Folate Intake and Risk of Urothelial Carcinoma: A Systematic Review and Meta-Analysis of Epidemiological Studies

Gu, Yi; Zeng, Jie; Zou, Yixin; Liu, Chang; Fu, Hongjuan; Chang, Hui

doi:10.1080/01635581.2021.1973518

Cited by 3 publications

(2 citation statements)

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“…( 2016 ) Incident endometrial cancer Folate intake PCs, NCCs, CCs PubMed, Embase and Web of Science Search date NR 5 PCs OR (highest vs. lowest) = 1.05, 95% CI: 0.90–1.20; I 2 = 19.8% Positive association for type II but not type I endometrial cancer in one study (OR Q4 vs. Q1 1.71 (0.87, 3.36), Q4 > 560 vs. Q1 < 250 μg/day total folate) (Uccella et al., 2011 ); null or negative associations in other studies Gu et al. ( 2022 ) Urothelial carcinoma Folate intake and P/S folate PCs, NCCs, CCs Pubmed and eMBASe databases Until October 2019 8 PCs +2 NCCs [9 assessed dietary folate intake and 1 plasma folate] RR (highest vs. lowest) = 0.97, 95% CI: 0.87–1.09, p = 0.638; I 2 0% Positive associations in two studies (Bassett et al., 2019 ) (RR Q5 vs. Q1 1.27, 95% CI 0.81, 2.00; <9.3 vs. >17.0 nmol/L) and (Michaud et al., 2002 ) (RR Q5 vs. Q1 1.16, 95% CI 0.82, 1.64; median Q1 257.3 vs. Q5 400.2 μg/day natural folate); null or negative associations in other studies Hezaveh et al. ( 2021 ) Incidence of non‐melanoma skin cancer (BCC, SCC or both) or overall skin cancer Folate intake Cohort studies and CCs Scopus, ISI Web of Science and PubMed From 2000 to July 2021 4 PCs Not pooled (few studies and heterogeneous) Positive association in two studies with BCC risk (RR positive in all quintiles vs. Q1 < 284 μg/day total folate, RR Q5 vs. Q1 1.19, 95% CI 1.01, 1.40 (van Dam et al., 2000 ); positive in all quintiles versus Q1, median Q1 208 μg/day total folate, RR Q5 vs. Q1 : 1.2 95% CI:1.1–1.3 (Fung et al.…”

Section: Flow Chart For the Selection Of Studies On Dose–response For...mentioning

confidence: 95%

Scientific opinion on the tolerable upper intake level for folate

Turck,

Bohn,

Castenmiller

et al. 2023

EFS2

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Following a request from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for folic acid/folate. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of folate (including folic acid and the other authorised forms, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts), namely risk of cobalamin-dependent neuropathy, cognitive decline among people with low cobalamin status, and colorectal cancer and prostate cancer. The evidence is insufficient to conclude on a positive and causal relationship between the dietary intake of folate and impaired cognitive function, risk of colorectal and prostate cancer. The risk of progression of neurological symptoms in cobalamin-deficient patients is considered as the critical effect to establish an UL for folic acid. No new evidence has been published that could improve the characterisation of the dose-response between folic acid intake and resolution of megaloblastic anaemia in cobalamin-deficient individuals. The ULs for folic acid previously established by the Scientific Committee on Food are retained for all population groups, i.e. 1000 μg/day for adults, including pregnant and lactating women, 200 μg/day for children aged 1-3 years, 300 μg/day for 4-6 years, 400 μg/day for 7-10 years, 600 μg/day for 11-14 years and 800 μg/ day for 15-17 years. A UL of 200 μg/day is established for infants aged 4-11 months. The ULs apply to the combined intake of folic acid, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts, under their authorised conditions of use.It is unlikely that the ULs for supplemental folate are exceeded in European populations, except for regular users of food supplements containing high doses of folic acid/5-methyltetrahydrofolic acid salts. K E Y W O R D S folate, folic acid, 5-methyltetrahydrofolic acid salt, tolerable upper intake level 2 of 119 |

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Section: Flow Chart For the Selection Of Studies On Dose–response For...mentioning

confidence: 95%

Scientific opinion on the tolerable upper intake level for folate

Turck,

Bohn,

Castenmiller

et al. 2023

EFS2

View full text Add to dashboard Cite

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“…The association of folate intake with the incidence of non-CRC cancers is inconsistent and was reviewed in detail elsewhere [141]. Higher intake of folate was associated with a reduced risk of squamous cell carcinoma of the head and neck [142] and esophageal [143][144][145], oral [146], pancreatic [147,148], and bladder cancers [149,150]. We should note that the higher intake in these studies was unlikely to represent excess folate intake and the analysis was not stratified to isolate the effects of intake that approach or exceed the UL.…”

Section: Folate Intake Association With Other Cancers and Overall Can...mentioning

confidence: 99%

Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review

Fardous,

Heydari

2023

Nutrients

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This review delves into the intricate relationship between excess folate (vitamin B9) intake, especially its synthetic form, namely, folic acid, and its implications on health and disease. While folate plays a pivotal role in the one-carbon cycle, which is essential for DNA synthesis, repair, and methylation, concerns arise about its excessive intake. The literature underscores potential deleterious effects, such as an increased risk of carcinogenesis; disruption in DNA methylation; and impacts on embryogenesis, pregnancy outcomes, neurodevelopment, and disease risk. Notably, these consequences stretch beyond the immediate effects, potentially influencing future generations through epigenetic reprogramming. The molecular mechanisms underlying these effects were examined, including altered one-carbon metabolism, the accumulation of unmetabolized folic acid, vitamin-B12-dependent mechanisms, altered methylation patterns, and interactions with critical receptors and signaling pathways. Furthermore, differences in the effects and mechanisms mediated by folic acid compared with natural folate are highlighted. Given the widespread folic acid supplementation, it is imperative to further research its optimal intake levels and the molecular pathways impacted by its excessive intake, ensuring the health and well-being of the global population.

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The Hidden Dangers of Excess Folate, Uncovering the Molecular Mechanisms

FARDOUS,

Heydari

2023

Preprint

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This review delves into the intricate relationship between folate (Vitamin B9) intake, especially its synthetic form, folic acid, and its implications on health and disease. While folate plays a pivotal role in the one-carbon cycle, essential for DNA synthesis, repair, and methylation, concerns arise from its excessive intake. The literature underscores potential deleterious effects, such as an increased risk of carcinogenesis, disturbances in DNA methylation, and impacts on embryogenesis, pregnancy outcomes, neurodevelopment, and disease risk. Notably, these consequences stretch beyond the immediate effects, potentially influencing future generations through epigenetic reprogramming. We probe into the molecular mechanisms underlying these effects, including accumulation of unmetabolized folic acid, Vitamin B12 dependent mechanisms, altered one carbon metabolism, altered methylation patterns, and interactions with critical receptors and signaling pathways. Furthermore, we emphasize differences in the effects and mechanisms mediated by folic acid compared to natural folate. Given the widespread folic acid supplementation, it is imperative to further research its optimal intake levels, and the molecular pathways impacted by its excessive intake, ensuring the health and well-being of the global population.

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Folate Intake and Risk of Urothelial Carcinoma: A Systematic Review and Meta-Analysis of Epidemiological Studies

Cited by 3 publications

References 70 publications

Scientific opinion on the tolerable upper intake level for folate

Scientific opinion on the tolerable upper intake level for folate

Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review

The Hidden Dangers of Excess Folate, Uncovering the Molecular Mechanisms

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