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Oral, Olfactory, and Topical Ingredients Modulating Cardiac Vagal Tone and Stress Physiology Biomarkers

Publicerad: 24 August 2026·Olympia R&D Bulletin·Permalink: olympiabiosciences.com/rd-hub/ingredients-autonomic-stress-biomarkers/·200 källhänvisningar·≈ 49 min lästid
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Despite human evidence for various ingredients modulating cardiac vagal tone and stress physiology, significant challenges remain in establishing regulatory approval, with no EU or Polish approved health claims currently existing. Additionally, evidence strength varies substantially by ingredient and population, complicating product development and claim substantiation.

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Many natural ingredients, from omega-3s in fish oil and almonds to certain probiotics and even lavender essential oil, show promise in helping our bodies handle stress and maintain a healthy heart. These substances appear to improve how our nervous system balances stress and relaxation, often measured by changes in our heart's rhythm, which acts like a "brake" for our stress response. For instance, some ingredients can make the heart more adaptable to stress, while others might help reduce stress hormones. However, despite this scientific evidence, none of these ingredients currently have official health claims approved in the EU or Poland for these specific benefits.

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In humans, which individually identifiable oral nutraceutical, microbiota-directed/FSMP-relevant, topical, or olfactory cosmetic ingredients produce controlled changes in cardiac vagal/autonomic biomarkers or stress physiology, and what is the applicable EU/Poland regulatory category and evidentiary strength?

Omega-3 fatty acids, dietary nitrate, whole almonds, heat-treated postbiotic L. gasseri CP2305, ashwagandha, Acanthopanax senticosus, a nine-strain probiotic preparation, phosphatidylserine/phosphatidic acid complex, and—among olfactory/topical ingredients—lavender, β-caryophyllene, phytoncide terpenes, bergamot, orange, and yuzu essential oils each produce controlled changes in cardiac vagal or stress physiology biomarkers in at least one adequately designed human trial, with probiotics and prebiotics broadly achieving Grade B evidence (cortisol/validated symptom reduction) and the remaining oral and olfactory ingredients achieving Grade A direct autonomic evidence in specific populations and doses; no EU or Polish approved health claim exists for any of these ingredients in relation to cardiac autonomic or stress physiology endpoints.

Abstract

Across 200 controlled human intervention studies, a range of individually identifiable oral, olfactory, and topical ingredients produce measurable changes in cardiac vagal or autonomic biomarkers, though the evidentiary strength and consistency vary substantially by ingredient class. Among oral nutrients, omega-3 fatty acids (DHA-rich fish oil at 1–6 g/day) most consistently increase HF-HRV, RMSSD, and SDNN across healthy, at-risk, and clinical populations in a dose-dependent manner [1–4], qualifying as Grade A for direct autonomic effects. Dietary nitrate from beetroot improves vagal recovery post-exercise and supports HRV across acute and sustained protocols [5, 6]. Whole almonds (63 g/day, 6 weeks) increase HF-HRV specifically during mental stress [7, 8], and acute heat-treated postbiotic L. gasseri CP2305 increases RMSSD within 60 minutes of ingestion [9]. Ashwagandha [10], Acanthopanax senticosus [11], and a nine-strain probiotic (OMNi-BiOTiC STRESS Repair) in major depression [12] each yield Grade A direct autonomic signals in their respective populations, while phosphatidylserine/phosphatidic acid complex (400 mg/day) attenuates cortisol and ACTH responses to psychosocial stress specifically in chronically stressed individuals [13]. Notably, L-carnitine (1.5 g/day, 24 weeks) produced the sole significant adverse autonomic signal—a decrease in RMSSD and HF power indicating vagal withdrawal [14]. The majority of probiotic and prebiotic trials achieve Grade B evidence only, with consistent but modest reductions in cortisol and validated stress scores across multiple strains and durations [15–17] but without concurrent HRV instrumentation. Among olfactory and topical ingredients, lavender inhalation most consistently increases HF-HRV under resting and mild-stress conditions across diverse populations [18–20], though its direction reverses to sympathoactivation during active cognitive loading [21] and some apparent benefits may reflect breathing-pattern confounds [22]; β-caryophyllene, phytoncide terpenes, orange, bergamot, and yuzu essential oils each carry at least one Grade A autonomic study, all of small sample and acute design. No EU or Polish regulatory source within the reviewed literature attributes an approved health claim to any ingredient for cardiac autonomic, stress physiology, or relaxation endpoints; the applicable regulatory category is therefore not established in this review for all ingredients examined.

Flow Diagram

Paper search

We performed a semantic search across over 138 million academic papers from the Elicit search engine, which includes all of Semantic Scholar and OpenAlex.

We ran these queries:

  • "(heart rate variability OR HRV OR RMSSD OR HF-HRV OR cardiac vagal tone OR autonomic nervous system) dietary supplement nutraceutical botanical amino acid randomized controlled trial"
  • "(cortisol OR salivary alpha-amylase OR electrodermal OR sympathetic OR stress physiology) probiotic prebiotic postbiotic psychobiotic food supplement medical food bioactive peptide randomized controlled trial"
  • "(heart rate variability OR autonomic nervous system OR cortisol OR stress) essential oil fragrance olfactory topical transdermal cosmetic ingredient randomized controlled trial human"

The searches returned 900 total results from Elicit.

We retrieved 882 papers most relevant to the query for screening.

Screening

Abstract screening

We screened in sources based on their abstracts that met these criteria:

  • Human controlled intervention: Is this a primary report of a completed controlled or randomized intervention study in human participants? Exclude reviews, protocols, editorials, animal/in-vitro studies, and conference abstracts without a primary completed study.
  • Eligible ingredient exposure: Does the title or abstract identify an oral nutrient, amino acid, botanical, lipid, phytochemical, probiotic/prebiotic/postbiotic, bioactive peptide, identifiable FSMP-relevant formulation, or topical/inhaled cosmetic or sensory ingredient? Exclude drugs, electrical stimulation, acupuncture, breathing/meditation, and massage-only interventions.
  • Relevant outcome domain: Does the title or abstract report or plausibly evaluate an autonomic biomarker, stress-physiology biomarker, or validated stress, anxiety, sleep, or relaxation outcome?
  • Ingredient identifiability: Is the active ingredient, botanical, strain, peptide, or formulation sufficiently named to permit extraction at full text? Exclude generic, uncharacterized multi-ingredient interventions when individual constituents cannot plausibly be separated.

Papers that failed any strict criterion were automatically excluded. For the remaining papers, we considered all screening questions together and made a holistic judgement about whether to screen in each paper.

515 papers passed abstract screening and moved to full-text screening.

At abstract screening, the number of papers excluded for each primary reason was:

  • Human controlled intervention: n = 100
  • Eligible ingredient exposure: n = 197
  • Relevant outcome domain: n = 60
  • Ingredient identifiability: n = 10

Full-text screening

We then screened papers based on their full text using these additional criteria:

  • Confirmed human controlled study: Confirm a completed randomized or controlled human intervention study with an appropriate comparator.
  • Confirmed eligible intervention: Confirm that the intervention route and named active ingredient/formulation meet the protocol scope; exclude prescription/OTC drugs, device stimulation, behavioral-only and massage-only interventions.
  • Extractable outcome: Confirm that the report provides an autonomic biomarker, stress-physiology biomarker, or validated symptom outcome with enough information to characterize the direction and timing of the result.
  • Report availability: Confirm that sufficient full text is available to assess eligibility and extract results. If not, mark this reason specifically as full text not available rather than as ineligible.

Papers that failed any strict criterion were automatically excluded. For the remaining papers, we considered all screening questions together and made a holistic judgement about whether to include each paper in the final analysis.

243 papers passed full-text screening and moved to data extraction.

At full-text screening, the number of papers excluded for each primary reason was:

  • Confirmed human controlled study: n = 6
  • Confirmed eligible intervention: n = 1
  • Extractable outcome: n = 1
  • Report availability: n = 6
  • No full text: n = 258

Data extraction

We asked a large language model to extract each data column below from each paper. We gave the model the extraction instructions shown below for each column.

  • Ingredient identity and standardisation: Extract the common and scientific name (if botanical), chemical form, strain designation (if microbial), peptide identity, and any stated standardisation or formulation.
  • Product route and category: Extract oral, enteral/FSMP, topical, transdermal, inhaled/olfactory, or other route. Do not infer legal regulatory status.
  • Population and clinical context: Extract sample size analyzed, age, sex distribution if reported, health condition, and setting.
  • Design and comparator: Extract randomization/blinding/design, intervention and comparator, and funding/conflict information if reported.
  • Dose and duration: Extract dose, frequency, exposure duration, and assessment time point(s).
  • Direct autonomic biomarkers: Extract RMSSD, HF-HRV, respiratory sinus arrhythmia, cardiac vagal tone indices, PEP, heart rate, blood pressure, and electrodermal activity results with units/time point and between-group effect where reported. State 'not reported' when absent.
  • Stress physiology biomarkers: Extract cortisol, salivary alpha-amylase, catecholamines, inflammatory stress biomarkers, and relevant time points/results. State 'not reported' when absent.
  • Validated symptom outcomes: Extract validated stress, anxiety, sleep, relaxation, or mood instruments with time point and result. State 'not reported' when absent.
  • Adverse events and tolerability: Extract adverse events, withdrawals, contraindications, and safety findings as reported.
  • Evidence grade: Classify as Grade A only when the controlled human study reports an interpretable direct autonomic effect; Grade B when it reports stress physiology or validated symptoms without a direct autonomic effect; otherwise classify as insufficient for Grade A/B and explain briefly.
  • Key limitation: Identify the most consequential study-level limitation relevant to interpreting autonomic or relaxation claims, such as unblinding, very small sample, mixed intervention, missing comparator, biomarker timing, or non-extractable effect size.

Report

Due to the limitations of the AI model, we are only able to process 200 sources while writing a report. This report was written using the 200 sources that had the highest screening scores out of the 243 sources that we screened in and extracted data from.

Results

Characteristics of Included Studies

The 200 sources span a broad range of intervention categories—probiotics, prebiotics, postbiotics, short-chain fatty acids, phospholipids, dietary macronutrient manipulations, polyphenols, botanical extracts, vitamins and minerals, amino acids and peptides, omega-3 fatty acids, and olfactory/topical essential oil preparations—tested against autonomic, neuroendocrine, and validated psychological outcomes in controlled human intervention designs. The majority are randomised, double-blind, placebo-controlled trials (RCTs); a smaller number use crossover, quasi-experimental, or single-blind designs. Population health status ranges from healthy volunteers and occupationally stressed cohorts to clinical groups with depression, PTSD, fibromyalgia, renal disease, or cardiovascular conditions. Sample sizes are frequently small (fewer than 60 analysed participants in the majority of studies), and intervention durations range from a single acute session to 24 weeks of daily supplementation. Full text was retrieved for all 200 citations included in the extractions.

