Increasing cancer risk by taking b vitamins

[Nequals1Guy]

I'm wondering if anyone here has explored the concerns about folate supplements and the increased risk of prostate and colorectal cancer? It seems like most of the efforts to lower homocysteine utilize high folate and b12 intake. There's some researchers that I've read that claim too much folate is bad...like a precursor to cancer cells or something. I'd love to hear what others think.

[Stavia]

Interesting! Do you have any papers to link?

[Stavia]

I did some digging

http://www.nature.com/articles/srep12044

Numerous studies have investigated the effects of folic acid supplementation on colorectal cancer risk, but conflicting results were reported. We herein performed a meta-analysis based on relevant studies to reach a more definitive conclusion. The PubMed and Embase databases were searched for quality randomized controlled trials (RCTs) published before October 2014. Eight articles met the inclusion criteria and were subsequently analyzed. The results suggested that folic acid treatment was not associated with colorectal cancer risk in the total population (relative risk [RR] = 1.00, 95% confidence interval [CI] = 0.82–1.22, P = 0.974). Moreover, no statistical effect was identified in further subgroup analyses stratified by ethnicity, gender, body mass index (BMI) and potential confounding factors. No significant heterogeneity or publication bias was observed. In conclusion, our meta-analysis demonstrated that folic acid supplementation had no effect on colorectal cancer risk.

[Stavia]

Cancer risk with folic acid supplements: a systematic review and meta-analysis.
Wien TN1, Pike E, Wisløff T, Staff A, Smeland S, Klemp M.
Author information
Abstract
Objective To explore if there is an increased cancer risk associated with folic acid supplements given orally. Design Systematic review and meta-analysis of controlled studies of folic acid supplementation in humans reporting cancer incidence and/or cancer mortality. Studies on folic acid fortification of foods were not included. Data sources Cochrane Library, Medline, Embase and Centre of Reviews and Dissemination, clinical trial registries and hand-searching of key journals. Results From 4104 potential references, 19 studies contributed data to our meta-analyses, including 12 randomised controlled trials (RCTs). Meta-analysis of the 10 RCTs reporting overall cancer incidence (N=38 233) gave an RR of developing cancer in patients randomised to folic acid supplements of 1.07 (95% CI 1.00 to 1.14) compared to controls. Overall cancer incidence was not reported in the seven observational studies. Meta-analyses of six RCTs reporting prostate cancer incidence showed an RR of prostate cancer of 1.24 (95% CI 1.03 to 1.49) for the men receiving folic acid compared to controls. No significant difference in cancer incidence was shown between groups receiving folic acid and placebo/control group, for any other cancer type. Total cancer mortality was reported in six RCTs, and a meta-analysis of these did not show any significant difference in cancer mortality in folic acid supplemented groups compared to controls (RR 1.09, 95% CI 0.90 to 1.30). None of the observational studies addressed mortality. Conclusions A meta-analysis of 10 RCTs showed a borderline significant increase in frequency of overall cancer in the folic acid group compared to controls. Overall cancer incidence was not reported in the seven observational studies. Prostate cancer was the only cancer type found to be increased after folic acid supplementation (meta-analyses of six RCTs). Prospective studies of cancer development in populations where food is fortified with folic acid could indicate whether fortification similar to supplementation moderately increases prostate cancer risk.

http://www.ncbi.nlm.nih.gov/pubmed/22240654

95% confidence interval either 1 or very close to 1. I'm not worried. Plus most of us who supplementation take methyl-folate not folic acid.

Great stuff N-guy! Keep us thinking!

[apod]

I'm wondering if anyone here has explored the concerns about folate supplements and the increased risk of prostate and colorectal cancer? It seems like most of the efforts to lower homocysteine utilize high folate and b12 intake. There's some researchers that I've read that claim too much folate is bad...like a precursor to cancer cells or something. I'd love to hear what others think.

If I recall, this seems to be more closely related to the oxidized, unnatural folic acid form (which preferentially binds to folate binding proteins and receptors with no biological function before it is slowly and often poorly metabolized into the active form.) I'm not sure if there's as much research showing carcinogenic potential from supplementing 5-MTHF, particularly in the context of something like a C667T polymorphism which lowers natural 5-MTHF levels (which might raise the risk of some cancers by itself?) Unmetabolized synthetic folic acid (pteroylmonoglutamic acid) in the blood is associated with decreased natural killer cytotoxicity, while foods rich in the natural pteroylpolyglutamate forms of THF, 5-MTHF, 10-CHO-THF and 5-CHO-THF are often inversely associated with cancer development.

Perhaps hedging against folate consumption with Green Tea (or straight EGCG) could be useful. I believe green tea exerts anti-cancerous activity through an anti-folate mechanism.

[Nequals1Guy]

I think the issue for me and possibly others is the lack of change experienced in lowering homocysteine through supplementation with the methyl variety of B vits. The answer that I most often get is "take more if it's not lowering or get on Cerefolin" or something like that. Does the risk outweigh the benefits? What about the risk of nerve damage when taking high amounts of B vits? Personally, I've seen that as I titrate higher doses of B vits (all methyl varieties) my bowel movements slow to a crawl. That worries me. I wonder if I'm damaging the nerves in my gut. I don't think giant (like massive) hard bm's every 2-3days is normal! When I back off the B's I return to normal after a week or so. ... All for what? My homocysteine to be lowered? Is there compelling evidence to support the need to lower homocysteine below 9? (Mine is considered normal at 13 but based on everyone here I feel like my 13 is a death sentence). Thanks for hearing my frustrations. Don't anyone take it personal. It's a forum.

[Julie G]

Is there compelling evidence to support the need to lower homocysteine below 9? (Mine is considered normal at 13 but based on everyone here I feel like my 13 is a death sentence).

Waves, N=1Guy! We actually have pretty strong evidence that lowering homocysteine will both improve cognition and increase hippocampal volume. Read Stavia's primer to check out references, etc. Because I'm not as focused on atherosclerosis, I'm unaware of any research that demonstrates an actual risk reduction from lowering homocysteine...doesn't mean it doesn't exist.

Very weird that B vitamins affect your bowels!!!

[SusanJ]

Hey, N, check out the methylation post. If you know your methylation snps, you might find that you need a different homocysteine lowering strategy. For example, you might do better with TMG if your BHMT snps are variants.

We know that Bredesen likes to see low homocysteine, so you might want to search the site for that discussion.

That said, I am homozygous for MTHFR C677T and only take 400 mcg/day of methylfolate. That number is where I've settled because of a combination of lab results and how I feel. If you're concerned about your levels being too high, get an RBC blood test. And include a Methylmalonic Acid test to make sure you are utilizing your B12. If it's high, you'll want to keep an eye on B12 levels even if they come back in range, and maybe even switch to a mixed form.

And it's a good question to ask since an old style cancer drug still in use, methotrexate, is a folate antagonist - it prevents cells from using folate to make DNA and RNA and slows the growth of cancer cells.

[Stavia]

Great discussion. Please keep the questions going. We very much welcome debate. We certainly don't want to be an echo chamber.
N-guy we have mainly been focused on the prevention of dementia and there is experimental evidence according to neuroscientist Dr Ram Rao that amyloid starts to accumulate at homocysteine levels >7. However of course there are no trials showing altering just this one biomarker reduces dementia.
I have not personally reviewed the evidence that lowering homocysteine reduces end point cardiovascular events. Do you know of a literature review re this? We would all be extremely interested.

[Nequals1Guy]

... If you know your methylation snps, you might find that you need a different homocysteine lowering strategy. For example, you might do better with TMG if your BHMT snps are variants.

I am homozygous for MTHFR C677T