- [Jeff] Welcome to "Healthy Minds."

I'm Dr. Jeff Borenstein.

Everyone is touched by psychiatric conditions, either themselves or a loved one.

Do not suffer in silence.

With help, there is hope.

(uplifting instrument plays) Today on "Healthy Minds."

- The risk of mental illness in a child is about one in 10.

The risk of spina bifida is about one in a thousand, and yet every woman takes folic acid to avoid that one in a thousand risk.

We ought to think about every woman taking choline to avoid that mental illness risk, which is one in 10, not one in a thousand.

If we could make sure that the baby built a better brain before it was born, perhaps we could prevent it from ever becoming mentally ill. - [Jeff] That's today on "Healthy Minds."

This program is brought to you in part by the American Psychiatric Association Foundation and the John & Polly Sparks Foundation.

(calm instrument plays) Welcome to "Healthy Minds."

I'm Dr. Jeff Borenstein.

What if there was a natural safe supplement that a woman can take during pregnancy to increase the likelihood of their child developing in a healthy way and decrease the risk of that child, ultimately, as they get older, developing a psychiatric condition?

Today I speak with leading researcher, Dr. Robert Friedman, about such a supplement, choline.

(uplifting instrument plays) Bob, thank you for joining us today.

- Jeff, it's my pleasure to be here.

Thank you.

- I wanna jump right in and ask you to tell us about choline.

What does it do and why is it so important?

- Choline is a natural substance.

It's found in foods.

Your body can make a little bit of it, but if you're pregnant, probably not all you need to build your baby, because choline has a number of roles in baby building.

It helps build every cell in the baby.

It also helps the baby manage the way it uses its genes, its DNA.

And finally, it's a very important molecule for timing the assembly of the brain and the baby has to figure out how to build an entire human brain in just nine months, and choline is critical for that.

- So obviously, we almost take it for granted, but what an amazing accomplishment it is for in just nine months to develop such a complex organ.

What should people do in terms of making sure that they have enough choline?

- Choline is present in food, but most women, we know from dietary surveys, can't quite eat enough to supply the optimal amount to make sure that everything goes as well as possible for the baby.

So just like folic acid, which is also present in food, and women take a supplement to make sure they have enough, we recommend that women take a supplement of choline when they are pregnant to make sure that they have enough for the baby.

- And tell us a little bit about what the research is that's helped determine that this is such an important thing to do.

- Like many researchers, we were interested in finding genes that were important in mental illness because we wanted to direct treatment to those genes.

That's the strategy, for example, that cancer has used.

Cancer researchers find genes that cause cancer, then they can design medications that work to counteract the effect of those genes.

Many of us in this field thought we could do the same thing for mental illness.

And in the process, we did discover one such gene called CHRNA7, and what's important about it is that it's involved in actually a range of mental illnesses, schizophrenia, bipolar disorder, attention deficit disorder, and some cases of autism spectrum disorder.

And we began to design medications to try to combat the effect of this gene when suddenly, I had a realization that we were actually trying to do something that didn't make sense because we knew that the genes were much more active in building the baby's brain than they were in operating the brain after someone had already been born.

And so if we were trying to treat mental illness when it appeared, we were actually trying to treat something that had happened long ago while the baby was building its brain.

If you think about it, it's like there are cracks in the way the baby builds its brain because of genes that eventually will be associated with mental illness.

If we could make sure that the baby built a better brain before it was born, perhaps we could prevent it from ever becoming mentally ill. And the way to do that was to attack the gene whose deficit we'd found before the baby was born.

In order to do that, we had to figure out how that gene is normally activated.

And in the process, we discovered that it was actually choline that was doing it.

Whenever you make a great insight into science, of course, you immediately find someone did it before you, and other researchers had already shown that many women are deficient in choline during pregnancy.

So if more choline would help them build a baby's brain, and if many women were deficient, it seemed to us obvious the thing to do would be to supplement choline and try to make sure that every mother had an adequate level to do everything that choline needed to do for her baby.

