Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2018 Feb 1;107(2):208-216.
doi: 10.1093/ajcn/nqx019.

Is folic acid safe for non-muscle-invasive bladder cancer patients? An evidence-based cohort study

Huakang Tu  1 , Colin P Dinney  2 , Yuanqing Ye  1 , H Barton Grossman  2 , Seth P Lerner  3 , Xifeng Wu  1
Affiliations
Observational Study

Is folic acid safe for non-muscle-invasive bladder cancer patients? An evidence-based cohort study

Huakang Tu et al. Am J Clin Nutr. .

Abstract

Background: Patients with cancer are highly concerned about food choices and dietary supplements that may affect their treatment outcomes. Excess folic acid (synthetic folate) from supplements or fortification can lead to accumulation of unmetabolized folic acid in the systemic circulation and urine and may promote cancer growth, especially among those with neoplastic alterations.

Objective: We investigated the prospective association between synthetic compared with natural folate intake and clinical outcomes in non-muscle-invasive bladder cancer (NMIBC), which is a highly recurrent disease.

Design: In a cohort of 619 NMIBC patients, folate intake at diagnosis was assessed with a previously validated food-frequency questionnaire and categorized according to tertiles. After a median follow-up of 5.2 y, 303 tumor recurrence and 108 progression events were documented from medical record review. Multivariable Cox proportional hazards and logistic models were used to estimate adjusted HRs and ORs with 95% CIs.

Results: Synthetic folic acid intake was positively associated with a risk of recurrence among NMIBC patients (medium compared with low intake-HR: 1.72; 95% CI: 1.20, 2.48; P = 0.003; high compared with low intake-HR: 1.80; 95% CI: 1.14, 2.84; P = 0.01). Patients with a higher folic acid intake were more likely to have multifocal tumors at diagnosis (medium or high compared with low-OR: 2.08; 95% CI: 1.08, 4.02; P = 0.03). In contrast, natural folate intake tended to be inversely associated with the risk of progression (medium or high compared with low-HR: 0.68; 95% CI: 0.44, 1.04; P = 0.08).

Conclusions: A high intake of synthetic folic acid, in contrast to the natural forms, is associated with an increased risk of recurrence in NMIBC and multifocal tumors at diagnosis, which suggests that folic acid may be unsafe for NMIBC patients. These findings provide some evidence for nutritional consultation with regard to folate intake among NMIBC patients.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Risk of recurrence along time after diagnosis by synthetic folic acid intake (A) and risk of progression along time after diagnosis by natural folate intake (B). For synthetic folic acid intake, among men: low (<228.0 µg/d), medium (228.0–557.4 µg/d), and high (>557.4 µg/d) intakes; among women: low (<353.4 µg/d), medium (353.4–593.4 µg/d), and high (>593.4 µg/d) intakes. For natural folate intake, among men: low (<283.5 µg/d), medium (283.5–365.6 µg/d), and high (>365.6 µg/d) intakes; among women: low (<296.7 µg/d), medium (296.7–408.3 µg/d), and high (>408.3 µg/d) intakes. HRs (medium or high compared with low) and P values were based on sex- and treatment-stratified Cox models adjusted for age, race/ethnicity, education, smoking status, BMI, multivitamin use, total energy intake, alcohol consumption, tumor stage, and tumor grade.
FIGURE 2
FIGURE 2
Risk of recurrence by synthetic folic acid intake among patients who received TUR only (A) and patients who received BCG treatment after TUR (B). For synthetic folic acid intake, among men: low (<228.0 µg/d), medium (228.0–557.4 µg/d), and high (>557.4 µg/d) intakes; among women: low (<353.4 µg/d), medium (353.4–593.4 µg/d), and high (>593.4 µg/d) intakes. HRs (medium or high compared with low) and P values were based on sex-stratified Cox models adjusted for age, race/ethnicity, education, smoking status, BMI, multivitamin use, total energy intake, alcohol consumption, tumor stage, and tumor grade. BCG, bacillus Calmette-Guérin; TUR, transurethral resection.
See this image and copyright information in PMC

Comment in

References

    1. American Cancer Society Cancer facts & figures 2016. Atlanta: American Cancer Society; 2016.
    1. Vinata BL, Merseburger AS, Hautmann SH. Bladder tumors: molecular aspects and clinical management. 1st ed.New York:Humana Press;2010.
    1. Sanli O, Dobruch J, Knowles MA, Burger M, Alemozaffar M, Nielsen ME, Lotan Y. Bladder cancer. Nat Rev Dis Primers 2017;3:17022. - PubMed
    1. Letasiova S, Medve'ova A, Sovcikova A, Dusinska M, Volkovova K, Mosoiu C, Bartonova A. Bladder cancer, a review of the environmental risk factors. Environ Health 2012;11(Suppl 1):S11. - PMC - PubMed
    1. Chang SS, Boorjian SA, Chou R, Clark PE, Daneshmand S, Konety BR, Pruthi R, Quale DZ, Ritch CR, Seigne JD, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol 2016;196(4):1021–9. - PubMed

Publication types