Comparative Carcinogenic Effects of Folic Acid vs. 5-Methyltetrahydrofolate Supplementation on Colon Cancer Progression in a Rodent Model
Bibliographic record
Abstract
High folic acid (FA) intake may be associated with adverse health outcomes, including colon cancer promotion. 5-methyltetrahydrofolate (5MTHF) has been proposed as a safer alternative form of folate supplementation. We compared the effects of FA and 5MTHF supplementation on the progression of aberrant crypt foci (ACF; earliest colon cancer precursor). Male Sprague Dawley rats (n = 120) received a control diet (1mg FA or equimolar 5MTHF) at weaning and ACF were induced by azoxymethane. Six weeks post-induction, rats were randomized to the control or supplemental (10mg FA or equimolar 5MTHF) diets for 18 weeks. Plasma folate concentrations were assessed using microbiological assay and compared. Colorectal tumor incidence, multiplicity and burden (sum of tumor diameters) were determined and compared. 5MTHF resulted in higher plasma folate concentration compared to FA (p < 0.05). Tumor incidence (adenoma, p = 0.5; adenocarcinoma, p = 0.60) did not differ between the folate forms. Both FA and 5MTHF supplementation resulted in a higher number of adenocarcinomas compared to respective controls. 5MTHF groups had higher tumor burden compared to the corresponding levels of FA (p < 0.05). 5MTHF resulted in higher tumor burden than FA and was at least as effective as FA in increasing the number of adenocarcinomas in predisposed rats harboring ACF. 5MTHF does not confer a safer alternative to FA supplementation with regards to colon cancer promotion and may in fact have a higher colon tumor promoting effect than FA supplementation. Notwithstanding the inherent limitations associated with animal models, our study suggests that future studies are warranted to compare biochemical and biologic effects and safety of FA and 5MTHF supplementation. Canadian Institutes of Health Research.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".