The impact of folate and folic acid on colorectal cancer survival

To deal with the disease and side-effects of cancer treatment, many individuals diagnosed with cancer use dietary supplements. There are concerns about excessive intake of specific nutrients that may accelerate tumour growth or interfere with cancer treatment. We are delighted with the support by World Cancer Research Fund/Wereld Kanker Onderzoek Fonds, that enables us to study the role of folic acid in relation to treatment outcomes as well as potential underlying mechanistic routes in patients diagnosed with colorectal cancer – Dr Dieuwertje Kok

Grant title

Folate versus folic acid: connecting treatment tolerance to prognosis in colorectal cancer survivors

Background

The vitamin folate is found in foods such as green leafy vegetables. It is commonly used in supplements and in fortified foods such as bread and cereals in its synthetic form, folic acid. There are substantial concerns about excessive intake of specific nutrients including folate that may speed up tumour growth or interfere with cancer treatment, and that having high folate levels may increase the risk of a recurrence in survivors of large bowel cancer.

Importantly, folate and folic acid may also interfere with chemotherapy commonly prescribed to individuals with large bowel cancer, as these drugs work through blocking folate-related processes. Consequently, effectiveness and tolerance of treatment may be affected, resulting in more treatment-related side-effects.

There is also a high use of supplements with high doses of folic acid, and the lack of specific guidelines on intake of folate and folic acid before, during and after cancer treatment means further research on this topic is needed.

Aims and objectives

The aim of this project is to improve understanding of the relationship between folate, folic acid and their respective sources (diet and supplements) and clinically relevant outcomes in survivors of large bowel cancer. Specifically, we will focus on prognosis, chemotherapy-induced side-effects, and personal genetic and gene-regulating marks that may explain differences between individuals.

How it will be done

The proposed project will be implemented within the COLON study, which is a study of newly 2,300 diagnosed patients with large bowel cancer who are followed before, during and after therapy. Participants provided detailed information on dietary habits, use of dietary supplements and other lifestyle factors though questionnaires. Blood samples were collected from the participants at diagnosis and 6 months after diagnosis. These blood samples can be used to measure concentrations of folate, folic acid and related biomarkers. In the proposed project, the intake and concentrations of folate and folic acid will be studied in relation to severe or long-term side-effects of chemotherapy, such as treatment modifications, fatigue and neuropathy, as well as risk of recurrence and survival.

Potential impact

This project will improve our understanding of the roles of folate and folic acid in relation to clinical outcomes relevant to survivors of large bowel cancer. The data may support further development of guidelines on dietary and supplemental intake of folate and folic acid before, during and after treatment.

Grant publications

• Joann Kiebach, Judith de Vries-ten Have, Fränzel J.B. van Duijnhoven, Dieuwertje E. Kok, Anne-Sophie van Lanen, Ewout A. Kouwenhoven, Johannes H.W. de Wilt, Ruud W.M. Schrauwen, Ellen Kampman, Renate M. Winkels, Evertine Wesselink; Hematocrit Is Associated with Cancer-Related Fatigue in Colorectal Cancer Survivors: A Longitudinal Analysis. Cancer Epidemiol Biomarkers Prev 1 March 2024; 33 (3): 411–418.
• van Lanen, AS., Kok, D.E., Wesselink, E. et al. Pre- and post-diagnostic dairy intake in relation to recurrence and all-cause mortality in people with stage I-III colorectal cancer. Eur J Nutr 62, 2891–2904 (2023).
• Nienke R.K. Zwart, Mira D. Franken, Wim J.E. Tissing, Floor J.E. Lubberman, Jill A. McKay, Ellen Kampman, Dieuwertje E. Kok, Folate, folic acid, and chemotherapy-induced toxicities: A systematic literature review, Critical Reviews in Oncology/Hematology, Volume 188, 2023, 104061, ISSN 1040-8428.