Folic Acid vs Folate: Everything You Need To Know

07/06/2021 | 7 min. read

Healthy Directions Staff Editor

Healthy Directions Staff Editor

There are a lot of different B vitamins and most of them have another name they go by, as is the case with vitamin B9, otherwise known as folate.

Folate is often used interchangeably with folic acid, but they are not the same. Folate generally refers to a whole category of chemical compounds, one of which happens to be folic acid.

The interchablility of the two terms is confusing especially since they are quite distinct, although the distinction that is generally being referred to depends on the context in which you find yourself.

Chemistry vs Nutrition

In the world of nutrition folate generally refers to sources of vitamin B9 obtained from natural sources that are coenzyme activatable such as levomefolic acid, while vitamin B9 made synthetically referred to as folic acid.

Folic acid, otherwise known as pteroylmonoglutamic acid, is the more stable, inactive form of folate and is, therefore, able to be easily sold, delivered, and added to fortified foods.

However, from organic chemistry and a biochemistry perspective folate and folic acid refer to the different acid and base forms of folate structures and are therefore basically identical.

Chemical differences

Although people tend to think of the chemistry in the body as a static formula that has a clear if this then that, the superposition of electrons in the chemical world give rise to a very fluid state of chemistry within the body.

Chemicals are constantly being drawn to and away from each other, swapping electrons and protons (H+), and moving towards equilibrium. But, even equilibrium is a variable force that is affected by all the neighboring systems that change where equilibrium is.

For this reason, folic acid and folate are fairly identical from a biochemical perspective since which form it takes is primarily dependent on the environment it finds itself in.

Acid-Base Chemistry

For example, In proton dense concentrations (low pH) these protons will get pushed onto other molecules that can accept them.

One structure that really resists picking up an extra proton is called a carboxyl group. This group is made up of two oxygens connected to a single carbon, with a partial negative charge and room for another proton (H+). In a static chemical mindset, we might say that there is a single double bond and a single bond, but chemistry is quite dynamic so functional groups like this form what are called resonance structures.

Essentially all it means is that oxygen has the double bond flip-flops, but since electrons are quantum particles it might just be better to treat both bonds as being one and a half bonds in terms of strength.

The movement of electrons that makes resonance structures possible is happening on a smaller scale even when the carboxyl group is protonated (has the proton attached). This creates a small force that in a neutral solution makes the proton likely to dissociate and instead move to a portion of a molecule that really wants an extra electron, which further decreases the likelihood of the carboxyl group getting a proton.

However, if there are enough protons present in the solution then the concentration overcomes the strength of the bond and links up with the molecule forming the acid form of the molecule. From this perspective, folate and folic acid have no difference aside from what solution they are in.

Does It Matter?

One of the important reasons to know why this difference might make an impact is due to the vital need our bodies have for a usable form of Vitamin B9. Vitamin B9 is involved in many biological mechanisms, especially with nucleic acids -- DNA and RNA.

Since the neural tube develops within the first 28 days of pregnancy, doctors recommend all women of childbearing age consume folate.

Low levels of vitamin B9 are associated with an increased risk of several health conditions, including:

  • Birth defects. Low folate levels in pregnant women have been linked to birth abnormalities, such as neural tube defects. The two most common neural tube defects are anencephaly (a brain defect) and spina bifida (a spinal cord defect).
  • Cancer risk. Poor levels of folate are also linked to increased cancer risk.

For these reasons, many people will supplement vitamin B9, and many countries have fortified foods that reintroduce this nutrient into the diet.

Folate

As discussed, when talking about folates it is important to take it from a nutritional perspective and not a biochemical perspective.

In reality, folate is really a category of compounds encompassing even folic acid, but from a nutrition standpoint folate refers to the naturally occurring form of vitamin B9.

Folates are coenzyme activatable, which means that they can associate with enzymes in the gut ensuring that they are all activated before entering the bloodstream. In your digestive system, folate is converted to 5-methyltetrahydrofolate (5-MTHF), an active form of folate, before being absorbed into the body.

Folic Acid

In contrast, a folic acid is a synthetic form of vitamin B9, generally found in the form of pteroylmonoglutamic acid.

Folic acid is generally inactive and more stable than folate, which means that it tends not to react with enzymes in the gut. Instead of all of the folic acid being converted to 5-MTHF before entering the bloodstream only some is.

The remaining folic acid has to be converted by other tissues like in the liver, which takes time. As a result, unmetabolized folic acid has been found in people’s bloodstreams, even in the fasted state.

Although, this has been shown to be reduced by other factors that make the conversion process more efficient, like vitamin B6.

What Does Unmetabolized Folic Acid Do?

Folic acid is quite popular in the food industry with fortified foods and is found in some supplements as well, which only increases the prevalence of unmetabolized folic acid in the bloodstream for the general population.

Several studies show that chronically elevated levels of unmetabolized folic acid may have adverse health effects, including:

  • Increased tumor/cancer risk. High levels of unmetabolized folic acid have been correlated with an increased risk for tumors. However, no mechanisms have yet been found that would be able to establish causation.

The research on the topic of unmetabolized folic acid is still ongoing and many of the health implications are relatively actively unclear. More research and understanding of the mechanisms need to be clarified before conclusions can be drawn about the causation role of unmetabolized folic acid.

Getting Vitamin B9

It’s best to get vitamin B9 from foods and other high folate natural ingredients including asparagus, avocados, brussels sprouts, and dark green leafy vegetables like spinach and lettuce. These vegetables are even the namesake of folate; folate has the Latin word “folium” which literally means leaf. Folate can also be found in fortified breakfast cereals, flour, pasta, rice, beans, lentils, orange juice, broccoli, beef liver, and strawberries.

While the risk of unmetabolized folic acid is still relatively unknown, it might be best to err on the side of caution and avoid the overconsumption of fortified foods and supplementation with folic acid.

Supplements that contain the bioactivatable form of folate are the best alternative to folic acid when considering supplementation. Supplemental methyl folate, bioavailable folate, is available in the form of levomefolate calcium or levomefolate magnesium.

Summary

Nutrition and chemistry define folate and folic acid differently. In chemistry, folate and folic acid are just the deprotonated and protonated forms of the same class of molecules -- folate.

However, in nutrition folate and folic acid refer to subsections of folates based on their bioactivatablitily. Folate refers to naturally available folates typically found in vegetables that readily transform to bioavailable forms before absorption.

On the other hand, folic acid is synthesized in a lab, more stable, and tends not to transition to usable forms in the body without extra processing. This leads to unmetabolized folic acid buildup in the bloodstream and may possibly have adverse health effects.

To stay on the safe side, get your vitamin B9 from diet and supplements while avoiding folic acid and fortified foods.

Healthy Directions Staff Editor