Andrew Huberman claims in one if his podcasts episodes that:

[...] because starches cause the release of serotonin in the brain and lend themselves to a state of sleepiness. Now, I should mention that about about 25% of individuals have genes that encode for enzymes that allow them to eat large amounts of carbohydrate and not suffer from this lethargy.

Timestamped Video: https://youtu.be/aXvDEmo6uS4?t=4333

Sadly he doesn't reference any kind of study or data that this claim is based on. I am aware that serotonin is involved in digestion and that most serotonin found in the human body is in the gut. Though I do not know what its function is there or if this is even relevant for this question, given that Huberman specifically states

starches cause the release of serotonin in the brain [emphasis mine]

This aligns with my knowledge that Serotonin doesn't cross the blood brain barrier, so the Serotonin released in the gut cannot make its way to the brain somehow. I am also confused how or why Serotonin would cause lethargy, though this still fits with the typically reported side effects of Serotonin Reuptake Inhibtors.

I am also not surprised that this trait varies between individuals, but Huberman's claim is phrased like the difference is not just forming a normal distribution arising from many genes and instead that the distribution seems to be at least bimodal, i.e. "about 25% of people" do not experience this at all.

There are two previous questions on the tiredness after eating,

What is the biological basis for tiredness after eating? Why do the humans become sleepy after meals?

but neither really discuss anything related to serotonin in the brain, or deal with the factors underlying between-individual differences. One of the answers brings up

Sugary foods lead to the production of insulin. Insulin stimulates cells to take up glucose from blood. It also mobilizes tryptophan to brain. Once in brain, tryptophan triggers formation of serotonin, a hormone involved in controlling mood and slumber.

but this answer only references a blog with no further citations, but is at least some kind of explanation.

My questions is thus:

Is there some well known paper or review underlying this claim that he is implicitly referencing and potentially overly simplifying?

And if this isn't some well known paper, which I can read up on myself, but someone else can answer my more specific questions: What are the enzymes that influence the "post carb lethargy" in such a strong way and how do they attenuate the serotonin released in the brain?

  • $\begingroup$ I don't know about an enzyme that may or may not influence sleepiness after starchy meals, but I do know a fair amount about the physiological effect of somnolence after eating: medicalsciences.stackexchange.com/a/1087/169. If there is an enzyme that allows sleepiness after carbohydrate ingestion, I certainly have it. If I can't sleep, a bowl of cereal helps immensely. :) $\endgroup$ Dec 8 '21 at 3:14

The video is likely referencing alpha amylase, which is encoded in humans by AMY1A, a gene that is know to have a high level of inter-individual copy number variation. Some scientists have speculated that production of this enzyme in the brain can have an impact on neurotransmitter levels and thus memory in Alzheimer’s Disease (AD)1:

Since we have previously discovered the presence of α-amylase in the brain, we find it tempting to speculate that production of α-amylase is one of these factors. How the very high AMY1A copy number variability (and potentially thereby very high production of brain α-amylase) can be implicated in the lowered AD risk and episodic memory remains to be investigated. But since α-amylase is known to efficiently degrade polysaccharides (such as glycogen) in the periphery, we find it likely that the enzyme has a similar role in the brain. The enzyme might thus be important for the degradation of glycogen in astrocytes and neurons [20, 28], which is known to be crucial for neurotransmitter production and memory formation [21, 29, 30]. The presence of α-amylase in activated astrocytes and neuronal synapses, found in our previous studies [19, 31], supports this idea.


  1. Byman E, Nägga K, Gustavsson AM; Netherlands Brain Bank, Andersson-Assarsson J, Hansson O, Sonestedt E, Wennström M. Alpha-amylase 1A copy number variants and the association with memory performance and Alzheimer's dementia. Alzheimers Res Ther. 2020 Nov 21;12(1):158.
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    $\begingroup$ My initial reaction was that he must be referring to one of the genes/enzymes that explain the observation that neurotransmitter release by brain neurons may be controlled by carbohydrate (but not protein). 'Carbohydrate consumption--acting via insulin secretion and the "plasma tryptophan ratio"--increases serotonin release; protein intake lacks this effect.' (ref). I have not been able to find the enzyme, but tryptophan hydroxylase must be a likely candidate? $\endgroup$
    – user338907
    Dec 7 '21 at 14:54
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    $\begingroup$ While alpha amylase seems interesting, I am fairly sure that this is not what Professor Huberman was referencing in the podcast. The connection to serotonin specifically seems like a stretch, especially when there are much older results establishing a link to serotonin specifically like @user338907 linked. This would actually be good enough for me to accept as an answer if you want to post it as such, there are enough details in the paper to narrow down the enzymes involved. $\endgroup$ Dec 11 '21 at 21:29

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