Luteolin - A Brain Fog Reducer? A Mast Cell, Fibromyalgia and ME/CFS Inquiry

I've tried Luteolin or Quercetin:

  • Luteolin had very positive effects

    Votes: 1 7.1%
  • Luteolin had moderately positive effects

    Votes: 1 7.1%
  • Luteolin had no effects

    Votes: 5 35.7%
  • Luteolin had negative effects

    Votes: 1 7.1%
  • Quercetin had very positive effects

    Votes: 2 14.3%
  • Quercetin had moderately positive effects

    Votes: 3 21.4%
  • Quercetin had no effects

    Votes: 3 21.4%
  • Quercetin had negative effects

    Votes: 5 35.7%

  • Total voters


Founder of Health Rising and Phoenix Rising
Staff member
Brain Fog

[/fright]Mast cell activation syndrome (MCAS) or disorder (MCAD) has been recognized relatively recently. Like other newly recognized disorders that cause a bewildering array of symptoms, people with MCAS were dismissed for many years as being hypochondriacs or being depressed.

The symptomatic overlap between mast cell activation syndrome (MCAS), chronic fatigue syndrome (ME/CFS) and fibromyaglia (FM) is impossible to ignore. One of the symptoms found commonly in all three diseases is cognitive disruption or "brain fog" in ME/CFS and fibrofog in FM. Brain fog is also commonly found in diseases associated with related diseases such as celiac disease, mastocytosis, and postural orthostatic tachycardia syndrome (POTS) as well as neuroimmune diseases such as Alzheimer's and autism.

Why brain fog is so common in these diseases and not others is unclear, but Dr. Theorharis Theoharides - a mast cell researcher who has done work in ME/CFS and Julian Stewart, a POTS/ME/CFS researcher - believe the culprit could be inflammatory molecules produced by activated mast cells.

Mast Cells

Mast cells are immune cells that litter the body and are found around the blood-brain barrier and in the brain. Generally associated with allergic reactions mast cells can generate an astonishing variety of substances that are not associated with allergies.

Theoharides and Stewart believe substances produced by mast cells trigger the microglial cells in the brain to produce inflammatory molecules such as histamine, tumor necrosis factor (TNF), prostaglandins, etc. When these molecules reach back and trigger mast cells to produce more inflammatory mediators a vicious cycle is borne.

Mast cells located close to the hypothalamus - a part of the brain of great interest in ME/CFS and FM - contain most of the histamine in the brain.

A Little History of MCAS

The first major review proposing that mast cell activation played a role in diseases such as multiple sclerosis, interstitial cystitis, showed up in 1996. In 1998 Gui proposed mast cells provided the link between infection, stress and food allergy problems in irritable bowel syndrome. Mast cells were fingered in interstitial cystitis in the late 1990's, and Theoharides showed that stress induces mast cell activation and histamine release in 2002.

The overlap between mast cell activation and postural orthostatic tachycardia syndrome (POTS) - another syndrome producing a bewildering array of symptoms - showed up in 2005. (The study concluded that MCAS should be considered in POTS patients with flushing.)

Diagnostic criteria were first formally proposed, however, only in 2010, and MCAS was still being described as a "newly recognized disorder" in 2012. Interest appears to have picked up significantly since 2010. In Jan. 2016, the National Institute of Allergy and Infectious Diseases (NIAID) published a video alerting the public and doctors to presence of mast cell disorders (see below).

Mast Cell Activation Disorders by the National Institute of Allergy and Infectious Diseases (NIAID)

The "Mast Cell Master" and Luteolin

Theoharis Theoharides PhD, "The Mast Cell Master" has been touting luteolin for some time and has produced a supplement line containing it. Theoharides is not just another doctor with a line of supplements. A Tufts researcher, Theorharides published the first major review of mast cell activation disorders in 1996 ("The Mast Cells: A Neuroimmunoendocrine Master Player"), and has co-authored hundreds of studies and articles since then. (A recent one focused on the effects of the gut on the brain: Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation.)

Since 2008, a flavinoid called luteolin has captured Theoharides attention. Theoharides apparently stumbled upon luteolin after noticing it's molecular similarities to cromolyn, a mast cell stabilizing drug used in food allergy. Since 2008 Theoharides has published nine studies and papers on luteolin.

In 2009, in a paper published in the Journal of Neuroinflammation, Theoharides proposed that luteolin could be helpful in multiple sclerosis.

