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

Huakang Tu; Colin P. Dinney; Yuanqing Ye; H. Barton Grossman; Seth P. Lerner; Xifeng Wu

doi:10.1093/ajcn/nqx019

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

Huakang Tu, Colin P. Dinney, Yuanqing Ye, H. Barton Grossman, Seth P. Lerner, Xifeng Wu

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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.

Original language	English (US)
Pages (from-to)	208-216
Number of pages	9
Journal	American Journal of Clinical Nutrition
Volume	107
Issue number	2
DOIs	https://doi.org/10.1093/ajcn/nqx019
State	Published - Feb 2018

Keywords

Bladder cancer
Clinical outcome
Dietary factor
Folate
Folic acid
Non-muscle-invasive bladder cancer
Prognosis
Progression
Recurrence
Survivorship

ASJC Scopus subject areas

Medicine (miscellaneous)
Nutrition and Dietetics

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10.1093/ajcn/nqx019

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@article{1e82447722f94a2788fa42ff65487527,

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

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.",

keywords = "Bladder cancer, Clinical outcome, Dietary factor, Folate, Folic acid, Non-muscle-invasive bladder cancer, Prognosis, Progression, Recurrence, Survivorship",

author = "Huakang Tu and Dinney, {Colin P.} and Yuanqing Ye and Grossman, {H. Barton} and Lerner, {Seth P.} and Xifeng Wu",

note = "Funding Information: Supported in part by a grant from the National Cancer Institute at the NIH (P50 CA 91846; to XW). Additional funding was provided by the Center for Translational and Public Health Genomics at MD Anderson Cancer Center. Supplemental Figure 1 is available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/ajcn/. Address correspondence to XW (e-mail: xwu@mdanderson.org). Abbreviations used: BCG, bacillus Calmette-Gu{\'e}rin; FFQ, food-frequency questionnaire; NMIBC, non–muscle-invasive bladder cancer; TUR, transurethral resection. Received May 26, 2017. Accepted for publication November 3, 2017. First published online February 26, 2018; doi: https://doi.org/10.1093/ ajcn/nqx019. Funding Information: Supported in part by a grant from the National Cancer Institute at the NIH (P50 CA 91846; to XW). Additional funding was provided by the Center for Translational and Public Health Genomics at MD Anderson Cancer Center. Publisher Copyright: {\textcopyright} 2018 American Society for Nutrition. All rights reserved.",

year = "2018",

month = feb,

doi = "10.1093/ajcn/nqx019",

language = "English (US)",

volume = "107",

pages = "208--216",

journal = "American Journal of Clinical Nutrition",

issn = "0002-9165",

publisher = "American Society for Nutrition",

number = "2",

}

TY - JOUR

T1 - Is folic acid safe for non-muscle-invasive bladder cancer patients? An evidence-based cohort study

AU - Tu, Huakang

AU - Dinney, Colin P.

AU - Ye, Yuanqing

AU - Grossman, H. Barton

AU - Lerner, Seth P.

AU - Wu, Xifeng

N1 - Funding Information: Supported in part by a grant from the National Cancer Institute at the NIH (P50 CA 91846; to XW). Additional funding was provided by the Center for Translational and Public Health Genomics at MD Anderson Cancer Center. Supplemental Figure 1 is available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/ajcn/. Address correspondence to XW (e-mail: xwu@mdanderson.org). Abbreviations used: BCG, bacillus Calmette-Guérin; FFQ, food-frequency questionnaire; NMIBC, non–muscle-invasive bladder cancer; TUR, transurethral resection. Received May 26, 2017. Accepted for publication November 3, 2017. First published online February 26, 2018; doi: https://doi.org/10.1093/ ajcn/nqx019. Funding Information: Supported in part by a grant from the National Cancer Institute at the NIH (P50 CA 91846; to XW). Additional funding was provided by the Center for Translational and Public Health Genomics at MD Anderson Cancer Center. Publisher Copyright: © 2018 American Society for Nutrition. All rights reserved.

PY - 2018/2

Y1 - 2018/2

N2 - 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.

AB - 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.

KW - Bladder cancer

KW - Clinical outcome

KW - Dietary factor

KW - Folate

KW - Folic acid

KW - Non-muscle-invasive bladder cancer

KW - Prognosis

KW - Progression

KW - Recurrence

KW - Survivorship

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JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

IS - 2

ER -

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

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