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Luteolin, sleep and isorhamnetin

A few days ago, we wrote about an animal study in which a modest dose of luteolin improved sleep as a whole, and especially deep sleep. As results of animal studies can often not be extrapolated to humans, we started looking for epidemiological studies on the association between sleep and luteolin. We found one - plus perhaps another interesting sleep enhancing flavonoid.


Luteolin, sleep and isorhamnetin


Epidemiological study
The epidemiological study we are referring to appeared in 2025 in the Journal of Nutritional Biochemistry. [J Nutr Biochem. 2025 Sep:143:109944.] The data on which the study is based were collected in the American National Health and Nutrition Examination Survey and analyzed by researchers from Guangzhou University of Chinese Medicine in China.

Based on food diaries filled out by the American participants, the researchers calculated approximately how many polyphenols the Americans consumed daily. Because the participants had also answered questions about sleep, the Chinese researchers were able to calculate whether there was a link between polyphenol intake and sleep.

And yes, there certainly was an association.

Results
A relatively high intake of luteolin reduced the risk of sleep problems. To be more precise, the 33.3 percent [a tertile] with the highest intake of luteolin had about a 15 percent lower risk of sleep problems than the 33.3 percent [another tertile] with the lowest intake.

The flavonoid isorhamnetin provided even better protection. Americans in the tertile with the highest intake of isorhamnetin had nearly an 18 percent lower risk of sleep problems. Moreover, they slept a little longer.

Click on the table below for a larger version.


Luteolin, sleep and isorhamnetin


Luteolin versus isorhamnetin
So, isorhamnetin might be an even better sleep enhancer than luteolin. If so, this is likely because isorhamnetin breaks down less rapidly in the bloodstream than luteolin—and is also better able to penetrate brain cells.

Luteolin, quercetin, and isorhamnetin are similar. We discussed the differences between the structure and pharmacokinetic properties of luteolin and quercetin a few days ago. You can see the difference in the planar chemical structure of the three molecules below.

Isorhamnetin has a methoxy group on the third carbon atom of the B-ring, whereas both luteolin and quercetin have a hydroxyl group.

This methoxy group inhibits enzymes that deactivate polyphenols in the bloodstream by attaching sugar groups to them. The same methoxy group also makes the molecule lipophilic, allowing it to enter the brain and penetrate brain cells more easily.


Luteolin, sleep and isorhamnetin


In foods
Just like quercetin, luteolin and isorhamnetin are found in vegetables, fruits, and herbs.

Here you will find a table that tells you how much luteolin is present in free and bound forms in foods. The table comes from a review published in 2017 in the International Journal of Agricultural and Life Sciences. [IJALS. 2017;3(2):195-207.]

A table is also circulating on the web that gives an idea of ​​the concentration of isorhamnetin in regular foods. You can find it here. We have not been able to identify its scientific source.

Only a few percent of all luteolin and isorhamnetin molecules are 'free' and therefore bioavailable. The rest are attached to sugar groups. Microorganisms in the gut cleave these groups off. Thanks to these microorganisms, the body can absorb approximately 18 percent of the molecules. In 2010, researchers from Harbin Medical University in China published an estimate of the daily intake of quercetin, luteolin, and isorhamnetin by students. [Br J Nutr. 2010 Jan;103(2):249-55.]

Although polyphenol intake in China is higher than in the West, the study provides an idea of ​​what intake of luteolin and isorhamnetin is 'normal'.


Luteolin, sleep and isorhamnetin


The human equivalent of the dose of unbound luteoline that researchers administered to their test animals in the animal study we wrote about earlier was 15-25 milligrams.

If you take into account that almost all luteoline in the diet is bound and only 18 percent of that luteoline is ultimately absorbed in an unbound form, you realize that it is not possible to obtain that dose through regular food products.

More:
Tiny amount of luteolin deepens deep sleep | Animal study 07.07.2026
Luteolin, a testosterone booster from parsley 10.09.2021
L6N, the stamina factor in moso bamboo 03.02.2018
Animal study: luteolin lowers estradiol level 04.09.2015
Luteolin, the anti-oestrogen in celery 20.08.2013

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