Luteolin: Neuroprotective, Anti-inflammatory, Antihistamine

Staying healthy as we age - a natural brain health supplement

Jun 26, 2024

Luteolin is a flavonoid found in herbs and vegetables. Research shows that it has numerous anti-inflammatory and antimicrobial effects. Anti-inflammatory, neuroprotective… sounds like a winner for longevity and healthspan.

Let’s dive into the research on luteolin, and then, you can decide if it is worthwhile to add it to your arsenal for healthy aging.

Luteolin:

You will find the flavone luteolin in parsley, carrots, artichokes, celery, thyme, chamomile tea, olive oil, oranges, and oregano. Flavonoids, such as luteolin, are produced by plants as a cellular defense against microorganisms or UV radiation. Many of these molecules also bring cellular health benefits to us when we consume them.[ref]

A quick note to prevent confusion: Luteolin is not the same as lutein (yellow plant pigment used for macular degeneration).

Neuroprotective effects of luteolin:

Luteolin may have benefits for preventing Alzheimer’s. Let me explain:

O-glycosylation of amyloid precursor protein (APP) is required for the production of amyloid β, which builds up in plaques in the brains of Alzheimer's patients. Inhibiting this process, at least in theory, could decrease amyloid β in the brain. Let me emphasize that this is theoretical and not proven in human studies.

Luteolin selectively inhibits the type of O-glycosylation (Mucin-type O-glycosylation) involved in amyloid β formation.[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.

What else does luteolin do in the brain? A new study shows that luteolin increases complex I and complex II in the mitochondria. Researchers found this by screening over a thousand natural compounds to see what increased cellular ATP without causing cytotoxicity.[ref] This could mean that luteolin increases ATP production in the brain. Another new study just found that in elderly people, higher complex I activity in the brain is linked to feelings of well-being, while low complex I is linked to depression and isolation.[ref]

Luteolin as an anti-inflammatory:

In cell studies, luteolin inhibits TNF-alpha and IL-6 released via suppressing NF-κB.[ref] TNF-alpha and IL-6 are inflammatory cytokines that are normally released during acute inflammation. However, when TNF-alpha and IL-6 remain elevated, this causes the problems seen with chronic inflammation.

Other studies show that luteolin reduces IL-6 production in response to bacterial infections.[ref] Again, preventing an overactive inflammatory response is a good thing for many situations in health as we age.

Luteolin and apigenin (another flavonoid) have been shown to inhibit IL-31 and IL-33 in microglial cells.[ref] IL-31 is an inflammatory cytokine produced by activated T lymphocytes and plays a role in chronic inflammatory diseases.

Antihistamine properties of luteolin:

Luteolin can act as a mast cell stabilizer and reduce histamine release.[ref][ref] This may be of benefit to anyone dealing with mast cell activation syndrome, histamine intolerance, or allergies.

Some researchers think that brain fog is due to neuroinflammation and histamine release. They theorize that luteolin should be helpful for brain fog, pointing to studies on it improving attention in kids with autism.[ref]

Luteolin and sleep:

Animal studies show that luteolin has a sleep-inducing effect - at least when given along with a sleep drug. Interestingly, this hypnotic effect was driven by interactions with the adenosine receptor. (The build-up of adenosine and binding with the adenosine receptor drives us to need to sleep each night.) Additionally, luteolin increased sleep time and non-REM sleep.[ref]

Note that while luteolin may help with sleep quality, it doesn’t make you sleepy to take it during the daytime. However, if you have problems with sleep, you may want to try taking it before bedtime to see if it helps.

Luteolin inhibits cell proliferation in cancer:

A bunch of cell studies show that luteolin induces apoptosis (cell death) in cancer cells. Additionally, it induces cell cycle arrest - stopping the cancer cells from reproducing. Various studies point to a couple of ways that luteolin stops cancer cell proliferation including through inhibiting the IGF1 receptor and via acting on GSK-3β. Recent studies also show that luteolin downregulates mTOR and upregulates P53 (tumor suppressor gene).[ref][ref][ref][ref]

Can you take enough supplemental luteolin to actually make a difference? Clinical trials on luteolin for cancer prevention are lacking, so I don’t know. There are studies, though, on using luteolin along with chemotherapy or radiation, so perhaps there will be studies on prevention soon.[ref]

Absorption and Metabolism of luteolin:

Luteolin can be absorbed when taken orally or when used transdermally (it is a relatively small molecule).

Studies show that oral luteolin shows up in the bloodstream after an hour to an hour and a half.[ref] It has a half-life of 5-7 hours.[ref]

Studies on colon cancer cells show that liposomal luteolin (luteolin in oil) is much more effective than free luteolin.[ref] Thus, taking a powdered luteolin supplement along with some fat may increase absorption - or opt for a liposomal formulation.

COMT interaction:
Luteolin is metabolized, or broken down, using the COMT enzyme. People with low COMT production due to genetic variants may want to be cautious with high doses of luteolin. If stacking luteolin with other supplements that interact with COMT, watch for mood swings or irritability as side effects since COMT also helps to regulate neurotransmitter levels. Other supplements that interact with COMT include methylfolate, methylB12, and SAMe.

Drug interactions?

Research points to luteolin inhibiting CYP2B6, CYP2C9, and CYP2D6, which are CYP450 enzymes that are also used in breaking down some prescription medications.[ref]

Talk to your doctor or pharmacist before taking luteolin if you have any questions about whether it is right for you, especially if you take a prescription drug.

Luteolin may inhibit estrogen, so I would err on the side of caution and avoid it while pregnant or trying to conceive.[ref] (Talk with your OB/GYN, of course)