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Modeling how iso-caloric macronutrient substitutions are longitudinally associated with plasma kynurenines in colorectal cancer survivors up to 12 months post-treatment

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 impro...

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Main Authors: Holthuijsen, Daniëlle (Author) , van Roekel, Eline H. (Author) , Bours, Martijn J. L. (Author) , Ueland, Per M. (Author) , Breukink, Stéphanie O. (Author) , Janssen-Heijnen, Maryska L. G. (Author) , Konsten, Joop L. (Author) , Keulen, Eric T. P. (Author) , McCann, Adrian (Author) , Brezina, Stefanie (Author) , Gigić, Biljana (Author) , Kok, Dieuwertje E. (Author) , Ulrich, Cornelia M. (Author) , Weijenberg, Matty P. (Author) , Eussen, Simone J. P. M. (Author)
Format: Article (Journal)
Language:English
Published: July 2025
In: The journal of nutritional biochemistry
Year: 2025, Volume: 141, Pages: 1-10
ISSN:1873-4847
DOI:10.1016/j.jnutbio.2025.109910
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.jnutbio.2025.109910
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0955286325000737
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Author Notes:Daniëlle D. B. Holthuijsen, Eline H. van Roekel, Martijn J. L. Bours, Per M. Ueland, Stéphanie O. Breukink, Maryska L. G. Janssen-Heijnen, Joop L. Konsten, Eric T. P. Keulen, Adrian McCann, Stefanie Brezina, Biljana Gigic, Dieuwertje E. Kok, Cornelia M. Ulrich, Matty P. Weijenberg, Simone J. P. M. Eussen
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Summary: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.
Item Description:Gesehen am 20.10.2025
Physical Description:Online Resource
ISSN:1873-4847
DOI:10.1016/j.jnutbio.2025.109910

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