Many know folic acid, but what is folate? It is often used synonymously. Today we look at exactly this difference and clarify why here the terms is essential to know. Because only that would be rather duller, we also look at the function of folate in your diet. We’ll look at why it’s a powerful and all too often forgotten building block, at least in Western conventional medicine, and most importantly, how you can optimize your folate levels.
Sounds like a lot, doesn’t it? Admittedly, it is and I’ll try to focus on the most important things so that you can apply the knowledge in a practical and simple way. You don’t want to do a PhD in biochemistry & physiology, I guess, but just want to live healthy – like all of us. In fact, books could be (and have been) written on this subject. So just the most important things in a nutshell – if there are any questions left, feel free to write them in the comments.
Our journey into the world of folate begins with taxonomy and why it matters. Folic acid does not equal folate. Rather, folic acid equals bullshit and must be consistently avoided, as we will learn later. On we go with our tour, against the backdrop of this controversial statement!
A little Taxonomy: The Importance of Folate vs. Folic Acid
The Three Folate Forms
Folate is also known as vitamin B9. As a vitamin, folate is essential, which means that you cannot make it yourself and it performs tasks in the body that only it can do. Therefore, deficiencies can occur – and although clinical deficiencies are rare, subclinical levels are the rule.
Our body mainly uses three different forms of folate:
- Folic Acid
- Folinic Acid
- L-Methylenetetrahydrofolate (aka 5-MTHF or Methylfolate)
Apart from these, there are other isomers, i.e. forms that look chemically the same, but those are less important for us.
Folate Form Nr. 1: Folic Acid
Folic acid is probably the best-known form. You can see it in the picture below as ‘Folic Acid‘ at the very beginning. Many even think that Vitamin B9 = Folic Acid (including countless professionals in the medical & nutrition world). However, this is wrong. Yes, absolute statement – it is completely wrong.
It is exciting to note that folic acid does not occur anywhere in nature, it is purely synthetic. Thus it has only been found on our planet since the 20th century. To be used, folic acid must first be converted into its active form in the body, which is 5-MTHF. In the process, folic acid is first converted into folinic acid by an enzyme called dihydrofolate reductase1Here’s more for all you nerds on DHFR on Genecards
Folate Form Nr.2 : Folinic Acid
Folinic acid is often seen as just the intermediate step from the useless, synthetic folic acid to the natural, active methylfolate.2I will use MTHF or methylfolate for methylenetetrahydrofolate for simplicity, even though the correct name would be 5-MTHF. There are other forms like 5,10-MTHF or 10-MTHF that exist, but for us that would just add too much confusion here. You can see it in the picture, at the very end, as ‘5-formyl-THF’. Yet folinic acid is also an active form of folate in the body and occurs naturally. Also, there is a task that only folinic acid can do – it acts as a substrate for the:
- Synthesis of the two DNA purine bases: adenine & guanine
This does not work without folinic acid. The next step of synthesis is MTHF from folinic acid.
A very well-known enzyme called methylenetetrahydrofolate reductase (MTHFR) is the gatekeeper of this process.3Gatekeeper because there are certain gene variations (SNIPs) that can slow down MTHFR strongly. Also, all other enzymes of the methylation process like DHFR, MTR/MTRR, or BHMT can be slowed down in their function by certain SNIPs.
Folate Form Nr 3: L-5-Methylentetrahydrofolate aka Methylfolate
Methylfolate is the active main form of folate. It serves as the starting material of the entire methylation – if one can speak of a beginning in a circle. Methylation is the overarching term for three cycles:
- The folate cycle is purely for the production of methylfolate, the upper picture shows the whole cycle
- The methionine cycle has the goal to produce SAMe, the main methyl donor of the body.
- The transsulfuration pathway is virtually the recycling pathway to get rid of excess homocysteine
As you are probably already thinking, this is highly complicated biochemistry with many interactions. You certainly don’t need to memorize it. The point is that methyl folate is the active folate form – it is strictly required for methylation to function.
Folic Acid is the Wrong Name, Folate the Correct One
So as you note – folic acid is wrong. And reductionistic. Taxonomy is very important here!