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StudyFull text retrieved?Intervention categoryActive ingredient(s)RoutePopulationN analysedDurationEvidence grade
K. Schmidt et al., 2014 [23]YesPrebioticFOS, B-GOS [23]Oral [23]Healthy volunteers [23]45 [23]3 weeks [23]B [23]
Prebiotic intake reduces the w (Schmidt et al., 2014 duplicate) [24]YesPrebioticFOS, B-GOS [24]Oral [24]Healthy volunteers [24]45 [24]3 weeks [24]B [24]
Mon-Chien Lee et al., 2025 [25]YesProbiotic (psychobiotic)L. plantarum PS128 (live), L. paracasei PS23 (heat-treated) [25]Oral [25]Stressed adults (firefighters, PSS ≥14) [25]116 [25]8 weeks [25]B [25]
H. Andersson et al., 2016 [26]YesProbioticL. plantarum 299v [26]Oral [26]Healthy young adults under exam stress [26]41 [26]14 days [26]B [26]
A. Allen et al., 2016 [27]YesProbiotic (psychobiotic)B. longum 1714 [27]Oral [27]Healthy males [27]22 [27]4 weeks [27]B [27]
Hanna M. T. Edebol Carlman et al., 2022 [28]YesProbioticB. longum R0175, L. helveticus R0052, L. plantarum R1012 [28]Oral [28]Healthy adults [28]22 [28]4 weeks per arm [28]B [28]
Shu-I Wu et al., 2022 [29]YesPostbioticHeat-killed L. paracasei PS23 (HK-PS23) [29]Oral [29]Highly stressed clinical nurses [29]70 [29]8 weeks [29]B [29]
Marcus Boehme et al., 2023 [30]YesProbioticB. longum NCC3001 [30]Oral [30]Healthy adults, mild-to-moderate stress [30]45 [30]6 weeks [30]B [30]
Akito Kato-Kataoka et al., 2016 [15]YesProbioticL. casei Shirota (fermented milk) [15]Oral [15]Healthy medical students [15]47 [15]8 weeks [15]B [15]
B. Dalile et al., 2020 [17]YesSCFA (microbiota-directed)Colon-delivered acetate, propionate, butyrate [17]Enteral/FSMP [17]Healthy men [17]66 [17]1 week [17]B [17]
M. Messaoudi et al., 2011 [31]YesProbioticL. helveticus R0052, B. longum R0175 [31]Oral [31]Healthy volunteers (low UFC subgroup) [31]25 [31]30 days [31]B [31]
Teng Ma et al., 2021 [32]YesProbioticL. plantarum P-8 [32]Oral [32]Stressed adults [32]79 [32]12 weeks [32]B [32]
C. Quero et al., 2021 [33]YesSynbioticB. lactis CBP-001010, L. rhamnosus CNCM I-4036, B. longum ES1 + FOS [33]Oral [33]Athletes and sedentary adults [33]27 [33]30 days [33]B [33]
L. Wauters et al., 2022 [34]YesProbioticL. rhamnosus CNCM I-3690 [34]Oral [34]Healthy students [34]92 [34]4 weeks [34]B [34]
Akito Kato-Kataoka et al., 2016a [16]YesProbioticL. casei Shirota (fermented milk) [16]Oral [16]Healthy medical students [16]49 [16]8 weeks [16]B [16]
H. Chong et al., 2019 [35]YesProbioticL. plantarum DR7 [35]Oral [35]Stressed adults [35]111 [35]12 weeks [35]B [35]
N. Matsuura et al., 2021 [36]YesProbioticL. lactis subsp. cremoris YRC3780 [36]Oral [36]Healthy young men [36]27 [36]8 weeks [36]B [36]
J. Hellhammer et al., 2014 [13]YesPhospholipidPhosphatidylserine/phosphatidic acid complex (PAS 400/PAS 200) [13]Oral [13]Healthy chronically stressed men [13]72 [13]42 days [13]B [13]
N. West et al., 2021 [37]YesProbioticL. acidophilus DDS-1, B. animalis subsp. lactis UABla-12 [37]Oral [37]Night shift workers [37]87 [37]14 days [37]B [37]
K. Nishida et al., 2019 [38]YesPostbioticHeat-inactivated L. gasseri CP2305 [38]Oral [38]Healthy young adults (medical students) [38]60 [38]24 weeks [38]B [38]
Katrin Chaborski et al., 2015 [39]YesAmino acid + micronutrientSpecific amino acid composition with micronutrients [39]Oral [39]Psychologically stressed patients with cardiological disorders [39]32 [39]12 weeks [39]B [39]
L. Brenner et al., 2020 [40]YesProbioticL. reuteri DSM 17938 [40]Oral [40]Veterans with mTBI and PTSD [40]31 [40]8 weeks [40]A [40]
C. Tsang et al., 2019 [41]YesPolyphenolHigh-polyphenol dark chocolate (500 mg flavonoids) [41]Oral [41]Healthy adults [41]26 [41]4 weeks [41]B [41]
J. Hellhammer et al., 2004 [42]YesPhospholipidSoy lecithin phosphatidic acid/phosphatidylserine complex (PAS) [42]Oral [42]Healthy adults [42]80 [42]3 weeks [42]B [42]
A. Adikari et al., 2020 [43]YesProbioticL. casei Shirota [43]Oral [43]Male football players [43]20 [43]8 weeks [43]B [43]
Maryam Ahmadi-Khorram et al., 2025 [44]YesProbioticL. acidophilus, L. casei, L. rhamnosus [44]Oral [44]Underweight adults [44]90 [44]8 weeks [44]B [44]
P. Gualtieri et al., 2020 [45]YesProbioticMulti-strain (Streptococcus thermophilus, B. animalis, B. bifidum, L. bulgaricus, L. lactis, L. acidophilus, L. plantarum, L. reuteri) [45]Oral [45]Adults with anxiety [45]97 [45]12 weeks [45]B [45]
Laura Márquez-Morales et al., 2021 [46]YesProbiotic (fermented beverage)L. plantarum, L. paracasei, L. brevis [46]Oral [46]Medical students with academic stress [46]45 [46]8 weeks [46]B [46]
G. Moschonis et al., 2024 [47]YesProbioticL. fermentum LF16, L. rhamnosus LR06, L. plantarum LP01, B. longum 04 [47]Oral [47]Subthreshold depression [47]39 [47]12 weeks [47]B [47]
J. Hellhammer et al., 2014a [48]YesPhospholipidPS/PA complex (PAS) [48]Oral [48]Healthy chronically stressed men [48]72 [48]42 days [48]B [48]
Sélima Zahar et al., 2022 [49]YesBioactive peptideEgg protein hydrolysate (EPH; tryptophan-rich) [49]Oral [49]Healthy adults [49]44 [49]Acute (150 min) [49]A [49]
Hoda Soltani et al., 2019 [50]YesDietary macronutrientHigh carbohydrate DGA-based whole food diet [50]Oral [50]Overweight/obese women [50]43 [50]8 weeks [50]B [50]
Eric Climent et al., 2025 [51]YesProbiotic + FSMPB. breve CNCM I-4035, B. animalis lactis CECT 8145, L. paracasei CNCM I-4034 + oral nutritional supplement [51]Oral [51]Malnourished haemodialysis patients [51]31 [51]6 months [51]B [51]
B. Oaks et al., 2020 [52]YesLipid-based nutrient supplementLNS (including omega-3 ALA, micronutrients) [52]Oral [52]Children 4–6 years (follow-up of gestational/early-life RCT) [52]364 [52]Gestational + early childhood [52]B [52]
M. Karbownik et al., 2020 [53]YesProbiotic (yeast)Saccharomyces boulardii CNCM I-1079 [53]Oral [53]Healthy medical students [53]50 [53]30 days [53]A [53]
Yuichi Tsuda et al., 2020 [54]YesAmino acidArginine, valine, serine mixture [54]Oral [54]Healthy recreationally active men [54]15 [54]Acute (single dose) [54]B [54]
Reiko Tanihiro et al., 2026 [9]YesPostbioticHeat-treated L. gasseri CP2305 [9]Oral [9]Healthy adults [9]28 [9]Acute (single dose) [9]A [9]
J. Vázquez-Castellanos et al., 2025 [55]YesProbioticL. rhamnosus CNCM I-3690 [55]Oral [55]Healthy students [55]79 [55]4 weeks [55]B [55]
A. Schaafsma et al., 2021 [56]YesWhey protein + prebioticWhey protein, B-GOS, tryptophan, tryptic casein hydrolysate, Mg, Zn, vitamins [56]Oral [56]Adults with sleep disturbances [56]70 [56]3 weeks [56]B [56]
S. Talbott et al., 2013 [57]YesBotanicalMagnolia officinalis + Phellodendron amurense (Relora) [57]Oral [57]Moderately stressed adults [57]56 [57]4 weeks [57]B [57]
N. Johnstone et al., 2021 [58]YesPrebioticGalacto-oligosaccharides (GOS) [58]Oral [58]Healthy young females [58]64 [58]28 days [58]B [58]
A. Kao et al., 2019 [59]YesPrebioticB-GOS [59]Oral [59]Adults with psychosis [59]39 [59]12 weeks [59]Insufficient [59]
M. Coman et al., 2023 [60]YesProbiotic + botanicalSYNBIO (L. rhamnosus 501, L. paracasei 502) + elderberry extract [60]Oral [60]Airline crew members [60]37 [60]30 days [60]Insufficient [60]
G. Önning et al., 2023 [61]YesProbioticL. plantarum HEAL9 [61]Oral [61]Moderately stressed adults [61]129 [61]12 weeks [61]B [61]
K. Walden et al., 2023 [62]YesProbioticL. plantarum LP01, L. fermentum LF16, L. rhamnosus LR06, B. longum 04 [62]Oral [62]Healthy adults [62]70 [62]6 weeks [62]B [62]
M. Bloemendaal et al., 2020 [63]YesProbioticEcologic Barrier (9-strain mix) [63]Oral [63]Healthy females [63]56 [63]28 days [63]B [63]
Huiying Wang et al., 2019 [64]YesProbioticB. longum 1714 [64]Oral [64]Healthy adults [64]40 [64]4 weeks [64]B [64]
A. Hansen et al., 2020 [65]YesVitaminVitamin D3 (cholecalciferol, 1600 IU/day) [65]Oral [65]Forensic inpatients (male) [65]86 [65]~4.5 months [65]A [65]
Wendelien Merens et al., 2005 [66]YesBioactive peptideα-Lactalbumin (tryptophan-rich protein) [66]Oral [66]Recovered depressed subjects and controls [66]43 [66]1 day (acute) [66]B [66]
R. Baião et al., 2022 [67]YesProbioticBio-Kult Advanced (14-strain) [67]Oral [67]Adults with moderate depression [67]71 [67]4 weeks [67]B [67]
Tokiko Shinjo et al., 2018 [68]YesBioactive proteinLactoferrin (bovine) [68]Oral [68]Healthy young women [68]16 [68]Acute (single dose) [68]A [68]
Yan Zheng et al., 2021 [69]YesProbioticL. rhamnosus Probio-M9 [69]Oral [69]Healthy stressed postgraduates [69]12 [69]21 days [69]B [69]
Georgios Tzikos et al., 2025 [70]YesProbioticB. animalis LMG P-21384, B. breve DSM 16604, B. longum DSM 16603, L. rhamnosus ATCC 53103 [70]Oral [70]GI cancer surgery/chemotherapy patients [70]266 [70]4 weeks [70]B [70]
D. Kalman et al., 2008 [71]YesBotanicalRelora (Magnolia officinalis + Phellodendron amurense) [71]Oral [71]Premenopausal overweight women [71]40 [71]6 weeks [71]B [71]
J. Takanari et al., 2016 [72]YesBotanicalEnzyme-treated asparagus extract (ETAS) [72]Oral [72]Healthy volunteers [72]25 [72]28 days per arm [72]A [72]
Takumi Watanabe et al., 2022 [73]YesPostbioticHeat-killed L. plantarum SNK12 [73]Oral [73]Healthy adults [73]66 [73]4 weeks [73]B [73]
C. Stewart et al., 2015 [74]YesLipid-based nutrient supplementLNS (micronutrients + omega-3 ALA) [74]Oral [74]Pregnant women (rural Malawi) [74]1391 [74]Throughout pregnancy [74]B [74]
C. Rauch et al., 2025 [75]YesPrebioticSoluble fibre, inulin-type fructan, resistant starch, β-GOS [75]Oral [75]Endurance athletes [75]16 [75]8 weeks [75]B [75]
Deepti Aswani et al., 2022 [76]YesProbioticBio-Kult Advanced (14-strain) [76]Oral [76]Adults with low mood [76]80 [76]4 weeks [76]B [76]
Robin M. Voigt et al., 2025 [77]YesPrebioticInulin, resistant starch type 2, resistant maltodextrin, rice bran [77]Oral [77]Veterans with PTSD [77]70 [77]12 weeks [77]Insufficient [77]
P. Roman et al., 2018 [78]YesProbioticL. rhamnosus GG, L. casei, L. acidophilus, B. bifidus [78]Oral [78]Fibromyalgia patients [78]31 [78]8 weeks [78]B [78]
N. Boyle et al., 2019 [79]YesPhospholipidBovine milk-derived phospholipids (incl. PS, SPH, PC, PE) [79]Oral [79]High-perfectionist men [79]54 [79]6 weeks [79]B [79]
L. Billeci et al., 2022 [80]YesProbioticDe Simone Formulation (8-strain; Vivomixx/Visbiome) [80]Oral [80]Children with ASD [80]46 [80]6 months [80]Insufficient [80]
L. Sempach et al., 2024 [81]YesProbioticDSFormulation (8-strain; Vivomixx/Visbiome) [81]Oral [81]Adults with depression [81]43 [81]4 weeks [81]B [81]
R. Morales-Torres et al., 2023 [82]YesProbioticL. helveticus R0052, B. longum R0175 (Cerebiome) [82]Oral [82]Healthy adults [82]135 [82]4 weeks [82]B [82]
D. Camfield et al., 2013 [83]YesMultivitaminB6, B9, B12 (plus vitamins C, D, E and botanicals) [83]Oral [83]Healthy adults [83]138 [83]16 weeks [83]B [83]
Nazanin Heidarzadeh-Rad et al., 2020 [84]YesProbioticL. helveticus R0052, B. longum R0175 [84]Oral [84]Adults with mild-to-moderate depression [84]78 [84]8 weeks [84]B [84]
Papalini S. et al., 2018 [85]YesProbioticEcologic Barrier (9-strain) [85]Oral [85]Healthy females [85]58 [85]28 days [85]B [85]
Teng Ma et al., 2020 [86]YesProbioticL. plantarum P-8 [86]Oral [86]Stressed adults [86]79 [86]12 weeks [86]B [86]
R. Salleh et al., 2021 [87]YesProbioticL. casei Shirota [87]Oral [87]University badminton players [87]30 [87]6 weeks [87]B [87]
D. Motei et al., 2023 [88]YesPostbioticB. breve BB091109 β-glucan extract [88]Oral [88]Healthy females (40–55 years) [88]30 [88]12 weeks [88]B [88]
Sabrina Moerkl et al., 2025 [12]YesProbioticOMNi-BiOTiC STRESS Repair (9-strain) [12]Oral [12]Major depression patients and healthy controls [12]86 [12]3 months [12]A [12]
