- How does serotonin have adequate levels of serotonin? - Having adequate levels of serotonin is absolutely critical for people depressed, as well as people who are not depressed, to feel a sense of wellbeing, just overall sense of wellbeing, being okay with who they are and where life is at, being able to lean into effort and all these things.

It's absolutely critical that we have adequate levels of serotonin in the brain. Now, you may have heard, and it is absolutely true, that 90% of the serotonin manufactured in your body is in the gut. Now, what you don't often hear is that serotonin stays in the gut, right? We hear these days, oh, you know, most of your serotonin is manufactured in your gut, which has given millions of people the false impression that if you get your gut serotonin right, somehow it's traveling up to your brain and performing all the important roles that serotonin plays in your brain.

That's not how it works at all. Fortunately, however, there are ways that you can modify the levels of serotonin in your gut, and indeed the levels of serotonin in your gut powerfully impact the levels of serotonin in your brain. And this occurs, you guessed it, by way of the vagus.

It's a super cool mechanism, and it's one that you can exert some positive control over, in order to, for instance, increase your baseline levels of mood in order to increase levels of serotonin, if that's something that you seek. Here's the pathway and the mechanism, and I'm going to provide this in kind of top contour form.

In the future, I'll do an entire episode about serotonin, but here's the idea. In your gut, you have cells, including neurons, but you also have a lot of other cells, mostly other cells, frankly. And there's a particular category of cells called the enterochromafin cells. You don't need to know that name, but if you want, they're the enterochromafin cells, and they manufacture serotonin.

They do that through a beautiful pathway involving an enzymatic reaction that converts tryptophan from the food you eat, tryptophan's an amino acid, gets converted eventually into serotonin. There are a bunch of steps in there in the biochemistry, gets converted into serotonin. That serotonin binds to the ends of neurons, the axons of neurons in the vagus nerve that innervate your gut, not just your stomach, but your large intestine and your small intestine.

Remember, those sensory afferents, those sensory axons that extend into the body have receptors on them, right? The serotonin in the gut, assuming you're getting enough tryptophan, and assuming the milieu of your gut is correct, we'll talk about what that means and how you can exert control over it, get the milieu right, that serotonin binds to the ends of those axons in the gut and stimulates a particular category of them that then relays the signal up and through nodos ganglion, you now are familiar with these names, up into the brain to the nucleus tractus solitaris, okay, that NTS again, and then the nucleus tractus solitaris, doesn't just communicate with locus coeruleus and with nucleus basalis, it also sends a powerful signal to what's called the dorsal raphe nucleus.

The dorsal raphe nucleus in your brain is responsible for the release of the majority of the serotonin in your brain. So when you hear that most of the serotonin in your body is made in your gut, that's true and it stays in your gut, but the levels of serotonin are communicated to the brain by the vagus and then stimulates the release of serotonin from the dorsal raphe nucleus.

So the question therefore becomes, if we want to increase levels of serotonin in the brain or simply to maintain healthy levels of serotonin in the brain for somebody who's not depressed or maybe somebody who's having low mood, just to keep elevated levels of mood and proper levels of serotonin overall, because it's involved in lots of things, not just mood, we need to make sure that we're getting adequate production of serotonin in the gut.

And again, adequate production of serotonin in the gut has a bunch of other positive effects on the immune system, on gut motility. In fact, having adequate levels of serotonin in the gut is powerfully associated with having a healthy gut and not having irritable gut. Irritable bowel syndrome is something that vexes many people.

You know, it might sound kind of funny to those of you that don't have, oh, you have an irritable bowel. People with IBS, irritable bowel syndrome, oftentimes suffer tremendously. They can't go out to dinner. They can't eat foods that other people offer them. They'll eat a bunch of foods for a while and feel fine.

Then they feel terrible. It's not just about having diarrhea. Often they have a bunch of other gut issues and it's correlated with a bunch of other major problems over time. We're going to do an entire episode about gut health as it relates to IBS. There are things that you can do to improve IBS.

One of them is to keep your, or get your gut levels of serotonin right. How do you do that? Well, one way to do that is to make sure that the microbiota of your gut are healthy and that they are diverse. The best way to do that, not using any kind of supplementation, is to make sure that you're ingesting one to four servings of low sugar fermented foods per day.

I've talked about this before on the podcast. This is based on beautiful data from my colleague, Justin Sonnenberg, and Christopher Gardner at Stanford, showed that the ingestion of one to four servings of low sugar fermented foods per day. So these would be things like kimchi, sauerkraut, again, low sugar.

Look at the labels. This is the stuff that would need to be refrigerated. We're not talking about pickles kept on the non-refrigerated shelf and the non-refrigerated section of the grocery store, but rather the brine and the pickles that don't have a ton of sugar. So the sour pickles, that is, that are kept in the refrigerator, things like kimchi, things like kombucha.

