Folic acid supplements and chemotherapy side effects in colorectal cancer
What it found
In people with colorectal cancer having capecitabine chemotherapy, taking folic acid supplements and having folic acid in the blood were linked to more treatment side effects.
Folate from food and blood folate levels were not linked to these side effects.
What they found
Studies in people
Side effects were common
Just over half of the patients (153 out of 290, or 53%) had their capecitabine treatment changed because of side effects, such as dose reductions, switching regimens, or stopping early.
Folic acid supplements
People who took supplements containing folic acid during chemotherapy were more likely to have treatment changes due to side effects. Taking these supplements at diagnosis was not linked to side effects.
Folic acid in blood
Having folic acid detected in the blood at diagnosis and during treatment was linked to a higher risk of side effects that changed treatment.
Folate from food
The amount of folate eaten from food, and the levels of folate in the blood, were not linked to treatment changes from side effects.
What the authors conclude
“This study suggests a potential association between folic acid and capecitabine-induced toxicities, providing a rationale to study diet-drug interactions and raise further awareness of the use of dietary supplements during oncological treatment.”
Also in their conclusions
- They say the study suggests a potential link between folic acid and capecitabine-induced side effects.
- They call for more research on diet-drug interactions and for more awareness about dietary supplement use during cancer treatment.
How it was done
Capecitabine works by blocking an enzyme involved in folate metabolism, and there are concerns that high folate intake during chemotherapy might affect treatment toxicity. It was unclear whether natural folate or the synthetic form, folic acid, plays a role.
They followed 290 patients with stage II to III colorectal cancer receiving capecitabine from the COLON study. They asked about diet and supplement use at diagnosis and during chemotherapy, measured folate and folic acid in blood samples, and recorded any treatment changes due to side effects.
What it can’t tell you
- This was an observational study, so it can show links but cannot prove that folic acid causes the side effects.
- It is possible that patients who were already more likely to have side effects were also more likely to take supplements.
- The study cannot show whether folic acid affects the effectiveness of chemotherapy or long-term outcomes.
Who paid
- Authors work at
- Wageningen University & Research, the Netherlands; Hospital Gelderse Vallei, the Netherlands; Northumbria University, United Kingdom
The paper
- Title
- Intake and biomarkers of folate and folic acid as determinants of chemotherapy-induced toxicities in patients with colorectal cancer: a cohort study
- Type
- Study
- Evidence
- Studies in people
- Summarised from
- Full text
- Licence
- CC BY. Words in quotation marks are the authors’; the rest is our summary.
- Cite
- Kok DE, van Duijnhoven FJ, Lubberman FJ, et al (2024). Intake and biomarkers of folate and folic acid as determinants of chemotherapy-induced toxicities in patients with colorectal cancer: a cohort study. The American journal of clinical nutrition. doi:10.1016/j.ajcnut.2023.11.023Free full textPubMed 38070682DOI
Summary written 26 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error