A curious new study [1].
"We identified 56 men with prostate cancer {the South Texas Veterans Healthcare System} undergoing androgen deprivation in which folate levels had been determined. 15 out of 16 (94%) men initiating ADT had increases in their folate, which is substantially more than 67% in {the ADT} maintenance group"
"We identified more rapid time to death from prostate cancer if folate levels increased to levels >200 ng/ml above their baseline ..."
Folate is a vitamin [B9] & can only come from the diet, or via synthetic folic acid.
In the U.S. folic acid is added to grains (including rice), as mandated by the FDA, so a high-carb diet might account for a high intake.
I have written about folate as a methyl donor & its role in the hypermethylation (silencing) of tumor suppressor genes in PCa cells,
There are mice studies going back 50 years that show that castration affects folate co-enzymes, resulting in a reduction of folate clearance [2].
56 men seems like a small study. However, we have control over dietary folate/folic acid. Why wait for the definitive study?
Would be interesting to see this study replicated in a country that has resisted folic acid fortification of food.
-Patrick
[1] sciencedirect.com/science/a...
Rise in serum folate after androgen deprivation associated with worse prostate cancer-specific survival
Author links open overlay panelMichael A.LissM.D.KeithAshcraftPh.D.ArpanSatsangiM.D., Ph.D.DeanBacichPh.D.
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doi.org/10.1016/j.urolonc.2... rights and content
Highlights
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Folate may rise after suppression of testosterone.
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Folate rises in mice after castration.
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Folate rise of >200 ng/ml from baseline is associated with prostate cancer death.
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Folate rise after initiating androgen deprivation.
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This study is not causal but does provide plausibility and proof of concept.
Abstract
Introduction
High folate has an association with advanced prostate cancer and levels of testosterone. Herein, we perform a translational study to investigate the inverse response of serum folate in prostate cancer patients initiating androgen deprivation therapy (ADT) and a mirrored animal model.
Methods
A retrospective study was performed using the South Texas Veterans Healthcare System to identify patients with prostate cancer on ADT. We documented testosterone and folate levels before and after ADT initiation (defined by a reduction in testosterone by 50 ng/ml) as compared to those already on ADT (maintenance). Our primary outcome was overall mortality with secondary outcome of prostate cancer-specific mortality. In parallel, we tested castration of C57BL/6J mice on folate-defined diet to determine if folate levels change with response to androgen deprivation. Students’ t test on continuous variables and Chi-squared test on dichotomous variables was performed along with Kaplan-Meier for time to event analysis.
Results
We identified 56 men with prostate cancer undergoing androgen deprivation in which folate levels had been determined. 15 out of 16 (94%) men initiating ADT had increases in their folate, which is substantially more than 67% in maintenance group (P = 0.04). We identified more rapid time to death from prostate cancer if folate levels increased to levels >200 ng/ml above their baseline (P = 0.03). Mice models demonstrated a significant rise in serum red blood cell folate after mice were castrated (P = 0.03) by an average of 1.5x over pre-castrated baseline level. By contrast, sham-castrated mice showed no increase in serum folate levels over baseline.
Conclusion
Our study suggests that men with substantial rises in folate after initiating ADT may be associated with worse prostate cancer-specific and overall survival. Our translational experiments in mice confirmed correlation between rising in folate levels post-castration. Given this study, further investigation is warranted on the role of dietary folate consumption during initiation of ADT and progression to castrate-resistant prostate cancer.
Keywords
Castrate resistant prostate cancerAndrogen deprivation therapyFolate
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