Takumi Watanabe et al., 2025 [89]YesPostbioticHeat-killed L. plantarum SNK12 [89]Oral [89]Healthy adults with mild sleep complaints [89]50 [89]4 weeks [89]B [89]
A. De Lorenzo et al., 2017 [90]YesProbioticMulti-strain (9 strains including Streptococcus, Bifidobacterium, Lactobacillus, Lactococcus spp.) [90]Oral [90]Women with obesity/NWO [90]48 [90]3 weeks [90]B [90]
A. Madison et al., 2021 [91]YesOmega-3 fatty acidEPA (347.5 mg) + DHA (58 mg) per capsule [91]Oral [91]Sedentary, overweight middle-aged adults [91]138 [91]4 months [91]B [91]
M. Höferl et al., 2016 [92]YesEssential oil (olfactory)East Indian sandalwood, W. Australian sandalwood, lavender [92]Inhaled/olfactory [92]Healthy adults [92]32 [92]Acute (~90 min) [92]B [92]
A. Sgoifo et al., 2020 [93]YesEssential oil (topical cosmetic)Juniperus phoenicea gum, Copaifera officinalis resin, Aniba rosaeodora wood oil, Juniperus virginiana oil [93]Topical [93]Healthy women [93]40 [93]28 days + acute test [93]A [93]
Pin-Hsuan Lin et al., 2021 [94]YesEssential oil (olfactory)Sandalwood (S. spicatum) and lavender (L. angustifolia) blend [94]Inhaled/olfactory [94]Junior college students [94]43 [94]Acute (15 min) [94]A [94]
Mi Hee Kim & E. Ha, 2014 [95]YesEssential oil (olfactory)Lavender + sweet orange blend (2:1) [95]Inhaled/olfactory [95]Nursing students in clinical training [95]75 [95]2 weeks [95]A [95]
Hyunjin Baik et al., 2018 [96]YesEssential oil (olfactory)Abies holophylla (α-pinene, β-pinene, limonene, linalool) [96]Inhaled/olfactory [96]Healthy workers [96]14 [96]Acute (≥20 min) [96]A [96]
M. Moss et al., 2026 [97]YesEssential oil (olfactory)Stressless blend (frankincense, copaiba) [97]Inhaled/olfactory [97]Stressed adults [97]75 [97]2 weeks [97]B [97]
Eri Watanabe et al., 2015 [98]YesEssential oil (olfactory)Bergamot (Citrus bergamia) [98]Inhaled/olfactory [98]Healthy females [98]41 [98]Acute (15 min) [98]A [98]
Tamaki Matsumoto et al., 2013 [18]YesEssential oil (olfactory)Lavender (Lavandula angustifolia) [18]Inhaled/olfactory [18]Women with premenstrual symptoms [18]17 [18]Acute (10 min) [18]A [18]
T. Igarashi, 2013 [99]YesEssential oil (olfactory)Linalool/linalyl acetate-rich oils [99]Inhaled/olfactory [99]Pregnant women [99]13 [99]Acute (5 min) [99]A [99]
Wakako Yogi et al., 2021 [100]YesEssential oil (olfactory)Lavender (L. angustifolia) [100]Inhaled/olfactory [100]Healthy adults [100]9 [100]Acute (during 90 min sleep) [100]A [100]
L. Chien et al., 2011 [19]YesEssential oil (olfactory)Lavender [19]Inhaled/olfactory [19]Women with insomnia (midlife) [19]67 [19]12 weeks [19]A [19]
S. Nomura et al., 2016 [21]YesEssential oil (olfactory)Lavender, jasmine [21]Inhaled/olfactory [21]Healthy men [21]17 [21]Acute (30 min task) [21]A [21]
Tadaaki Satou et al., 2024 [101]YesEssential oil (topical)Lavender (L. angustifolia), 1% [101]Topical [101]Healthy women [101]10 [101]Acute (10 min) [101]A [101]
J. Kiecolt-Glaser et al., 2008 [102]YesEssential oil (olfactory)Lavender (L. angustifolia), lemon (Citrus limonum) [102]Inhaled/olfactory [102]Healthy adults [102]56 [102]Acute (multiple visits) [102]A [102]
Doho Kim, 2019 [103]YesEssential oil blend (olfactory)Lavender, bergamot, mandarin, lemon, cedarwood, Roman chamomile [103]Inhaled/olfactory [103]Adults [103]64 [103]Acute (30 min) [103]A [103]
Seo-Yeon Choi et al., 2014 [104]YesEssential oil (olfactory)Neroli oil (Citrus aurantium var. amara) [104]Inhaled/olfactory [104]Postmenopausal women [104]63 [104]5 days [104]B [104]
Choyun Kim & Chorong Song, 2022 [105]YesEssential oil (olfactory)Fir (Abies holophyla) [105]Inhaled/olfactory [105]University students [105]26 [105]Acute (3 min) [105]A [105]
J. Seo, 2009 [106]YesEssential oil (olfactory)Aroma essential oil blend (unspecified) [106]Inhaled/olfactory [106]Female high school students [106]36 [106]Crossover [106]B [106]
Shichun Pei et al., 2024 [107]YesOlfactory compoundsβ-caryophyllene, linalool, citral [107]Inhaled/olfactory [107]Healthy adults [107]48 [107]Acute (20 min) [107]A [107]
Chiu-Yen Wu et al., 2020 [108]YesEssential oil (topical massage)Lavender, 5% [108]Topical [108]Female university employees [108]110 [108]Acute (single session) [108]A [108]
E. Karadağ et al., 2017 [109]YesEssential oil (olfactory)Lavender (2%) [109]Inhaled/olfactory [109]Coronary artery disease patients (ICU) [109]60 [109]15 days [109]B [109]
Ryuichiro Masubuchi et al., 2025 [110]YesEssential oil (olfactory)Geranium (Pelargonium graveolens) 1% [110]Inhaled/olfactory [110]Fibromyalgia patients [110]10 [110]3 months per arm [110]A [110]
Yejung Ko et al., 2013 [111]YesEssential oil blend (olfactory)Maychang, lavender, rosewood (3:5:2) [111]Inhaled/olfactory [111]Nursing students [111]65 [111]5 days [111]B [111]
G. Seol et al., 2013 [112]YesEssential oil (olfactory)Clary sage (S. sclarea), lavender (L. angustifolia) [112]Inhaled/olfactory [112]Female urinary incontinence patients [112]34 [112]Acute (60 min) [112]A [112]
R. Schneider, 2021 [113]YesEssential oil (olfactory)AromaStick Balance (peppermint, cypress, geranium, ginger) [113]Inhaled/olfactory [113]Healthy adults [113]80 [113]Acute [113]B [113]
I. Chamine & B. Oken, 2016 [114]YesEssential oil (olfactory)Lavender (L. angustifolia) [114]Inhaled/olfactory [114]Healthy adults (mean age 58) [114]92 [114]Acute (4-hour visit) [114]B [114]
Tyler Bahr et al., 2018 [115]YesEssential oil blend (topical)dōTERRA AromaTouch blend (peppermint, Deep Blue, AromaTouch, lavender, melaleuca) [115]Topical [115]Healthy adults [115]18 [115]3 weeks [115]A [115]
Winai Sayorwan et al., 2012 [116]YesEssential oil (olfactory)Rosemary (Rosmarinus officinalis) [116]Inhaled/olfactory [116]Healthy adults [116]20 [116]Acute (20 min) [116]A [116]
N. Rajai et al., 2016 [117]YesEssential oil (olfactory)Lavender (Lavendula spica) [117]Inhaled/olfactory [117]CABG surgery patients [117]60 [117]Acute (20 min) [117]A [117]
A. Tayebi et al., 2015 [118]YesEssential oil (olfactory)Lavender (Lavendula spica) [118]Inhaled/olfactory [118]Haemodialysis patients [118]60 [118]4 weeks [118]A [118]
Seung-Jae Heo et al., 2023 [119]YesPhytoncide/terpene (olfactory)Chamaecyparis obtusa (phytoncide terpenes) [119]Inhaled/olfactory [119]Gynaecological cancer survivors [119]55 [119]8 weeks [119]A [119]
J. Tsai et al., 2020 [120]YesEssential oil (olfactory)Blended essential oil (unspecified) [120]Inhaled/olfactory [120]Women with menopausal syndrome [120]84 [120]4 weeks [120]A [120]
Tamaki Matsumoto et al., 2014 [121]YesEssential oil (olfactory)Yuzu (Citrus junos) [121]Inhaled/olfactory [121]Healthy women [121]20 [121]Acute (10 min) [121]A [121]
T. Yoshizawa et al., 2015 [122]YesEssential oil (olfactory)Cyperi rhizoma, Perillae herba [122]Inhaled/olfactory [122]Healthy females [122]25 [122]Acute (2.5 min) [122]A [122]
Kavya C Gowda et al., 2025 [123]YesEssential oil (olfactory)Lavender (L. angustifolia) [123]Inhaled/olfactory [123]Healthy volunteers [123]60 [123]Acute (20 min) [123]A [123]
I. Chamine & B. Oken, 2015 [124]YesEssential oil (olfactory)Lavender (L. angustifolia) [124]Inhaled/olfactory [124]Healthy adults (mean age 58) [124]81 [124]Acute [124]Insufficient [124]
E. Mezzacappa et al., 2010 [125]YesOlfactory/fragranceCoconut fragrance [125]Inhaled/olfactory [125]Healthy adults [125]32 [125]Acute (25 min) [125]A [125]
A. Dehkordi et al., 2017 [126]YesEssential oil (olfactory)Damask rose (Rosa damascena) [126]Inhaled/olfactory [126]Haemodialysis patients [126]56 [126]4 weeks [126]B [126]
Pao-Ju Chen et al., 2017 [127]YesEssential oil (topical)Lavender (L. angustifolia) 2% [127]Topical [127]Healthy pregnant women [127]52 [127]20 weeks [127]B [127]
GholamReza Mahmoodi-Shan et al., 2021 [128]YesEssential oil (olfactory)Jasmine (Jasminum) [128]Inhaled/olfactory [128]Laparotomy candidates [128]84 [128]Acute (60 min) [128]B [128]
Kadriye Sayın Kasar et al., 2020 [129]YesEssential oil (olfactory)Lavender (L. angustifolia) [129]Inhaled/olfactory [129]Myofascial pain syndrome patients [129]66 [129]Acute (during injection) [129]B [129]
Cheng-Hua Ni et al., 2013 [130]YesEssential oil (olfactory)Bergamot (Citrus aurantium subsp. bergamia) [130]Inhaled/olfactory [130]Pre-operative ambulatory surgery patients [130]109 [130]Acute (30 min) [130]A [130]
C. Scandurra et al., 2022 [131]YesEssential oil (olfactory)Neroli (Citrus aurantium) [131]Inhaled/olfactory [131]Women in labour [131]88 [131]Throughout labour [131]B [131]
Tamaki Matsumoto et al., 2016 [132]YesEssential oil (olfactory)Yuzu (Citrus junos) [132]Inhaled/olfactory [132]Healthy women [132]21 [132]Acute (10 min) [132]A [132]
T. Bahrami et al., 2017 [133]YesEssential oil (topical)Lavender (L. angustifolia; reflexology massage) [133]Topical [133]Older women with acute coronary syndrome [133]90 [133]Acute [133]B [133]
B. Park et al., 2014 [134]YesEssential oil (olfactory)Orange (Citrus sinensis) [134]Inhaled/olfactory [134]Healthy men [134]13 [134]Acute (120 s) [134]A [134]
Mariza Pereira et al., 2026 [135]YesEssential oil (olfactory)Peppermint (Mentha piperita), lavender (L. angustifolia) [135]Inhaled/olfactory [135]Hospital employees [135]36 [135]15 days [135]A [135]
T. Hinton et al., 2019 [136]YesGABA-fortified teaGABA (γ-aminobutyric acid) in oolong tea [136]Oral [136]Healthy university students [136]30 [136]Acute [136]A [136]
Fadilla Zennifa et al., 2025 [137]YesOlfactory compoundWhite musk aromatic oil (linalool, hedione, galaxolide, tonalide) [137]Inhaled/olfactory [137]Healthy adults [137]10 [137]Acute (10 min) [137]A [137]
Deep Shikha et al., 2024 [138]YesOlfactory compoundCitrus essential oil [138]Inhaled/olfactory [138]Healthy men [138]30 [138]Acute [138]A [138]
Farhad Moslemi et al., 2019 [139]YesEssential oil (olfactory)Citrus aurantium (neroli, 30%) [139]Inhaled/olfactory [139]ACS patients [139]140 [139]2 days (3×/day) [139]B [139]
M. Morozova et al., 2025 [140]YesEssential oil (olfactory)Lavender, African stone (Hyraceum) [140]Inhaled/olfactory [140]Healthy adults [140]20 [140]Acute (5 min per scent) [140]A [140]
Panida Hanphitakphong & Somruthai Poomsalood, 2024 [141]YesEssential oil (olfactory)Lavender soy wax candle [141]Inhaled/olfactory [141]Adolescents with moderate stress [141]52 [141]Acute (20 min) [141]B [141]
Yasmin Elsaddik Valdivieso et al., 2025 [142]YesEssential oil (olfactory + VR)“Beach” essential oil (Yankee Candle) [142]Inhaled/olfactory [142]Healthy adults [142]30 [142]Acute (45 min) [142]A [142]
J. Lee & Myung-Haeng Hur, 2021 [143]YesEssential oil (olfactory)Lavender, ylang-ylang, marjoram, neroli blend [143]Inhaled/olfactory [143]Cholecystectomy patients [143]69 [143]2 days post-surgery [143]A [143]
Z. Farsi et al., 2021 [144]YesEssential oil (olfactory)Rosa damascena (40%) [144]Inhaled/olfactory [144]Emergency nurses [144]60 [144]Acute (10 min) [144]B [144]
E. C. Dilrukshi et al., 2024 [145]YesOlfactory compoundBlack pepper (Piper nigrum; β-caryophyllene) [145]Inhaled/olfactory [145]Healthy men [145]20 [145]Acute (30 min task) [145]A [145]
Lekamge Sugeeswari et al., 2017 [146]YesOlfactory compounds (8 aromas)Chocolate, strawberry, green tea, apple, citrus ginger, chamomile, cedarwood, musk [146]Inhaled/olfactory [146]Healthy men [146]6 [146]Acute [146]A [146]
T. Komori et al., 2018 [147]YesEssential oil (topical + olfactory)Lemon, tuberose, labdanam blend in jojoba oil [147]Topical + inhaled [147]Healthy women [147]20 [147]5 sessions (1/week) [147]A [147]
Sang Wook Lee et al., 2023 [148]YesEssential oil (olfactory)Marjoram (Origanum majorana), 3% [148]Inhaled/olfactory [148]COVID-19 ICU nurses [148]57 [148]Acute (2 h) [148]B [148]
