Non-Cochrane · aetiology · PM41440166

Evaluating Salivary Cortisol and Alpha-Amylase as Candidate Biomarkers in Anorexia Nervosa: A Systematic Review and Meta-Analysis.

Seura Takahiro, Nanba Yuuna · European journal of investigation in health, psychology and education · 2025 · PubMed · doi:10.3390/ejihpe15120260

Findings

11 findings

Population
Patients with anorexia nervosa (any age or sex)Anorexia nervosa (diagnosed by clinical evaluation or DSM/ICD criteria; exposure)Healthy normal-weight controlsSalivary cortisol level
Various collection times · Overall (all reports)
SMD 0.69 [0.54, 0.85]
GRADE not reported
17 studies · 1189 participants
Patients with anorexia nervosa (any age or sex)Anorexia nervosa (diagnosed by clinical evaluation or DSM/ICD criteria; exposure)Healthy normal-weight controlsSalivary alpha-amylase level
Various collection times · Sensitivity analysis excluding four studies with possibly overlapping datasets
SMD -1.12 [-2.16, -0.09]
GRADE not reported
2 studies
Patients with anorexia nervosa (any age or sex)Anorexia nervosa (diagnosed by clinical evaluation or DSM/ICD criteria; exposure)Healthy normal-weight controlsSalivary cortisol level
Various collection times · Sensitivity analysis excluding four studies with possibly overlapping datasets
SMD 0.68 [0.5, 0.85]
GRADE not reported
13 studies
Patients with anorexia nervosa (any age or sex)Anorexia nervosa (diagnosed by clinical evaluation or DSM/ICD criteria; exposure)Healthy normal-weight controlsSalivary alpha-amylase level
Various collection times · Overall (all reports)
SMD -0.48 [-1.05, 0.1]
GRADE not reported
6 studies · 438 participants
Patients with anorexia nervosa (any age or sex)Anorexia nervosa (diagnosed by clinical evaluation or DSM/ICD criteria; exposure)Healthy normal-weight controlsSalivary cortisol level
Various collection times · Meta-regression on mean patient age (after excluding four studies)
Meta-regression coefficient (SMD per unit of age) -0.005 [-0.41, 0.3]
GRADE not reported
Studies not reported
Patients with anorexia nervosa (any age or sex)Anorexia nervosa (diagnosed by clinical evaluation or DSM/ICD criteria; exposure)Healthy normal-weight controlsSalivary cortisol level
Various collection times · Meta-regression on mean patient BMI (after excluding four studies)
Meta-regression coefficient (SMD per BMI unit) 0.021 [-0.07, 1.5]
GRADE not reported
Studies not reported
Patients with anorexia nervosa (any age or sex)Anorexia nervosa (diagnosed by clinical evaluation or DSM/ICD criteria; exposure)Healthy normal-weight controlsSalivary cortisol level
Various collection times · Subgroup by measurement method: ELISA (after excluding four studies)
Unresolved: the two extractors disagree on this row.
SMD 0.76 [0.54, 0.98]
GRADE not reported
Studies not reported
Patients with anorexia nervosa (any age or sex)Anorexia nervosa (diagnosed by clinical evaluation or DSM/ICD criteria; exposure)Healthy normal-weight controlsSalivary cortisol level
Various collection times · Subgroup by measurement method: Other methods (RIA, EIA, LIA) (after excluding four studies)
Unresolved: the two extractors disagree on this row.
SMD 0.55 [0.27, 0.83]
GRADE not reported
Studies not reported
Individuals of any age or sex with anorexia nervosa (AN) and healthy normal-weight controlsAnorexia nervosa (diagnosed by clinical evaluation or DSM/ICD criteria); Saliva collected within 30 min after awakeningHealthy normal-weight controlsSalivary cortisol level
30 min after awakening · Subgroup by timing of saliva collection: 30 min after awakening
SMD 0.97 [0.60, 1.34]
GRADE not reported
4 studies
Individuals of any age or sex with anorexia nervosa (AN) and healthy normal-weight controlsAnorexia nervosa (diagnosed by clinical evaluation or DSM/ICD criteria); Saliva collected in the morning (AM)Healthy normal-weight controlsSalivary cortisol level
Morning (AM) · Subgroup by timing of saliva collection: AM
SMD 0.53 [0.24, 0.83]
GRADE not reported
8 studies
Individuals of any age or sex with anorexia nervosa (AN) and healthy normal-weight controlsAnorexia nervosa (diagnosed by clinical evaluation or DSM/ICD criteria); Saliva collected in the afternoon or evening (PM)Healthy normal-weight controlsSalivary cortisol level
Afternoon or evening (PM) · Subgroup by timing of saliva collection: PM
SMD 0.71 [0.45, 0.97]
GRADE not reported
8 studies

