If you're a woman of childbearing age you know that every medical appointment includes a recommendation that you take folic acid supplements. The reason for this is simple, too little folic acid has been proven to cause severe neural tube defects in a developing fetus. While all doctors know that too little folic acid is harmful, they generally do not know that too much folic acid may also have toxic effects as well. Luckily, there is a safer alternative: folate.
Folic acid vs. Folate - what's the difference?
Folic acid is a synthetic form of folate that is found in supplements and fortified foods, whereas folate is the natural form commonly found in whole foods. Both folic acid and folate go through their own metabolic pathway to turn them into the bioavailable 'final' form of folate, called methylfolate (5-MTHF). Ultimately, methylfolate (5-MTHF) is what your body needs to be healthy.
MTHFR mutations reduce conversion to methylfolate
A large subset of the population with certain variations in the MTHFR gene are unable to fully breakdown both folic acid and folate into its final state, methylfolate (5-MTHF). That means you may not be getting enough methylfolate even when you're taking the recommended amount in your supplement because your body cannot process it properly.
The easiest way to find out if you have a MTHFR mutation is to ask your doctor to run a panel or to do it on your own have your DNA sequenced by 23andme and then follow these instructions. I recently did both and found out that I have a compound heterozygous mutation in this gene which simply means that I have a 50% reduction in my ability to break down folic acid into methylfolate.
Here's why folic acid (the synthetic form) is harmful
When you ingest large amounts of synthetic folic acid found in supplements and fortified foods, some of it may not be metabolized into methylfolate and it may run free in your body. The un-metabolized folic acid (called 'UMFAs') may be toxic as some studies have found that theycontribute to the development of several types of cancer. While too much synthetic folic acid results in UMFAs, too much folate from whole foods does not create UMFAs and is not harmful to your health. Thus, folate is the safer alternative.
The research is ongoing and not fully proven yet but there is compelling evidence building that UMFAs are harmful. In one study, supplementation with folic acid was found to be associated with an increased risk of breast cancer (1). Another study found a higher rate of prostate cancer in those supplementing with folic acid (2). In 2012, a study found a correlation between the childhood eye cancer called Retinoblastoma with folic acid intake of the child's parents. Mothers who took folic acid supplements while pregnant and had the genetic MTHFR mutation in which they could not turn folic acid into folate, were 4 times more likely to have a child with Retinoblastoma than the control. The study found that “both insufficient folate intake and increased folic acid intake have been associated with the development of carcinomas in adults and with the promotion of neoplastic lesions and genetic damage in rodent models" (3).
The metabolic pathway: folic acid vs. dietary folate
In sum, your body's goal is to convert both folic acid and dietary folate into methylfolate (5-MTHF) which is the form that can be used by your cells. Unmetabolized folic acid (UMFAs) is a product of folic acid ingestion through supplementation and food fortification that may result in potential toxic effects. A better alternative is dietary folate (through foods and supplements made from whole foods), which is safe even in excess amounts. Both folic acid and folate are affected by MTHFR mutations and may reduce the conversion to methylfolate (5-MTHF).
If you have a MTHFR mutation it is best to increase your dietary folate. You may also consider taking a supplement directly in the form of methylfolate. In this article, find out which of the 5 best folate supplements will work best for your situation.
Your doctor is clueless about folic acid vs. folate
Don't be surprised that your doctor does not know about the dangers of folic acid nor that there is a simple and safe alternative: folate. The vast majority of doctors do not receive nutrition education in medical school, so they never learn the difference between folic acid and folate. After explaining to one of my doctors the reasons why I would not take folic acid supplements, he responded saying "I need to learn more about nutrition".
What your doctor learned in medical school (which is true) is that too little folic acid can cause terrible birth defects and that's why they push the folic acid supplements. They are generally not aware that too much folic acid may have serious consequences, especially for those with a MTHFR mutation. So the next time your doctor recommends taking folic acid, take folate instead. Remember they both are converted into methylfolate (5-MTHF) so it's the same thing, just safer. You can get folate by eating whole foods (the Wholesome app ranks which foods are the most rich in folate) or by taking a whole food supplement. After doing heavy research into supplements, here are the 5 best folate supplements that I recommend.
Folic acid is in fortified foods, not just supplements
Unfortunately saying no to folic acid supplements is not enough to avoid it. If you eat any breads, pastas, rice, cereals, or flours, they are all fortified heavily with folic acid. Since 1998 the FDA has been fortifying with folic acid mandatory with the goal of reducing birth defects. But it is likely that too much folic acid in our diets is causing harm especially if you are eating these things everyday (4). A 2009 study looked at colon cancer in Chile before and after the start of the flour fortification program with folic acid and found that "fortification programs could be associated with an additional risk of colon cancer" (5).
What you can do
So what do you do when too little folate causes birth defects and too much folic acid may increase your risk of cancer?
1. Avoid folic acid and get as much folate from whole foods as you can. There is no danger in eating too much natural folate like there is with folic acid. Folate helps the development of red blood cells, reduces levels of homocysteine in the blood which supports cardiovascular health, and it supports nervous system function.
The Wholesome app can help you get know if you're getting enough folate in your diet. It allows you to track toward the USDA's recommended goal based on your age and gender. It also has an easy access list of the foods with the most folate.
If you are pregnant or trying to get pregnant you will need need to increase the amount of folate in your diet from 400mcg to 600mcg (source: NIH). In the Wholesome app settings, simply update your profile to 'pregnant' and the app will set your goal to 600mcg per day. If you have a MTFHR mutation, you should set your goal higher as not all of the folate that you eat will be absorbed.
2. Have a blood test performed by your doctor to measure your actual level of folate. I had this done recently and found out mine were way above the recommended amount (finally some validation that I don’t need those pills!). Your doctor may also run your homocysteine level which is an amino acid that can be elevated when you are deficient in folate. High homocysteine levels can put you at risk for cardiovascular disease (source).
3. Find a better folate supplement. If your levels of folate are low or you are trying to get pregnant find a supplement that says 'folate', '5-methyltetrahydrofolate', or '5-MTHF' on the label and avoid anything that says 'folic acid'. After doing my own research, I have found that these are the 5 best folate (prenatal) supplements. Before you buy, read the nutrition label because most multivitamins contain folic acid.
4. Assuming you are getting enough folate, avoid packaged goods with folic acid listed on the label – that probably means less cereal and energy bars. Sometimes the labels are confusing, for example, cliff energy bars list “folate” under vitamins but then in the ingredients it says “folic acid”. Eat whole foods instead.
5. Find out if you have a MTHFR mutation that can impact your ability to metabolize folic acid and puts you more at risk.
Here is an easy way to find out if you have a MTHFR mutation.
At a minimum, do your best to get natural folate from whole foods rather than simply relying on folic acid supplementation.
About the author
Jessica Glago is the CoFounder of the Wholesome App. After having two different cancers in her childhood she developed the app with the help of her husband to get more healthfulness out of her diet. To date, Wholesome for iOS has had over 250,000 downloads and over 1.5 million whole foods tracked. The app has been featured on BuzzFeed, LikeHacker, CultofMac, and The Seattle Times.