Immune and metabolic effects of African heritage diets versus Western diets in men: a randomized controlled trial.
Temba GS, Pecht T, Kullaya VI, Vadaq N, Mosha MV, Ulas T, Kanungo S, van Emst L, Bonaguro L, Schulte-Schrepping J, Mafuru E, Lionetti P, Mhlanga MM, van der Ven AJ, Cavalieri D, Joosten LAB, Kavishe RA, Mmbaga BT, Schultze JL, Netea MG, de Mast Q
- DOI
- 10.1038/s41591-025-03602-0
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-20
Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/712c948e-f591-4917-862a-3e29d617289a is authoritative.
How this rating was calculated
- IntegrityIntegrity concern ×4−2★
- ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
- ClaimsTreatment effect not shown to be clinically meaningful−0.5★
- ReportingStudy design partially met−0.25★
- ReportingEthical approvals partially met−0.25★
- Statistics were not checked: no recomputable values were found in this text — no test statistic reported with its degrees of freedom, no effect estimate printed with both a 95% CI and a p-value, and no percentage printed with both its count and its denominator.
- 01Efficacy rests on an unvalidated surrogate endpoint
The primary outcomes are changes in immune and metabolic profiles (plasma proteome, cytokine production, metabolome, transcriptome), which are surrogate biomarkers. The paper does not demonstrate target engagement at the tested dose (no PK/PD data) nor cite validated evidence linking these surrogates to clinical outcomes. The claim of 'anti-inflammatory' and 'pro-inflammatory' effects is based on biomarker changes without established clinical relevance.
“Primary outcomes were changes in the immune and metabolic profile before and after the intervention and at the 4-week follow-up.”
- 02Treatment effect not shown to be clinically meaningful
The reported effects are changes in biomarker levels (e.g., cytokine responses, protein concentrations) without anchoring to clinically meaningful thresholds or minimal clinically important differences. For example, the switch to WD increased CRP (P=0.020) but the magnitude is not contextualized. The paper acknowledges limitations: 'the study only provided molecular insights into short-term changes in immunometabolic features and pathways because of dietary practices but did not assess long-term clinical outcomes.'
“the study only provided molecular insights into short-term changes in immunometabolic features and pathways because of dietary practices but did not assess long-term clinical outcomes.”
This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.
The paper is a well-conducted open-label randomized controlled crossover trial with strong data and code availability, thorough statistical methods, and transparent reporting. The main weaknesses are missing details on randomization method, blinding rationale, power analysis, and explicit ethics approval and informed consent statements.
Both reviewers classified the study as interventional, and this was adopted. The evaluation covered all eight dimensions; several sub-criteria were not applicable (e.g., animal-related items). The reviewers agreed on all dimension statuses, so no divergence needed reconciliation.
Numerical inconsistencies
1 finding · worst lowValues that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.
- Internal contradictions in the reported numbersAssessed
- lowinternal contradictionThe median age reported as 25.6 years with IQR 21-27.2 seems inconsistent; the median should be within the IQR, but 25.6 is plausible. However, the IQR lower bound (21) and upper bound (27.2) suggest a median closer to 24. This is a minor concern.
“Seventy-seven healthy adult men (median age = 25.6 years; interquartile range (IQR) = 21–27.2)”
ResultsFind in source - lowinternal contradictionIn the metabolome results, the text says 'while 74 increased and 24 decreased after the intervention compared to the baseline' but this appears to be a repetition of the previous sentence's time point; likely a typo.
“while 74 increased and 24 decreased after the intervention compared to the baseline”
ResultsFind in source - lowinternal contradictionThe number of participants in the AHD to WD group is reported as 23 in one place and 22 in another, with one withdrawal noted.
men living in rural areas ( n = 23) who habitually consumed a Kilimanjaro heritage-style diet and switched to a Western-style diet for 2 weeks; ... After one participant withdrew from the study before the end of the intervention, the first group included young rural-living men ( n = 22)
Figure 1reviewer’s wording - lowinternal contradictionThe number of participants in the fermented beverage group is reported as 22 in the text but 21 in the transcriptome analysis.
the fermented beverage group ( n = 21) ... Fermented beverage consumption resulted in 26 upregulated and 104 downregulated DEGs
Figure 5reviewer’s wording
Overstated conclusions
3 findings · worst highConclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.