S. Ghasemi et al., 2017 [149]YesEssential oil (olfactory)Rose, lavender [149]Inhaled/olfactory [149]Open-heart surgery patients [149]160 [149]Until extubation [149]Insufficient [149]
Fatemeh Teymouri et al., 2020 [150]YesEssential oil (olfactory)Lavender (L. angustifolia) [150]Inhaled/olfactory [150]Post-coronary angiography patients [150]70 [150]Acute (20 min) [150]B [150]
Sugeeswari Lekamge et al., 2017 [151]YesOlfactory compounds (8 aromas)Same 8-aroma set as Lekamge Sugeeswari 2017 [151]Inhaled/olfactory [151]Healthy men [151]6 [151]Acute [151]A [151]
Junfang Xie et al., 2025 [152]YesOlfactory (plant scent)Green money plant (Zanthoxylum piperitum) scent [152]Inhaled/olfactory [152]Dental clinic patients [152]40 [152]Acute (4 min per condition) [152]A [152]
Sun-hee Han et al., 2002 [153]YesEssential oil (olfactory)Aromatherapy blend (unspecified) [153]Inhaled/olfactory [153]College women with dysmenorrhoea [153]Not clearly stated [153]Acute [153]B [153]
Bum-Jin Park et al., 2009 [154]YesOral nutraceutical + olfactoryMilk casein peptide + eucalyptus essential oil flavour [154]Oral [154]Healthy men [154]15 [154]Acute (2 h) [154]B [154]
S. Yun et al., 2012 [155]YesEssential oil blend (olfactory)Lemon, lavender, rosewood, rose blend [155]Inhaled/olfactory [155]Breast cancer patients on radiotherapy [155]33 [155]6 weeks [155]B [155]
Eriko Kawai et al., 2017 [156]YesEssential oil (olfactory)Sweet marjoram (Origanum majorana), 1% [156]Inhaled/olfactory [156]Healthy adults [156]18 [156]Acute (6–10 min) [156]A [156]
Yui Kikuchi et al., 2026 [22]YesEssential oil (olfactory)Lavender (1%) [22]Inhaled/olfactory [22]Healthy adults [22]20 [22]Acute (5 min) [22]A [22]
L. Argueta-Figueroa et al., 2026 [20]YesEssential oil (olfactory)Lavender (L. angustifolia) [20]Inhaled/olfactory [20]Third molar surgery patients [20]30 [20]Acute (40 min) [20]A [20]
Fatemeh Mahmoodabadipoor et al., 2024 [157]YesEssential oil (olfactory)Citrus aurantium, chamomile [157]Inhaled/olfactory [157]Cardiac care unit patients [157]76 [157]Not specified [157]A [157]
Maliheh Shirzad et al., 2021 [158]YesEssential oil (olfactory)Rose essential oil [158]Inhaled/olfactory [158]Rhinoplasty candidates [158]68 [158]Perioperative [158]B [158]
V. Dikariyanto et al., 2020 [7]YesWhole food/nutWhole almonds (Prunus dulcis) [7]Oral [7]Adults at moderate CVD risk [7]105 [7]6 weeks [7]A [7]
L. Pomportes et al., 2014 [159]YesBotanical/stimulantMulti-vitamin-mineral + guarana (Paullinia cupana, 300 mg) [159]Oral [159]Healthy adults [159]56 [159]Acute (3 h) [159]A [159]
S. Zajączkowski et al., 2019 [14]YesAmino acidL-carnitine-L-tartrate (1.5 g/day) [14]Oral [14]Healthy elderly women [14]13 [14]24 weeks [14]A [14]
J. Jurado-Castro et al., 2022 [160]YesPhytochemicalBeetroot juice (inorganic nitrate) [160]Oral [160]Trained men [160]11 [160]Acute (pre-exercise) [160]A [160]
Rachel Matthews et al., 2023 [161]YesPhytochemicalWatermelon juice (L-arginine, L-citrulline) [161]Oral [161]Healthy young adults [161]18 [161]2 weeks [161]A [161]
C. J. R. Benjamim et al., 2020 [5]YesPhytochemicalBeetroot extract (Beta vulgaris, 600 mg) [5]Oral [5]Healthy active men [5]12 [5]Acute (pre-exercise) [5]A [5]
H. Young et al., 2015 [162]YesBioactive peptideChicken extract (EOC; carnosine, anserine) [162]Oral [162]Healthy young adults [162]46 [162]10 days [162]A [162]
S. Fukuda et al., 2015 [163]YesMulti-nutrient (FSMP)B vitamins, vitamin C, carnitine, CoQ10, galacto-oligosaccharide, zinc [163]Oral [163]Haemodialysis patients [163]172 [163]12 weeks [163]A [163]
M. C. de Freitas et al., 2018 [164]YesNucleotideAdenosine-5′-triphosphate (ATP, 400 mg) [164]Oral [164]Hypertensive women [164]11 [164]Acute (pre-exercise) [164]A [164]
L. Sant’Ana et al., 2020 [165]YesBotanical/alkaloidCitrus aurantium dry extract (synephrine, 6%) [165]Oral [165]Trained men [165]10 [165]Acute [165]B [165]
Y. Okita et al., 2009 [166]YesGABA-containing foodVegetable tablets containing GABA (kale) [166]Oral [166]Healthy men [166]7 [166]Acute [166]A [166]
Takeru Sato et al., 2024 [11]YesBotanicalAcanthopanax senticosus Harms (ASH) [11]Oral [11]Community-dwelling elderly [11]28 [11]4 weeks [11]A [11]
K. Gustafson et al., 2013 [4]YesOmega-3 fatty acidDHA (algal oil, 600 mg/day) [4]Oral [4]Pregnant women (fetal outcomes) [4]46 [4]From ~14 weeks gestation [4]A [4]
J. Castro-Marrero et al., 2016 [167]YesCoenzymeCoQ10 (50 mg) + NADH (5 mg) [167]Oral [167]Chronic fatigue syndrome patients [167]80 [167]8 weeks [167]A [167]
Seyedeh Parya Barzanjeh et al., 2022 [168]YesCholine compoundAlpha-glycerylphosphorylcholine (A-GPC, 1000 mg) [168]Oral [168]Overweight/obese women [168]12 [168]Acute [168]A [168]
V. Dikariyanto et al., 2020a [8]YesWhole food/nutWhole almonds (Prunus dulcis) [8]Oral [8]Habitual snack consumers (moderate CVD risk) [8]105 [8]6 weeks [8]A [8]
W. Shell et al., 2010 [169]YesMulti-ingredientGABA + 5-HTP + choline + ginkgo + whey protein (Gabadone) [169]Oral [169]Adults with sleep disorders [169]18 [169]1 week [169]A [169]
A. Yadav et al., 2026 [170]YesBotanicalAjwain (Trachyspermum ammi, 3 g twice daily) [170]Oral [170]Stage 1 hypertension patients [170]99 [170]21 days [170]Insufficient [170]
María Medrano et al., 2022 [171]YesMulti-ingredient nootropicL-tyrosine, acetyl-L-carnitine, citicoline, GPC, taurine, caffeine, L-theanine, mango/huperzia extracts [171]Oral [171]Young healthy adults [171]26 [171]Acute [171]Insufficient [171]
Christopher E. Zwilling et al., 2020 [172]YesMulti-ingredient + exerciseHMB, lutein, phospholipids, DHA, B12, folic acid [172]Oral [172]Active duty Airmen [172]148 [172]12 weeks [172]A [172]
M. Trivedi et al., 2022 [173]YesMulti-vitamin/mineral + adaptogenVitamins A, B6, B12, C, D3, E; minerals; ginseng [173]Oral [173]Adults with psychological symptoms [173]84 [173]180 days [173]B [173]
Chee Huei Phing & Ong Yong Chee, 2019 [174]YesBioactive peptideAlpha-s1-casein tryptic hydrolysate (150 mg) + L-theanine (50 mg) [174]Oral [174]Adults with sleep disorders [174]70 [174]4 weeks [174]B [174]
M. Botek et al., 2021 [175]YesMolecular hydrogenHydrogen-rich water (HRW, 1260 mL) [175]Oral [175]Healthy females [175]14 [175]Acute (50 min) [175]A [175]
A. Zheng & T. Moritani, 2008 [176]YesCoenzymeCoQ10 (30 mg, single dose) [176]Oral [176]Healthy men [176]11 [176]Acute [176]A [176]
D. Ninio et al., 2008 [1]YesOmega-3 fatty acidDHA-rich fish oil (1.56 g DHA + 0.36 g EPA/day) [1]Oral [1]Sedentary overweight adults [1]46 (HRV subset) [1]12 weeks [1]A [1]
S. Kristensen et al., 2016 [177]YesOmega-3 fatty acidMarine n-3 PUFA (EPA 50%/DHA 50%, 3 g/day) [177]Oral [177]Psoriatic arthritis patients [177]145 [177]24 weeks [177]A [177]
R. Bloomer et al., 2016 [178]YesBotanicalRosemary (R. officinalis) + daylily (H. fulva; CLOCK) [178]Oral [178]Adults with sleep difficulties [178]32 [178]6 weeks [178]B [178]
V. Bond et al., 2014 [179]YesPhytochemicalBeetroot juice (nitrate, 500 mL) [179]Oral [179]Young healthy women [179]13 [179]Acute [179]A [179]
S. Lee et al., 2017 [180]YesPhytochemicalα-Lipoic acid (ALA, 600–1200 mg/day) [180]Oral [180]T2DM with cardiac autonomic neuropathy [180]75 [180]24 weeks [180]Insufficient [180]
Hidde P. van Steenwijk et al., 2023 [181]YesPhytochemicalSulforaphane (25 mg; broccoli sprouts) [181]Oral [181]Healthy adults [181]12 [181]Acute [181]A [181]
Kokila Thiagarajah et al., 2022 [182]YesBioactive peptideAlpha-s1-casein tryptic hydrolysate (150 mg) + L-theanine (50 mg; RLX2) [182]Oral [182]Adults with poor sleep [182]39 [182]4 weeks [182]B [182]
Shirin Ghotboddin Mohammadi et al., 2025 [183]YesAntioxidantAstaxanthin (ASX, 20 mg/day) [183]Oral [183]Chronic heart failure patients [183]80 [183]8 weeks [183]B [183]
Y. Muramoto et al., 2025 [184]YesMolecular hydrogenHydrogen-rich jelly (HRJ, 10 g) [184]Oral [184]Healthy adults [184]48 [184]Acute (3 doses) [184]A [184]
Brian M. Kliszczewicz et al., 2018 [185]YesBotanical/alkaloidCitrus aurantium (p-synephrine, 100 mg) + caffeine (100 mg) [185]Oral [185]Healthy active men [185]10 [185]Acute [185]A [185]
A. Zheng & T. Moritani, 2008a [186]YesBotanical (Kampo)Ginseng (250 mg), oriental bezoar (50 mg), glycyrrhiza (50 mg) [186]Oral [186]Healthy men [186]10 [186]Acute [186]A [186]
M. Mahadevan et al., 2025 [10]YesBotanicalAshwagandha (Withania somnifera; Zenroot, 125 mg, 1.5% withanolides) [10]Oral [10]Mildly-to-moderately stressed adults [10]90 [10]84 days [10]A [10]
Tyler W LeBaron et al., 2019 [187]YesMolecular hydrogenHRW tablets (DrinkHRW, 5 mg H₂) [187]Oral [187]Healthy adults [187]19 [187]Acute (2 days) [187]A [187]
Janis Fiedler et al., 2022 [188]YesMineral saltSodium citrate (600 mg/kg) [188]Oral [188]Endurance-trained men [188]12 [188]16 h recovery [188]Insufficient [188]
A. Alyahya et al., 2024 [6]YesPhytochemical + lifestyleBeetroot juice (nitrate, 6 mmol) + increased PA [6]Oral [6]Hypertrophic cardiomyopathy patients [6]28 [6]16 weeks [6]A [6]
A. Lopresti et al., 2024 [189]YesAntioxidant blendAstaxanthin (9 mg) + grape juice extract (250 mg) + vitamin E (12 mg) [189]Oral [189]Adults with subjective memory complaints [189]Not clearly stated [189]12 weeks [189]Insufficient [189]
Sanjoy K Deb et al., 2025 [190]YesLipid mediatorPalmitoylethanolamide (PEA; Levagen+, 600 mg) [190]Oral [190]Moderately stressed female students [190]16 [190]6 weeks [190]A [190]
Vrushali Gersappe et al., 2024 [191]YesBotanical blendKaraCalm (Valeriana, Passiflora, Ocimum sanctum, Ziziphus, Rosmarinus, Nigella sativa) [191]Oral [191]Healthy adults with mild stress [191]48 [191]56 days [191]B [191]
H. A. A. Ibrahim et al., 2025 [192]YesOmega-3 fatty acidEPA (400 mg) + DHA (200 mg; ratio 2:1) [192]Oral [192]Overweight/obese children [192]60 [192]3 months [192]A [192]
B. Campbell et al., 2016 [193]YesThermogenic/stimulantCaffeine (150 mg) + green tea extract + guarana + chromium + yerba mate [193]Oral [193]Healthy women [193]13 [193]Acute [193]A [193]
M. Eckstein et al., 2022 [194]YesCarbohydrateGlucose, fructose, glucose+fructose (1 g/kg body mass) [194]Oral [194]Healthy adults [194]15 [194]Acute (2 h) [194]A [194]
N. Boyle et al., 2021 [195]YesMulti-ingredientMagnesium (150 mg) + B vitamins + green tea (125 mg, 40% L-theanine) + rhodiola (222 mg) [195]Oral [195]Moderately stressed adults [195]100 [195]Acute [195]A [195]
Nicholas Sjoberg et al., 2010 [2]YesOmega-3 fatty acidDHA-rich fish oil (0.52–1.56 g DHA/day) [2]Oral [2]Overweight/obese adults [2]46 (HRV subset) [2]12 weeks [2]A [2]
J. Tikkanen et al., 2023 [3]YesOmega-3 fatty acid + vitaminEPA (460 mg) + DHA (380 mg)/day + vitamin D3 (2000 IU/day) [3]Oral [3]Adults ≥50 years [3]911 [3]2 years [3]A [3]
Chui Dh et al., 2014 [196]YesMarine nutraceuticalLD-1227 (collagen elastin, protein, unsaturated fatty acids, phospholipids; 400 mg) [196]Oral [196]Work-stressed adults [196]48 [196]2 months [196]B [196]
Teerapong Rattanatantikul et al., 2020 [197]YesBotanical blendSoy isoflavone + black cohosh + chasteberry + evening primrose oil [197]Oral [197]Post-menopausal women [197]101 [197]12 weeks [197]B [197]
Atef Salem et al., 2025 [198]YesPhytochemicalBeetroot juice powder (450 mg nitrate) vs. creatine monohydrate (0.3 g/kg) [198]Oral [198]Physically active men [198]11 [198]Acute [198]A [198]
L. Caulfield et al., 2011 [199]YesMineralZinc sulfate (25 mg/day; prenatal) [199]Oral [199]Children (54 months; follow-up of prenatal RCT) [199]165 [199]Prenatal through gestation [199]A [199]
I. Mariano et al., 2020 [200]YesPhytoestrogenSoy isoflavone (100 mg; 93.5% daidzein) [200]Oral [200]Healthy postmenopausal women [200]28 [200]10 weeks [200]A [200]

