Luteolin for mast cells, histamine and brain fog?

Fresh mint, wooden mortar and pestle on the old table.

Citations always at the bottom of the post

According to Dr. Theoharides at Tufts University School of Medicine, brain fog is defined as a “constellation of symptoms” encompassing the loss of mental acuity, the ability to concentrate and multitask, and the loss of short and long term memory. It’s frequently experienced by patients with chronic fatigue syndrome, fibromyalgia, mastocytosis and mast cell activation (in my experience histamine intolerance also), and is an “early clinical presentation of Alzheimer’s disease”. Dr. Theoharides and others believe brain fog may be caused by inflammatory cytokines released in the brain. A survey of mast cell patient symptoms revealed that over ninety percent of patients suffered from it. It seems like the research is also pointing to neuro-inflammation as the driving force of Alzheimer’s. As mast cell degranulation occurs in the brain, this whole issue has been on my mind for some time and I’m grateful to have found my answer.

My grandmother was fine until a hip operation in the south of Spain (in the 80s – dear lord, why didn’t she travel to London or New York?). Just a day later she was complaining of severe memory loss, culminating in a swift decline into what doctors hesitated to actually call Alzheimer’s, but which certainly looked like it. I’ll never be able to erase the day the woman who raised me forgot how to chew.

Fast forward a generation and we’re starting to see similar issues emerge, at a far later age. Jump another generation and at 20 years old I was forgetting where I parked my car, couldn’t add double digits in my head (I tested in the top 5% of the US in Math and English at eight years old), would forget the name of the street I’m en route to, having to look it up every twenty seconds or so. Stress exacerbated the situation – despite all the gains made in the last five years, the day of my driving test I couldn’t lead the examiner to where I had parked the car just ten minutes earlier. Yes, that was pretty much an immediate fail.

While there’s much at play in brain fog, SOD genes for example, mitochondrial dysfunction etc, sometimes resolving a seemingly small piece of the puzzle can yield exciting results.

I recently explained to folks attending my 90 minute online workshop: beyond the low histamine diet, that a symptoms sheet is essential. It helped me figure out that sugar, be it from fruit or sweets, was my number one brain fog trigger. It wasn’t just brain fog, histamine foods with lots of sugar induced nystagmus (involuntary eye movements), an immediate narcoleptic-like episode with an inability to move my body, extreme eye floaters, unquenchable thirst and serious fatigue.

Once out of the diet, and replaced by a ton of nutrient dense healing antihistamine and anti-inflammatory property rich foods (like those in the Anti-Cookbook and Man Food), most of the symptoms lifted, but for the brain fog. I tried everything, including a number of powdered quercetin supplements.

Meditation helped immensely, as did the yoga – I cover everything I’ve learned in retraining my brain over the years in my two hour workshop: Using the Brain to Heal the Body. You can purchase it here.

But still I couldn’t quite shift what felt like a wet blanket wrapped around my brain. Knowing my memories were just beyond my grasp was maddening beyond belief.

I could now throw out a ton of really intense medical terms like microglial, cytokine release, auto-immune T cell activation, but suffice to say, luteolin has been found, more so than other studied bioflavonoids, to be useful in dampening brain inflammation linked to brain fog and other memory issues. I came to understand however that nearly all of the 3000 flavonoids are hard to absorb in powder form, and that less than ten percent of orally ingested flavonoids are absorbed at all.

Which is why I turned to Dr. Theoharides’ Neuroprotek supplement. This luteolin, quercetin and rutin supplement combines the flavonoids with oil, thereby apparently increasing absorption. It changed my life in so many ways but the most meaningful has been throwing off the shackles of my repressed brain function.

For an extensive list of luteolin (and other flavonoid) rich foods, check out this USDA report I found a few years back. I used it to come up with a list of foods to include in my diet.

