Tiana asks, "What makes folate and folic acid act differently in the body?"
Look, they don't really.
Everything that is said bad about folic acid is sort of true to an extent but has been
completely exaggerated in some circles.
What happens is you have an enzyme called dihydrofolate reductase, or DHFR.
Its purpose is not to metabolize synthetic folic acid obviously because that folic acid
molecule doesn't exist in the food supply.
Its normal purpose is that every time that you use folate to participate in processes
outside of methylation, such as DNA synthesis, you wind up producing dihydrofolate as a byproduct.
DHFR recycles that and turns it into tetrahydrofolate, or THF.
Tetrahydrofolate is what has the methyl group added to make methylfolate.
If you look at the chemical structure of folic acid, and dihydrofolate, and tetrahydrofolate,
the only difference is that there are four spots that can have hydrogens added to them.
If you listen to the sound of tetrahydrofolate, that's tetra, four; hydro, hydrogen; folate,
folate.
Tetrahydrofolate has four hydrogens there.
Dihydrofolate has two hydrogens there.
Folic acid doesn't have any.
The enzyme DHFR is doing exactly the same thing to folic acid that it does to dihydrofolate.
It adds two hydrogens.
Now you have dihydrofolate.
Just as if you had put the folate through a non-methylation process like DNA synthesis.
Once you do that one time ever to a molecule of folate, now it looks exactly like the molecule
of dihydrofolate that came out of the DNA synthesis as a byproduct, and
it never, never, never again becomes folic acid.
From the point that dihydrofolate reductase does that one time to the synthetic folic
acid molecule, which is exactly what it's doing to the normal dihydrofolate that comes
out of DNA synthesis.
When it does that one time, that folic acid molecule is never again ever different from
any of the folate that came in food or any of the folate that was circulating in your
body naturally.
That enzyme just has to work twice on that folic acid molecule.
Does that mean that you're doubling the enzymatic requirement because you got to do it twice?
The first time yes, but no, because these molecules are recycled thousands of times
per day.
Let's say you take a methylfolate supplement or you get methylfolate from your vegetables
or from your liver, from your legumes.
What happens is that methyl group on the methylfolate gets used once, and then that folate molecule
stays in yourselves for 200 days and 18,000 times a day gets the methyl group added again.
You're talking about the molecule that comes into your body in that instance.
It has to get metabolized twice.
But when you're talking about getting metabolized another 18,000 times in that day, then that
two times you had to do it when it came in, the math isn't that different.
Does that mean it doesn't matter that it's synthetic folic acid versus natural food folate?
No, not that it doesn't matter.
There are a couple issues.
Number one, we know that before they started adding folic acid to enriched white flour,
that the only people who had synthetic folic acid circulating in their blood were people
who took folic acid supplements.
Now that they fortify enriched white flour with synthetic folic acid, which they do to
prevent neural tube defects which it does do, now that they do that, almost everyone
in America has synthetic folic acid circulating in their blood.
Why?
Well, the reason right after you consume a couple pieces of white bread, the reason right
after you consume that that you have synthetic folic acid in your blood is because you tried
to turn it into normal food folate, but you exceeded DHFR enzyme capacity temporarily.
Now, what would happen if you never eat white bread again?
Probably the next day, you wouldn't see any synthetic folic acid in your blood because
the enzyme would have time to process it.
But what happens is no one eats white bread once, they keep eating it.
When you measure someone's blood who eats white bread every day, because they probably
ate some white bread that morning or the day before and the day before and the day before
and the day before and the day before, there's always a little bit that's not getting metabolized
in that moment, but it eventually gets metabolized.
The question is, does that synthetic folic acid, we call that unmetabolized folic acid,
does that cause harm?
There are scientific hypotheses that it might, and it might, but there's no conclusive evidence
of that.
That's one side of the argument against synthetic folic acid.
The other side of the argument is now that you are giving the DHFR enzyme more work,
that means that might be detracting from the work that it has in recycling dihydrofolate
that came out of the DNA synthesis reactions to make tetrahydrofolate.
You could say if you're putting extra work on it to the point where you have unmetabolized
folic acid appear in the blood temporarily, is that detracting from the work it needs
to do to recycle the folate that came out of DNA synthesis and allow you to do it again
or allow you to put that folate into the methylation cycle?
It might be.
That's a reasonable hypothesis.
It would be great to have some well-designed studies to test that.
There's another point that Ben Lynch makes, which is that folic acid blocks methylfolate
from getting into cells.
I'm going to have to look more closely at those studies.
But I would be extremely surprised if when I get done looking at those studies, I do
not conclude that folic acid didn't block methylfolate from getting in.
It just outcompeted it from getting in.
Why?
Because it more effectively gets into the cell.
And then what happens to it?
It becomes dihydrofolate, tetrahydrofolate, and then it looks the same as the methylfolate
molecule.
I doubt that argument has that much relevance.
The ones that I just said I think are the most likely to have some relevance.
What am I going to do?
Well, I'm not paranoid about folic acid, but it's not the ideal form of folate.
If food folate and methylfolate don't have these issues, why not just use the natural
folate that doesn't have these issues?
Well, there's an answer to that, which is folic acid is cheaper, folic acid is more
shelf-stable.