Note: Two citations represent the same study (K. Schmidt et al., 2014 and "Prebiotic intake reduces the w") and are treated as a single source in the analysis below. The 200 entries thus reflect 199 distinct reports.

The pool divides into approximately 80 Grade A studies (direct autonomic outcome reported), 90 Grade B studies (stress physiology or validated symptom outcomes only), and approximately 9 studies classified as insufficient for Grade A or B (either no interpretable between-group effect on any relevant outcome, mixed interventions that cannot be disentangled, or no pertinent outcomes reported). Sample sizes for Grade A studies ranged from 6 to 911 analysed participants, though the median was under 30, reflecting the small-to-moderate scale typical in this literature. Essential oil/olfactory studies accounted for the majority of Grade A entries, largely because those studies routinely measure HRV or heart rate in real time. Probiotic and prebiotic trials were predominantly Grade B, reporting cortisol or validated questionnaire scores without concurrent HRV instrumentation.

Effects

Oral Nutrients and Microbiota-Directed Ingredients

Omega-3 Fatty Acids

Omega-3 supplementation produced the most consistent Grade A autonomic signal across diverse populations and durations. DHA-rich fish oil at 6 g/day (1.56 g DHA/day) administered for 12 weeks to overweight adults with CVD risk factors significantly increased HF power (p = 0.01), consistent with enhanced parasympathetic tone, and reduced resting heart rate (p = 0.008) [1]. A dose-response relationship was observed: across doses of 2, 4, and 6 g/day of DHA-rich fish oil, the LF:HF ratio declined with increasing dose (r = −0.34, p = 0.02), while large artery compliance improved correspondingly (r = 0.34, p = 0.006) [2]. At 1 g/day of marine omega-3 (EPA 460 mg + DHA 380 mg), RMSSD increased significantly over 2 years relative to placebo (p = 0.040; net change +8.84%, 95% CI 0.41–17.97%) [3], with accompanying ECG changes indicative of heightened vagal tone including increased PR-interval (p = 0.005) and P-wave duration (p = 0.03) [3]. In psoriatic arthritis patients, 3 g/day of n-3 PUFA (50% EPA/50% DHA) for 24 weeks produced a statistically significant per-protocol increase in RR interval (p = 0.01) and reduction in heart rate (p = 0.01), though not in the intention-to-treat analysis [177]. DHA supplementation (600 mg/day from algal oil) during pregnancy significantly increased fetal SDNN (p = 0.017) and RMSSD (p = 0.007) at 24–36 weeks gestation [4], and maternal omega-3 (2.5 g/day, 4 months) reduced overall cortisol during a TSST (2.5 g/day group: −19% vs. placebo; p = 0.03) and improved post-stress IL-10 (anti-inflammatory) stress reactivity (p = 0.05) [91]. A study in overweight/obese children (60 participants, 3 months) showed significant increases in RMSSD (p = 0.017), SDNN (p = 0.009), and pNN50 (p = 0.043) with omega-3 supplementation [192].

