention Studies
Self-Assessment
Since 2024

Consumption of ultra-processed foods and health status: a systematic review and meta-analysis

Nutrition & Health
Meta-analysis
High
Read study

A systematic review and meta-analysis of 23 observational studies (10 cross-sectional, 13 prospective cohorts) examining associations between ultra-processed food consumption and health status, including cardiometabolic outcomes and mortality.

Intervention Studies
2015-2024

DHEA as a Biomarker of Stress: A Systematic Review and Meta-Analysis

Stress Biomarkers
Meta-analysis
High
Read study

A systematic review and meta-analysis of 14 acute-stress studies (631 participants) testing whether DHEA/DHEA-sulfate levels change with acute stress and can serve as a stress biomarker, measured in blood or saliva.

Biomarker Studies
2015-2024

Emotion-regulation strategies across psychopathology: A meta-analytic review

Stress Resilience
Meta-analysis
High
Read study

A meta-analysis of 241 effect sizes from 114 studies examining how six dispositional emotion-regulation strategies (acceptance, avoidance, problem solving, reappraisal, rumination, suppression) relate to symptoms of anxiety, depression, eating, and substance-use disorders.

Biomarker Studies
Self-Assessment
Before 2015

Yoga Nidra for hypertension: A systematic review and meta-analysis

Intervention
Meta-analysis
High
Read study

A systematic review and meta-analysis of 5 RCTs and 3 non-RCTs (482 participants) assessing Yoga Nidra for hypertension, with change in systolic and diastolic blood pressure as the primary outcome.

Intervention Studies
Since 2024

The association between psychological stress and metabolic syndrome: A systematic review and meta‐analysis

Stress Biomarkers
Meta-analysis
High
Read study

A systematic review and meta-analysis examining whether psychological stress is associated with metabolic syndrome and whether the association differs by source of stress (occupational, general, etc.).

Biomarker Studies
Self-Assessment
2015-2024

Efficacy of Mindfulness-Based Interventions for Attention and Executive Function in Children and Adolescents—a Systematic Review

Intervention
Systematic review
High
Read study

A systematic review of 13 randomized/quasi-randomized controlled trials evaluating mindfulness-based interventions (including yoga and meditation) for attention and executive function in children and adolescents, with study quality rated on the PEDro scale.

Intervention Studies
2015-2024

Dietary protein intake and bone health

Nutrition & Health
Systematic review
High
Read study

A systematic review of RCTs and prospective cohort studies (through Feb 2019) evaluating the effect of high versus low dietary protein intake alone on bone mineral density and bone biomarkers in adults.

Intervention Studies
2015-2024

Dietary sugar consumption and health: umbrella review

Nutrition & Health
Systematic review
High
Read study

An umbrella review of 73 existing meta-analyses (83 health outcomes) evaluating the quality and validity of evidence on dietary sugar consumption and health, spanning observational studies and RCTs.

Intervention Studies
2015-2024

Exercise training and bone mineral density in postmenopausal women: an updated systematic review and meta-analysis of intervention studies with emphasis on potential moderators

Intervention
Meta-analysis
High
Read study

An updated systematic review and meta-analysis of 80 controlled exercise trials (at least 6 months, 5,581 participants) examining exercise effects on bone mineral density in postmenopausal women and potential moderators such as bone status and supervision.

Intervention Studies
2015-2024

The association between acute stress & empathy: A systematic literature review

Cognition & Stress
Systematic review
High
Read study

A systematic review of how acute stress affects empathy, synthesising evidence on affective empathy (including stress contagion between people) and cognitive empathy (emotion recognition and perspective taking) and the contextual factors that shape these effects.

Biomarker Studies
2015-2024

The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations

Nutrition & Health
Systematic review
High
Read study

A National Osteoporosis Foundation scientific statement based on a systematic review of literature since 2000 on modifiable lifestyle factors (nutrients, food patterns, physical activity, contraceptives) influencing peak bone mass in youth, with an evidence-grading system.