A few of the luteolin and quercetin rich food highlights (all found in my books of course!):

Thyme, oregano, lovage, dill, fennel, red onions, watercress, kale, apple, asparagus, peas, spring onion, arugula, peppermint.

While stress continues to affect my memory, the meditation techniques I apply to my life continue to help me access memories and emotions once locked tight in a drawer I no longer had a key to. I encourage anyone suffering this life altering symptom to research your genes for contributing factors like SOD, to explore flavonoid supplementation with your doctor, and to take steps to control your reaction to stress, but most of all to invest just thirty minutes a day into a consistent meditation practice, which is now proven to lower brain inflammation levels.

You’ll find recipes full of foods with antihistamine and anti-inflammatory properties my books Anti-Recipes and The Anti-Cookbook

CLICK HERE TO CREATE YOUR OWN PERSONALISED HEALING HISTAMINE PLAN. 

CITATIONS

Theoharis C. Theoharides, MS, MPhil, PhD, MD, Julia M. Stewart, RN. “Brain “fog,” focal neuroinflammation and beneficial effect of luteolin”.

Alves,L., Correia,A.S., Miguel,R., Alegria,P.and Bugalho,P., 2012. Alzheimer’s disease: a clinical practice-oriented review. Front Neurol 3, 63.

Alzheimers Association. 2015 Alzheimer’s Disease Facts and Figures.  2015. 2015.
Ref Type: Report

Arsenijevic,D., Onuma,H., Pecqueur,C., Raimbault,S., Manning,B.S., Miroux,B.et al, 2000. Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat.Genet. 26, 435-439.

Asadi,S., Zhang,B., Weng,Z., Angelidou,A., Kempuraj,D., Alysandratos,K.D.et al, 2010. Luteolin and thiosalicylate inhibit HgCl(2) and thimerosal-induced VEGF release from human mast cells. Int J Immunopathol.Pharmacol. 23, 1015-1020.

Bai,Y., Onuma,H., Bai,X., Medvedev,A.V., Misukonis,M., Weinberg,J.B.et al, 2005. Persistent nuclear factor-kappa B activation in Ucp2-/- mice leads to enhanced nitric oxide and inflammatory cytokine production. J Biol.Chem. 280, 19062-19069.

Baptista,F.I., Henriques,A.G., Silva,A.M., Wiltfang,J.and da Cruz e Silva OA, 2014. Flavonoids as therapeutic compounds targeting key proteins involved in Alzheimer’s disease. ACS Chem.Neurosci. 5, 83-92.

Brewer,J.H., Thrasher,J.D., Straus,D.C., Madison,R.A.and Hooper,D., 2013. Detection of mycotoxins in patients with chronic fatigue syndrome. Toxins.(Basel) 5, 605-617.

Chen,H.Q., Jin,Z.Y., Wang,X.J., Xu,X.M., Deng,L.and Zhao,J.W., 2008. Luteolin protects dopaminergic neurons from inflammation-induced injury through inhibition of microglial activation. Neurosci.Lett. 448, 175-179.

Chen,Z., Zheng,S., Li,L.and Jiang,H., 2014. Metabolism of flavonoids in human: a comprehensive review. Curr Drug Metab 15, 48-61.

Corbett,A., Smith,J.and Ballard,C., 2012. New and emerging treatments for Alzheimer’s disease. Expert.Rev.Neurother. 12, 535-543.

Corcoran,M.P., McKay,D.L.and Blumberg,J.B., 2012. Flavonoid basics: chemistry, sources, mechanisms of action, and safety. J Nutr Gerontol.Geriatr. 31, 176-189.

Crago,B.R., Gray,M.R., Nelson,L.A., Davis,M., Arnold,L.and Thrasher,J.D., 2003. Psychological, neuropsychological, and electrocortical effects of mixed mold exposure. Arch.Environ.Health 58, 452-463.

Dirscherl,K., Karlstetter,M., Ebert,S., Kraus,D., Hlawatsch,J., Walczak,Y.et al, 2010. Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype. J Neuroinflammation. 7, 3.