Included primary studies 19

Open in Studies
StudyYearAlso included byOutcomes it informs hereTrial data
Paszynska 2015
Salivary enzyme activity in anorexic persons—a controlled clinical trial.
PMID:25753979
20151 other reviewnot statednot extracted yet
Paszynska 2017
Enzyme activities in parotid saliva of patients with the restrictive type of anorexia nervosa.
PMID:28068524
20171 other reviewnot statednot extracted yet
A. M. Monteleone 2015
Childhood trauma and cortisol awakening response in symptomatic patients with anorexia nervosa and bulimia nervosa.
PMID:25808182
2015this review onlynot statednot extracted yet
A. M. Monteleone 2016
Underweight subjects with anorexia nervosa have an enhanced salivary cortisol response not seen in weight restored subjects with anorexia…
PMID:27236605
2016this review onlynot statednot extracted yet
A. M. Monteleone 2018
Deranged emotional and cortisol responses to a psychosocial stressor in anorexia nervosa women with childhood trauma exposure: Evidence…
PMID:29936175
2018this review onlynot statednot extracted yet
dos Santos 2007
Absence of circadian salivary cortisol rhythm in women with anorexia nervosa.
PMID:17289511
2007this review onlynot statednot extracted yet
Oskis 2012
Diurnal patterns of salivary cortisol and DHEA in adolescent anorexia nervosa.
PMID:22356124
2012this review onlynot statednot extracted yet
P. Monteleone 2011a
Asymmetry of salivary cortisol and α-amylase responses to psychosocial stress in anorexia nervosa but not in bulimia nervosa.
PMID:21284914
2011this review onlynot statednot extracted yet
P. Monteleone 2011b
Abnormal diurnal patterns of salivary α-amylase and cortisol secretion in acute patients with anorexia nervosa.
PMID:21745126
2011this review onlynot statednot extracted yet
Paszynska 2016
Salivary alpha-amylase, secretory IgA and free cortisol as neurobiological components of the stress response in the acute phase of…
PMID:26983011
2016this review onlynot statednot extracted yet
Paszynska 2020
Is there a link between stress and immune biomarkers and salivary opiorphin in patients with a restrictive-type of anorexia nervosa?
PMID:30880537
2020this review onlynot statednot extracted yet
Putignano 2001
Salivary cortisol measurement in normal-weight, obese and anorexic women: comparison with plasma cortisol.
PMID:11454512
2001this review onlynot statednot extracted yet
Schmalbach 2020
Cortisol reactivity in patients with anorexia nervosa after stress induction.
PMID:32778654
2020this review onlynot statednot extracted yet
Schorr 2015
Cortisol Measures Across the Weight Spectrum.
PMID:26171799
2015this review onlynot statednot extracted yet
Seed 2002
Basal activity of the HPA axis and cognitive function in anorexia nervosa.
PMID:14609004
2002this review onlynot statednot extracted yet
Shibuya 2011
Changes in salivary cortisol levels as a prognostic predictor in children with anorexia nervosa.
PMID:21906636
2011this review onlynot statednot extracted yet
Vaz-Leal 2018
Blunted cortisol response to stress in patients with eating disorders: Its association to bulimic features.
PMID:29464867
2018this review onlynot statednot extracted yet
Westwater 2021
Dissociable hormonal profiles for psychopathology and stress in anorexia and bulimia nervosa.
PMID:32460904
2021this review onlynot statednot extracted yet
Zonnevylle-Bender 2005
Adolescent anorexia nervosa patients have a discrepancy between neurophysiological responses and self-reported emotional arousal to…
PMID:15893382
2005this review onlynot statednot extracted yet

Overlap with other reviews

Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.

Review question

ElementPlanned (methods)Found (results)
PopulationIndividuals of any age or sex, adults and childrenPatients with AN and healthy controls aged 14 to 31 years; 18 female-only studies and 1 mixed-sex (441 AN and 556 controls in the 19 studies)
InterventionExposure: patients diagnosed with anorexia nervosa by clinical evaluation or DSM/ICD criteriaAnorexia nervosa (cortisol: 517 AN; alpha-amylase: 218 AN)
ComparisonHealthy normal-weight control groupHealthy controls (cortisol: 672; alpha-amylase: 220)
OutcomesSalivary cortisol and/or alpha-amylase (means or medians with SD, SE or IQR)Salivary alpha-amylase (6 studies, 8 reports); salivary cortisol (17 studies, 24 reports)
Study designsObservational studies (cross-sectional, cohort, case-control) or interventional trials (baseline values)19 observational studies, mostly cross-sectional (NOS: 4 satisfactory, 12 good, 3 very good)
TimingNot specifiedNot specified