Folate and Folic acid: Beyond pregnancy

You’ve probably heard about the importance of folic acid in pregnancy. Folate (vitamin B9) is a critical nutrient in the formation of the fetal neural tube, that will later form the baby’s brain and entire nervous system. Women take folate or folic acid in pregnancy to reduce the chances of neural tube defects, and the first trimester of pregnancy is the most important time for this supplementation.

Without sufficient folate, red blood cells (produced in the bone marrow) are too large, and don’t work as effectively. This is called macrocytic anaemia. The haematologist Lucy Willis studied macrocytic anaemia in pregnancy in India in the 1920s and 30s. She discovered that eating a nutritional yeast both prevented and treated it. Folate was found to be the crucial nutrient from the yeast, and animal studies have since confirmed this.

Folate and the synthetic folic acid, have since been found to play a critical role in cell division, and of course there’s a lot of that going on in pregnancy: far more than just blood cell production! Folate is crucial for synthesis of DNA in the nucleus of every new cell. The fetus grows from one cell to nearly a billion cells in its first 10 weeks, and all of those cell divisions need folate.

What does folate do for those of us who are not pregnant?

As adults, our bodies are replacing our cells on an ongoing basis, so it is important for us too. It is needed to make DNA for healthy cell replication, and RNA so your genes can make the proteins you need to function on a day-to-day basis. So it is absolutely necessary for the formation and function of all of your cells. Folate deficiency has been linked with an increased risk of cardiovascular disease, cancer and cognitive dysfunction. 

But folic acid is a synthetic vitamin: it is the synthetic and cheaper form of folate, and is the form found in many supplements and fortified foods. It takes three conversion steps to change folic acid into the active form (5 MTHF). Folate is the natural form - the form the human race has always consumed. Yet we have noticed that, even in good medical literature, the terms folate and folic acid are often used interchangeably. Folic acid is referred to as though it were a natural nutrient, not a synthetically produced one, and vegetables are said to contain folic acid, when in fact they contain folate.

Folic acid isn’t quite as benign as naturally occurring folate, as it isn’t as fully converted into 5 MTHF as folate is, and so can build up in the bloodstream and may even prevent folate from functioning optimally. Although still controversial, correlations have been seen between increased unmetabolized folic acid levels (UMFA) and colon and prostate cancers. Interestingly, in areas where foods are fortified with folic acid, UMFA has been found to correlate with increased breast cancers, but this is not the case in areas where foods are not fortified. This has provided food for thought and for more research, especially as UMFA has been found in umbilical cord blood and in infants. 

Currently, folic acid remains the form generally used by people trying to conceive and while pregnant, because it is the form that has been more studied. Unfortunately, given that a natural substance cannot be patented, there is a lot less incentive to assess the potential benefits of the natural form than to continue the current synthetic folic acid production and use.

Some people have genetic variations (called SNPs) that affect folate metabolism. These are referred to as methylation defects, and people with these SNPs aren’t able to use folate as effectively in their biochemistry. This is not uncommon! It is estimated to affect about 40% of the global population. These folk do much better if they keep up maximal veggie intake and supplement folate, so they have more to use with their less efficient genetics. Methylation impairment leads to oxidative stress and chronic inflammation, precursors to many significant health concerns.*

There are several SNPs that affect folate metabolism. These can cause different imbalances which range from reducing folate activation, or decreasing B12 levels, to impairing day-to-day detox capability and increasing norepinephrine (adrenalin) and dopamine levels. Reduced folate activation promotes a build-up of unmetabolized folic acid (UMFA) in those whose diet or pills are supplemented with folic acid rather than folate.

The supplemental form that we currently prefer is 5MTHF, (5-tetrahydromethylfolate). This is the active form that the body makes from the folate in your diet, so supplementing this form skips the steps that the genetic SNPs slow down. It gives your system a start on getting that biochemistry going right, even if your genes aren’t optimal for doing that. 

In any B supplement or multivitamin, look for the 5 MTHFR form of folate in the list of ingredients. If you can’t find that, at least get one that contains folate, rather than folic acid.

The RDA of folate for a non-pregnant adult is 400 micrograms, and 600 for women of childbearing age, but of course the RDA is the minimum amount required to avoid a deficiency disease. And it doesn’t take those SNPs into account. Plus, as natural folate is water-soluble, if you consume more than you need right now, you’ll just excrete it.

Where do you find folate in your diet? Legumes are a fabulous source, and green leafy vegetables, eggs, beets and asparagus, nuts and seeds are other excellent sources. Indeed the word folate is derived from the Latin folium, which means leaf: the clue is in the name!

*Antioxidants explained

Macrocytic anaemia can be caused by either low folate or low vitamin B12, or both. There is a caution about only supplementing folate, as that can help the macrocytic anaemia, but at the same time mask the symptoms of a B12 deficiency. This can cause significant health problems if left unattended. Therefore B12 and folate are often seen together in supplements, so both bases are covered.