Drzezga,A., Becker,J.A., Van Dijk,K.R., Sreenivasan,A., Talukdar,T., Sullivan,C.et al, 2011. Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden. Brain 134, 1635-1646.

Echtay,K.S., 2007. Mitochondrial uncoupling proteins–what is their physiological role? Free Radic.Biol.Med. 43, 1351-1371.

Empting,L.D., 2009. Neurologic and neuropsychiatric syndrome features of mold and mycotoxin exposure. Toxicol.Ind.Health 25, 577-581.

Emre,Y., Hurtaud,C., Nubel,T., Criscuolo,F., Ricquier,D.and Cassard-Doulcier,A.M., 2007. Mitochondria contribute to LPS-induced MAPK activation via uncoupling protein UCP2 in macrophages. Biochem.J 402, 271-278.

Farr,S.A., Price,T.O., Dominguez,L.J., Motisi,A., Saiano,F., Niehoff,M.L.et al, 2012. Extra virgin olive oil improves learning and memory in SAMP8 mice. J Alzheimers.Dis. 28, 81-92.

Fatokun,A.A., Liu,J.O., Dawson,V.L.and Dawson,T.M., 2013. Identification through high-throughput screening of 4′-methoxyflavone and 3′,4′-dimethoxyflavone as novel neuroprotective inhibitors of parthanatos. Br J Pharmacol 169, 1263-1278.

Franco,J.L., Posser,T., Missau,F., Pizzolatti,M.G., Dos Santos,A.R., Souza,D.O.et al, 2010. Structure-activity relationship of flavonoids derived from medicinal plants in preventing methylmercury-induced mitochondrial dysfunction. Environ.Toxicol.Pharmacol 30, 272-278.

Galli,S.J., Tsai,M.and Piliponsky,A.M., 2008. The development of allergic inflammation. Nature 454, 445-454.

Gonzalez-Correa,J.A., Navas,M.D., Lopez-Villodres,J.A., Trujillo,M., Espartero,J.L.and De La Cruz,J.P., 2008. Neuroprotective effect of hydroxytyrosol and hydroxytyrosol acetate in rat brain slices subjected to hypoxia-reoxygenation. Neurosci.Lett. 446, 143-146.

Gordon,W.A., Cantor,J.B., Johanning,E., Charatz,H.J., Ashman,T.A., Breeze,J.L.et al, 2004. Cognitive impairment associated with toxigenic fungal exposure: a replication and extension of previous findings. Appl.Neuropsychol. 11, 65-74.

Grosso,C., Valentao,P., Ferreres,F.and Andrade,P.B., 2013. The use of flavonoids in central nervous system disorders. Curr Med Chem.

Gupta,S., Ellis,S.E., Ashar,F.N., Moes,A., Bader,J.S., Zhan,J.et al, 2014. Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. Nat.Commun. 5, 5748.

Hanrahan,J.R., Chebib,M.and Johnston,G.A., 2011. Flavonoid modulation of GABA(A) receptors. Br J Pharmacol 163, 234-245.

Harwood,M., nielewska-Nikiel,B., Borzelleca,J.F., Flamm,G.W., Williams,G.M.and Lines,T.C., 2007b. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem.Toxicol. 45, 2179-2205.

Harwood,M., nielewska-Nikiel,B., Borzelleca,J.F., Flamm,G.W., Williams,G.M.and Lines,T.C., 2007a. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem Toxicol 45, 2179-2205.

Heneka,M.T., Carson,M.J., Khoury,J.E., Landreth,G.E., Brosseron,F., Feinstein,D.L.et al, 2015. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 14, 388-405.

Hollman,P.C., de Vries,J.H., van Leeuwen,S.D., Mengelers,M.J.and Katan,M.B., 1995. Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am.J Clin.Nutr. 62, 1276-1282.