- Efficacy rests on an unvalidated surrogate endpointAssessed
- Treatment effect not shown to be clinically meaningfulAssessed
- Conclusions only partially backed by the presented evidenceAssessed
4 major claims checked against the paper's own evidence: 1 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.
- partialReviewers 1, 2The findings underscore the importance of preserving indigenous dietary practices to mitigate NCD risk factors.The study shows short-term benefits of heritage diets, but the claim about preserving practices is a broader inference that goes beyond the direct evidence.Evidence: Discussion section.
“These findings show the metabolic and immune effects of dietary transitions and the consumption of fermented beverages, underscoring the importance of preserving indigenous dietary practices to mitigate noncommunicable disease risk factors in sub-Saharan Africa.”
AbstractFind in source - supportedReviewers 1, 2Switching from heritage to Western diet promotes a pro-inflammatory state with impaired whole-blood cytokine responses.The paper provides direct evidence from proteomics, cytokine assays, and transcriptomics showing increased inflammatory proteins and decreased cytokine responses.Evidence: Results sections on plasma proteome, cytokine production, and transcriptome.
“The switch from heritage-style to Western-style diet affected different metabolic pathways associated with noncommunicable diseases and promoted a pro-inflammatory state with impaired whole-blood cytokine responses to microbial stimulation.”
AbstractFind in source - supportedReviewers 1, 2Switching from Western to heritage diet or consuming fermented beverage has anti-inflammatory effects.The paper shows reductions in inflammatory proteins and increases in anti-inflammatory cytokines (IL-10) in these arms.Evidence: Results sections on plasma proteome and cytokine production.
“In contrast, the switch from Western-style to heritage-style diet or consuming the fermented beverage had a largely anti-inflammatory effect.”
AbstractFind in source - supportedReviewers 1, 2Some immune and metabolic changes persist at 4-week follow-up.The paper reports sustained changes in several proteins, cytokines, and transcriptomic signatures at follow-up.Evidence: Results sections on proteome, cytokine, and transcriptome follow-up analyses.
“Some of the observed changes in the immune and metabolic profiles persisted at the follow-up, suggesting a sustained impact from the short-term intervention.”
AbstractFind in source
Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.
- INADEQUATESurrogate endpointThe primary outcomes are changes in immune and metabolic profiles (plasma proteome, cytokine production, metabolome, transcriptome), which are surrogate biomarkers. The paper does not demonstrate target engagement at the tested dose (no PK/PD data) nor cite validated evidence linking these surrogates to clinical outcomes. The claim of 'anti-inflammatory' and 'pro-inflammatory' effects is based on biomarker changes without established clinical relevance.
“Primary outcomes were changes in the immune and metabolic profile before and after the intervention and at the 4-week follow-up.”
- INADEQUATEEffect sizeThe reported effects are changes in biomarker levels (e.g., cytokine responses, protein concentrations) without anchoring to clinically meaningful thresholds or minimal clinically important differences. For example, the switch to WD increased CRP (P=0.020) but the magnitude is not contextualized. The paper acknowledges limitations: 'the study only provided molecular insights into short-term changes in immunometabolic features and pathways because of dietary practices but did not assess long-term clinical outcomes.'
“the study only provided molecular insights into short-term changes in immunometabolic features and pathways because of dietary practices but did not assess long-term clinical outcomes.”
Data authenticity concerns
None foundAn adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.
Checked — nothing surfaced.
Reporting gaps
2 findings · worst mediumRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
- Ethics/consent reporting incompleteAssessed
- Study-design details incomplete (controls, blinding, power)Assessed
The introduction cites prior cross-sectional studies and literature on Western diets, heritage diets, and fermented foods, acknowledging limitations of cross-sectional designs. The rationale for the RCT is clearly stated, and the study objectives follow logically from the cited evidence. Limitations of prior research are addressed by the choice of an interventional design.
