There is a lot of buzz around folates and folic acid.
Health professionals often find the terminology around folate and folic acid confusing. They use the words folic acid supplements when they mean folate, folinic acid or 5-methyltetrahydrofolate (active form). The mix up occurs because folate has become an umbrella term for many forms of folate. Each study may use a specific form of folate such as 5-methyltetrahydrofolate but by the time the study makes it to the media, for convenience, it’s being referred to as folate. This creates a game of broken telephone lines between the researcher and the public, leading to confusion.
There are many forms of folate. Fortunately, you only need to know about the forms of folate relevant to you. It is easy to get confused, so we are going to walk you through why each form of folate is important.
Is Folic Acid Equal To Folate?
Folates are found naturally in food and folic acid is a man made synthetic form. The body prefers to use naturally occurring folates over the folic acid. Folic acid is a stable synthetic compound making it easy to fortify food with. Folic acid can be found in supplements and fortified foods (ex. Bread, baked goods, cereals or any other foods made with folate enriched wheat). We need less than 200 micrograms of folate per day! But, if you have an MTHFR mutation your body will often require more than 200 micrograms of folate per day.
Folic acid has no function in your body until it is made into dihydrofolate. Having too much folic acid in the system blocks the pathway for naturally occurring folates. Folic acid inhibits the DHFR enzyme from making natural folates into dihydrofolate.This is why folic acid supplements are usually a bad idea. Not until recently, due to advances in technology, 5-methyltetrahydrofolate and folinic acid became available for supplementation.
Supplementing with 5-methyltetrahydrofolate or folinic acid is better than folic acid. Depending on your unique situation a folate supplement may not be the best option for you or may require different supplementation strategies. A combination of 5-methyltetrahydrofolate and folinic acid at ratios specific to your condition may be recommended or some of you will do better on just active methyl folate. Working with a healthcare practitioner who is specialized in working with clients with MTHFR mutations is recommended because not getting the ratios right can lead to more health problems.
For more information on MTHFR and folic acid and folic acid supplements read our article “Why isn’t folic acid good for those with an MTHFR mutation?” and for more information about supplementing folate read “A guide to folate supplementation”
Why Is Folate Important?
Folate is widely studied because it plays many critical roles within the body. Folate plays a role in the following processes:
- Synthesis of DNA and RNA
- Use of S-adenosyl methionine (SAM) for the transfer of methyl groups
- Production and recycling of neurotransmitters
- Creation of functional red blood cells (RBC), white blood cells (WBC) and blood platelets
A lack of folate can lead to harmful conditions, especially before or during pregnancy. Low folate levels are linked to:
- Neural tube defects
- Spina bifida
- Poor quality sperm
- Blood clotting issues leading to increased risk of thrombosis
- Behavioral issues such as ADD/ADHD
- Increased sensitivity to allergens
- Low birth weight caused by
- Premature birth
- Slow prenatal growth rate
- Multiple miscarriages
Folinic acid (also known as calcium folinate or 5-formyltetrahydrofolate) is a cofactor in many reactions playing a role in:
- Purine synthesis
- Pyrimidine synthesis
- Amino acid conversion
- All are important for synthesis of DNA
5-methyltetrahydrofolate is the active form of folate in the body. Once made, it plays a role in the processes mentioned above but it also plays a vital role in the homocysteine cycle.
If 5-MTHF is out of balance you can start running into problems. Supplementing 5-methyltetrahydrofolate without professional guidance may lead to biochemical imbalances within your body. These imbalances can cause a variety of side effects including:
- sore muscles
- achy joints
- severe anxiety
- suicidal thoughts
What Are Natural Sources Of Folate?
Folate primarily comes from some of the healthiest foods you can eat. Dark green leafy greens. Here is a list of foods known to be high in folate:
- Swiss Chard
- Collard greens
- Romaine lettuce
- Brussel sprouts
Folate can also be found in some nuts, lentils, and beans. For a more detailed article about folate containing foods including folate-fortified foods, click here.
Overview Of The Folate Cycle
The diagram below shows a simplified process of the necessary steps to turn folate to its active form 5-MTHF within the body.
Starting with dietary folate, you can see it is ready to jump right into the folate cycle. The folate you eat is quickly made into dihydrofolate (DHF). DHF is given electrons by the enzyme dihydrofolate reductase (DHFR) using one molecule of nicotinamide adenine dinucleotide phosphate (NADPH, a common electron donor within the body and participates in many biochemical reactions) to make tetrahydrofolate (THF).
The diagram shows DHFR is quicker at making THF from dietary folate compared to folic acid. This is because the DHFR enzyme has more attraction to dietary folate and only needs to help with one reaction. Folic acid requires two reactions with the DHFR enzyme to become THF. The first reaction of folic acid is slow. The slow reaction process uses up available DHFR enzymes, blocking them from using natural folates.
The more folic acid present within the system, the slower folate metabolism becomes. If the system becomes saturated with folic acid, some research suggests DHFR enzymes can become completely blocked. A building up of folic acid begins, causing the folate cycle to become out of balance. Anytime an important biochemical process within the body becomes out of sync with its natural cycles there are negative health consequences. If you are trying to become pregnant or are experiencing treatment-resistant health issues, bringing the folate cycle back into its natural cycle is important for ensuring a healthy pregnancy and restoring the body’s methylation system. For a more in-depth article on the folate cycle read our article “The Folate Cycle In Detail”
Changing Your Relationship To Folate
There are major differences between types of folates. Keeping this in mind when choosing what to eat throughout the day. Avoiding foods fortified with folic acid is a good place to start. Unfortunately, folic acid fortification is mandatory in 53 countries around the world. Food such as bread, baked good, cereals are made with enriched wheat and are going to be fortified with folic acid. Making the choice to substitute folate fortified food for food containing natural folates can make a big difference in maintaining a healthy and functioning folate cycle.
Make sure you are including more dark leafy greens in your diet. Refer to our folate containing foods list to get a general sense of what contains folate when planning out your meals. MTHFR mutations decrease your ability to process folate. If you have an MTHFR mutation, avoiding foods fortified with folic acid and getting your natural folates into your diet should be a priority for you. If your health conditions persist after improving your dietary folate intake, you should speak with your healthcare practitioner about supplementing with a combination of active folates. Your situation may be more complex, requiring a specific supplementation strategy to restore a natural and healthy folate cycle.
You can watch Carolyn’s “What is MTHFR?” webinar for more information about MTHFR and folate.
Take home message
The key message here is that we should avoid folic acid where possible, particularly in supplement form and fortified foods, particularly if you have an MTHFR gene mutation. You should be getting as much folate as you can from your diet in the way of leafy green vegetables, and if you have health conditions speak to your practitioner about supplementing with various combinations of active folates ie: folinic acid or 5-MTHF.
 Aarabi, M., San Gabriel, M. C., Chan, D., Behan, N. A., Caron, M., Pastinen, T., … & Trasler, J. (2015). High-dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism. Human molecular genetics, 24(22), 6301-6313.
Hekmatdoost, A., Vahid, F., Yari, Z., Sadeghi, M., Eini-Zinab, H., Lakpour, N., & Arefi, S. (2015). Methyltetrahydrofolate vs Folic Acid Supplementation in Idiopathic Recurrent Miscarriage with Respect to Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms: A Randomized Controlled Trial. PloS one, 10(12), e0143569.
 Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. (1998). Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. National Academies Press (US).
 Jacques, P. F., Bostom, A. G., Williams, R. R., Ellison, R. C., Eckfeldt, J. H., Rosenberg, I. H., … & Rozen, R. (1996). Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation, 93(1), 7-9.