Hollman,P.C., Katan,M.B., 1997. Absorption, metabolism and health effects of dietary flavonoids in man. Biomed.Pharmacother. 51, 305-310.

Inoue,T., Suzuki,Y., Yoshimaru,T.and Ra,C., 2008. Reactive oxygen species produced up- or downstream of calcium influx regulate proinflammatory mediator release from mast cells: Role of NADPH oxidase and mitochondria. Biochim.Biophys.Acta 1783, 789-802.

Jager,A.K., Saaby,L., 2011. Flavonoids and the CNS. Molecules. 16, 1471-1485.

Jang,S., Dilger,R.N.and Johnson,R.W., 2010. Luteolin inhibits microglia and alters hippocampal-dependent spatial working memory in aged mice. J Nutr. 140, 1892-1898.

Jang,S., Kelley,K.W.and Johnson,R.W., 2008. Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. Proc Natl Acad Sci U.S.A. 105, 7534-7539.

Jang,S.W., Liu,X., Yepes,M., Shepherd,K.R., Miller,G.W., Liu,Y.et al, 2010. A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone. Proc.Natl.Acad.Sci.U.S.A 107, 2687-2692.

Jones,Q.R., Warford,J., Rupasinghe,H.P.and Robertson,G.S., 2012. Target-based selection of flavonoids for neurodegenerative disorders. Trends Pharmacol Sci 33, 602-610.

Kao,T.K., Ou,Y.C., Lin,S.Y., Pan,H.C., Song,P.J., Raung,S.L.et al, 2011. Luteolin inhibits cytokine expression in endotoxin/cytokine-stimulated microglia. J Nutr.Biochem. 22, 612-624.

Kawanishi,S., Oikawa,S.and Murata,M., 2005. Evaluation for safety of antioxidant chemopreventive agents. Antioxid.Redox.Signal. 7, 1728-1739.

Kempuraj,D., Madhappan,B., Christodoulou,S., Boucher,W., Cao,J., Papadopoulou,N.et al, 2005. Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells. Br J Pharmacol 145, 934-944.

Kempuraj,D., Tagen,M., Iliopoulou,B.P., Clemons,A., Vasiadi,M., Boucher,W.et al, 2008. Luteolin inhibits myelin basic protein-induced human mast cell activation and mast cell dependent stimulation of Jurkat T cells. Br J Pharmacol 155, 1076-1084.

Kilburn,K.H., 2009. Neurobehavioral and pulmonary impairment in 105 adults with indoor exposure to molds compared to 100 exposed to chemicals. Toxicol.Ind.Health 25, 681-692.

Kimata,M., Shichijo,M., Miura,T., Serizawa,I., Inagaki,N.and Nagai,H., 2000. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clin Exp Allergy 30, 501-508.

Kizaki,T., Suzuki,K., Hitomi,Y., Taniguchi,N., Saitoh,D., Watanabe,K.et al, 2002. Uncoupling protein 2 plays an important role in nitric oxide production of lipopolysaccharide-stimulated macrophages. Proc.Natl.Acad.Sci.U.S.A 99, 9392-9397.

Larsen,F.O., Clementsen,P., Hansen,M., Maltbaek,N., Gravesen,S., Skov,P.S.et al, 1996. The indoor microfungus Trichoderma viride potentiates histamine release from human bronchoalveolar cells. APMIS 104, 673-679.

Li,W., Sperry,J.B., Crowe,A., Trojanowski,J.Q., Smith,A.B., IIIand Lee,V.M., 2009. Inhibition of tau fibrillization by oleocanthal via reaction with the amino groups of tau. J Neurochem. 110, 1339-1351.

Li,Y., Maedler,K., Shu,L.and Haataja,L., 2008. UCP-2 and UCP-3 proteins are differentially regulated in pancreatic beta-cells. PLoS.ONE. 3, e1397.

