Folate Intake: How Much Is Too Much for Optimal Health?

Key takeaways:
~ Balance is key with folate.
~ Having enough folate helps to protect against cancer.
~ Excess folate is linked to the growth of tumors.

Understanding Folate: Risks and Benefits of Getting Too Much

Folate is needed for cells to replicate, which is one reason it is so important to get enough during pregnancy and why it is included in prenatal vitamins. However, rapid cellular growth is also a hallmark of many types of cancer. Tumors that grow and divide rapidly also thrive when folate is abundant. In fact, one of the first successful anti-cancer drugs was an anti-folate drug that blocks cancer cell growth by reducing folate.[ref]

Folate is essential for DNA synthesis. It helps prevent DNA errors, but too much can promote tumor growth if cancer is present.[ref]

Thus, the balance of getting enough folate for your individual needs is important. Often, there is a focus on dramatically increasing folate levels with certain genetic variants, such as MTHFR.

Here’s an example that may surprise some of you:

The MTHFR C677T variant, which reduces the synthesis of methylfolate (active folate), is associated with a bunch of negative health outcomes. Many clinicians immediately recommend high doses of methylfolate.

But… carrying two “bad” copies of the MTHFR C677T variant also significantly reduced the risk of colon cancer and a number of other types of cancer.[ref][ref][ref][ref]

For example, a meta-analysis found that two copies of the C677T variant (AA genotype) decrease the risk of colon cancer by about 20%. Another meta-analysis found that two copies of the C677T variant (AA genotype) were protective against prostate cancer.[ref]

How much folate is needed?

In the US and much of the world, folic acid is added to cereals, bread, enriched white rice, and anything with wheat (pizza, pop-tarts, cookies, crackers, etc). Folic acid is a synthetic form of folate that is stable in foods and during baking.

For reference, a serving of Cheerios has 235 mcg of added folic acid,  a serving of bread has ~150 mcg of added folic acid, and a cup of enriched white rice has ~100 mcg of added folic acid.[ref]

Scenario:
Suppose your breakfast is 1 c. of Cheerios, lunch includes a sandwich with two slices of white bread, and your dinner is burrito (in a flour tortilla) with white rice — you would be getting more than 500 mcg of added folic acid in addition to any natural folate in the food.

The RDA for folate is 400 mcg/day DFE. DFE stands for dietary folate equivalents (DFE). The tolerable upper limit is set at 1,000 mcg/day from supplements or fortification (limit for adults, lower for teens and children).[ref]

What are dietary folate equivalents?
The DFE refers to how supplemental forms of folate equate to folate that you get from food. Food folate is equal to one dietary folate equivalent (DFE), which makes sense. Folic acid and methylfolate are more available to be absorbed in the intestines.

Here’s how they are factored:

1 DFE = 1mcg of folate from food = 0.6 mcg folic acid or 0.5 methylfolate

Back to my scenario: If you eat breakfast cereal, a sandwich with two slices of enriched bread, and a burrito with rice for dinner (totaling at least 500 mcg of folic acid), you end up with 833 mcg DFE just from added folic acid. Then you read about MTHFR and decide that you need a methylfolate supplement… the most common supplement dosage you’ll find is 1 mg. (1 mg is 1,000 mcg, equivalent to 2,000 mcg DFE.)  You can see how you quickly exceed the upper limit recommended for folate.

Conclusion:

I don’t have all the answers here, but I worry that some people are going overboard on folate and may not understand the risks vs. benefits. I’ve seen so many articles and podcasts recommending methylfolate supplements at relatively high doses for anyone with an MTHFR variant, but I don’t see much on the possible negative consequences.

The research clearly shows a tradeoff — more is not always better when it comes to folate, folic acid, and methylfolate. Please read through the studies for yourself.

To optimize folate, I think individuals need to take into account their age, homocysteine levels, cancer risk factors, family history of cancer, genetic variants in the folate pathway, and how much nitrite is in their water and diet. Plus, there are probably other environmental factors (like nitrates in groundwater) that I don’t know about!

If you are worried about excess folate but want to support cellular health with an MTHFR variant, consider creatine. About 40% of methyl groups go towards the synthesis of creatine, so supplementing with creatine helps to take the burden off the system. You can read more in the MTHFR article and the Creatine article. Also, keep in mind that you could cut a 1 mg (1,000 mcg) methylfolate tablet in half or in fourths to dial in a lower dose.

Related articles and topics:

DHFR and MTHFR: Folic Acid Metabolism