Thursday, October 20, 2011

Patients with high serum folate levels have increased prostate cancer cell growth

A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (Figueiredo et al., J Natl Cancer Inst 2009; 101(6): 432-435). As tumor cells in culture proliferate (grow) directly in response to available folic acid, the goal of this study was to determine if there is a similar relationship between patient folate status, and the proliferative capacity of tumors in men with prostate cancer.  We determined serum folate and/or prostate tissue folate in 87 randomly selected patients undergoing surgery for prostate cancer, and compared to tumor proliferation in a subset.

the findings indicate that:

1)  Fasting serum folate levels were positively correlated with prostate tumor tissue folate content (n = 15; r  = 0.577, P < 0.03). That means that steady-state levels of circulating folate are an indicator of how much folate is in the prostate tumor tissue of the same patient.  Interestingly, this was not the same for non cancerous prostate tissue suggesting the tumor has the ability to take up more folate than normal tissue.

2)  The average serum folate was 62.6 nM (ranging from 7.5-145.2 nM) -- wow! that is a HUGE range!  keep in mind that deficient folate levels are less 6.81nM, while adequate levels are greater than 13.62nM.  So some of the patients are in the inadequate range, and some of them have more than ten-fold the adequate level. 

3)  39.5% of patients used supplements containing folic acid (the chemical form of folate, not found in nature).

4)  The top 25% of patients had serum folates above 82 nM, six times the level considered adequate. Of these, 48% reported NO SUPPLEMENT use. So how did they get serum folates that were so high? Before folic acid fortification of the diet, mandated in the U.S. in 1998, almost all adults were considered folate deficient or to have inadequate folate levels....definitely a bad thing from many aspects...but seems to be the opposite, which would be OK if high levels of folate just meant more of the good stuff....more of that miracle vitamin..

5) Among 50 patients with Gleason 7 prostate cancer, the number of cells actively growing at the time the tumor was resected from the patient was 6.17% in the tumors from patients with the highest folate levels, and 0.86%  in the tumors from patients with the lowest serum folate, respectively (P < 0.0001).  That's a big difference.

Take home message:

Increased cancer cell proliferation in men with higher serum folate concentrations is consistent with an increase in prostate cancer incidence observed with folate supplementation. Unexpectedly, more than 25% of patients had serum folate levels greater than sixfold adequate. Nearly half of these men reported no supplement use, suggesting either altered folate metabolism and/or sustained consumption of folic acid from fortified foods.  So if you have prostate cancer, one suggestion would be to avoid taking folic acid supplements unless your doctor specifically okay's it.  As for natural folates from food, it is highly unlikely anyone could eat enough spinach, liver or yeast (or other natural sources of  folate) to get high serum folate levels. Fortified foods on the other hand, are supplemented with folic acid.  So while folate is a miracle vitamin and deficiency can actually cause at least some cancers, too much might not be a good thing for everyone...

you can read all about this study at  "Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate", by Tomaszewski et al. - and yes, this is a publication from our own lab...we are currently following up on these findings....

UPDATE SEPTEMBER 3RD 2012:  Our research for this paper was funded by the National Institutes of Health, therefore we have made it publicly available 12 months after publication in The Prostate, as per the PHS mandate - that means if you click on the above link, it will now take you to the whole paper for free.

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