- What dose should people be taking in terms of having that adequate amount of choline?

- There've actually been five clinical trials of choline supplementation.

So by a clinical trial, I mean, some women get choline, and some women just get the choline that's in their diet.

So some get a supplement, some get a placebo.

And what all the trials have converged on is that a thousand milligram supplement per day in addition to whatever the mother gets in her diet, seems to be the optimal amount.

That's about less than one third of what the FDA considers the safe amount of choline.

So it's well within a safety range.

- Are there any side effects or risks associated with taking choline at this level?

- There are no risks that we know of for pregnant women.

There are some side effects that can occur.

One of them is a smelly odor because some of the choline will sometimes get into the large intestine where the microbiome, the bacteria that live in our large intestine can sometimes metabolize choline.

Women can avoid that side effect in a couple of ways.

One, to make sure that when they take their choline supplement, they take it with a glass of water and they divide it into several doses a day.

The other is to use another form of choline called phosphatidylcholine, which is actually the form normally found in food.

The capsules are a bit bigger and they're more expensive, but the women will avoid side effects that way.

Most women can take either form and do perfectly well, and the babies do perfectly well.

- In the research that you've conducted, you followed these babies over time, and I'd like you to share with us what your findings are.

- So ideally, if I could live long enough, we would treat mothers with choline, we'd wait nine months for a baby, and then we'd wait about 25, 30 years and see how the kids did.

But that would mean I'd have to live till about 110, 120, and that's not likely.

So we do have a lot of young people involved in the research and maybe they'll be around that long.

But in practice, what we do is try to assess the child's developmental path a bit earlier.

And so what we target is four-year-olds.

So we're still with our mothers for almost five years, and they've been very good at staying with us.

And we look to see what happened at four years of age.

And what we discovered in the words of the child psychiatrist who works with us is we've got really great kids.

These kids can pay attention, they can focus, they can maintain their work at a task like learning.

And they're also sociable.

They're easily mixing with other children, they're bonding with their parents.

They're doing everything that a four-year-old ought to do.

And if we test them on formal tests of intelligence, they're particularly good at tasks which require them to maintain attention.

So that's what a 4-year-old looks like whose mother has had an optimal dose of choline.

Babies who are gonna go on and have mental illnesses usually don't look like that.

They have difficulty paying attention.

Their minds tend to wander.

They're also socially withdrawn.

They have difficulty making friends with other children.

And so while we don't know who will get mental illness and who will not, for sure, we know that the kids who've gotten optimal doses of choline are on the kinds of pathways that end up with a mentally healthy adult.

And the kids who do not have optimal doses of choline are on a pathway that's much more likely to lead to mental illness or just other difficulties in life.

Kids who are socially withdrawn and can't pay attention, even if they never get a mental illness, will have problems all their lives.

- So really, the potential benefit here is twofold.

One is down the road as the child becomes a teenager, late teen, early twenties, young adulthood, reducing the risk of potentially developing schizophrenia or other psychiatric conditions, but more immediately, showing stronger results in some of the abilities and tasks that we wanna see a 4-year-old perform, and obviously, you'll follow that over time as they get older as well.

- Right.

So no parent or very few parents have children because they're afraid the child will be mentally ill. No one expects a child to be mentally ill, but everyone wants a kid who's bright and happy and can play with other kids.

And that's what we can promise someone who takes a choline supplement.

There's one other aspect of what choline does that's important, and that is we're not only treating the baby, we're also treating the placenta.

And the placenta has a couple of roles that are very important for the baby.

Obviously, the placenta is important in nourishment, and so babies in their last trimester tend to gain weight very quickly, almost a pound a week.

That weight gain in some women does not occur because their placenta becomes inflamed.

If that happens, choline is very effective at combating that inflammation and allowing the baby to continue to grow.

So when we give choline to mothers, we also get babies that are much more likely to be normal birth weight.

The second thing that choline does is that it helps develop some systems in the placenta, which are important for timing labor.

