- Grant awarded: November 2020
This project investigates whether and how potential diet-dependent neuro-inflammatory metabolites of the kynurenine pathway are longitudinally associated with worse health related quality of life, including higher rates of depression, anxiety, cognitive impairment and fatigue among colorectal cancer survivors up to 5 years post-treatment.
– Simone Eussen
Background
More people are surviving colorectal cancer (CRC) due to improved diagnosis and treatment. However, this means there are more people living with the long-term side-effects of CRC and this can affect their health and quality of life. Side-effects include depression, anxiety, fatigue and cognitive impairment, many of which are exacerbated by stress, inflammation, and a poor diet, but the molecular reasons for this are largely unknown. For example, small molecules in our body, known as metabolites, can be increased or decreased by our diet, stress and inflammation.
An imbalance in these metabolites, such as increased levels of harmful metabolites and decreased levels of beneficial metabolites, can lead to depression. The kynurenine pathway is one such metabolic process that is affected by stress and inflammation
Early research suggests that vitamin-B, a Mediterranean diet, and a ketogenic diet might lessen side-effects after CRC. Our research will expand on this to discover how and why diet affects quality of life in CRC survivors through metabolites.
Aims and objectives
This 4-year project aims to investigate associations between the kynurenine pathway and quality of life in CRC survivors up-to five years post-treatment. The research will evaluate whether:
- diet affects the concentration of metabolites from the kynurenine pathway in the blood, between six weeks and one year after CRC treatment,
- increased concentrations of kynurenine metabolites are associated with lower quality of life, cognitive impairment, fatigue, depression, and anxiety between six weeks and five years after CRC treatment, and
- concentrations of kynurenine metabolites are the underlying cause of the associations between diet and quality of life between six weeks and five years after CRC treatment.
How it will be done
This work will be performed using data from the EnCoRe study, which collects information on stage I-III CRC patients at diagnosis, and then six weeks, six months, one year, two years, and five years after treatment has ended.
Information collected includes plasma kynurenines at diagnosis, six weeks (n=252), six months (n=207) and one year (n=167) post-treatment. Detailed information on dietary intake and quality of life is also available at these time slots. Our project will investigate intake of specific vitamins (vitamins B2 and B6) and minerals (iron, zinc, copper and magnesium), because of their important roles in the kynurenine pathway.
In addition, intake of macronutrients will be studied because tryptophan, the precursor of kynurenine, is an essential amino acid (which thus needs to be ingested through our diet) and associations of carbohydrates and fats with kynurenines have not been studied yet.
Finally, the project will investigate a holistic approach to dietary intake by evaluating the impact of following dietary guidelines or patterns including WCRF’s (combination of diet and physical activity), the Mediterranean diet, and the Dutch Healthy Diet.
Statistical analyses will be used to show:
- how changes in dietary quality affects metabolites of the kynurenine pathway over time,
- how changes in kynurenine metabolites affect quality of life over time, and
- whether and how the link between dietary quality and quality of life is directly caused by these kynurenine metabolites.
Relevant factors such as age, gender, smoking, overweight, alcohol consumption, physical activity, number of other diseases, kidney function, and type of cancer treatment, will be accounted for in these analyses
Potential impact
This project will enhance our understanding of the role of kynurenine metabolites as an underlying factor in the relationship between diet quality and quality of life in CRC survivors. This will provide new leads for dietary intervention studies to improve quality of life among CRC survivors.
Grant publications
- Daniëlle D.B. Holthuijsen, Eline H. van Roekel, Martijn J.L. Bours, Per M. Ueland, Stéphanie O. Breukink, Maryska L.G. Janssen-Heijnen, Eric T.P. Keulen, Andrea Gsur, Dieuwertje E. Kok, Arve Ulvik, Matty P. Weijenberg, Simone J.P.M. Eussen,
Longitudinal associations of macronutrient and micronutrient intake with plasma kynurenines in colorectal cancer survivors up to 12 months posttreatment, The American Journal of Clinical Nutrition, Volume 118, Issue 5, 2023, Pages 865-880, ISSN 0002-9165, https://doi.org/10.1016/j.ajcnut.2023.08.003. - Holthuijsen DDB, Bours MJL, Roekel EHV, Breukink SO, Janssen-Heijnen MLG, Keulen ETP, Ueland PM, Midttun Ø, Brezina S, Gigic B, Gsur A, Kok DE, Ose J, Ulrich CM, Weijenberg MP, Eussen SJPM. Longitudinal Associations of Adherence to the Dietary World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) and Dutch Healthy Diet (DHD) Recommendations with Plasma Kynurenines in Colorectal Cancer Survivors after Treatment. Nutrients. 2022 Dec 3;14(23):5151. doi: 10.3390/nu14235151. PMID: 36501181; PMCID: PMC9738623.