Lin,T.Y., Lu,C.W., Chang,C.C., Huang,S.K.and Wang,S.J., 2011. Luteolin inhibits the release of glutamate in rat cerebrocortical nerve terminals. J Agric.Food Chem. 59, 8458-8466.

Liu,R., Gao,M., Qiang,G.F., Zhang,T.T., Lan,X., Ying,J.et al, 2009. The anti-amnesic effects of luteolin against amyloid beta(25-35) peptide-induced toxicity in mice involve the protection of neurovascular unit. Neuroscience 162, 1232-1243.

Lopez-Lazaro,M., 2009. Distribution and biological activities of the flavonoid luteolin. Mini.Rev Med Chem 9, 31-59.

Martinez-Lapiscina,E.H., Clavero,P., Toledo,E., San,J.B., Sanchez-Tainta,A., Corella,D.et al, 2013. Virgin olive oil supplementation and long-term cognition: the PREDIMED-NAVARRA randomized, trial. J Nutr.Health Aging 17, 544-552.

Mecocci,P., Tinarelli,C., Schulz,R.J.and Polidori,M.C., 2014. Nutraceuticals in cognitive impairment and Alzheimer’s disease. Front Pharmacol. 5, 147.

Middleton,E.J., Kandaswami,C.and Theoharides,T.C., 2000. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer. Pharmacol Rev 52, 673-751.

Mohagheghi,F., Bigdeli,M.R., Rasoulian,B., Hashemi,P.and Pour,M.R., 2011. The neuroprotective effect of olive leaf extract is related to improved blood-brain barrier permeability and brain edema in rat with experimental focal cerebral ischemia. Phytomedicine. 18, 170-175.

Mohagheghi,F., Bigdeli,M.R., Rasoulian,B., Zeinanloo,A.A.and Khoshbaten,A., 2010. Dietary virgin olive oil reduces blood brain barrier permeability, brain edema, and brain injury in rats subjected to ischemia-reperfusion. ScientificWorldJournal. 10, 1180-1191.

Moura,D.S., Georgin-Lavialle,S., Gaillard,R.and Hermine,O., 2014. Neuropsychological Features of Adult Mastocytosis. Immunol Allergy Clin North Am 34, 407-422.

Moura,D.S., Sultan,S., Georgin-Lavialle,S., Barete,S., Lortholary,O., Gaillard,R.et al, 2012. Evidence for cognitive impairment in mastocytosis: prevalence, features and correlations to depression. PLoS.ONE. 7, e39468.

Parker-Athill,E., Luo,D., Bailey,A., Giunta,B., Tian,J., Shytle,R.D.et al, 2009. Flavonoids, a prenatal prophylaxis via targeting JAK2/STAT3 signaling to oppose IL-6/MIA associated autism. J Neuroimmunol. 217, 20-27.

Passamonti,S., Terdoslavich,M., Franca,R., Vanzo,A., Tramer,F., Braidot,E.et al, 2009. Bioavailability of flavonoids: a review of their membrane transport and the function of bilitranslocase in animal and plant organisms. Curr.Drug Metab 10, 369-394.

Petra AI, Panagiotidou S, Stewart JM, Conti Pand Theoharides TC, 2014. Spectrum of mast cell activation disorders. Expert.Rev Clin Immunol 10, 729-739.

Pitt,J., Roth,W., Lacor,P., Smith,A.B., III, Blankenship,M., Velasco,P.et al, 2009. Alzheimer’s-associated Abeta oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal. Toxicol.Appl.Pharmacol. 240, 189-197.

Pizza,V., Agresta,A., D’Acunto,C.W., Festa,M.and Capasso,A., 2011. Neuroinflamm-aging and neurodegenerative diseases: an overview. CNS.Neurol Disord Drug Targets. 10, 621-634.

Rea,W.J., Didriksen,N., Simon,T.R., Pan,Y., Fenyves,E.J.and Griffiths,B., 2003. Effects of toxic exposure to molds and mycotoxins in building-related illnesses. Arch.Environ.Health 58, 399-405.