These findings are consistent across healthy, at-risk, and clinical populations, and across acute to chronic durations (2 weeks to 2 years). The predominant direction of effect is a shift towards parasympathetic dominance, reflected in HF power, RMSSD, and SDNN. The key limitation across the omega-3 literature is that most individual studies are underpowered (n < 70 with HRV instrumentation), and the mixed EPA/DHA ratios used across studies introduce uncertainty about which fraction drives the autonomic effect.

Inorganic Dietary Nitrate (Beetroot)

Inorganic nitrate from beetroot juice and extract consistently produced autonomic and cardiovascular effects across multiple study designs. In a pre-exercise acute model, 600 mg beetroot extract significantly accelerated vagal recovery post-exercise, with RMSSD, HF-HRV, SDNN, SD1, and SD2 all showing quicker return towards resting values compared to placebo [5]. In trained men, acute beetroot juice (400 mg nitrate) produced a lower RMSSD during exercise compared to placebo (12.9 ± 6.3 vs. 26.9 ± 18 ms; p = 0.023) while RMSSD-Slope was higher (BJ 3 ± 3 vs. placebo 0.5 ± 0.7; p = 0.025) [160], suggesting a distinct pattern of autonomic loading during effort. In physically active men (n = 11, acute crossover), beetroot juice (450 mg nitrate) produced significantly higher RMSSD, SDNN, and HF power at both pre- and post-session time points compared to placebo [198]. Sustained 16-week nitrate-rich beetroot juice (6 mmol/day) combined with increased physical activity in hypertrophic cardiomyopathy patients significantly increased HF power (7.54 ± 2.14 vs. 8.78 ± 1.60 ms², p < 0.01) and LF power (p < 0.01) [6]. In healthy normotensive African-American women, acute beetroot juice increased SDNN at rest and during moderate exercise with no significant LF effect [179]. Beetroot juice (6.4 mmol nitrate) acutely reduced RMSSD during resistance exercise in a within-session model, an effect interpreted as altered autonomic loading rather than impaired vagal tone [160]. The mixed-intervention study combining beetroot with increased exercise [6] limits attribution to nitrate alone.

Coenzyme Q10 and NADH

CoQ10 30 mg as a single acute oral dose significantly increased total power of HRV during low-intensity cycling exercise (p < 0.05), with HF and LF power showing non-significant trends to increase (p < 0.1) [176], suggesting augmented overall autonomic activity rather than specific vagal enhancement. Combined CoQ10 (50 mg) + NADH (5 mg) twice daily for 8 weeks in chronic fatigue syndrome significantly reduced maximum heart rate during a cycle ergometer test (p = 0.022) [167], though HRV parameters were not reported. These findings support a modest autonomic effect of CoQ10 at the doses tested.

Phosphatidylserine / Phosphatidic Acid Complex

Two studies from the same group examined PAS (soy-derived phosphatidylserine + phosphatidic acid). At 400 mg PAS/day (six weeks), ACTH (p = 0.010), salivary cortisol (p = 0.043), and serum cortisol (p = 0.035) responses to the TSST were normalised in chronically high-stressed men, while low-stressed men showed no benefit [13]; neither 200 mg/day nor any dose affected heart rate or pulse transit time [13]. A dose-finding predecessor study found that 400 mg PAS (three weeks) produced pronounced blunting of ACTH and salivary and serum cortisol responses to TSST and attenuated post-stressor subjective distress, while 600 mg and 800 mg daily doses showed no such selectivity, suggesting an inverted-U dose-response [42]. These studies classify as Grade B since no direct HRV biomarker was measured [13, 42], but their cortisol data are among the most rigorously designed in this collection, with clear effect specificity to the high-stress subgroup.

Probiotics and Postbiotics

Probiotic studies overwhelmingly achieved Grade B classification, with their primary evidence resting on cortisol modulation and validated questionnaire improvement. The sole Grade A probiotic result comes from Moerkl et al. (2025), where OMNi-BiOTiC STRESS Repair (9-strain, 1.5 × 10¹⁰ CFU twice daily, 3 months) in major depression patients significantly increased morning RMSSD, HF-HRV (lnHF), logRSA, and reduced heart rate compared to placebo [12], establishing that this multi-strain preparation can produce an interpretable direct autonomic effect in a depressed clinical population.

In the Grade B tier, cortisol effects were observed with multiple strains and formulations: B-GOS prebiotic significantly reduced the cortisol awakening response (CAR) compared to placebo [23]; colon-delivered SCFAs (acetate, propionate, butyrate, equivalent to fermentation of 10–20 g arabinoxylan oligosaccharides) attenuated the cortisol response to TSST in healthy men at both doses versus placebo [17]; L. rhamnosus CNCM I-3690 prevented stress-induced STAI increases (p = 0.01) and protected against PSS increases in high-cortisol-responders (p = 0.01) in students facing academic exams [34]; L. casei Shirota prevented the stress-induced cortisol surge observed in the placebo group before national medical examinations [16] and preserved gut microbiota diversity [16]; heat-killed L. paracasei PS23 (300 mg/day, 8 weeks) significantly reduced serum cortisol in stressed nurses [29]; the dual-strain PS128/HT-PS23 (Neuralli Mood) reduced ACTH and norepinephrine without changing cortisol [25]; and heat-killed L. plantarum SNK12 (low dose) reduced salivary cortisol (p = 0.021) and the LF/HF ratio (p = 0.012) [73], and in a second trial also reduced salivary cortisol (p = 0.016) and plasma TNF-α (p = 0.037) alongside sleep improvements [89]. The heat-treated postbiotic L. gasseri CP2305 (1 × 10¹⁰ cells, single acute dose) significantly increased RMSSD compared to placebo within 60 minutes of ingestion, alongside reductions in VAS stress and POMS2 tension-anxiety scores [9], earning Grade A.

The Hellhammer (2004) PAS and Hellhammer (2014) PAS findings represent the clearest dose-specificity evidence in the oral stress physiology literature: benefit was confined to 400 mg/day in chronically stressed subjects and disappeared at lower or higher doses [13, 42]. Among probiotic formulations, effect sizes on cortisol were generally modest and often reached significance only in subgroups (high-stress, high-cortisol, or clinical populations), which is a recurrent finding across this literature.

Magnolia/Phellodendron (Relora) at 500 mg/day for four weeks reduced salivary cortisol exposure by 18% (p < 0.05) and improved multiple POMS mood subscales including a 42% reduction in anger [57] in moderately stressed subjects; a smaller pilot study in premenopausal women found reduced state anxiety but no significant cortisol change [71]. Ashwagandha (Withania somnifera, Zenroot 125 mg, 1.5% withanolides, 84 days) significantly improved PSS, BAI, and PSQI scores, and transiently increased RMSSD and SDNN on day 14 (p values not stated beyond significance) [10], with no effect on serum cortisol or salivary alpha-amylase [10]. Enzyme-treated asparagus extract (ETAS, 150 mg/day, 28 days) increased the LF/HF ratio during a cognitive stressor, increased salivary sIgA, improved self-rated fatigue and sleep quality, and enhanced work performance, without changing serum or salivary cortisol [72].

L-Carnitine

L-carnitine-L-tartrate (1.5 g/day, 24 weeks) in elderly women produced a significant adverse autonomic finding: RMSSD fell from 23.87 ± 8.84 ms to 14.35 ± 4.72 ms (p = 0.034) and HF power from 155.6 ± 88.53 to 79.38 ± 52.66 ms² (p = 0.049), indicating vagal withdrawal [14]. This is the only oral ingredient in this review associated with a statistically significant reduction in cardiac parasympathetic indices, raising a safety concern for long-term carnitine supplementation in this demographic, though the very small sample (n = 13) warrants caution in interpretation [14].

Hydrogen-Rich Water

Acute hydrogen-rich water (HRW, 1260 mL) produced a relative increase in sympathetic activity (SDNN/RMSSD ratio) at 25 and 35 minutes post-ingestion without altering vagal indices [175]. A distinct study with hydrogen-rich jelly (10 g, three administrations) produced significantly lower CVRR during stand-up (p = 0.047) and lower LF/HF ratio during resitting (p = 0.027) [184], suggesting a modulating effect on orthostatic autonomic transitions. HRW tablets also reduced exercising heart rate during minutes 1–9 of a graded treadmill test (121 ± 26 vs. 126 ± 26 bpm; p < 0.001) [187]. These findings are preliminary given very small samples (n = 14–19) and inconsistent direction of effect across delivery formats [175].

Dietary Carbohydrates

Increasing dietary carbohydrate as part of a DGA-compliant whole-food diet (8 weeks) reduced salivary cortisol at multiple post-TSST time points (−0.35 to −0.51 log nmol/L; all p < 0.05), specifically in participants at the 90th percentile of carbohydrate intake increase [50]. The manipulation confounded carbohydrate with an overall dietary quality shift, and no between-group significance was found for the overall cohort, limiting generalisability [50]. In an acute crossover, oral glucose, fructose, and combined glucose+fructose (1 g/kg body mass) each significantly reduced HRV (SDNN, RMSSD, pNN50; all p < 0.001) and elevated blood pressure compared to sucralose placebo, with the magnitude of HRV suppression correlating with glycaemia rate-of-change [194]. These data suggest that high glycaemic loads suppress cardiac vagal tone acutely in proportion to glycaemic excursion.

Vitamin D

Vitamin D3 (1600 IU/day) administered over approximately 4.5 months during winter to forensic inpatients maintained normal HF-HRV responses to an experimental stress procedure post-intervention (p < 0.001), while the placebo group—whose vitamin D levels fell to a classic spring nadir—showed sustained elevated stress responses (p < 0.001) [65]. No significant between-group effect on serotonin or cortisol was found [65]. This study stands out because it used a within-treatment longitudinal design in a controlled institutional setting; the implication is that adequate vitamin D status is necessary for normal psychophysiological reactivity rather than supplementation per se conferring a pharmacological benefit [65].

Almonds

Two reports from the same ATTIS trial (Dikariyanto et al., 2020 and Dikariyanto et al., 2020a) independently confirm that 63 g/day whole almonds for 6 weeks significantly increased HF power during a mental stress Stroop task (mean difference 124 ms²; 95% CI 11, 237; p = 0.031) relative to isocaloric control snacks [7, 8], with no effect during resting or physical stress conditions. The Stroop-specific activation of the HF-HRV improvement aligns with a stress-buffering rather than baseline resting autonomic enhancement mechanism. Both reports describe the same 105 participants and should be treated as a single dataset with two publications.

Galacto-Oligosaccharides (GOS) / Whey-Based Sleep Product

A whey protein + GOS-based dairy product consumed nightly for three weeks reduced early-morning salivary cortisol versus placebo (p = 0.045) and increased Bifidobacterium relative abundance (p = 0.02) [56]. A separate GOS prebiotic study in healthy young women (28 days) lowered salivary cortisol secretion and reduced attentional bias to negative stimuli [58].

Polyphenol-Rich Dark Chocolate

High-polyphenol dark chocolate (500 mg total flavonoids per 25 g/day, 4 weeks) significantly reduced total daily cortisol, morning cortisol, and the cortisol/cortisone ratio (all p < 0.001) without affecting PANAS mood scores [41]. This is among the most metabolically specific cortisol findings in the review, with the authors proposing inhibition of 11β-hydroxysteroid dehydrogenase type 1 as a mechanism [41].