And if choline levels are extremely low as occurs in some very highly stressed women, there isn't enough choline to help the placenta develop those systems, and those babies are born early.

And a baby who is born before full gestation, before the full 40 weeks of pregnancy or 39 weeks, those babies who were born before 39 to 40 weeks will have more problems learning to read when they hit first grade, they'll have more problems with behavior.

If we can keep them in the womb until at least 39 to 40 weeks, they're going to do a lot better, and choline helps with that.

So if we think about who's actually going to recommend choline, which is obstetricians, that's what they really want.

They want a healthy baby, normal birth weight, delivered on time.

And so we're working very much to make sure that obstetricians understand that that's a real benefit of choline that everyone can see immediately.

- I wanna ask you about another potential benefit, which is if an individual experiences an infection, for instance, COVID during pregnancy, the potential that choline is also, in addition, protective of the fetus during that time as well.

- So again, we think about the placenta because the placenta is the key connection between the mother and the baby.

So when you get an infection, usually about four o'clock in the afternoon, if it's the flu or COVID, or just really a bad respiratory infection, you get that feeling that if I don't get home pretty quick and get into bed, I'm really gonna be hurting.

I think everyone knows that kind of sick feeling.

That means something bad's gonna happen.

And so what that actually means is that a virus or a bacteria has already entered your bloodstream and it is already signaling your body that there's something foreign inside.

And your body has an immediate emergency response, which is to try to get rid of everything foreign by releasing a whole bunch of chemicals called cytokines, and cytokines seek anything that's foreign, tag it as foreign, and then your white blood cells come along and try to scavenge it up.

Later on, of course, you'll make antibodies, and those are very specific.

But early in an infection, you're in the panic mode.

And that's what you feel when you feel that dreaded feeling.

Unfortunately, the placenta belongs to the baby, not the mother.

And so it's also foreign tissue.

So these cytokines begin to tag placental cells and then white blood cells move in to try to attack.

Some of them are actually generated by the baby, so the baby is actually attacking its own placenta.

All of that means the placenta can't do its main job, which is to nourish the baby and give the baby oxygen.

And so the baby is temporarily, during this emergency phase while the mother's trying to save herself, the baby is depriving itself of what it needs to build its brain, and unfortunately, the baby can't go back in time.

If it misses a stage in brain development, it's gone forever.

Forever.

I mean, for its lifetime.

Choline is very effective at combating this inflammation for the baby.

And so it allows the placenta to keep functioning and it allows the baby to keep building its brain, while the mother attends to trying to fight off her infection.

The infection will never reach the baby except for very rare viruses like Zika.

But it will damage the baby by damaging the placenta.

- When should a pregnant woman start taking the choline?

What's the timeframe?

How does it work in terms of the nuts and bolts?

- Women can begin choline at any time.

They can certainly begin at preconception.

Most of the research studies begin it at the beginning of the second trimester, and that's really the most critical time because normally, when a woman gets pregnant, her choline levels will be pretty good at conception and they'll stay good in the first trimester.

But in the second trimester, they begin to fall naturally as the baby's demands go way up.

And her morning sickness also has kicked in, which means that she's maybe eating less.

So second trimester is really the most critical time, and then third trimester to make sure the baby grows.

So second and third trimesters for sure, and if she can, preconception and during the first trimester would be great as well.

But as soon as she realizes she's pregnant, if she hasn't been on choline, that's the time to start.

- Obviously, in consultation with the OB-GYN doctor.

- Right.

We always ask women to check with their OB-GYNs, but the association of obstetrics and gynecology, the American College of Obstetrics and Gynecology, is very cooperative with women supplementing their choline.

- Is there any benefit or need for it to continue after the baby is born?

- After the baby's born, the woman can certainly continue her choline if she wants.

Breast milk is normally extremely high in choline.

It will be even 10% higher maybe if she takes extra choline.

But the baby's need for a lot of choline is pretty much past.