By ‘folate‘ we mean the totality of the active forms – i.e. methyl folate, folic acid & folinic acid plus a few of their alternative forms that appear in the picture above. Unfortunately all lab testing confuses this taxonomy, too, unless you specifically order them.
So the correct name for vitamin B9 = folate.
What are the Functions of Folate in the Human Body?
Folate acts as a Donor of Methyl Groups
Folate in the body is one of the main methyl donors. Your body swaps these dietary methyl groups over to other molecules. Along with vitamin B12 & choline/betaine, it is the main dietary input of methyl groups.
Its donor property is needed in exactly one place in the methionine cycle, namely to make methionine again from homocysteine4Methionine can also be called methylhomocysteine in other words.
That’s all it does, but this one reaction can only be fulfilled by methylfolate, the true 5-MTHF. Not by folic acid. There is no substitute and this reaction is mandatory for the methylation processes to occur. What that means let’s look at next.
The Role of Methylation for Optimal Health
Methylation is simply the process of moving a methyl group from A to B using an enzyme. For more on methylation, you can read this post about it. The enzymes that do this are called methyltransferases because they transfer methyl groups. This group of enzymes affects about 250(!) reactions in your body and is fundamental for:
- The production of the neurotransmitters serotonin, melatonin, norepinephrine & epinephrine from the basic building block tetrahydrobioptrine (BH4).
- The degradation of neurotransmitters after their use
- Gene regulation, as methylation turns genes on and off.
- Phase II detoxification, since methylation is used to inactivate many substances.5For example, dopamine is methylated to hydroxyindoleacetic acid (HIAA) to render it inactive and excreted in the urine. This is what happens to MANY other substances.
- Histamine Degredation6Extracellular diaminooxidase (DAO) & intracellular histamine N-methyltransferase (HNMT) are methyl dependent.
- Purine bases cannot be synthesized without folinic acid. Purine bases also known as adenine & guanine make up half of your DNA. No purines? No Bueno.
- Many DNA repair enzymes function by methylation.
- Effective energy production (creatine, carnitine, ATP, CoQ10).
- A basic substance of cell membranes (phosphatidylcholine)
Why Folic Acid is harmful & you need to avoid it
Dihydrofolate reductase is damn slow
We have actually already met this enzyme – it turns folic acid into folinic acid in two steps. The problem with DHFR is that it works at different speeds depending on the starting material:
- The first step: The conversion of folic acid to DHF is slow
- The second step: The natural conversion of DHF to THF is fast
Therefore, the increased conversion of folic acid to DHF takes up resources that are needed elsewhere. Also, the substances inhibit each other. This leads to large amounts of folic acid known to end up in the blood unmetabolized (UMFAs). This is an unnatural condition that causes some problems and should not exist. These rising levels were also the reason Ireland immediately ended its folic acid program for elders.7Unmetabolized folic acid prevalence is widespread in the older Irish population despite the lack of a mandatory fortification program
Folic Acid reduces the Capacity of Folate-binding Proteins
Folinic acid & 5-MTHF do not bind as well to folate-binding proteins as folic acid.8Folate-binding proteins These proteins are present in high levels in blood serum and breast milk (frighteningly so!). Their job is to folate around – from cell to cell or mother to child. The unanswered big questions are:
- What if the increased binding of folic acid to folates, leads to rapidly increasing birth diseases that are consistent with methylation problems: like neural disorders & mental disabilities from Down to ADHD to autism, metabolic disorders, growth disorders, hormone problems, mental problems
- Could they occur because the child had too little folate because the suppliers were stuffed with folic acid?
