Luteolin: Antihistamine, Memory, and Brain Fog

Key takeaways:
~ Luteolin is a flavonoid found in fruits, vegetables, and herbs.
~ It possesses a variety of anti-inflammatory, antihistamine, antioxidant, and antibacterial properties, according to research studies.
~ It is neuroprotective, bringing benefits to the brain for memory and possibly protecting against neurodegenerative diseases.

In this article, I dive into the research studies on luteolin, explaining the clinical trials and examining animal research on how it works. I’ll also explain how it is absorbed and how it interacts with genetic variants, such as COMT.

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Luteolin: Benefits, foods, and supplement options

Luteolin is a flavonoid found in small amounts in several herbs and vegetables. Plants produce flavonoids, such as luteolin, as a cellular defense against pathogens or UV radiation. Many of these plant molecules also bring health benefits to us when we consume them.[ref]

Luteolin-rich foods:
Parsley, carrots, artichokes, celery, thyme, chamomile tea, olive oil, oranges, green peppers, and oregano contain the flavone luteolin.

Luteolin Supplements:
As a natural herbal supplement, luteolin is readily available at health food stores and online (e.g. Amazon, iHerb, etc). Normal dosages range from 100 mg – 500 mg in dried herb or liposomal forms, however, most supplements and studies are in the 100 mg range. Be sure to check the reviews for any supplement you choose.

Luteolin vs. lutein: Luteolin is not to be confused with lutein, a plant pigment that can help with macular degeneration.

Luteolin as an antihistamine and mast cell stabilizer:

Research shows that luteolin can act as a mast cell stabilizer and reduce histamine release.[ref][ref] This may benefit anyone dealing with mast cell activation syndrome (MCAS) or histamine intolerance. Several mast cell researchers and clinicians recommend luteolin for preventing mast cell degranulation.

Brain Fog in MCAS:
The ‘brain fog’ term applies to the inability to think clearly or concentrate. According to some researchers, inflammation along with histamine release causes brain fog in people with mast cell activation disorders. The researchers believe that luteolin can help with brain fog, citing studies that show it can improve focus in children with autism.[ref].

Related article: Brain Fog and Genetics

Neuroprotective effects of luteolin:

Research shows that luteolin may have clinically meaningful neuroprotective effects. This is important since a lot of research studies only show very minor benefits that aren’t really meaningful.

Brain fog:
Studies show that luteolin may help with cognitive dysfunction caused by inflammation. Luteolin decreases the cytokines that cause inflammation in the brain.[ref]

Other research explains that luteolin may help specifically with “brain fog” by decreasing neuroinflammation.[ref]

Long Covid:
Some researchers think that luteolin may help with brain fog, or cognitive issues, in long Covid.[ref] The mechanism of how luteolin could help seems logical, but there aren’t any clinical trials on luteolin for Long Covid (yet).

Neurodegenerative diseases such as Alzheimer’s:
The creation of amyloid-beta, which builds up in plaques in Alzheimer’s sufferers’ brains, requires the O-glycosylation of the amyloid precursor protein. Inhibiting this process could reduce amyloid in the brain, at least in theory. Let me be clear: this is purely theoretical and has not been confirmed in human investigations.

Luteolin selectively inhibits the type of O-glycosylation (Mucin-type O-glycosylation) involved in the formation of amyloid-β.[ref]
Animal studies show luteolin inhibits neuroinflammation by controlling microglia activation.[ref]
In a mouse study of Alzheimer’s, luteolin protects against amyloid β memory dysfunction and also increases levels of endogenous antioxidants, including Mn-SOD, Cu/Zn-SOD, and glutathione.

Keep in mind that mouse and cell studies don’t always pan out when it comes to Alzheimer’s research… but for luteolin, there is little risk and a lot of potential benefits.

Luteolin as an anti-inflammatory:

Research also shows that luteolin may reduce or prevent chronic inflammation.

In cell studies, luteolin inhibits TNF-alpha and IL-6 released via suppressing NF-κB.[ref] TNF-alpha and IL-6 are linked to many chronic diseases caused by elevated inflammatory cytokines.
In other research, luteolin reduces IL-6 (interleukin 6), an inflammatory cytokine produced in response to bacterial infections.[ref]
In microglial cells, luteolin and another flavonoid, apigenin, suppress IL-31 and IL-33.[ref] IL-31 is an inflammatory cytokine produced by activated T lymphocytes, and it plays a role in chronic inflammatory diseases.

All in all, the research shows luteolin as a specific anti-inflammatory to target elevated TNF, IL-6, IL-31, and IL-33.