[/fleft]A 2012 case series study found that luteolin improved gut and allergy symptoms in about 75 percent of autistic children, eye contact and attention problems in about 50 percent, and social interaction issues in about 25 percent. The next year Theoharides asserted that the ability of flavinoids such as luteolin and quercetin to reduce inflammation in multiple ways (including reducing cytokine levels) made them superior to the traditional COX inhibiting anti-inflammatories.

In 2013 Theoharides provided evidence suggesting that luteolin was a kind of master anti-inflammatory agent. He cited studies suggesting it was able to reduce oxidative stress, inflammation, mast cell degranulation, mast cell cytokine release, thimerosal-induced inflammatory mediator release, microglial activation and auto-immune T cell activation.

Theoharides also proposed that a subset of autism patients have a "brain allergy" caused by mast cell activation. He believes that in autism, a substance called CRH that is emitted by the hypothalamus in response to stress activates the brain's mast cells.

In 2014 Theoharides expanded the role mast cells may play in disease by suggesting that they provide the missing link between immune activation and autoimmunity. His hypothesis was based on a 2012 study showing that mast cell activation releases mitchondrial factors (mtDNA and ATP) which, he believes, trigger an auto-inflammatory response. (These cellular stress factors have popped up in Naviaux's and the Light's work work as well)

In 2015, citing the deficiencies of the only clinically available mast cell stabilizer, cromolyn, Theoharides urgently called the for development of more effective drugs and introduced a more effective mast cell stabilizer called tetramethoxyluteolin. An analogue of luteolin, tetramethoxyluteolin was more effective than luteolin and cromolyn at reducing mast cell release of histamine and other substances. (Both substances were more effective than cromolyn.)

Theoharides also showed that significant immune changes had occurred in autistic children who had improved on luteolin.


[/fright]Under the auspices of Algonot Inc., Dr. Theoharides created a line of flavinoid-rich supplements including Neuroprotek which contains luteolin, quercetin, and rutin. Algonot states that the flavinoids in Neuroprotek have been engineered to increase bioavailability. (Theoharides asserts that less than 10% of the flavinoids in our diet are absorbed, and most are metabolized to inert substances in our liver.)

Another supplement called FibroProtek contains CoQ10, willow bark and the same flavinoids.

Have you tried luteolin, quercetin and/or rutin or Algonot's formulations? If you have did they have any effect on your brain-fog, fatigue or other symptoms. Please let us know.

More on Mast Cells
Health Rising is not affiliated with Algonot or Dr. Theoharides in any way


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Who Me?

Well-Known Member
I had definitive positive results from quercetin. Nothing from luteolin. Also benefit from rutin which is in neuroprotek.

I took them separately in case I had a reaction to one but I'm getting some neuroprotek when I remember to order it.

@Cort. I thought you were going to make a mast cell histamine subforum?


Am watching this with interest - thank you, Cort. I'm from an allergic/atopic family. We also have a fair whack of autoimmune illness - rheumatoid arthritis, Sjogren's, hypothyroidism, but all can lead full lives. I have severe ME/CFS (no full life here!) and some family members have FM. The thing that caught my eye about this was that my ME/CFS was triggered by viral meningitis, and for 2 weeks prior to meningitis I had crazy urticaria - had never had them before and they continued for well over a year afterwards. Will be interested to see how this all pans out.


Well-Known Member
I found Neuroprotek brilliant for calming inflamed brain. I have a number of mast cell issues, comparatively mild, but persistent. Stress of any sort definitely exacerbates.


Well-Known Member
Ah ha! Salicylates.... that was the reasoning behind Curcumin or Turmeric possibly being bad instead of good for you --- it depends on a salicylates sensitivity, MCAS type stuff etc. I just looked it up in one of my MCAS books. Turmeric is SUPER high in salicylates.

I had wondered about this on another thread -- no clue which one it was now, so I am posting here. Ha!


Active Member
I respond badly to turmeric too. I don't respond badly to aspirin, so maybe it's not the salicylates. I do also respond badly to a range of antioxidants and peroxynitrite scavengers, so I'm thinking that's the cause.

There was something in lettuce that provided a small benefit for a while. Dandelion root coffee seemed to have the same effect. That might have been due to luteolin, except that luteolin capsules had no effect when I tried them later. Apigenin did provide a small reduction in brainfog for a while, before it stopped working. Lettuce and dandelions both have apigenin, so maybe that was the active chemical. Too late to check that now. Too many of the things that actually do work on ME do so for only for a short time.

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