The same applies, of course, to problems related to all the numerous effects of methylation in adults! Just a few questions on the side…
Folic Acid blocks Folate Receptors
There is also the problem that folic acid binds more strongly to receptors and blocks them just like the transport proteins.9https://www.drbenlynch.com/folic-acid-side-effects/
This leads to exactly the same effects as above, even intensifies the drama. The effect is that the true folates (folinic acid & methylfolate) have it tougher to attach to the places where they are needed.10Folic acid supplementation does not reduce intracellular homocysteine, and may disturb intracellular one-carbon metabolism
How much Methylfolate do I need? + Best Sources for Folate
Avoid a Folate Deficiency – your daily Requirements
The official Recommendation & the Issue
According to the DGE-recommendation, it should be 300mcg of folate per day for an adult, or 600mcg of synthetic folic acid.11https://www.dge.de/wissenschaft/referenzwerte/folat/?L=0
Unfortunately, it’s not quite that easy. First of all, the recommendation for folic acid is complete garbage. Second, the exact requirement is highly individual and depends on:
- Gene variants, called SNIPs, in the corresponding enzymes such as MTHFR, BHMT & Co.
As you can see, it is not that easy. MTHFR SNIPs in particular strongly influence the requirements. On the other hand, a well-functioning ‘short route’ can lower the demand drastically. The short route is the alternative recycling pathway from homocysteine to methionine, not via folate, but choline. The prerequisite for this, however, is a very good supply of glycine, choline, serine, and betaine – the first two are zoonutrients that you solely find in animal foods.
My Recommendation to hit your Folate Requirements
My recommendation is therefore to determine the exact amount by subjective feeling.
First of all, you should use a nutrient calculator to determine how much folate you consume on average per day. This is very easy to do online. The following values all refer to dietary folate:
- I would aim for at least 200mcg of dietary folate per day, better more.
- Most of the time the 300-400mcg recommendation is quite good, as long as you don’t have bad MTHFR SNIPs.12For example C677T as homozygote or A1298C.
But it does not stop there. Try supplementing on a trial basis – with ~400mcg of methylfolate*. Test wheather it offers you positive effects. If it does, you probably need more dietary folates and/or cofactors:
- You need to eat enough collagen-containing connective tissue for glycine and enough choline (500mg+) for the short route to function well.
- Equally necessary is to eat plenty of riboflavin (3-5mg/day) to lower the demand for folate.
- You can use supplemented methylfolate on days when you need it – say stressful, thinking-intensive, or physically demanding days.
On a nose-to-tail animal diet you get plenty of riboflavin, choline, B12 and glycine. Folate is rarer in animals, suggesting that modern guideline levels are probably overstated.
My hypothesis is that many are deficient in the previous 4 substances and burn through more of their folate. We’ll look closely at the best sources of folate & the other 4 later.
Diertary folates are always superior. Also, supplementation with 5-MTHF can have strong effects as it is a powerful supplement and ramps up your overall methylation processes – thus also bringing up many neurotransmitter levels. If in doubt, feel free to write me.
Blood Testing to gauge your Folate Status
Almost all laboratory tests measure total folate in blood serum. This includes all folate forms and lumps them together. Total bullshit. For a decent assessment you need:
- The individual folate forms listed according to quantities
- Amounts of SAMe & SAH (to determine end products)
- Unmetabolized folic acid (if you consume folic acid)
- Homocysteine levels (to look at recycling)
- Levels of all other cofactors such as all B12 forms13mehtyl-, adenosly-, and hydroxocobalamin, riboflavin, and Co
- Markers of oxidative stress such as nitrotyrosine (NOS) & glutathione levels
- and finally the total folate
That is a lot more than is tested by centralized medicine. With these values you can determine exactly how your methylation works and where it lacks. You can also see whether you are full of the harmful folic acid and how the other two forms are doing.
Fortunately, you can now get all of this tested well online. Of course, these tests are better done with a professional for evaluation. Feel free to write me with any questions.
The best Dietary Sources for Folate
Dietary folates need to be the main source. It occurs here almost exclusively as methyl folate.
Below are the best sources. It is important to note that folate is heat sensitive and you will have a 10-30% loss with frying & cooking.14Effect of Different Cooking Methods on Folate Content in Chicken Liver & Folate losses in beef liver due to cooking and freezing methods
Offal: Liver & Kidney
Liver & kidney are the two richest sources of folate in the food world:
- Goose liver is all in front with 730 mcg per 100g.
- Beef liver contains 230mcg per 100g.
- Beef kidneys come with 210mcg per 100g.