Through protecting against inflammatory cytokine over-production, luteolin protects against oxidative stress in cells.[ref]

Luteolin and sleep:

Animal studies show that luteolin has a sleep-inducing effect – at least when given with a sleep drug.

Interestingly, this hypnotic effect was driven by interactions with the adenosine receptor. The build-up of adenosine and its binding with the adenosine receptor drives us to need to sleep each night, so the interaction with the adenosine receptor theoretically would only increase sleepiness at the end of the day (not making you sleepy during the day). Additionally, the research showed that luteolin increased sleep time and non-REM sleep.[ref]

Luteolin as an antimicrobial:

Cell studies show that luteolin acts as an antimicrobial agent against several common bacterial and viral pathogens.

It stops the growth of Staphylococcus aureus (staph infection).[ref]
Luteolin acts as an antiviral agent against one of the causes of encephalitis (Flaviviridae virus).[ref]
In trials for SARS-CoV-1, luteolin blocks viral entry into host cells. Some researchers theorize it may also be helpful for SARS-CoV-2, but clinical trials are needed.[ref]
Cell studies also show that luteolin has antiviral activity against the flu virus (H1N1).[ref]

Luteolin inhibits cell proliferation in cancer:

First and foremost, let me emphasize that I am not advocating for anyone to self-treat cancer with supplements. Instead, this research summary provides broad cancer prevention advice. Talk with your doctor if you have any questions.

In epidemiological research, eating fruits and vegetables has been linked to lower cancer risk. However, epidemiological studies that ask people what they eat and then associate that with an outcome are really just vague pointers towards a possible link. Perhaps people who naturally eat many vegetables are also likely to have genetic variants in their taste receptors. It is possible these variants could also impact cancer risk.

Multiple studies have shown that luteolin induces apoptosis (cell death) in cancer cells in vitro. It also causes cell cycle arrest, which prevents cancer cells from replicating.

Studies show that luteolin inhibits cancer cell proliferation in two ways: by blocking the IGF1 receptor and by acting on GSK-3. Recent studies also show that luteolin downregulates mTOR and upregulates P53 (tumor suppressor gene).[ref][ref][ref][ref]

A recent cell study on breast cancer showed that luteolin inhibited certain cancer-promoting genes. Additionally, it increased cytotoxicity when combined with certain chemotherapy drugs.[ref]

While it is excellent that luteolin works to stop many different types of cancer cells from proliferating in a petri dish, the question remains whether this works at obtainable levels in real life. In other words, can you take enough supplemental luteolin to actually make a difference – without side effects? It is a question that needs clinical trials for answers.

What about just eating foods rich in flavonoids? A trial looking at cancer prevention from consuming flavonoid-rich vegetables, including luteolin content, found no difference in cancer risk among women who consumed the most flavonoids compared to the least.[ref]

Luteolin for skin health and sunburns:

A clinical trial found that a nanoparticle formula containing a luteolin-rich plant extract decreased UVB-induced erythema (e.g., sunburns). The formula seemed to work when applied before UVB exposure and, to some extent, after exposure. After exposure, the luteolin-rich plant extract was as effective as the hydrocortisone cream.[ref]

Luteolin in cholesterol levels:

There is a ton of research on cholesterol, and much of it seems contradictory — what is the right amount? Instead of looking only at total cholesterol or just LDL cholesterol, researchers are now dialing in the specific types of cholesterol-related lipid particles.

In general, apoB-containing lipoproteins, such as LDL and chylomicron remnants, link to plaque buildup in the arteries (not good).[ref] Luteolin acts on HNF4α, a nuclear transcription factor, in regulating the secretion of apolipoprotein B (apo B) containing lipoproteins.[ref] This means that luteolin is acting upstream of the production of cholesterol in the liver — regulating the production of cholesterol.

Gut Microbiome, liver health:

The gut microbiome and intestinal barrier integrity are essential in preventing fatty liver disease (NAFLD).

Luteolin protects against fatty liver by improving intestinal barrier integrity. It also increases microbial diversity in the gut, according to animal studies.[ref]

Xanthine oxidoreductase is the enzyme needed for purine metabolism, which results in the formation of uric acid. Excess uric acid is linked to gout and gouty arthritis. Inhibiting xanthin oxidoreductase is one way of treating gout. Luteolin has been shown to inhibit xanthine oxidoreductase.[ref]

Related article: NAFLD and genetics

Absorption, Side Effects, and Metabolism of Luteolin:

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