The other day someone made a comment on the Dr. Schulze article:

 i was wondering the label say folic acid that is a synthetic B9, real food B( reads folate whats up with that

Grammar notwithstanding, this was an insightful remark.  I replied:

Good point. Folic acid is found in a lab, and supplementary folate in its true form doesn’t exist because it’s too unstable.

And I got this response:

i dont understand your comment on folate, folate is natural how can you say it doesnt exist or is unstable that doesnt make sense to me, folic acid is a petrochemical that i understand, folate is present in foods im confused

Okay people, let’s settle this once and for all.

Folate, Folic Acid, Methyl Folate: Differences

Folic acid is the most commonly used form of supplementary folate.  It’s very stable and is not found in nature.

5-Methyltetrahydrofolate, or 5-MTHF, is the circulating form of folate found in your body.  Your liver takes folic acid and turns it into 5-MTHF.  You can buy supplementary 5-MTHF as either quatrefolic acid or Metafolin.  It’s also made in a lab.

The form of folate found in food is called 7,8-dihydro folate.  It’s the halfway-child between 5-MTHF and folic acid.  It doesn’t exist in supplementary form.

Folate is a generic term which usually refers to any folate-like molecule that’s at least partially reduced. Ie, the non-folic acid kinds.

The Difference, In Pictures

Here’s a picture that explains the most important difference between folate and folic acid:

 

This is the pteridine moiety of folate.  Do you see those two extra sticks on the folic acid version?  That means it’s fully oxidized, which means its stable.

Its stability is what makes it easy to produce.  Folic acid costs about $50/kg to manufacture.  If you want to make the real thing the price goes up to about $15,000.

Making unstable molecules is expensive.

Important Stuff

In addition to being easy to manufacture it’s believed folic acid is absorbed better than dietary folate because its more stable and only has one glutamate molecule on its side chain.  [footnote]Dietary folates have about 4-10 glutamate molecules in their side chain.[/footnote]

Despite not being found in nature your body can still metabolize folic acid because the enzyme that acts on dietary folate also recognizes folic acid.

You need 400 mcg/day of folic acid and your body can tolerate up to 5-10 g at a time without experiencing adverse side effects.  It’s very safe.  It’s also good at preventing folate defects.

However folic acid also proposes problems.

Why?

It was originally believed that folic acid was metabolized in your gut.  But it actually happens in your liver.  Liver DHFR (the folic acid enzyme) varies 5x in its activity from person-to-person.

Even better, liver DHFR varies 1300x in its specificity for folic acid.  So while some of us are gorging on the folic acid fire hose, others are still searching for water in the desert…….even on the same diet.

Saturated DHFR down regulates the activity of MTHFR, the rate-limiting enzyme in folate synthesis.  People who don’t metabolize folic acid often have a pseudo-folate deficiency because their MTHFR enzyme gets shut off.  These people ought to be taking 5-MTHF, not folic acid.

Unmetabolized folic acid competes with other folate molecules for folate receptors and might crowd out the real folate your body gets.

For most people this doesn’t mean much, however the abundance of folic acid in the food supply has left way more of it coursing through our veins than was originally intended and there are no long-term trials on the health consequences of having lots of unmetabolized folic acid in your body.

It’s an unsettled question how much of a health issue this is.

Further Reading:

Here’s a good website on the MTHFR gene and its implications for human health.

Here’s a (scary) graph from Sigma Aldrich on all the different variations folate takes on in your body.

My favorite mommy-bloggers take on folate vs folic acid.

Have a nice day!