Reinhard,M.J., Satz,P., Scaglione,C.A., D’Elia,L.F., Rassovsky,Y., Arita,A.A.et al, 2007. Neuropsychological exploration of alleged mold neurotoxicity. Arch.Clin Neuropsychol. 22, 533-543.

Rossignol,D.A., Frye,R.E., 2012. A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Mol.Psychiatry 17, 389-401.

Rousset,S., Emre,Y., Join-Lambert,O., Hurtaud,C., Ricquier,D.and Cassard-Doulcier,A.M., 2006. The uncoupling protein 2 modulates the cytokine balance in innate immunity. Cytokine 35, 135-142.

Ryu,J.W., Hong,K.H., Maeng,J.H., Kim,J.B., Ko,J., Park,J.Y.et al, 2004. Overexpression of uncoupling protein 2 in THP1 monocytes inhibits beta2 integrin-mediated firm adhesion and transendothelial migration. Arterioscler.Thromb.Vasc.Biol. 24, 864-870.

Seelinger,G., Merfort,I.and Schempp,C.M., 2008. Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin. Planta Med. 74, 1667-1677.

Sheikh,I.A., Ali,R., Dar,T.A.and Kamal,M.A., 2012. An overview on potential neuroprotective compounds for management of Alzheimer’s disease. CNS.Neurol.Disord.Drug Targets. 11, 1006-1011.

Shenassa,E.D., Daskalakis,C., Liebhaber,A., Braubach,M.and Brown,M., 2007. Dampness and mold in the home and depression: an examination of mold-related illness and perceived control of one’s home as possible depression pathways. Am.J Public Health 97, 1893-1899.

Shim,S.Y., Park,J.R.and Byun,D.S., 2012. 6-Methoxyluteolin from Chrysanthemum zawadskii var. latilobum suppresses histamine release and calcium influx via down-regulation of FcepsilonRI alpha chain expression. J Microbiol.Biotechnol. 22, 622-627.

Shoemaker,R.C., House,D.E., 2006. Sick building syndrome (SBS) and exposure to water-damaged buildings: time series study, clinical trial and mechanisms. Neurotoxicol.Teratol. 28, 573-588.

Sismanopoulos,N., Delivanis,D.A., Alysandratos,K.D., Angelidou,A., Therianou,A., Kalogeromitros,D.et al, 2012. Mast cells in allergic and inflammatory diseases. Curr.Pharm.Des 18, 2261-2277.

Skaper,S.D., Facci,L.and Giusti,P., 2013. Mast cells, glia and neuroinflammation: partners in crime? Immunology 141, 314-327.

Skaper,S.D., Giusti,P.and Facci,L., 2012. Microglia and mast cells: two tracks on the road to neuroinflammation. FASEB J 26, 3103-3117.

Smith,J.H., Butterfield,J.H., Pardanani,A., DeLuca,G.C.and Cutrer,F.M., 2011. Neurologic symptoms and diagnosis in adults with mast cell disease. Clin Neurol Neurosurg. 113, 570-574.

Solanki,I., Parihar,P., Mansuri,M.L.and Parihar,M.S., 2015. Flavonoid-based therapies in the early management of neurodegenerative diseases
1. Adv.Nutr. 6, 64-72.

Swindle,E.J., Metcalfe,D.D., 2007. The role of reactive oxygen species and nitric oxide in mast cell-dependent inflammatory processes. Immunol.Rev. 217, 186-205.

Swindle,E.J., Metcalfe,D.D.and Coleman,J.W., 2004. Rodent and human mast cells produce functionally significant intracellular reactive oxygen species but not nitric oxide. J.Biol.Chem. 279, 48751-48759.

Tagen,M., Elorza,A., Boucher,W., Kepley,C.L., Shirihai,O.and Theoharides,T.C., 2009. Mitochondrial uncoupling protein 2 (UCP2) inhibits mast cell activation and reduces histamine content. J Immunol 183, 6313-6319.