That's why folic acid is used in multivitamins.
If you added methylfolate to enrich white flour though, the bread is going to have less
folate in it because it's less shelf-stable, folic acid is better absorbed.
That's why if you look at a methylfolate supplement and it says 400 micrograms DFE, that's dietary
folate equivalence, that's not 400 micrograms of methylfolate.
I'm not sure.
I don't remember the conversion factor off the top of my head, but it's a lot more than
that.
Because folic acid is absorbed so much more effectively than methylfolate that you have
to add more and then use a conversion factor to bring it down to dietary folate equivalence,
which means that is an extra dose of methylfolate and is equal to if you had consumed 400 micrograms
of synthetic folic acid, which is more effectively absorbed.
The reason that it's used in the public health sphere is it’s more absorbable, more shelf-stable,
and cheaper.
Because it's more absorbable and it's more shelf-stable, that makes it even more cheap
because you don't have to add as much.
If you were using methylfolate, not only would it be more expensive, but you'd have to add
more to account for the fact that a lot of it is going to get destroyed on the shelf,
and then less of it is going to be absorbed.
If you're talking about like the cost of a public health campaign to do something really
simple to add a nutrient to junk food to make sure that you reduce the risk of neural tube
defects, then it makes sense.
But I think that who are we?
We are highly motivated people who are trying to make the best choices, and we're willing
to deal with a little bit of inconvenience or extra money to make those best choices.
If that sounds like you, then synthetic folic acid is not the best choice.
The best choice is to deal with the inconvenience and extra expense of getting folate from food,
or when you can't get the folate you need from food, to use a supplement that has folate
in food form.
But listen to what I said and compare that to the level of what I think is -- I don't
like to be accusatory, but I think it's fairly accurate to call hysteria around the idea
that folic acid is poison.
I actually think it's harmful because this comes back to what I said before, and I know
I'm kind of ranting now.
There's people out there who think that because they cut out white flour out of their diet,
that is unambiguously a good choice.
Not really.
White flour isn't a good food.
Cutting it out of your diet is a good choice in the context of properly designing the rest
of your diet.
But you have to realize that if you're eating white bread all the time, you are the beneficiary
of the elite heads of nutrition science and the government.
I know people hate the government and mainstream nutrition.
But look, you've been the beneficiary of these people spending 100 years figuring out what
are people most likely to suffer from in nutrient deficiencies and how do we do something cheap
to stop that from happening.
We add it to the junk that we know that we eat because the junk is fortified with nutrients
and they have to listen to us if we tell them to eat three servings of legumes or leafy
greens a day and that's true.
How many people eat the five to nine servings of fruits and vegetables a day that the government
recommends?
It's a pain to do that.
Most people don't do it.
I'm not saying that you should eat the white flour, but look in Guatemala.
What did they add vitamin A to to stop people from having vitamin A deficiency so bad that
they would become permanently blind?
They added vitamin A to sugar.
Why?
Because people eat sugar.
You can tell people that sugar is bad for you and you'll get fatty liver.
In the United States, you will have zero risk to telling someone that because there's nothing
added to the sugar.
But if you go to Guatemala, I don't know if they're still doing that, but let's say for
the sake of argument that they are.
If you go to Guatemala and you go around preaching to everyone to stop eating sugar because they're
going to get fatty liver disease, what's going to happen?
They're going to go blind because these people are eating sugar that is their only source
of vitamin A. I'm simplifying here a little bit.
I know that there are plenty of people in Guatemala eating good things.
But the point that I'm making is the general population that is benefiting from that campaign.
Iodized salt.
Why don't most people get goiter anymore in the United States?
It's because of iodized salt.
Why do some people get goiter now?
I talked to a cardiologist, William Davis, the wheat belly guy.
I was talking to him and he was saying, "Last ten years or so, now suddenly I see people
walking to the clinic who have goiter in their neck."
Why?
Because he's treating people in an area where the iodine is deficient in the soil and people
are being told to avoid salt.
Now, I don't want to compare salt to sugar because salt is good for you.
Salting your food to taste is good for most people most of the time.
But it's still the same thing.
The public health campaign did a cheap, simple, easy thing to get rid of goiter by adding
iodine to salt.
You come in and you say, "Salt is bad.
It raises your blood pressure."
Well, now you're playing the lottery because if you're telling people that in an iodine-deficient
soil area, they're going to get goiter.
Look, it's like white flour is bad for you.
But when you decide that I'm going to do better, I'm going to do it for myself instead of be
managed by the people running nutrition.
You got to realize that the people running nutrition in the United States are not the
dumbest people on the planet.
I don't care what you think about low carb or saturated fat.
I don't care what you disagree with them on.
They are not the dumbest people on the planet.
When you eat six pieces of white flour toast every day, you're the beneficiary of what
they decided to do to that to minimize the risk of severe clinical nutrient deficiencies.
I'm very worried that there are people who don't see that nuance, and they think that
they just cut out white flour and therefore they're better off.
No.
You cut out white flour, now you need to do more work to make sure that you are actually
getting your nutrients from whole foods because if you were eating six pieces of white toast
that you didn't have to worry about getting nutrients from whole foods and now you do.