Phospholipids (Bovine Milk-Derived)

Bovine milk-derived phospholipids (2.7 g/day for 6 weeks, including 300 mg PS) in high-perfectionist men improved post-stress reaction time (p = 0.01) and increased mid-stress energetic arousal (p = 0.03), but produced significantly augmented systolic and diastolic blood pressure in the phospholipid condition (p < 0.04 and p = 0.01 respectively) [79], without attenuating salivary cortisol. This blood pressure elevation warrants attention as a potential adverse autonomic finding in perfectionist or stress-vulnerable individuals.

Bioactive Peptides and Amino Acids

Lactoferrin (bovine, 800 mg, acute single dose) administered before a calculation task attenuated the task-induced suppression of parasympathetic activity: the high-frequency HRV increase and LF/HF decrease observed under placebo were blunted with lactoferrin (both p < 0.026) [68], indicating that lactoferrin stabilises rather than shifts autonomic tone under cognitive stress. Egg protein hydrolysate (EPH, tryptophan-rich, 1 g in a food matrix, acute) produced significantly higher HF-HRV relative to placebo (effect size approximately −0.05 Hz, p = 0.0019) [49], though mood questionnaire outcomes did not differ. An amino acid mixture of arginine, valine, and serine (acute single dose pre-exercise) suppressed the exercise-induced cortisol surge (p not stated beyond significant) [54]. GABA (2.01 mg in oolong tea) acutely reduced an immediate stress score (p < 0.001) and improved HRV total power and HF power in a 30-participant pre-post design [136]. Vegetable tablets containing GABA from kale prevented the heart rate increase and LF/HF rise observed with control tablets in a very small (n = 7) acute crossover [166]. Alpha-s1-casein tryptic hydrolysate (150 mg) + L-theanine (50 mg) improved PSQI sleep domains significantly and reduced salivary cortisol by 34.6% (p = 0.007) over four weeks [182]. A multi-ingredient formula combining GABA and 5-HTP (Gabadone, 1 week) improved HRV parasympathetic function as well as sleep latency and duration [169].

Acanthopanax senticosus (ASH)

Four-week supplementation with ASH in elderly individuals produced significant improvements in CVRR, HF power, heart rate, and blood pressure (all p < 0.05) relative to placebo, validated against pharmacopoeia standards for eleutheroside B and E content [11]. This is one of the few botanical adaptogen studies in this review providing a direct autonomic endpoint in a placebo-controlled design.

Thermogenic/Stimulant Ingredients

Citrus aurantium + caffeine (100 mg each, acute) produced significantly elevated epinephrine and norepinephrine during the ingestion period compared to placebo, with no corresponding changes in RMSSD or HF-HRV at rest [185]. A multi-ingredient thermogenic supplement containing caffeine (150 mg), green tea, guarana, chromium, and yerba mate significantly elevated metabolic rate and produced significant blood pressure effects (both systolic and diastolic; p < 0.05) without a significant heart rate change [193]. These stimulant formulations thus produce sympathoactivation at the catecholamine and haemodynamic level without clearly perturbing cardiac vagal indices, suggesting cardiac autonomic accommodation to adrenergic stimulation.

Multi-vitamin-mineral supplementation with 300 mg guarana (vs. caffeine or placebo, acute crossover) maintained HRV stability during the first hour post-ingestion, whereas caffeine and placebo both showed HRV decline; decision-making speed also improved with the guarana preparation [159]. The multi-ingredient composition limits attribution to guarana specifically [159].

A Kampo formulation combining ginseng (250 mg), oriental bezoar (50 mg), and glycyrrhiza (50 mg) increased HF power (p < 0.05) and decreased heart rate (p < 0.05) at 60 minutes post-dose [186]. Sulforaphane (25 mg, acute), counterintuitively, caused a pro-inflammatory response and reduced parasympathetic indices (RMSSD, pNN50, HF all lower; all p < 0.05) following a high-calorie challenge [181], possibly reflecting hormetic activation rather than relaxation.

Palmitoylethanolamide (PEA)

PEA (Levagen+, 600 mg/day, 6 weeks) significantly increased SDNN (+9.70 ± 6.02 ms) compared to a decrease in placebo (−5.72 ± 3.14 ms; p = 0.024) in moderately stressed female students [190]. RMSSD trended upward but did not reach significance (p = 0.087), and salivary cortisol was unchanged [190]. This is a small pilot (n = 16) but represents the first human autonomic evidence for PEA at this dose [190].

Olfactory and Topical Ingredients

Lavender (Lavandula angustifolia)

Lavender inhalation is by far the most studied olfactory ingredient in this review, appearing across more than 25 studies in acute, sub-chronic, and chronic designs, and across healthy volunteers, clinical, and occupational populations.

Acute Grade A findings are numerous and largely consistent in direction. In healthy females, 10-minute lavender inhalation significantly increased HF power compared to water control, with effects persisting for up to 25 minutes post-inhalation [18]. In healthy adults with insomnia, 12-week biweekly lavender inhalation significantly decreased heart rate and increased SDNN, RMSSD, and HF power in both the 4th and 12th weeks [19]. The combined cold foot bath + lavender inhalation study (n = 60, single session) demonstrated significant between-group differences in LF and HF power and significant reductions in diastolic and systolic blood pressure [123]. Topical lavender at 1% (applied to skin without olfactory stimulation) tended to increase HF activity with a statistically significant between-period increase in parasympathetic index when differences pre- vs. during treatment were examined [101], suggesting a pharmacological skin-absorption pathway independent of the olfactory route. Lavender aromatherapy massage (5%, topical, single session) produced significant increases in RMSSD (p < 0.001), HF (p = 0.004), SDNN (p < 0.001), VLF (p < 0.001), and TP (p < 0.001) relative to massage with almond oil [108]. A 40-minute peri-surgical lavender inhalation significantly reduced heart rate (p = 0.021) and respiratory rate (p = 0.011) and cortisol (p < 0.0001) in dental surgery patients [20].

However, not all lavender findings are consistent. Nomura et al. (2016) found that lavender inhalation during a 30-minute cognitive task paradoxically decreased HF power (p < 0.01) and increased sympathetic indices compared to control, while simultaneously reducing subjective stress and improving mood and concentration [21]. This divergence—physiological arousal with subjective relaxation—was also observed in the Morozova et al. (2025) study, where lavender inhalation reduced self-reported state anxiety significantly without producing measurable EEG or HRV changes [140]. The Kikuchi et al. (2026) crossover (n = 20, 5-minute lavender spray) found that physiological benefits (reduced HR, SBP, salivary amylase) were attributable primarily to deep breathing patterns rather than lavender aroma per se [22], directly challenging whether many acute lavender benefits reflect the olfactory compound or the breathing behaviour it encourages. The Chamine & Oken (2016) study (n = 92, rigorous design with blind and prime conditions) found pharmacologically specific benefits of lavender on working memory post-stress, but overall cortisol and chromogranin A did not differ by odour condition [114].

The most consistent conclusion from the lavender literature is that acute inhaled lavender reliably shifts HF power upward under resting or mild-stress conditions in healthy younger samples, with the effect size and reliability diminishing in clinical populations, older adults, and study designs controlling for breathing confounds.

Other Citrus Essential Oils and Individual Aromatic Compounds

Bergamot inhalation (15 minutes) reduced salivary cortisol significantly in resting healthy females (p = 0.003) [98] and reduced anxiety scores versus water vapor in pre-operative patients [130]. Orange essential oil inhalation (120 seconds) increased HF power and reduced blood pressure significantly [134]. Neroli oil inhalation (0.1% and 0.5%) for five days in postmenopausal women reduced MENQOL physical domain scores and diastolic blood pressure (both groups vs. control; p statistically significant) [104] without reaching autonomic Grade A. Citrus aurantium (neroli) inhalation in ACS patients (3×/day, 2 days) significantly reduced anxiety (STAI) versus paraffin placebo [139] but did not measure HRV. Jasmine inhalation for 60 minutes significantly reduced blood cortisol in laparotomy patients (160.7 to 93.15 vs. increase in controls; p = 0.001) [128] alongside anxiety reduction. Yuzu (Citrus junos) inhalation for 10 minutes produced significant reductions in salivary chromogranin A (CgA) immediately and 30 minutes post-inhalation [121] and reduced POMS total mood disturbance [121]; HF power and heart rate both showed improvement post-inhalation [132].

Individual aromatic compounds studied with olfactometry show differentiated autonomic profiles. β-caryophyllene inhalation (24.8 ppm, during a 20-minute stressor) produced the most pronounced reductions in both STAI subscales and heart rate, and significantly increased the ratio of facial expressions of happiness while reducing fear expressions [107]. Citral and linalool also produced anxiety reductions but less consistently across both STAI subscales [107]. Black pepper aroma (β-caryophyllene dominant) during a 30-minute calculation task suppressed the task-induced heart rate increase by 38.9% relative to the control (dipropylene glycol), suppressed the HRV reduction by 32.9%, and suppressed skin conductance increase by 15.5% relative to ginger [145]. Cedarwood, strawberry, green tea, apple, and citrus ginger all inhibited the task-induced elevation in HR and the suppression of HF-HRV during a cognitive stressor [146], while musk reduced skin conductance level during the task.

Phytoncide (terpenes from Chamaecyparis obtusa) diffused for 1 hour/day, 5 days/week, 8 weeks in cancer survivors significantly increased HF power (16.93% ± 20.42%; p = 0.001) and decreased LF power (p = 0.001), alongside reductions in cortisol (−24.94%; p < 0.001) and epinephrine (−5.29%; p < 0.001) [119]. Rosemary inhalation produced significant increases in heart rate, blood pressure, and respiratory rate—consistent with sympathetic activation—alongside EEG beta-wave enhancement [116], making it the principal olfactory ingredient associated with sympathoactivation in this collection. Sandalwood oils (East Indian, Western Australian) and lavender inhalation all produced significantly lower systolic blood pressure during recovery, with the Western Australian oil additionally reducing cortisol during the recreation phase [92]. Fir essential oil (3-minute inhalation) reduced ln(LF/HF) significantly in female participants [105]. White musk aromatic oil (10 minutes) significantly reduced the LF/HF ratio (p = 0.024) and reduced POMS fatigue-inertia and tension-anxiety subscales [137].

Marjoram (Origanum majorana) inhaled during a 2-hour nursing shift significantly reduced VAS-stress (p = 0.026) and state-anxiety (p = 0.001) without producing significant HRV changes, though heart rate increased slightly (p = 0.031) [148]. Extended aromatherapy massage (geranium Pelargonium graveolens 1%, crossover, 3 months per arm) in fibromyalgia patients suppressed a cortisol transient observed in the control arm [110] and prevented diastolic blood pressure increases [110], though sample size was very small (n = 10).

The cosmetic ECP (juniper, copaiba, rosewood, juniper oil) topically applied daily for 28 days then challenged with a psychosocial stress test produced a significant single-application increase in cardiac parasympathetic modulation (HRV) and, over the 28-day regime, dampened cortisol rise during the stressor, reduced state anxiety, improved POMS mood profile, and reduced anxiety-signalling non-verbal behaviour [93, 93, 93]. The AromaTouch blend (peppermint, lavender, melaleuca, among others; topical biweekly for 3 weeks) significantly reduced heart rate (−12.2% vs. −2.5% control; p implied significant) and showed a dramatic reduction in salivary CRP immediately and sustained cytokine reduction over 3 weeks in the EO group [115, 115], though the small sample (n = 18) and industry sponsorship are material limitations.

Multisensory Olfactory-Tactile Combinations

In a dental clinic setting, a within-subject design (n = 40) compared control, visual, tactile, olfactory, and combined tactile-olfactory conditions. The combined condition produced a 42.3% reduction in STAI-S scores, 66.0% decrease in LF/HF ratio, 81.6% increase in RMSSD (olfactory condition peak), 54.7% increase in SDNN, 15.9% decrease in HR, and 67.2% reduction in skin conductance [152]. A VR + olfactory ("Beach" scent, 45 minutes) crossover (n = 30) produced a 108% increase in HF-HRV from the Math Stress Test to the scented relaxation condition versus 44% without scent (p = 0.002) [142], establishing that olfactory augmentation of a VR relaxation environment confers additional, objectively measurable autonomic benefit.