Taliou,A., Zintzaras,E., Lykouras,L.and Francis,K., 2013. An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders. Clin Ther 35, 592-602.

Theoharides,T.C., 2009. Autism spectrum disorders and mastocytosis. Int J Immunopathol Pharmacol 22, 859-865.

Theoharides,T.C., 2013a. Atopic conditions in search of pathogenesis and therapy. Clin Ther 35, 544-547.

Theoharides,T.C., 2013b. Is  a subtype of autism “allergy of the brain”? Clin.Ther. 35, 584-591.

Theoharides,T.C., Alysandratos,K.D., Angelidou,A., Delivanis,D.A., Sismanopoulos,N., Zhang,B.et al, 2010. Mast cells and inflammation. Biochim Biophys Acta 1822, 21-33.

Theoharides,T.C., Angelidou,A., Alysandratos,K.D., Zhang,B., Asadi,S., Francis,K.et al, 2012. Mast cell activation and autism. Biochim.Biophys.Acta 1822, 34-41.

Theoharides,T.C., Asadi,S.and Panagiotidou,S., 2012. A case series of a luteolin formulation (NeuroProtek(R)) in children with autism spectrum disorders. Int J Immunopathol Pharmacol 25, 317-323.

Theoharides,T.C., Asadi,S.and Patel,A., 2013. Focal brain inflammation and autism. J Neuroinflammation 10.

Theoharides,T.C., Cochrane,D.E., 2004. Critical role of mast cells in inflammatory diseases and the effect of acute stress. J Neuroimmunol 146, 1-12.

Theoharides,T.C., Conti,P.and Economu,M., 2014. Brain inflammation, neuropsychiatric disorders, and immunoendocrine effects of luteolin. J Clin Psychopharmacol 34, 187-189.

Theoharides,T.C., Konstantinidou,A., 2007. Corticotropin-releasing hormone and the blood-brain-barrier. Front Biosci 12, 1615-1628.

Theoharides,T.C., Petra,A.I., Stewart,J.M., Tsilioni,I., Panagiotidou,S.and Akin,C., 2014. High serum corticotropin-releasing hormone (CRH) and bone marrow mast cell CRH receptor expression in a mastocytosis patient. J.Allergy Clin.Immunol. 134, 1197-1199.

Theoharides,T.C., Valent,P.and Akin C., 2015. Mast cells, mastocytosis and related diseases. New Engl J Med in press.

Theoharides,T.C., Zhang,B.and Conti,P., 2011. Decreased mitochondrial function and increased brain inflammation in bipolar disorder and other neuropsychiatric diseases. J Clin Psychopharmacol. 31, 685-687.

Thilakarathna,S.H., Rupasinghe,H.P., 2013. Flavonoid bioavailability and attempts for bioavailability enhancement. Nutrients. 5, 3367-3387.

Tsai,F.S., Peng,W.H., Wang,W.H., Wu,C.R., Hsieh,C.C., Lin,Y.T.et al, 2007. Effects of luteolin on learning acquisition in rats: involvement of the central cholinergic system. Life Sci. 80, 1692-1698.

United Nations, Department of Economic and Social Affairs PopulationDivision. World Population Prospects:The 2010 Revision.  2015.
Ref Type: Report

Valent,P., Akin,C., Arock,M., Brockow,K., Butterfield,J.H., Carter,M.C.et al, 2012. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol 157, 215-225.

Vauzour,D., 2014. Effect of flavonoids on learning, memory and neurocognitive performance: relevance and potential implications for Alzheimer’s disease pathophysiology. J Sci.Food Agric. 94, 1042-1056.

Verbeek,R., Plomp,A.C., van Tol,E.A.and van Noort,J.M., 2004. The flavones luteolin and apigenin inhibit in vitro antigen-specific proliferation and interferon-gamma production by murine and human autoimmune T cells. Biochem.Pharmacol. 68, 621-629.