Intervention Studies
2015-2024

Before-bedtime passive body heating by warm shower or bath to improve sleep: A systematic review and meta-analysis

Sleep & Stress
Meta-analysis
High
Read study

A systematic review and meta-analysis of 17 studies (13 with quantitative data) on before-bedtime water-based passive body heating (warm shower or bath) and its effects on sleep onset, efficiency, and quality.

Intervention Studies
2015-2024

"Give me a break!" A systematic review and meta-analysis on the efficacy of micro-breaks for increasing well-being and performance

Intervention
Meta-analysis
High
Read study

A systematic review and meta-analysis of 22 study samples (2,335 participants) estimating the efficacy of workplace micro-breaks for well-being (vigor, fatigue) and performance, and the conditions under which they help.

Intervention Studies
Self-Assessment
2015-2024

Dietary protein and bone health: a systematic review and meta-analysis from the National Osteoporosis Foundation1,2

Nutrition & Health
Meta-analysis
High
Read study

A systematic review and meta-analysis for the National Osteoporosis Foundation of 16 RCTs and 20 prospective cohorts evaluating dietary protein, alone and with calcium plus or minus vitamin D, on bone health measures in adults.

Intervention Studies
2015-2024

Swimming and cycling do not cause positive effects on bone mineral density: a systematic review

Intervention
Systematic review
High
Read study

A systematic review (PRISMA) of studies evaluating whether swimming and cycling improve bone mineral density, as non-weight-bearing exercise options considered for osteoporosis prevention.

Intervention Studies
2015-2024

High Versus low Dietary Protein Intake and Bone Health in Older Adults: a Systematic Review and Meta-Analysis

Nutrition & Health
Meta-analysis
High
Read study

A systematic review and meta-analysis of 12 cohort studies and 1 RCT examining dietary protein intake above the RDA on BMD/BMC, bone turnover markers, and fracture risk in adults aged 65 and older.

Intervention Studies
2015-2024

Dietary protein and bone health across the life-course: an updated systematic review and meta-analysis over 40 years

Nutrition & Health
Meta-analysis
High
Read study

An updated systematic review and meta-analysis of 127 papers (correlational, fracture-risk, and supplementation studies) over 40 years assessing dietary protein and bone health across the life-course.

Intervention Studies
2015-2024

Calcium intake and bone mineral density: systematic review and meta-analysis

Nutrition & Health
Meta-analysis
High
Read study

A random-effects meta-analysis of 59 RCTs comparing dietary and supplemental calcium (with or without vitamin D) on bone mineral density in people over 50.

Intervention Studies
2015-2024

Less Adaptive or More Maladaptive? A Meta–analytic Investigation of Procrastination and Coping

Stress Resilience
Meta-analysis
High
Read study

Meta-analysis integrating published and unpublished data (15 samples, N=4,357) on associations between trait procrastination and adaptive versus maladaptive coping, and testing whether coping explains the procrastination-stress relationship.

Biomarker Studies
Self-Assessment
2015-2024

Brief mindfulness meditation training alters psychological and neuroendocrine responses to social evaluative stress

Intervention
RCT
High
Read study

Sixty-six young adults were randomly assigned to a brief three-day mindfulness meditation training or an analytic cognitive-training control, then completed the Trier Social Stress Test with salivary cortisol, blood pressure, and self-reported stress measured. The study tested whether brief mindfulness training buffers stress reactivity and whether dispositional mindfulness moderates effects.

Intervention Studies
Saliva Stress Hormones
Before 2015

Effects of Soft Drink Consumption on Nutrition and Health: A Systematic Review and Meta-Analysis

Nutrition & Health
Meta-analysis
High
Read study

A meta-analysis of 88 studies examining associations between soft-drink consumption and nutrition and health outcomes, accounting for study design and funding source.

Intervention Studies
Before 2015

Evaluating the effect of stress management programmes at the work-site on absenteeism reduction: a systematic review

Intervention
Systematic review
High
Read study

A systematic review of nine experimental/quasi-experimental studies evaluating whether worksite stress-management programmes reduce employee absenteeism.