Besides these, offal is of course the best source of many other nutrients – especially important for methylation are B12, B6, zinc & choline. Otherwise meat contains no folate, also few other organs contain folate in these amounts. This is also one of my main problems with the ‘Only Meat’ carnivores.
Egg Yolks
For those who can tolerate eggs – I’m not one of them – raw egg yolks from well-raised chickens are a great choice to get enough folate, along with many other nutrients like omega-3 fats, choline, and cholesterol.
One single egg yolk contains around 40-80mcg of folate and 140mg of choline, depending on how they were raised & fed. That means as little as 5 raw egg yolks can contribute significantly to your folate levels and choline.15Folate Content and Yolk Color of Hen Eggs from Different Farming Systems + Natural Choline from Egg Yolk Phospholipids Is More Efficiently Absorbed Compared with Choline Bitartrate; Outcomes of A Randomized Trial in Healthy Adults
Leafy Greens
Leafy greens also contain many dietary folates:
- Spinach with 140mcg per 100g
- Kale with 170mcg per 100g
- fruits also contain folate, especially berries & melons with 30-60mcg per 100g
- legumes like chickpeas with 300mcg per 100g or lentils with 140mcg
First of all, these values look good and tempting. And even though many of these plants contain a lot of folate, they also protect it well. Leafy greens & legumes are full of anti-nutrients like oxalates or enzymatic inhibitors. Also, legumes contain lectins that actively attack the gut, phytates that prevent your nutrient absorption, and even phytoestrogens that act like estrogen. And these are just a select few! Also, the question is how much of it can really be absorbed bioavailable despite all the defenses.
Against this background of defenses and bioavailability, vegetables are not a good source of folate. Only fruits can play a complementary role and be a tasty alternative, which is very poor in antibodies.
The Role of Methylfolate Supplements to optimize your Methylation
Finally, we clarify the question of what role supplements containing methylfolate aka 5-MTHF* should play.
They serve clearly as an add-on – for demanding days or when you feel drained. These could be days like:
- You’re giving a lecture and you need to work highly-focused for hours at a time
- You train a lot or have a sports event coming up
- Currently, a lot is demanded of you: your infant and the work are draining you.
Taking Supplements as needed
Whenever many neurotransmitters are consumed or you are stressed you need more methylfolate, then supplementation AS NEEDED can help you. Also a good(!) multivitamin that contains the right forms of cofactors can do good here. This should also be taken AS NEEDED:
- If you are feeling generally bad or run down take a dose of the multivitamin.
- If the day ahead is very stressful and demanding, take a dose of 400mcg of 5-MTHF. If more will make you feel better after sufficient testing, take more.
You should never swallow pills every day for all eternity. This is important because too much can send you to the other end of the bell curve and feel just as miserable.
I hope this descent into the world of folate could help you understand the whole topic. The Internet upsets me with its false fixation on folic acid, I hope you see that now too! Because you now know better than all those big magazines that make reckless recommendations for folic acid supplements or huge amounts of unnecessary vegetables.
Until the next time,
Fußnoten & Quellen
- 1Here’s more for all you nerds on DHFR on Genecards
- 2I will use MTHF or methylfolate for methylenetetrahydrofolate for simplicity, even though the correct name would be 5-MTHF. There are other forms like 5,10-MTHF or 10-MTHF that exist, but for us that would just add too much confusion here.
- 3Gatekeeper because there are certain gene variations (SNIPs) that can slow down MTHFR strongly. Also, all other enzymes of the methylation process like DHFR, MTR/MTRR, or BHMT can be slowed down in their function by certain SNIPs.
- 4Methionine can also be called methylhomocysteine in other words
- 5For example, dopamine is methylated to hydroxyindoleacetic acid (HIAA) to render it inactive and excreted in the urine. This is what happens to MANY other substances.
- 6Extracellular diaminooxidase (DAO) & intracellular histamine N-methyltransferase (HNMT) are methyl dependent.
- 7
- 8
- 9
- 10
- 11
- 12For example C677T as homozygote or A1298C
- 13mehtyl-, adenosly-, and hydroxocobalamin
- 14
- 15