Keep in mind, some kombucha has alcohol. So keep that in mind if you're giving this to kids who shouldn't be ingesting alcohol. Any adults probably shouldn't be ingesting alcohol. Kombucha has very little alcohol, but if you're an alcoholic and you're completely avoiding alcohol, you should know that. Kombucha contains some alcohol.

Things like kefir, quality yogurts, low sugar yogurts. You can look up online, what are different low sugar fermented foods? These things are going to improve the gut microbiota that in turn promote the production of serotonin, if and only if, this is important, if and only if there's also sufficient levels of tryptophan in your dietary intake.

So you're going to want to take a look at what you're eating and just through a simple online search, you can figure out whether or not you're getting sufficient levels of tryptophan. Many people are familiar with the idea, because it's true, that turkey contains high levels of tryptophan. This is thought to be responsible for the post Thanksgiving dinner effect, although that's probably due to just eating a lot of food.

And when the gut is distended, the distension of the gut is communicated by mechanosensors up the vagus nerve sensory neurons and set in motion the so-called rest and digest, or I guess it would be like collapse and pass out. And in the case of Thanksgiving, collapse and pass out effect of having a lot of food in your gut, doesn't matter what the food is, but you're going to want to make sure that you're ingesting foods with sufficient levels of tryptophan.

So dairy products will do that. White turkey meat will do that. There are other foods that have tryptophan in them. I'm not going to bother to list those off now. You can simply look those up. So make sure you're getting enough tryptophan in your diet. Make sure that you're getting enough low sugar fermented foods, or if you're not doing that, and perhaps even if you are, you might think about supplementing your diet with probiotic on occasion, right?

I'm not talking about constantly taking high doses of probiotics. I actually don't recommend that, but for many people who are suffering low mood, supplementing with a quality probiotic can actually improve mood. And the purported mechanism by which that happens is the increase in serotonin that is allowed by improving the gut microbiota and including foods with enough tryptophan, which is the precursor to serotonin.

So what I've done here is I've created the real conceptual link, the anatomical link, and the chemical link between the production of serotonin in the gut and serotonin in the brain. And I wouldn't be talking about this if there wasn't actually data on this, I'll include links to a few papers about the, and here I'm quoting the title of a great paper, the interaction of the vagus nerve and serotonin in the gut brain axis.

There's also been at least one clinical trial study exploring how taking probiotics, and in this case, it was actually probiotics plus magnesium. It was magnesium orotate, which is just one form of magnesium, as well as I would say a low-ish dose of coenzyme Q10. Combining those three things in this paper entitled, Probiotics and Magnesium Orotate, it should have said probiotics and Magnesium Orotate and coenzyme Q10, but the title is Probiotics and Magnesium Orotate for the Treatment of Major Depressive Disorder, a Randomized Double Blind Control Trial.

And I want to emphasize that the results of this paper show that in the short term, there's an improvement in symptoms of major depression. That is symptoms of major depression were reduced through the administration of this combination of probiotics, magnesium orotate, and coenzyme Q10. However, it was a short-lived effect.

Now, it was also a short-lived treatment, but it was a short-lived effect that showed up in the, essentially starting about the four-week mark, and then carried out to 10 and 15 weeks, the effect disappeared. Now, this is important because what it suggests is that in the short-term, if you're seeking to improve your mood, or if you're suffering from major depression, please seek help for major depression.

This, of course, wouldn't be the only approach. You don't want to, you know, start being your own psychiatrist. This treatment very well could be combined with things, and should be combined probably with things like exercise, maybe with pharmacologic treatment, with antidepressant drugs. It really depends on the situation. But if you are somebody who's suffering from major depression or just mild depression, or if you're just seeking to maintain healthy serotonin levels, or improve your mood slightly, the consumption of things that are going to improve your gut microbiome absolutely is going to support that process.

This has been shown over and over again, because the gut microbiota create these short chain fatty acids that are critically involved in this biochemical pathway that converts tryptophan into serotonin. I'm going to repeat that because it's very important. The microbiota of the gut, if they're diverse and you have enough of them, are going to produce the short chain fatty acids that are critically required for the conversion of tryptophan, which again is going to come from your diet, into the serotonin of your gut, which in turn is going to be relayed.

And it's not the actual serotonin that's relayed, but the presence of serotonin at sufficient levels in the gut is communicated by the vagus nerve up to the dorsal raphe nucleus. Remember there's some stations in between, but it's communicated up to the dorsal raphe, and your dorsal raphe then releases serotonin in the brain.

Again, a beautiful coordination of the body and the brain, just as activity levels in the body and the brain are matched through the vagus, or from the brain to the body, depending on the direction of flow, right? Alertness in the brain, body becomes alert. alertness in the body, brain becomes alert.

Serotonin elevated in the gut, serotonin elevated in the brain. All of that happens by way of vagal signaling. alertness in the brain.