Intervention Studies
Before 2015

Work Stress, Caregiving, and Allostatic Load: Prospective Results From the Whitehall II Cohort Study

Allostatic Load
Prospective cohort
High
Read study

A prospective analysis of 7,007 Whitehall II civil servants testing whether baseline job strain and informal caregiving predict allostatic load (a 9-biomarker index) over two follow-ups spanning roughly a decade.

Allostatic Load Studies
2015-2024

Cognitive-behavioral stress management buffers decreases in dehydroepiandrosterone sulfate (DHEA-S) and increases in the cortisol/DHEA-S ratio and reduces mood disturbance and perceived stress among HIV-seropositive men

Intervention
RCT
High
Read study

An RCT in HIV-seropositive men randomized to a 10-week group cognitive-behavioral stress management (CBSM) intervention (n=43) or wait-list control (n=24), measuring DHEA-S, the cortisol/DHEA-S ratio, mood, and perceived stress before and after.

Intervention Studies
Before 2015

Short-term meditation training improves attention and self-regulation

Intervention
RCT
High
Read study

Forty undergraduate students were randomly assigned to five days of integrative body-mind meditation training or a relaxation-training control, with attention (Attention Network Test), mood, cortisol, and immune measures assessed. The study tested whether brief meditation improves attention and self-regulation.

Intervention Studies
Before 2015

Benefits of Expressive Writing in Lowering Rumination and Depressive Symptoms

Intervention
RCT
High
Read study

A controlled experiment in which depression-vulnerable college students wrote for three consecutive days in either an expressive-writing or control condition, with depression and rumination assessed up to six months later.

Intervention Studies
Before 2015

Mindfulness meditation modulates stress-eating and its neural correlates

Intervention
RCT
High
Read study

Sixty-six meditation-naive individuals prone to stress-eating were assigned to a 31-day web-based mindfulness meditation training or a health-training control, with behavioral measures and resting-state fMRI collected before and after. The study tested effects of mindfulness on stress-eating and its neural correlates.

Intervention Studies
Since 2024

Gut-microbiota-targeted diets modulate human immune status

Inflammation
RCT
High
Read study

A 17-week randomized prospective trial (n=18/arm) in healthy adults comparing high-fiber and fermented-food diets, with deep multi-omic microbiome and immune profiling including cytokine responses and inflammatory markers.

Intervention Studies
2015-2024

A 2-yr Randomized Controlled Trial on Creatine Supplementation during Exercise for Postmenopausal Bone Health

Nutrition & Health
RCT
High
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A 2-year RCT in 237 postmenopausal women randomized to creatine monohydrate or placebo during resistance training and walking, with femoral-neck BMD as the primary outcome plus hip geometry and function.

Intervention Studies
2015-2024

Allostatic load score and lifestyle factors in the SWAN cohort: A longitudinal analysis

Allostatic Load
Longitudinal
High
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A longitudinal analysis of 1,976 women from the SWAN cohort (at least seven waves) using Poisson mixed models to examine how lifestyle factors affect allostatic load over time.

Allostatic Load Studies
Since 2024

The effect of foot-bath with or without the essential oil of lavender on the autonomic nervous system: a randomized trial

HRV & Autonomic
RCT
High
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A randomized crossover trial in healthy young women tested whether a 10-minute hot foot-bath, with or without lavender essential oil, altered autonomic nervous system activity assessed via heart rate variability, fingertip blood flow, and respiratory rate. Autonomic balance was compared between foot-baths with and without the added oil.

Intervention Studies
HRV Analysis
Before 2015

The Effect of Cold Showering on Health and Work: A Randomized Controlled Trial

Intervention
RCT
High
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This large RCT randomized 3018 adults to take a hot-to-cold shower for 30, 60, or 90 seconds, or to a control group, for 30 consecutive days followed by 60 days of optional cold showering. Primary outcomes were self-reported illness days and sickness absence from work, with quality of life and work productivity as secondary outcomes.

