Abstract
IntroductionThis is the first report of possible direct stimulation of hormone-resistant prostate cancer or interference of docetaxel cytotoxicity of prostate cancer in a patient with biochemical relapse of prostatic-specific antigen. This observation is of clinical and metabolic importance, especially at a time when more than 80 countries have fortified food supplies with folic acid and some contemplate further fortification with vitamin B12.Case presentationOur patient is a 71-year-old Caucasian man who had been diagnosed in 1997 with prostate cancer, stage T1c, and Gleason score 3+4 = 7. His primary treatment included intermittent androgen deprivation therapy including leuprolide + bicalutamide + deutasteride, ketoconazole + hydrocortisone, nilandrone and flutamide to resistance defined as biochemical relapse of PSA. While undergoing docetaxel therapy to treat a continually increasing prostate-specific antigen level, withdrawal of 10 daily doses of a supplement containing 500 μg of vitamin B12 as cyanocobalamin, as well as 400 μg of folic acid as pteroylglutamic acid and 400 μg of L-5-methyltetrahydrofolate for a combined total of 800 μg of mixed folates, was associated with a return to a normal serum prostatic-specific antigen level.ConclusionThis case report illustrates the importance of the effects of supplements containing large amounts of folic acid, L-5-methyltetrahydrofolate, and cyanocobalamin on the metabolism of prostate cancer cells directly and/or B vitamin interference with docetaxel efficacy. Physicians caring for patients with prostate cancer undergoing watchful waiting, hormone therapy, and/or chemotherapy should consider the possible acceleration of tumor growth and/or metastasis and the development of drug resistance associated with supplement ingestion. We describe several pathways of metabolic and epigenetic interactions that could affect the observed changes in serum levels of prostate-specific antigen.
Highlights
This is the first report of possible direct stimulation of hormone-resistant prostate cancer or interference of docetaxel cytotoxicity of prostate cancer in a patient with biochemical relapse of prostatic-specific antigen
This case report illustrates the importance of the effects of supplements containing large amounts of folic acid, L-5-methyltetrahydrofolate, and cyanocobalamin on the metabolism of prostate cancer cells directly and/ or B vitamin interference with docetaxel efficacy
We describe several pathways of metabolic and epigenetic interactions that could affect the observed changes in serum levels of prostate-specific antigen
Summary
Our patient’s clinical course suggests that high doses of B vitamins (FA/folate and vitamin B12) may modulate the course of PSA failure in castrate-resistant/refractory prostate cancer. Our patient’s ingestion of large amounts of FA/folate and vitamin B12 was associated with PSA acceleration, while withdrawal of the supplements was associated with a significant PSA decline. Whether this result was secondary to the perturbation of the outlined metabolic interactions of B vitamers (Figure 2), due to DNA epimethylation with associated changes in gene expression, or due to other factors is unknown. Studies of patient use of health store supplements, many of which are known to affect DNA metabolism and DNA methylation markers, have revealed that up to 50% of cancer patients ingest large doses of vitamins and other supplements, such as probiotics, which contain “safe” bacteria that generate copious amounts of folates within the bowel. A copy of the written consent is available for review by the Editor-in-Chief of this journal
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