ArticlePloS one2014
Folic acid supplementation promotes mammary tumor progression in a rat model.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Pooled it
- Using 6S-5-methyltetrahydrofolate instead of folic acid in prenatal multivitamin reduces unmetabolized folic acid concentrations in the mother-fetus dyad: a 24-week randomized controlled trial.Frontiers in nutrition · 2026Trial
- Pro-Carcinogenic Implications of Folic Acid Supplementation During Chemically Induced Cutaneous Squamous Cell Carcinoma in Mice.Journal of biochemical and molecular toxicology · 2026Article
- Maternal dietary folate imbalance alters cerebellar astrocyte morphology and density in offspring.IBRO neuroscience reports · 2025Article
- How Increased Dietary Folic Acid Intake Impacts Health Outcomes Through Changes in Inflammation, Angiogenesis, and Neurotoxicity.Nutrients · 2025Review
- Glutathione Dynamics in the Tumor Microenvironment: A Potential Target of Cancer Stem Cells and T Cells.International journal of stem cells · 2024Review
- Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review.Nutrients · 2023Review
- Perinatal folate levels do not influence tumor latency or multiplicity in a model of NF1 associated plexiform-like neurofibromas.BMC research notes · 2023Article
- Dual Role of DUOX1-Derived Reactive Oxygen Species in Melanoma.Antioxidants (Basel, Switzerland) · 2023Article
- GPX3 expression was down-regulated but positively correlated with poor outcome in human cancers.Frontiers in oncology · 2023Article
- Folic acid depletion as well as oversupplementation helps in the progression of hepatocarcinogenesis in HepG2 cells.Scientific reports · 2022Article
- Loss of glucose 6-phosphate dehydrogenase function increases oxidative stress and glutaminolysis in metastasizing melanoma cells.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The influence of obesity on folate status, DNA methylation and cancer-related gene expression in normal breast tissues from premenopausal women.Epigenetics · 2021Article
- Dietary modulations of folic acid affect the development of diethylnitrosamine induced hepatocellular carcinoma in a rat model.Journal of molecular histology · 2021Article
- Article
- Tumor suppressor genes are differentially regulated with dietary folate modulations in a rat model of hepatocellular carcinoma.Molecular and cellular biochemistry · 2021Article
- Effect of Maternal Folate Deficiency on Growth Performance, Slaughter Performance, and Serum Parameters of Broiler Offspring.The journal of poultry science · 2020Article
- Folic Acid Induces Intake-Related Changes in the Mammary Tissue Transcriptome of C57BL/6 Mice.Nutrients · 2020Article
- Article
- Effects of folic acid withdrawal on transcriptomic profiles in murine triple-negative breast cancer cell lines.Biochimie · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Folic acid supplementation may prevent the development of cancer in normal tissues but may promote the progression of established (pre)neoplastic lesions. However, whether or not folic acid supplementation can promote the progression of established (pre)neoplastic mammary lesions is unknown. This is a critically important issue because breast cancer patients and survivors in North America are likely exposed to high levels of folic acid owing to folic acid fortification and widespread supplemental use after cancer diagnosis. We investigated whether folic acid supplementation can promote the progression of established mammary tumors. Female Sprague-Dawley rats were placed on a control diet and mammary tumors were initiated with 7,12-dimethylbenza[a]anthracene at puberty. When the sentinel tumor reached a predefined size, rats were randomized to receive a diet containing the control, 2.5x, 4x, or 5x supplemental levels of folic acid for up to 12 weeks. The sentinel mammary tumor growth was monitored weekly. At necropsy, the sentinel and all other mammary tumors were analyzed histologically. The effect of folic acid supplementation on the expression of proteins involved in proliferation, apoptosis, and mammary tumorigenesis was determined in representative sentinel adenocarcinomas. Although no clear dose-response relationship was observed, folic acid supplementation significantly promoted the progression of the sentinel mammary tumors and was associated with significantly higher sentinel mammary tumor weight and volume compared with the control diet. Furthermore, folic acid supplementation was associated with significantly higher weight and volume of all mammary tumors. The most significant and consistent mammary tumor-promoting effect was observed with the 2.5x supplemental level of folic acid. Folic acid supplementation was also associated with an increased expression of BAX, PARP, and HER2. Our data suggest that folic acid supplementation may promote the progression of established mammary tumors. The potential tumor-promoting effect of folic acid supplementation in breast cancer patients and survivors needs further clarification.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.