Debunking the Folic Acid / Cancer Connection

By Michael A. Smith, MD

Despite lingering fears, a high intake of folic acid is not associated with an increased risk of cancer.

This new information comes from a recent meta-analysis that was performed by an international team from institutions in the US, UK, Europe, and Australia, and is published in the early online version of The Lancet.1

In a news release, the lead co-author states, “The study provides reassurance about the safety of folic acid intake, either from supplements or through fortification when taken up to 5 years.2

Traditional Reasons for Supplementing with Folic Acid

The primary use of folic acid supplementation by conventional doctors is to treat megaloblastic anemia — a low number of large red blood cells — and to prevent neural tube defects in newborn babies.

Because of this, many countries started to fortify foods and drinks with folic acid. But then along came the cancer scare.

Research throughout the last 5 years suggested that excessive intake of folic acid could promote tumor growth and lead to a higher risk of developing cancer. So how exactly could folic acid promote cancer, if it does at all?

Well, it’s essential to numerous bodily functions including methylation of vitamin B12 and DNA synthesis — which are especially important for tissues that rapidly divide. This is why gastrointestinal symptoms and anemia can all develop with a folic acid deficiency, as they both occur in rapidly dividing tissues.

So, as the theory goes, high doses of folic acid could initiate rapid cell division, involving repeated cycles of DNA synthesis, increasing the risk of DNA mutations — the hallmark of cancer.

But this is not proven and even the American Cancer Society admits it doesn’t know how folic acid increases the risk of cancer … if it does at all.

Folic Acid Makes a Comeback

Researchers from the study assessed data from almost 50,000 people from 13 randomized clinical trials involving folic acid supplementation — about 25,000 taking folic acid and the other half not taking it.

They found that people who took daily folic acid for five years or less were not significantly more likely to develop cancer than those that didn’t take folic acid.1

A total of 1,904 new cases of cancer were reported in the folic acid group, compared to 1,809 in the placebo group — that’s 7.7% of the total folic users versus 7.3% of the total subjects in the control groups.1

The researchers went a step further in their analysis. They identified out of the data pool people taking the highest amount of daily folic acid and found that even for this group there was no increased risk of cancer over five years.1

One of the lead investigators, Dr. Robert Clarke, was optimistic about the results but he did caution that longer term trials need to be conducted before any definite conclusions are made.

The Optimal Form of Folic Acid

Bioactive folate is chemically known as 5-methyltetrahydrofolate and is the predominant biologically active form of folic acid in cells, the blood, peripheral tissues, and particularly the brain.3

Until recently, 5-methyltetrahydrofolate (5-MTHF) was available only in expensive prescription medicines and medicinal food products. Now, this active form of folate, which provides increased bioavailability together with protection against homocysteine-related health problems, is available as a dietary supplement.

Since 5-MTHF is the only form of folic acid used directly by the body, it doesn’t have to be converted and metabolized to be clinically useful, as does regular folic acid.3

Folic acid, as used in ordinary dietary supplements and vitamin-fortified foods, must first be converted to bioactive 5-methyltetrahydrofolate in order to be clinically effective.

These steps require several enzymes, adequate liver and gastrointestinal function, and sufficient supplies of niacin (B3), pyridoxine (B6), riboflavin (B2), vitamin C, serine, and zinc.3

Another advantage of 5-MTHF is that it is unlikely to mask a vitamin B12 deficiency, a shortcoming of folic acid. Folic acid, when administered as a single agent, may obscure the detection of vitamin B12 deficiency.3

The Bottom Line

So, here’s what I’m getting at: Folic acid is an important component of all tissues, especially ones that rapidly divide. For this reason, we have always suggested between 200 and 400 mcg a day of folic acid, even during the so-called cancer scare of the last few years.

And wouldn’t you know it — the “scary cancer risk” hype appears to be on its way out or is at least being seriously challenged these days.

So what does this mean to you? As far as we're concerned, feel free to keep supplementing with folic acid daily.


  1. The Lancet, Early Online Publication, 25 January 2013, doi:10.1016/S0140-6736(12)62001-7 (
  2., Accessed January 30, 2013.
  3. Altern Med Rev. 2006 Dec;11(4):330-7.


Anonymous said...

5-MTHF is called FOLATE, not Folic Acid

Anonymous said...

Folinic (5-CHO-THF) is another form that is used in a different part of the folate pathway and is also available.

While it is true that 5-MHTF doesn't have to be converted before it has any use like folic acid, it does have to be converted before it has use outside of the one carbon part of the folate pathway.

LifeExtension said...

Anonymous - Thanks for your input!

Anonymous said...

Are there long term studies being done do you know (10+ years)?

Anonymous said...

I'd like to know what the highest amount was that was taken during this study and what percentage of people were on that high amount.

LifeExtension said...

Anonymous - There was a 20 year study examining the effect of folic acid fortification on childhood cancers. Here's a link to the study:

LifeExtension said...

Anonymous - The highest amount recorded was 42mg. We're not sure of a percentage, but few people were taking that dose.

Christopher Nagy said...

For those with an excess of or unmetabolized Folic acid (the synthetic, unnatural form) from supplements, studies have demonstrated a decrease in Natural Killer Cell function/production. Likely an explanation for previous studies demonstrating an increase in cancer. This may also be caused by an MTHFR defect, one of the most common genetic defects we are aware of.

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