Synthesis

Apparent Contradictions and Their Resolution

Lavender: autonomic paradox.

The most consequential contradiction is between lavender studies reporting HF power increases (consistent with parasympathetic enhancement) and those—such as Nomura et al. (2016) [21] —reporting HF power decreases during active cognitive stressors. This resolves mechanistically when the context is distinguished: in resting or mildly stressed conditions, lavender inhalation consistently shifts the autonomic balance toward parasympathetic dominance, likely through olfactory limbic activation. During active cognitive loading, lavender has been reported to increase sympathetic arousal (reduced HF, increased nose-tip temperature, increased subjective concentration) [21], suggesting that lavender may not simply "relax" the system but optimises arousal level, supporting sympathetic activation when the context demands attentiveness. The divergence between physiological activation and subjective relaxation in several lavender studies [114, 140] further supports this interpretation: lavender may reduce the affective aversiveness of stress without necessarily reducing physiological arousal, analogous to the psychological dissociation between perceived effort and cardiac output under cognitive load. Critically, the Kikuchi et al. (2026) finding that breathing patterns (rather than the aroma) drive acute cardiovascular change [22] introduces a methodological confound that may partially explain the breadth of positive findings across lavender studies that did not control breathing. Future designs should standardise respiratory rate or use non-inhalation delivery routes (as in the topical Satou et al. study [101]) to disambiguate pharmacological from respiratory effects.

Sulforaphane: pro-inflammatory acute response.

Sulforaphane (25 mg, acute) produced a paradoxical reduction in parasympathetic indices (RMSSD, HF power; both p < 0.05) associated with a pro-inflammatory CRP response to a caloric challenge [181]. This contrasts with the common expectation of anti-inflammatory, autonomic-supportive effects from isothiocyanates. The finding is most consistent with an acute hormetic response—an initial pro-inflammatory, sympathoactivating perturbation that may be the mechanistic precursor to longer-term anti-inflammatory adaptation. This model predicts that repeated sulforaphane administration would show autonomic benefit over weeks that would not be visible in an acute crossover, and future studies should examine this trajectory.

Dietary nitrate: during-exercise vs. post-exercise divergence.

During resistance exercise, beetroot juice reduced RMSSD, which superficially appears as vagal withdrawal [160]. However, the RMSSD-Slope was higher in the BJ condition, indicating faster vagal re-engagement between sets—a pattern consistent with enhanced autonomic efficiency rather than impairment [160]. Post-exercise HRV recovery also favoured beetroot extract [5]. The apparent within-exercise RMSSD reduction thus reflects the autonomic cost of more sustained muscular effort (via enhanced nitric oxide-mediated oxygen delivery) rather than a direct vagolytic effect. This distinction is clinically important: the appropriate interpretation is that nitrate-rich beetroot supports vagal tone across the exercise-recovery cycle while transiently loading vagal channels during peak effort.

L-carnitine: vagal withdrawal.

L-carnitine-L-tartrate (1.5 g/day, 24 weeks) was uniquely associated with significant decreases in RMSSD and HF power in elderly women [14]. A plausible mechanism is that carnitine-enhanced mitochondrial fatty acid oxidation shifts cardiac energy metabolism in a way that increases sympathetic drive or reduces vagal modulation—a hypothesis consistent with epidemiological data linking elevated plasma TMAO (a carnitine metabolite via gut bacteria) to cardiovascular risk. Whether this applies to younger populations or shorter durations is unknown, but the signal in this small sample warrants replication with HRV monitoring as a primary outcome.

Probiotics: Grade B ceiling.

The probiotic literature almost universally fails to achieve Grade A classification not because probiotic effects on the autonomic nervous system are absent—the Moerkl et al. (2025) study demonstrates such effects clearly [12] —but because the vast majority of probiotic trials were not designed with real-time HRV instrumentation as a primary outcome. The cortisol reductions observed across multiple strains, the ACTH reduction with dual-strain PS128/HT-PS23 [25], and the consistent attenuation of exam-stress cortisol surges with L. casei Shirota [15, 16] collectively constitute substantial Grade B evidence for HPA axis modulation. The Grade A signal from the postbiotic heat-treated L. gasseri CP2305 (acute single dose, RMSSD increase, within 60 minutes) [9] suggests that vagal effects can manifest rapidly after postbiotic ingestion, possibly via gut-derived serotonin signalling, which was supported by the in vitro data from the same study [9].

Omega-3 dose-response.

The evidence across omega-3 studies suggests a near-linear relationship between DHA intake and parasympathetic augmentation within the range tested (0.52–1.56 g DHA/day). The Sjoberg et al. (2010) dose-response analysis is the clearest demonstration of this gradient [2], and it is corroborated by the 8.84% RMSSD increase with ~840 mg combined EPA+DHA/day over 2 years [3]. The mechanistic pathway likely involves altered membrane phospholipid composition affecting ion channel gating in cardiac vagal neurons.

What Can Be Concluded for Specific Populations and Conditions

For healthy, moderately stressed adults, the following oral ingredients have at minimum Grade B (and in some cases Grade A) evidence for cortisol or validated stress score reduction: prebiotics (B-GOS), GOS, probiotics (L. rhamnosus CNCM I-3690, L. casei Shirota, L. plantarum P-8, L. helveticus R0052 + B. longum R0175), postbiotics (heat-killed L. gasseri CP2305 for acute autonomic effects; heat-killed L. paracasei PS23 for cortisol), PS/PA complex at 400 mg, Magnolia/Phellodendron, GABA-fortified foods, almonds (during cognitive stress), and dietary nitrate. Among these, almonds [7], dietary nitrate [5, 160], and heat-treated L. gasseri CP2305 [9] have Grade A direct autonomic data.

For clinical populations with autonomic dysfunction, the evidence is sparser but more specific: omega-3 fatty acids have Grade A evidence in CFS-adjacent (psoriatic arthritis, overweight with CVD risk), and the 2-year VITAL ancillary study provides Grade A data in persons ≥50 years; CoQ10 + NADH improved max HR in CFS [167]; ASH improved multiple HRV indices in elderly community dwellers [11]; and OMNi-BiOTiC STRESS Repair improved morning vagal tone in major depression [12].

For olfactory/topical cosmetic ingredients, lavender is the most extensively tested with Grade A evidence in healthy, insomnia, peri-surgical, and occupational stress populations, though its effect direction is context-dependent. β-caryophyllene, phytoncide terpenes, orange essential oil, bergamot, yuzu, sweet marjoram, and fir essential oil each have at least one Grade A study supporting autonomic or stress-physiological effects, all in small samples and principally acute designs. The multi-ingredient cosmetic ECP (Sgoifo et al.) [93] is the only topical cosmetic preparation with Grade A HRV data from a sustained (28-day) application design in healthy women.

Regulatory Status

No EU or Polish regulatory source was identified within the reviewed studies attributing a health claim to any ingredient in this review specifically for cardiac autonomic, stress physiology, or relaxation endpoints. The PS/PA complex (PAS) holds US FDA GRAS status [13] but this is a US designation. Probiotic and prebiotic ingredients are regulated as food or food supplements in the EU, without approved Article 13 or 14 health claims for autonomic or stress outcomes. Botanical extracts including magnolia, phellodendron, ashwagandha, and asparagus extract are typically marketed as food supplements in the EU under Directive 2002/46/EC without specific autonomic claims. Essential oils and cosmetic topicals fall under Regulation (EC) 1223/2009 where physiological (autonomic) claims would require substantiation not yet established for any ingredient reviewed here. Regulatory category is therefore stated as not established in this review for all ingredients, as no official EU or Polish source within the reviewed literature attributed a specific cardiac autonomic or stress physiology health claim.

Safety Considerations

Across the 200 studies, the overall tolerability profile of the tested ingredients was favourable. Most probiotic and prebiotic studies reported no adverse events or mild gastrointestinal symptoms (bloating, flatulence) at rates comparable to placebo [30, 61, 62]. The most consequential safety signal is the vagal withdrawal (reduced RMSSD and HF power) associated with 24 weeks of L-carnitine supplementation [14]; the authors themselves flagged this as a potential adverse effect with implications for cardiac event risk [14]. Bovine milk phospholipids augmented blood pressure in high-perfectionist men [79]. Caffeine + citrus aurantium elevated catecholamines with attendant heart rate changes [185], and thermogenic blends produced significant blood pressure elevations warranting caution in individuals with hypertension risk [193]. One study (Jurado-Castro et al., 2022) reported a gastrointestinal withdrawal [160]. The essential oil literature contained no reports of systemic adverse events, though several studies appropriately excluded participants with known fragrance allergies or pulmonary conditions [109, 129].

Författarbidrag

O.B.: Conceptualization, Literature Review, Writing — Original Draft, Writing — Review & Editing. The author has read and approved the published version of the manuscript.

Intressekonflikt

The author declares no conflict of interest. Olympia Biosciences™ operates exclusively as a Contract Development and Manufacturing Organization (CDMO) and does not manufacture or market consumer end-products in the subject areas discussed herein.

Olimpia Baranowska

Olimpia Baranowska

VD & vetenskaplig chef · Civilingenjör i teknisk fysik och tillämpad matematik (abstrakt kvantfysik och organisk mikroelektronik) · Doktorand i medicinsk vetenskap (flebologi)

Founder of Olympia Biosciences™ (IOC Ltd.) · ISO 27001 Lead Auditor · Specialising in pharmaceutical-grade CDMO formulation, liposomal & nanoparticle delivery systems, and clinical nutrition.

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  2. 2. Inga produktspecifika påståenden.. Olympia Biosciences™ verkar uteslutande som en B2B-kontraktstillverkare. Forskningen, ingrediensprofilerna och de fysiologiska mekanismerna som diskuteras här är generella akademiska översikter. De refererar inte till, stöder inte eller utgör godkända hälsopåståenden för marknadsföring av något specifikt kommersiellt kosttillskott, livsmedel för medicinska ändamål eller slutprodukt som tillverkas i våra anläggningar. Ingenting på denna sida utgör ett hälsopåstående i enlighet med Europaparlamentets och rådets förordning (EG) nr 1924/2006.

  3. 3. Ej medicinsk rådgivning.. Innehållet utgör inte medicinsk rådgivning, diagnos, behandling eller kliniska rekommendationer. Det är inte avsett att ersätta konsultation med en kvalificerad vårdgivare. Allt publicerat vetenskapligt material representerar generella akademiska översikter baserade på referentgranskad forskning och bör tolkas uteslutande i ett B2B-formulerings- och R&D-sammanhang.

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Citera

APA

Baranowska, O. (2026). Oral, Olfactory, and Topical Ingredients Modulating Cardiac Vagal Tone and Stress Physiology Biomarkers. Olympia R&D Bulletin. https://olympiabiosciences.com/rd-hub/ingredients-autonomic-stress-biomarkers/

Vancouver

Baranowska O. Oral, Olfactory, and Topical Ingredients Modulating Cardiac Vagal Tone and Stress Physiology Biomarkers. Olympia R&D Bulletin. 2026. Available from: https://olympiabiosciences.com/rd-hub/ingredients-autonomic-stress-biomarkers/

BibTeX
@article{Baranowska2026ingredie,
  author  = {Baranowska, Olimpia},
  title   = {Oral, Olfactory, and Topical Ingredients Modulating Cardiac Vagal Tone and Stress Physiology Biomarkers},
  journal = {Olympia R\&D Bulletin},
  year    = {2026},
  url     = {https://olympiabiosciences.com/rd-hub/ingredients-autonomic-stress-biomarkers/}
}

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