Intervention Studies
Self-Assessment
2015-2024

Mild dehydration impairs cognitive performance and mood of men

Cognition & Stress
RCT
High
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In a randomized, single-blind crossover experiment, 26 young men completed treadmill-walking trials under exercise-induced dehydration (with or without a diuretic) versus a euhydrated control condition. Cognitive performance, mood (Profile of Mood States), and symptoms were assessed at roughly 1.6% body-mass loss.

Intervention Studies
Self-Assessment
Before 2015

Mild dehydration affects mood in healthy young women

Cognition & Stress
RCT
High
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Using a placebo-controlled crossover design, 25 young women underwent exercise-induced dehydration (with or without a diuretic) versus euhydration, with cognition, mood, and dehydration symptoms measured at rest and during exercise. Mean dehydration reached about 1.36% of body mass.

Intervention Studies
Self-Assessment
Before 2015

Resistance training and executive functions: a 12-month randomized controlled trial

Cognition & Stress
RCT
High
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This 12-month single-blind RCT randomized 155 community-dwelling women aged 65-75 to once-weekly or twice-weekly resistance training or to twice-weekly balance-and-tone control training. The primary outcome was executive cognitive function (Stroop test), with additional cognitive, gait, and brain-volume measures.

Intervention Studies
Before 2015

Sleep regularity is a stronger predictor of mortality risk than sleep duration: A prospective cohort study

Sleep & Stress
Prospective cohort
High
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Using more than 10 million hours of accelerometer data from 60,977 UK Biobank participants, the study derived a Sleep Regularity Index and compared how sleep regularity versus sleep duration predicted all-cause and cause-specific mortality over about 6-8 years. Models adjusted for demographic, lifestyle, and health factors.

Biomarker Studies
Since 2024

The CIRCORT database: Reference ranges and seasonal changes in diurnal salivary cortisol derived from a meta-dataset comprised of 15 field studies

Salivary Cortisol
Methodological/validation
High
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The CIRCORT database compiled 104,623 diurnal salivary cortisol samples from 18,698 individuals across 15 field studies to derive normative reference ranges and model diurnal cortisol with mixed-effects growth curves. It examined effects of age, sex, and season on salivary cortisol.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Reference ranges for ambulatory heart rate measurements in a middle-aged population

HRV & Autonomic
Methodological/validation
High
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Using 24-hour ECGs from 5,809 atrial-fibrillation-free adults aged 50-65 in the Swedish CArdioPulmonary Imaging Study, this study derived reference ranges for ambulatory heart rate in a healthy subset (n=3,942) and examined clinical correlates. Mean, minimum, daytime, and night-time heart rates were reported.

Biomarker Studies
Since 2024

Short Sleep Is Associated With Low Bone Mineral Density and Osteoporosis in the Women's Health Initiative

Sleep & Stress
Cross-sectional
High
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This cross-sectional analysis of 11,084 postmenopausal women in the Women's Health Initiative examined associations between self-reported sleep duration and quality and bone mineral density and osteoporosis, using DXA and adjusting for many health and lifestyle covariates.

Biomarker Studies
Self-Assessment
2015-2024

Time spent in outdoor light is associated with mood, sleep, and circadian rhythm-related outcomes: A cross-sectional and longitudinal study in over 400,000 UK Biobank participants

Sleep & Stress
Cross-sectional
High
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In over 400,000 UK Biobank adults, the study examined cross-sectional and longitudinal associations between self-reported time spent in daytime outdoor light and mood, sleep, and circadian outcomes. Analyses adjusted for demographic, lifestyle, and employment factors.

Biomarker Studies
Self-Assessment
2015-2024

Technical and clinical aspects of cortisol as a biochemical marker of chronic stress

Hair Steroids
Narrative review
Medium
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This review covers the technical and clinical use of cortisol as a biochemical marker of chronic stress, explaining how chronic stress links to allostatic load and comparing serum, salivary, urinary, and hair cortisol measurements. It highlights the difficulty of capturing long-term cortisol exposure due to circadian variation and protein binding.