It's not as important post-birth as it is pre-birth because a lot of that brain development has already occurred that requires choline.

She certainly can take it.

It's really not necessary.

If she decides not to breastfeed and to use formula instead, although the FDA doesn't mandate choline supplementation before birth, it requires choline supplementation in all formulas.

So any formula she buys is going to be choline supplemented.

We still recommend breast milk because breast milk contains phosphatidylcholine, which is the form that's more easily absorbed by the baby, whereas formula is just choline.

But either way, her baby's gonna do just fine.

- One of the potential benefits of choline supplementation during pregnancy is for people who are at higher risk of a child developing schizophrenia or other psychiatric illnesses, for instance, those who have the illness or a family history of it.

Could you speak about the benefits of the use of choline in that population versus the general population?

- There are many people who ask us the question in a slightly different way, which is, if you're trying to prevent mental illness, shouldn't you only target women who have mental illness for choline?

One of the things we learned and other researchers have learned worldwide is that the genetics of schizophrenia, bipolar disorder, attention deficit disorder, and autism are complicated.

And they involve many genes, some of which will likely come from the father and some of which will likely come from the mother.

And then they will combine sometimes in an unfortunate combination in the baby who's destined to become mentally ill. That genetics is so complicated, we can't predict it.

And having a mother who has a mental illness usually increases the risk of mental illness in the baby only slightly compared to the general population, about tenfold, but still not inevitability.

And so if we wanna prevent mental illness in everyone, we really have to target the entire population.

The risk of mental illness in a child is about one in 10.

The risk of spina bifida is about one in a thousand, and yet every woman takes folic acid to avoid that one in a thousand risk.

We ought to think about every woman taking choline to avoid that mental illness risk, which is one in 10, not one in a thousand.

Now what if the woman actually has a mental illness?

That would be the most severe test of whether choline would be effective or not.

We have given choline to women who have schizophrenia, and we can then look at the baby.

We use a brainwave test to see if that baby has some of the brainwave abnormalities that we associate with later schizophrenia, and we can decrease those significantly in those babies as well.

So if a mother already has choline illness, the chances already has a mental illness, the chances that choline will be effective in her are also very good.

- Sometimes something that sounds too good to be true is too good to be true, because this just sounds like such an important intervention that can make such a big difference.

How are people responding to this information as you've been sharing it with professionals, with families, et cetera?

- I think the response has been pretty good.

We try not to say that it's too good to be true.

I think it probably will be about 80% effective based on the statistics we have so far.

It's not a hundred percent effective.

There are some conditions in which it's not helpful, it's not harmful.

But for example, if the woman uses a lot of alcohol or a lot of street drugs, it's going to be difficult to say that choline is going to prevent her baby from having mental illness.

Another big problem during a pregnancy in America is maternal obesity and the effects of maternal obesity aren't attacked by choline.

And so there are lots of conditions that mothers can have that choline is not going to be effective for.

All we can do is hope that it's gonna be effective for some, and also, of course, we've only looked at four-year-olds and what will happen to these four-year-olds as they grow, we think we can predict, but we can't be entirely sure.

- Bob, I wanna thank you for joining us today and more importantly for this work that potentially will have an extraordinary impact for so many people.

And I'm just gonna share with you, I have two grandchildren and both of their mothers, two of my daughters did, at the suggestion of the OB-GYN physician, have choline supplementation.

So my thank you is a personal thank you as well.

- The most exciting part of this work for us is to see really great kids come to our laboratory and to hear stories like yours, Jeffrey.

So congratulations, grandfather.

- Thank you very much.

(calm uplifting music) Every parent wants to have a healthy child.

If you're thinking of becoming pregnant or are pregnant, now is the time to discuss with your OB-GYN, the potential use of choline supplementation.

Remember, with help, there is hope.

(calm uplifting music) Do not suffer in silence.

With help, there is hope.

(calm uplifting music) This program is brought to you in part by the American Psychiatric Association Foundation and the John & Polly Sparks Foundation.

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