“The study investigated the effects of switching from a Western-style diet to a Kilimanjaro heritage diet and vice versa, and the effects of consuming the fermented beverage ‘Mbege’.”
“The study investigated the effects of switching from a Western-style diet to a Kilimanjaro heritage diet and vice versa, and the effects of consuming the fermented beverage ‘Mbege’.”
The trial is described as randomized and open-label, with three arms and control participants, but the randomization method and unit are not specified. Blinding is not addressed beyond the open-label designation, and no rationale for the open-label design is given. No a priori power analysis is reported. Inclusion/exclusion criteria are partially reported (BMI range), and the analysis population is defined. Outlier handling is not explicitly described, but the analysis approach (LMM with covariates) is detailed. Controls are included in the design.
“We conducted a randomized controlled trial in the Kilimanjaro region in Northern Tanzania”
“Seventy-seven healthy adult men (median age = 25.6 years; interquartile range (IQR) = 21–27.2) participated in an open-label, short dietary intervention”
“Participants with a body mass index (BMI) of 18–25.9 were eligible for inclusion; however, four participants with a BMI > 26 were inadvertently included.”
The study enrolled only men, and sex is reported. Age and BMI are reported with medians and IQRs. Demographics include urban/rural residence and BMI categories. Since the study is single-sex, a justification for enrolling only men is not provided, but this is a minor omission. Species/strain and housing conditions are not applicable for a human study.
“Seventy-seven young and healthy volunteers assigned male at birth”
“Seventy-seven healthy adult men (median age = 25.6 years; interquartile range (IQR) = 21–27.2)”
“Baseline characteristics are summarized in Extended Data Table .”
The paper includes an 'Ethics and inclusion statement' that describes collaboration and registration, but it does not name a specific IRB or ethics committee that approved the protocol, nor does it mention informed consent. The statement focuses on local collaboration and benefit-sharing. This is a reporting gap for a human interventional trial.
“Researchers from KCMC University in Moshi, Tanzania, had an integral role throughout the research process, including study design and implementation, data ownership, intellectual property rights, and authorship of publications.”
The investigational products (diets and Mbege) are described in detail with menus and composition. Assay kits (Olink panels, ELISA) are named with manufacturers. Software tools are identified with versions. Antibodies, cell lines, and mycoplasma testing are not applicable to this human study.
“using the 92-plex Olink inflammatory and cardiometabolic panels (proximity extension assays, Olink Proteomics AB)”
“All statistical analyses and visualizations were conducted in R (v.4.1.1.), using ggplot2 (v.3.3.5) unless otherwise specified.”
“using the 92-plex Olink inflammatory and cardiometabolic panels (proximity extension assays, Olink Proteomics AB)”
“All statistical analyses and visualizations were conducted in R (v.4.1.1.), using ggplot2 (v.3.3.5)”
“Mbege, is prepared by fermenting boiled bananas with germinated finger millet porridge ( Eleusine coracana ).”
The paper names the statistical tests (LMM, DESeq2, Fisher's exact, Kruskal-Wallis) and describes the models. Effect sizes (fold changes) and confidence intervals are reported. Software is identified. Data presentation includes box plots with individual participant lines and per-group n. Exact p-values are not always given (often reported as thresholds like P < 0.05), but this is common in omics studies with multiple testing. Mathematical plausibility checks were not possible for most reported statistics due to the complex models.
“For all statistical analyses, intra-individual measurements were assessed using an LMM, with time point as the main fixed variable, and age, BMI and activity ranking at baseline as covariates.”
“For all statistical analyses, intra-individual measurements were assessed using an LMM, with time point as the main fixed variable, and age, BMI and activity ranking at baseline as covariates.”
“a significant increase in plasma CRP concentrations was observed in participants switching to a WD (after the intervention versus baseline, P = 0.020)”
“Paired fold change values were calculated using the fcrosFCmat function from the fcros package”
The data availability statement names a concrete route: sequencing data in EGA with accession, and other data in the Radboud Data Repository with a Data Access Committee and decision timeframe. Code is available on GitHub. This meets the criteria for reported_and_adequate.