Biomarker Studies
2015-2024

Pilot study of adrenal steroid hormones in hair as an indicator of chronic mental and physical stress

Hair Steroids
Cross-sectional
Medium
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In a cross-sectional pilot study of 40 healthy students, hair concentrations of cortisol, cortisone, and DHEA were related to physical activity, mental burden, subjective stress perception, depressiveness, anxiety, sense of coherence, and resilience to assess chronic HPA-axis activation.

Biomarker Studies
Hair Stress Hormones
2015-2024

A clinical allostatic load index is associated with burnout symptoms and hypocortisolemic profiles in healthy workers

Allostatic Load
Cross-sectional
Medium
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This study computed a clinically normed allostatic load index from 15 neuroendocrine, immune, metabolic, and cardiovascular biomarkers in 30 healthy workers, alongside diurnal and Trier Social Stress Test salivary cortisol and alpha-amylase, plus questionnaires on chronic stress, burnout, and depression.

Allostatic Load Studies
Saliva Stress Hormones
Before 2015

Hair cortisol and cortisone measurements for the diagnosis of overt and mild Cushing's syndrome

Hair Steroids
Methodological/validation
Medium
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This single-centre retrospective study measured hair cortisol and cortisone by LC-MS/MS in 48 women with overt or mild Cushing's syndrome and 84 controls, comparing diagnostic performance against standard tests across the two disease severities.

Biomarker Studies
Hair Stress Hormones
2015-2024

Allostatic load and heart rate variability as health risk indicators

HRV & Autonomic
Cross-sectional
Medium
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This study compared two health-risk indicator systems, allostatic load and heart rate variability, by computing an allostatic load score from eleven biomarkers plus cortisol and relating it to HRV measured with frequency-domain, time-domain, and Poincaré methods. It also assessed the feasibility of adding HRV indicators to allostatic load assessments.

Allostatic Load Studies
HRV Analysis
2015-2024

Hair Measurements of Cortisol, DHEA, and DHEA to Cortisol Ratio as Biomarkers of Chronic Stress among People Living with HIV in China: Known-Group Validation

Hair Steroids
Methodological/validation
Medium
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Using hair samples and self-report surveys from 60 people living with HIV in China, this pilot known-groups validation study compared hair cortisol, DHEA, and the DHEA-to-cortisol ratio between psychologist-classified high-stress and low-stress groups, examining whether antiretroviral status affected associations.

Biomarker Studies
Hair Stress Hormones
2015-2024

Stress and Health: A Review of Psychobiological Processes

Allostatic Load
Narrative review
Medium
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This review outlines psychobiological processes linking stress to health, covering the stress response and allostatic load and key mechanisms such as HPA-axis and cortisol regulation, the autonomic nervous system, and gene expression. It illustrates clinical relevance using infectious-disease risk.

Allostatic Load Studies
2015-2024

Work Stress and Employee Health: A Multidisciplinary Review

Allostatic Load
Narrative review
Medium
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This multidisciplinary review uses the allostatic load model as an organizing framework to synthesize evidence on how workplace psychosocial stressors affect health, spanning management, epidemiology, and physiology. It distinguishes primary, secondary, and tertiary allostatic load mediators and disease endpoints.

Allostatic Load Studies
Before 2015

Analysis of cortisol in hair – State of the art and future directions

Hair Steroids
Narrative review
Medium
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This methodological review evaluates the analysis of cortisol in hair as a retrospective index of integrated cortisol secretion over months, summarizing evidence on its validity as a marker of long-term systemic cortisol, its reliability across assessments, and robustness to confounders. It also considers extending hair analysis to other steroid hormones.

Biomarker Studies
Before 2015

Allostatic Load in Clinical Practice

Allostatic Load
Narrative review
Medium
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A narrative/clinical review discussing the role of allostatic load and allostatic overload in the balance between health and disease, and proposing a clinimetric staging system for its longitudinal development in clinical practice.