Vogler,S., Pahnke,J., Rousset,S., Ricquier,D., Moch,H., Miroux,B.et al, 2006. Uncoupling protein 2 has protective function during experimental autoimmune encephalomyelitis. Am.J Pathol. 168, 1570-1575.

Walle,T., 2007. Methylation of dietary flavones greatly improves their hepatic metabolic stability and intestinal absorption. Mol.Pharm 4, 826-832.

Wei,G., Hwang,L.and Tsai,C., 2014. Absolute bioavailability, pharmacokinetics and excretion of 5,7,30,40 -tetramethoxyflavone in rats. J Functional Foods 7, 136-141.

Weng Z, Patel A, Panagiotidou Sand Theoharides TC, 2014. The novel flavone tetramethoxyluteolin is a potent inhibitor of human mast cells. J Allergy Clin Immunol in press.

Weng, Z. and Theoharides, T. C. Luteolin inhibits inflammatory cytokine release and proliferation of human cultured keratinocytes: application in psoriasis. Exp Biology . 2013.
Ref Type: Journal (Full)

Xu,S.L., Bi,C.W., Choi,R.C., Zhu,K.Y., Miernisha,A., Dong,T.T.et al, 2013. Flavonoids induce the synthesis and secretion of neurotrophic factors in cultured rat astrocytes: a signaling response mediated by estrogen receptor. Evid.Based.Complement Alternat.Med. 2013, 127075.

Yamada,S., Isojima,Y., Yamatodani,A.and Nagai,K., 2003. Uncoupling protein 2 influences dopamine secretion in PC12h cells. J Neurochem. 87, 461-469.

Yang,Y., Oh,J.M., Heo,P., Shin,J.Y., Kong,B., Shin,J.et al, 2013. Polyphenols differentially inhibit degranulation of distinct subsets of vesicles in mast cells by specific interaction with granule-type-dependent SNARE complexes. Biochem.J 450, 537-546.

Yoo,D.Y., Choi,J.H., Kim,W., Nam,S.M., Jung,H.Y., Kim,J.H.et al, 2013. Effects of luteolin on spatial memory, cell proliferation, and neuroblast differentiation in the hippocampal dentate gyrus in a scopolamine-induced amnesia model. Neurol.Res. 35, 813-820.

Zhang,B., Alysandratos,K.D., Angelidou,A., Asadi,S., Sismanopoulos,N., Delivanis,D.A.et al, 2011. Human mast cell degranulation and preformed TNF secretion require mitochondrial translocation to exocytosis sites: Relevance to atopic dermatitis. J Allergy Clin Immunol 127, 1522-1531.

Zhu,L.H., Bi,W., Qi,R.B., Wang,H.D.and Lu,D.X., 2011. Luteolin inhibits microglial inflammation and improves neuron survival against inflammation. Int J Neurosci. 121, 329-336.

Zhu,X., Perry,G., Smith,M.A.and Wang,X., 2012. Abnormal mitochondrial dynamics in the pathogenesis of Alzheimer’s Disease. J Alzheimers.Dis.

Creswell, J. David, Adrienne A. Taren, Emily K. Lindsay, Carol M. Greco, Peter J. Gianaros, April Fairgrieve, Anna L. Marsland, Kirk Warren Brown, Baldwin M. Way, Rhonda K. Rosen, and Jennifer L. Ferris. “Alterations in Resting-State Functional Connectivity Link Mindfulness Meditation With Reduced Interleukin-6: A Randomized Controlled Trial.” Biological Psychiatry (2016). Web.

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Yasmina was an award-winning broadcast journalist with a decade of experience covering war zones for CNN and the BBC. She devoted her journalism skills to researching and writing about histamine. Click here to learn about her. Each post is carefully and fully referenced with the latest scientific research. Not sure where to start? Here’s a four week meal plan and overall Histamine Reset.

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