Serotonin: Gut vs Brain – What Really Matters for Mood?

27 Aug

If you’ve been hanging out in wellness circles for more than five minutes, you’ve probably heard the claim:

“90% of your serotonin is made in your gut—so your mood is all about gut health!”

It sounds catchy. It sounds feasible. And when you hear it repeated over and over (even by big names—yep, even Dr Mark Hyman posted this exact claim last week), it’s easy to see why people take it as fact.

But here’s the truth: it’s not how serotonin and mood actually work.

Gut Serotonin: A Digestive Workhorse

Yes, 90–95% of the body’s serotonin is made in the gut, by cells called enterochromaffin cells. But this pool of serotonin isn’t running your mood. It’s running your digestion.

Gut serotonin:

Keeps food moving (gut motility).
Talks to platelets, influences clotting.
Signals nausea and gut pain.

And most importantly: gut serotonin cannot cross the blood–brain barrier. It’s locked into the gut and bloodstream, completely separate from the serotonin that affects how you feel.

Brain Serotonin: The Mood Player

Only 5–10% of your serotonin is made in the brain and central nervous system. This is the serotonin that:

Regulates mood, sleep, appetite, and memory.
Is targeted by SSRIs (antidepressants).
Helps you feel calm, stable, and balanced.

So how does the brain actually make serotonin?

Step 1: You eat protein-rich foods containing tryptophan (turkey, eggs, nuts, seeds).
Step 2: Unlike serotonin, tryptophan can cross the blood–brain barrier via a special transporter (LAT1).
Step 3: Once inside the brain, enzymes get to work:
- Tryptophan hydroxylase (TPH2) converts tryptophan → 5-HTP. TPH2 requires iron and folate (via BH4), while vitamin D regulates the gene that switches this enzyme on.
- Aromatic L-amino acid decarboxylase converts 5-HTP → serotonin. This enzyme requires vitamin B6 (as P5P).
Step 4: Neurons (especially in the raphe nuclei) store and release this serotonin to regulate mood, sleep, appetite, and memory.

In other words, happy thoughts come from serotonin your brain makes, using tryptophan. NOT from the serotonin in your gut.

So How Does Gut Health Affect Mood?

Just because gut serotonin doesn’t control mood doesn’t mean gut health is off the hook. The gut-brain connection is very real, but it works through other mechanisms:

The vagus nerve: Think of it as a hotline from gut to brain. Signals about inflammation, fullness, and microbial activity travel straight up.
The microbiome: Gut bacteria produce metabolites like short-chain fatty acids (butyrate), influence tryptophan metabolism (serotonin’s precursor), and even produce GABA and dopamine.
Immune system & inflammation: A leaky or inflamed gut ramps up inflammatory cytokines that can alter brain chemistry and mood.
Nutrient absorption: If your gut isn’t absorbing B vitamins, zinc, magnesium, and omega-3s properly, your brain won’t have what it needs to make neurotransmitters.
Stress feedback loops: Poor gut health can heighten the stress response, fuelling anxiety and low mood.

So, yes, gut health matters for mood. Just not because serotonin magically floats from your gut into your brain.

The Bottom Line

Gut serotonin = digestion, not mood.
Brain serotonin = mood, sleep, memory, appetite.
Gut health still influences mental health, through microbiome signals, inflammation, nutrient absorption, and the vagus nerve.

Next time you see someone post “90% of serotonin is made in the gut, so that’s why gut health controls your mood,” know that the science is more interesting (and a lot more nuanced) than that.

Kelly Allan