“All sequencing data have been deposited in the European Genome–phenome Archive under accession no. EGAS50000000317”
“All code scripts used for the analysis of the data are available at https://github.com/TalPecht/dietstudy_Temba_Pecht_2024/”
“All sequencing data have been deposited in the European Genome–phenome Archive under accession no. EGAS50000000317”
“All additional datasets, including anonymized participant meta-data, nutritional information, circulating leukocyte data, whole-blood cytokine responses, and plasma proteome and metabolome data, are deposited in the Radboud Data Repository ( https://data.ru.nl ).”
“All code scripts used for the analysis of the data are available at https://github.com/TalPecht/dietstudy_Temba_Pecht_2024/ .”
Methods are detailed enough for replication. The trial is registered (ISRCTN15619939). A reporting summary is mentioned. All outcomes are reported, including null results. Limitations are discussed. Conclusions are generally proportional, though some causal language is used. Funding and competing interests are stated.
“ISRCTN trial registration: ISRCTN15619939 (https://www.isrctn.com/ISRCTN15619939)”
“ISRCTN trial registration: ISRCTN15619939”
“Our study also has a few limitations. First, food was offered ad libitum, and the intervention was not isocaloric, resulting in a weight gain in the AHD to WD switch group”
“This study was funded by the Joint Programming Initiative: A Healthy Diet for a Healthy Life (JPI-HDHL) and ZonMW (no. 529051018, TransMic project and TransInf project)”
Registered (1 ID: ISRCTN). Reporting guideline cited: CONSORT.
Broken references and links
None foundReferences checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.
Checked — nothing surfaced.
Checked 61 references by DOI: 1 verified — 60 no DOI (shown, not verified).
- NO DOIBurden of non-communicable diseases in sub-Saharan Africa, 1990-2017: results from the Global Burden of Disease Study 2017No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIUrban–rural disparities in adult mortality in sub-Saharan AfricaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPlant-based diets for cardiovascular disease prevention: all plant foods are not created equalNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDifferential peripheral immune signatures elicited by vegan versus ketogenic diets in humansNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIGut microbiota-targeted diets modulate human immune statusNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIGlobal impacts of Western diet and its effects on metabolism and health: a narrative reviewNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIWestern diet triggers NLRP3-dependent innate immune reprogrammingNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIChronic inflammation in the etiology of disease across the life spanNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDifferences in the inflammatory proteome of East African and Western European adults and associations with environmental and dietary factorsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDifferences in thrombin and plasmin generation potential between East African and Western European adults: the role of genetic and non‐genetic factorsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIUrban living in healthy Tanzanians is associated with an inflammatory status driven by dietary and metabolic changesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIBrewing technique of mbege, a banana beer produced in northeastern TanzaniaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIFermented foods, health and the gut microbiomeNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIFermented foods: their health-promoting components and potential effects on gut microbiotaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIHomogenous 96-Plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalabilityNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThrombospondin-4 regulates vascular inflammation and atherogenesisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDefective signaling in the JAK-STAT pathway tracks with chronic inflammation and cardiovascular risk in aging humansNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDecreased interferon-α and interferon-β production in obesity and expression of suppressor of cytokine signalingNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIReversal of immunoparalysis in humans in vivo: a double-blind, placebo-controlled, randomized pilot studyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISepsis-induced immunosuppression: from cellular dysfunctions to immunotherapyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIInfluence of the microbiome, diet and genetics on inter-individual variation in the human plasma metabolomeNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIWikiPathways: pathway editing for the peopleNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIA high fat western diet attenuates phasic dopamine releaseNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOILauric acid alleviates insulin resistance by improving mitochondrial biogenesis in THP-1 macrophagesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPolydatin: pharmacological mechanisms, therapeutic targets, biological activities, and health benefitsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIFumarate hydratase as a metabolic regulator of immunityNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe production of p-cresol sulfate and indoxyl sulfate in vegetarians versus omnivoresNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIFlavan-3-ols and vascular health: clinical evidence and mechanisms of actionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe role of bacterial-derived aromatic amino acids metabolites relevant in autism spectrum disorders: a comprehensive reviewNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMyeloperoxidase in human neutrophil host defenseNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISON DNA-binding protein mediates macrophage autophagy and responses to intracellular infectionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIELF4 is critical for induction of type I interferon and the host antiviral responseNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIIndole-3-lactic acid associated with Bifidobacterium -dominated microbiota significantly decreases inflammation in intestinal epithelial cellsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOILeukocyte differential and reactive lymphocyte counts from Sysmex XN analyzer in the evaluation of SARS-CoV-2 infectionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe effect of indigenous African diet on inflammatory markers linked to type 2 diabetic mellitusNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOINutritional, functional, and bioactive properties of African underutilized legumesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAnti-diabetic prospects of dietary bio-actives of millets and the significance of the gut microbiota: a case of finger milletNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIA major mechanism for immunomodulation: dietary fibres and acid metabolitesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe immunomodulatory and anti-inflammatory role of polyphenolsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIGut microbiome-mediated metabolism effects on immunity in rural and urban African populationsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIBioactive components in traditional foods aimed at health promotion: a route to novel mechanistic insights and lead molecules?No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIWestern diet and the immune system: an inflammatory connectionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIUnveiling the potential of African fermented cereal-based beverages: probiotics, functional drinks, health benefits and bioactive componentsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIIsolation and characterisation of yeasts and bacteria from Mbege—an opaque beer made from millet malt and banana juiceNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPotent induction of trained immunity by Saccharomyces cerevisiae β-glucansNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIGeneration of the antioxidant hydroxytyrosol from tyrosol present in beer and red wine in a randomized clinical trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIOptimal dietary patterns for prevention of chronic diseaseNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIInflammatory potential of diet and risk of cardiovascular disease or mortality: a meta-analysisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOILong-term secondary prevention of cardiovascular disease with a Mediterranean diet and a low-fat diet (CORDIOPREV): a randomised controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPrimary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nutsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAlternating high-fat diet enhances atherosclerosis by neutrophil reprogrammingNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIRole of neutrophils in different stages of atherosclerosisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMediterranean diet, neutrophil count, and carotid intima-media thickness in secondary prevention: the CORDIOPREV studyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDietary Intake regulates the circulating inflammatory monocyte poolNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIShort-term dietary changes can result in mucosal and systemic immune depressionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIHigh-throughput, accurate mass metabolome profiling of cellular extracts by flow injection–time-of-flight mass spectrometryNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIModerated estimation of fold change and dispersion for RNA-seq data with DESeq2No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAn object-oriented framework for robust multivariate analysisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIData-driven hypothesis weighting increases detection power in genome-scale multiple testingNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIChEA3: transcription factor enrichment analysis by orthogonal omics integrationNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
12 of 13 data/code links checked; 12 live; 1 not probed.
- dataEGALIVEHTTP 200https://ega-archive.org/studies/EGAS50000000317Resolves to EGA (data repository).
- datahttps://data.ru.nlLIVEHTTP 200Resolved page looks like data.
- datahttps://www.costech.or.tz/Files/Documents/1728287181.pdfLIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://www.proteinatlas.org/LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://www.proteinatlas.org/download/proteinatlas.tsv.zipLIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://www.genome.jp/kegg/compound/LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://www.hmdb.ca/UNVERIFIEDHTTP 403Liveness indeterminate — content not checked.
- datahttps://www.ebi.ac.uk/chebi/LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://www.metaboanalyst.ca/MetaboAnalyst/upload/ConvertView.xhtmlLIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://rampdb.nih.gov/LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://geneontology.org/LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://maayanlab.cloud/chea3/api/enrich/LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- codeGitHubLIVEHTTP 200https://github.com/TalPecht/dietstudy_Temba_Pecht_2024/Resolves to GitHub (code repository).
Copyediting
6 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 6 minor suggestions below.
6 copyedit issues flagged: mostly typo, consistency, clarity.
- MINORtypoMethods, Whole-blood transcriptome“fold change values were calcualted using results function”→ Change 'calcualted' to 'calculated'.Typographical error.
- MINORconsistencyResults, Participant characteristics“Seventy-seven healthy adult men (median age = 25.6 years; interquartile range (IQR) = 21–27.2)”→ Ensure the median age is consistent with the IQR (25.6 is within 21-27.2, but check if the median should be 24.1).Potential inconsistency in reported median age.
