Are folate and folic acid the same?
No. Folate is the naturally occurring form of vitamin B9. Folate is derived from the Latin ‘folium’, meaning leaf - and yes, green leafy vegetables are some of the foods highest in folate.
Folic acid is the synthetic form (made in a laboratory to be a similar chemical structure to folate, but not identical) of folate.
In food, folate occurs naturally as polyglutamate (which means ‘many’ glutamates). In our intestine, digestion breaks each of the glutamates off and adds a methyl group (this is a carbon and 3 hydrogen molecules) - a process known as methylation*.
*Methylation or the process of moving a methyl group (1 carbon and 3 hydrogen atoms), onto and off proteins, amino acids, enzymes and DNA is critical for our survival. Methylation is involved in turning our genes on and off, processing chemicals and toxins, building neurotransmitters (chemicals in our body that communicate information between our nerves), processing and metabolising hormones (chemicals in our body that communicate information between different organs), building immune cells, synthesising DNA and RNA, producing energy, and protecting our nerves by producing the outer sheath, myelin.
Folate, in its methylated monoglutamate (1 glutamate) form, can then be absorbed into the bloodstream and delivered to cells. The folate that reaches our cells is still inactive. To activate folate, vitamin B12 removes the methyl group. Of course vitamin B12 doesn’t do this selflessly - it keeps the methyl group for itself, which activates it too! This then allows the folate coenzyme and the vitamin B12 coenzyme to be active and available for DNA synthesis.
Folate and vitamin B12 work together to make red blood cells and help iron function properly in the body. A deficiency in folate or vitamin B12, can lead to macrocytic or megaloblastic anaemia which means that red bloods cells do not mature properly, leading to fewer, but larger red blood cells that cannot carry oxygen or travel through capillaries as efficiently as normal red blood cells.
Folate and vitamin B12 play important roles in the division of new cells and facilitate the production of DNA and RNA, our bodies’ genetic material. Fundamentally, a baby’s growth and development occurs because cells are dividing. So it is very important that we have adequate levels of folate during the early part of pregnancy when all of our babies growth is occurring by cell division. Women with impaired folate and/or vitamin B12 status are at increased risk for having babies with neural tube defects (NTDs).
Folate sounds like a really important nutrient right?
Right. But, by singling out folate as the holy grail for cell division and NTD prevention we might have missed a critical part of the spine and brain development story for our babies. You see, folate and vitamin B12, as well as choline, methionine and a myriad other cofactors are critical for methylation. Deficiencies in any of these nutrients can wreak havoc in the methylation pathways, disrupting the associated functions, including cell multiplication. The evidence we have now is that it is disruption in the methylation pathways in general that is likely contributing to risk of NTDs, not just folate status.
Unlike folate, folic acid needs to be methylated in the liver before it can be used by our bodies (this process doesn’t occur in our digestive tract like it does for folate). This conversion process can be slow and folic acid levels may stay high for a long time after taking a supplement. By supplementing with folic acid, we can mask a vitamin B12 deficiency, which, as we discussed above, is another nutrient critical for methylation and deficiencies in vitamin B12 are also a risk for NTD.
Let’s go back to our original question: are folate and folic acid the same? The answer is no. So why is the advice to take folic acid at least 1 month before conception and for the first trimester of pregnancy, and not folate?
Here’s a few good reasons. Folic acid is cheap to make. Much cheaper than running an organic farm of leafy greens (but is it really, what are the other 'costs' of this approach that might not be being measured...?'). It’s also more stable in pill form than folate. And guess what else? You can patent a chemical you’ve made, but you can’t do that with a naturally occurring substance. Perhaps have another read of that one, just so it’s clear in your mind. Folic acid, made in a laboratory, can be commercialised and marketed to you as the solution for your early baby-growing needs. Can you do that with folate? No.
This may sound a bit radical, but imagine if instead of fortifying our grain products and recommending a synthetic vitamin supplement, we instead supported our farmers. The same farmers who grow green leafy vegetables and legumes. Imagine if we then recommended high dose consumption of these, instead of a pill, for preconception health.
Dr Hayley Dickinson, PhD and Kendall Macdowell