{"doi":"10.1016/j.jnutbio.2025.109910","title":"Modeling how iso-caloric macronutrient substitutions are longitudinally associated with plasma kynurenines in colorectal cancer survivors up to 12 months post-treatment","abstract":"Dietary intake of several macronutrients is associated with plasma kynurenines after colorectal cancer (CRC), and kynurenines have been linked to health-related outcomes. It is unknown how macronutrient substitution affects plasma kynurenines, which may be relevant for developing guidelines to improve post-CRC quality of life through dietary changes. Using iso-caloric substitution models, we investigated how substituting one macronutrient with another is longitudinally associated with plasma tryptophan, kynurenines, and kynurenine ratios in CRC survivors. Measurements were performed at 6-weeks, 6-months, and 12-months post-treatment in 247 stage I-III CRC survivors. Macronutrient intake was measured by 7-d dietary records and plasma kynurenines by LC/MS-MS. For analysis, we applied linear mixed models with false discovery rate (FDR) to adjust for multiple testing. After FDR adjustment, substituting 100 kcal/d of total carbohydrates with 100 kcal/d of total protein was associated with higher plasma concentrations of kynurenic acid (KA), xanthurenic acid (XA), and a higher kynurenic acid-to-quinolinic acid (KA/QA) ratio. Substituting 100 kcal/d of total carbohydrates with 100 kcal/d of total fat was associated with higher tryptophan concentrations, higher KA/QA ratio, and a lower kynurenine-to-tryptophan ratio (KTR) and hydroxykynurenine ratio (HKr). Substituting 100 kcal/d of total fat with 100 kcal/d of total protein was associated with higher XA concentrations. Altogether, iso-caloric macronutrient substitutions, particularly substituting carbohydrates with protein or fat, were longitudinally associated with higher concentrations of potentially favourable kynurenines and ratios (i.e., KA, XA, and KA/QA ratio) and lower ratios with pro-inflammatory or neurotoxic properties (i.e., KTR and HKr) in CRC survivors up to 12-months post-treatment.","journal":"The Journal of Nutritional Biochemistry","year":2025,"id":563533,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":400519,"name":"Eline H. van Roekel","orcid":"0000-0002-9402-2029","position":1,"is_corresponding":false},{"id":400522,"name":"Martijn J.L. Bours","orcid":"0000-0002-5558-1258","position":2,"is_corresponding":false},{"id":392601,"name":"Per Magne Ueland","orcid":"0000-0002-1903-0571","position":3,"is_corresponding":false},{"id":400523,"name":"Stéphanie O. Breukink","orcid":"0000-0002-5445-4011","position":4,"is_corresponding":false},{"id":744847,"name":"Maryska L.G. Janssen‐Heijnen","orcid":"0000-0003-3575-6070","position":5,"is_corresponding":false},{"id":1442215,"name":"Joop Konsten","orcid":null,"position":6,"is_corresponding":false},{"id":400526,"name":"Eric T.P. Keulen","orcid":"0000-0001-6666-8773","position":7,"is_corresponding":false},{"id":764390,"name":"Adrian McCann","orcid":"0000-0002-5728-5321","position":8,"is_corresponding":false},{"id":286038,"name":"Stefanie Brezina","orcid":"0000-0001-5238-6900","position":9,"is_corresponding":false},{"id":392591,"name":"Biljana Gigic","orcid":"0000-0002-8085-2072","position":10,"is_corresponding":false},{"id":392598,"name":"Dieuwertje E. Kok","orcid":"0000-0001-7154-8207","position":11,"is_corresponding":false},{"id":85843,"name":"Cornelia M. Ulrich","orcid":"0000-0001-7641-059X","position":12,"is_corresponding":false},{"id":392603,"name":"Matty P. Weijenberg","orcid":"0000-0003-1695-4768","position":13,"is_corresponding":false},{"id":1311908,"name":"Simone J. P. M. Eussen","orcid":"0000-0003-0559-6838","position":14,"is_corresponding":false},{"id":1311907,"name":"Daniëlle D. B. Holthuijsen","orcid":"0000-0002-4352-6198","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:56:13.374766Z","pmid":"40158742","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}