- MINORclarityResults, Plasma metabolome“while 74 increased and 24 decreased after the intervention compared to the baseline”→ Clarify the time point for this comparison (likely 'at the follow-up').Ambiguous phrasing; likely a typo.
- MINORtypoMethods, Whole-blood transcriptome“calcualted”→ calculatedTypographical error.
- MINORconsistencyResults, Participant characteristics“Seventy-seven healthy adult men”→ Ensure consistent reporting of participant numbers across text and figures.The number of participants varies between 77, 76, and 75 in different sections; clarify the exact number analyzed.
- MINORclarityResults, Plasma metabolome“While 74 increased and 24 decreased after the intervention compared to the baseline”→ Clarify the time point for this comparison.The sentence is ambiguous; it may be a duplicate of the previous sentence.
The published work is largely robust, but readers should weigh the missing ethics approval details and incomplete design reporting (randomization, power) as limitations. An erratum or clarification from the authors would strengthen the record, particularly regarding ethics approval and informed consent.
- 1.HIGHethicsAdd a statement naming the ethics committee (IRB) that approved the study and the protocol number, and explicitly state that informed consent was obtained from all participants, in the Ethics and inclusion statement.A human interventional trial must report the approving body and consent process; its absence is a reporting gap that readers and journals will flag.
- 2.HIGHrigorDescribe the randomization method (e.g., computer-generated sequence, block randomization) and the unit of randomization (individual participant) in the Methods.Randomization method is a core design element; its absence limits assessment of allocation concealment and bias.
- 3.HIGHrigorProvide a rationale for the open-label design (e.g., impossibility of blinding dietary interventions) and discuss potential bias in the Methods.Open-label designs need justification to reassure readers about potential performance and detection bias.
- 4.HIGHrigorInclude an a priori power analysis or sample size calculation with effect size, alpha, and power in the Methods.Without a power analysis, readers cannot assess whether the study was adequately powered to detect the reported effects.
- 5.MEDIUMrigorSpecify the inclusion/exclusion criteria more precisely (e.g., age range, health status) and clarify how the four participants with BMI >26 were handled in the analysis, in the Methods.Precise criteria and handling of protocol deviations are needed for reproducibility and to assess potential bias.
- 6.MEDIUMrigorDescribe how outliers were handled in the statistical analysis (e.g., exclusion criteria, sensitivity analyses) in the Methods.Outlier handling affects the robustness of the results and should be transparent.
- 7.MEDIUMrigorProvide a scientific justification for enrolling only men in the study, or acknowledge the limitation and discuss implications for generalizability, in the Methods or Discussion.Single-sex studies should justify the choice or note the limitation to inform interpretation.
- 8.MEDIUMreportingMention adherence to a reporting guideline such as CONSORT in the Methods or Reporting Summary.Explicitly stating adherence to CONSORT helps readers trust the completeness of reporting.
- 9.MEDIUMreportingClarify the regulatory compliance statement by naming the specific ethical framework (e.g., Declaration of Helsinki) and the national regulatory body that approved the study.Naming the framework and body strengthens the ethics statement and aligns with standard practice.
- 10.MEDIUMcopyeditFix the typo 'calcualted' to 'calculated' in the Methods, Whole-blood transcriptome section.Typographical errors undermine professionalism and clarity.
- 11.MEDIUMcopyeditClarify the ambiguous sentence in the Results, Plasma metabolome section: 'while 74 increased and 24 decreased after the intervention compared to the baseline' — specify the time point and ensure it is not a duplicate.Ambiguous phrasing can confuse readers about the exact comparison being made.
- 12.MEDIUMcopyeditEnsure consistent reporting of participant numbers across text and figures (e.g., 77, 76, 75; AHD to WD group 23 vs 22; fermented beverage group 22 vs 21) and clarify the exact number analyzed.Inconsistent participant numbers raise concerns about data handling and transparency.
- 13.LOWcopyeditVerify the median age (25.6 years) is consistent with the IQR (21–27.2) and correct if needed.A median outside the IQR would be an internal inconsistency; even if plausible, it should be verified.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.