Allostatic Load Studies
2015-2024

Is there an independent association between burnout and increased allostatic load? Testing the contribution of psychological distress and depression

Allostatic Load
Cross-sectional
Medium
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In 3283 participants, this study tested whether burnout is associated with allostatic load independent of psychological distress and depression, measuring burnout, cynicism, professional efficacy, distress, depression, and an allostatic load index.

Allostatic Load Studies
2015-2024

The effects of single testosterone administration and stress induction on steroid hormone levels in hair

Hair Steroids
Methodological/validation
Medium
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A randomized, double-blind, placebo-controlled study testing whether single isolated events register in hair steroids, using a single 150 mg transdermal testosterone dose and an acute laboratory stressor (cold pressor test), with hair testosterone and cortisol measured by LC-MS/MS. It also explored contextual factors such as relationship status.

Biomarker Studies
Hair Stress Hormones
Since 2024

Detection of physiological concentrations of cortisol and cortisone in human hair

Hair Steroids
Methodological/validation
Medium
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A methodological study developing and validating an LC-MS technique to extract, purify, and quantify endogenous cortisol and cortisone in human hair, tested on 44 hair samples across a wide age range.

Biomarker Studies
Hair Stress Hormones
Before 2015

Cellular allostatic load is linked to increased energy expenditure and accelerated biological aging

Allostatic Load
Experimental/mechanistic
Medium
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A longitudinal in-vitro study profiling three human fibroblast lines across their lifespan under chronic glucocorticoid exposure to define the energetic and cellular basis of allostatic load, measuring energy expenditure, mitochondrial function, DNA-methylation clocks, and telomere shortening.

Allostatic Load Studies
2015-2024

Allostatic load biomarkers of chronic stress and impact on health and cognition

Allostatic Load
Narrative review
Medium
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This review presents the allostatic load model as a temporal cascade of multisystem physiological dysregulation contributing to disease, drawing on studies that use a neuroendocrine, immune, metabolic, and cardiovascular allostatic load index. It discusses the effects of chronic stress on physical and mental health and successful ageing.

Allostatic Load Studies
Before 2015

The streamlined Allostatic Load Index: a replication of study results

Allostatic Load
Cross-sectional
Medium
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In 12,477 German industrial employees, this study replicated a streamlined five-variable allostatic load index (built from diastolic blood pressure, waist circumference, HbA1c, LDL, and HRV) and tested its association with work stress measured by the effort-reward imbalance questionnaire.

Allostatic Load Studies
2015-2024

You look stressed: A pilot study on facial action unit activity in the context of psychosocial stress

Stress Biomarkers
Cross-sectional
Medium
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This correlative pilot study filmed 62 adults during the Trier Social Stress Test and used software to quantify 13 facial action units, relating them to salivary cortisol, subjective stress, heart rate, and high-frequency HRV responses. It examined how facial muscle activity maps onto the psychosocial stress response.

Biomarker Studies
Saliva Stress Hormones
2015-2024

Hair cortisol and self-reported stress in healthy, working adults

Hair Steroids
Cross-sectional
Medium
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In 132 public-sector employees, hair cortisol concentration (reflecting about 12 weeks of secretion) was compared with several self-reported stress measures, including perceived stress, effort-reward imbalance, ecological momentary assessment, and appraisal of stressful life events, with associations adjusted for confounders.

Biomarker Studies
Hair Stress Hormones
2015-2024

Hair cortisol and work stress: Importance of workload and stress model (JDCS or ERI)

Hair Steroids
Cross-sectional
Medium
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This study compared hair cortisol concentrations between a high-workload sample (n=81) and a normal-workload sample (n=91) and tested their relationship to two work-stress models, job demand-control-support and effort-reward imbalance. It examined whether workload moderated the stress-cortisol link.

Biomarker Studies
Hair Stress Hormones
2015-2024