July 17, 2024

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Harvard found why high-protein diet improves sleep quality

Harvard found why high-protein diet improves sleep quality

Harvard found why high-protein diet improves sleep quality.

“Cell”: The reason why high-protein diet improves sleep quality has finally been found!

For the first time, the Harvard team has discovered that the protein promotes the release of neuropeptides from the gut that activate specific dopaminergic neurons to suppress arousal

A colleague of mine has two particularly distinctive features.

The first one is that he can eat meat, and he can show off several large plates of meat at every dinner party; the second is that he can sleep, he seems to be able to fall asleep when he touches the pillow, and it is not easy to wake up. It is really enviable.

It never occurred to me that there might be a connection between these two features of his, or even the secret to a good night’s sleep.

On March22, a paper published by Harvard Medical School neuroscientist Dragana Rogulja in the journal Cell[1], this paper told us that eating meat gave people a good night’s sleep.

Using fruit flies and mice as research objects, Rogulja’s team revealed for the first time how a high-protein diet improves sleep quality .

It turns out that a high-protein diet can promote intestinal cells to secrete a neuropeptide called CCHa1. After CCHa1 enters the brain, it can activate dopaminergic neurons, promote the release of dopamine, and inhibit sleep and awakening caused by vibration.

Harvard found why high-protein diet improves sleep quality

Screenshot of paper home page

Sleep, especially deep sleep, is very important to human health.

People who are too easily awakened by external disturbances will feel restless during the day even after sleeping all night, seriously affecting their living and working conditions. If things go on like this, it will even lead to deterioration of physical health.

There are many factors that affect sleep. In addition to external environmental conditions, it is also regulated by genetic conditions. Scientists have discovered many genes that regulate sleep [2]. In recent years, some epidemiological studies have also found that there is also a certain relationship between dietary changes and sleep [3,4], but it is not certain whether there is a causal relationship between the two .

As a neuroscientist who studies sleep, Rogulja’s research focuses on how humans reversibly switch between sleep and wakefulness, so this time she intends to study how wakefulness is suppressed during sleep . Simply put, it is to study how to maintain sleep without being awakened by external disturbances.


Rogulja began by looking for genes involved in sleep arousal in fruit flies.

They found that in the hyperarousal phenotype in which the neuropeptide CCHa1 or its receptor CCHa1R was silenced, about 85 percent of flies aroused in response to low-intensity stimuli . Therefore, the neuropeptide CCHa1 attracted their attention.

Harvard found why high-protein diet improves sleep quality

Screening process for target genes

Consistent with previous studies, Rogulja and her colleagues also found that CCHa1 is distributed in nerve cells and intestinal endocrine cells, and that the intestinal cells that secrete CCHa1 are almost evenly distributed throughout the gut .

Harvard found why high-protein diet improves sleep quality

Distribution of CCHa1-secreting cells

Through targeted gene silencing, they found that only CCHa1 of intestinal cells was associated with arousal , and that silencing CCHa1 of intestinal cells increased the number of arousals during sleep in Drosophila. In other words, it was CCHa1 secreted by gut cells that suppressed arousal during sleep.

After discovering this function of intestinal cells, Rogulja immediately thought that diet might affect sleep through the gut.

So they immediately tested the effects of sugars (glucose, galactose, and fructose), fats (coconut oil, propionate, and caproate) and proteins (peptone) on the expression of CCHa1 in intestinal cells.

It was found that the activity of CCHa1-positive intestinal cells and the level of CCHa1 in these cells were significantly increased with peptone supplementation, while sugar and fat supplementation had no effect .

Effects of common diet, sugar, fat and peptone on CCHa1

When looking at the effect of a protein diet on sleep arousal in fruit flies, they found that flies supplemented with peptone to their diet were only half as likely to arouse from vibrations as those fed a normal diet. If intestinal cells were inhibited from secreting CCHa1, the inhibitory effect of high-protein diet on sleep arousal was also weakened .

The above findings suggest that it is indeed the ingested protein that promotes the production of CCHa1 in intestinal cells, which in turn inhibits awakening during sleep.

To test whether these findings apply to mammals, they tested the effect of a high-protein diet on sleep in mice.

The findings were similar to those in fruit flies, in that mice fed a high-protein diet were more difficult to arouse than those fed normal chow, and sugar and fat had no effect on arousal during sleep . And they also noticed that the high-protein diet had no effect on the total duration of sleep, but increased the total duration of REM sleep.

This means that the sleep quality of the mice has indeed improved. However, they did not examine changes in CCHa1 in mice.

Effect of high-protein diet on sleep in mice

At the end of the study, Rogulja’s team went back to fruit flies to find the neural pathways regulated by CCHa1.

They found that the neuropeptide CCHa1 secreted by intestinal cells can activate dopaminergic neurons PAMMB441B, leading to the release of dopamine, which in turn inhibits vibration-induced sleep arousal .

Although many studies have shown that dopamine promotes arousal [5], research by Rogulja’s team has shown that dopamine can also act on specific synapses to inhibit arousal. The specific mechanism behind it remains to be further explored.

Harvard found why high-protein diet improves sleep quality

Mechanism diagram

In general, this study constructed a protein diet-regulated sleep model, which is of great help to the follow-up research on the effect of diet on sleep. In addition, around this signaling pathway, some drugs for the treatment of insomnia may also be developed.

It should be pointed out that although this study fills a gap in the field of sleep-wake suppression, there are still many unknowns to be followed up.

For example, which subpopulation of dopamine neurons regulate sleep-wake suppression? Whether high-protein diet inhibits sleep-wake signaling pathway in mammals involves CCHa1 and so on .

Unraveling these questions may help us better understand sleep.

How are you sleeping well in a world where insomnia is a global problem?


[1].Iris Titos, Alen Juginović, Alexandra Vaccaro, et al. A gut-secreted peptide suppresses arousability from sleep. Cell. 2023. doi:10.1016/j.cell.2023.02.022

[2].Sehgal A, Mignot E. Genetics of sleep and sleep disorders. Cell. 2011;146(2):194-207. doi:10.1016/j.cell.2011.07.004

[3].Binks H, E Vincent G, Gupta C, Irwin C, Khalesi S. Effects of Diet on Sleep: A Narrative Review. Nutrients. 2020;12(4):936. doi:10.3390/nu12040936

[4]. Godos J, Grosso G, Castellano S, Galvano F, Caraci F, Ferri R. Association between diet and sleep quality: A systematic review. Sleep Med Rev. 2021;57:101430. doi:10.1016/j.smrv .2021.101430

[5]. Riemensperger T, Isabel G, Coulom H, et al. Behavioral consequences of dopamine deficiency in the Drosophila central nervous system. Proc Natl Acad Sci US A. 2011;108(2):834-839. doi:10.1073/ pnas.1010930108

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