Histamine’s Effect on Memory (Goldfish Brain)

Goldfish in a fishbowl isolated on white background histamine memory goldfish brainDifficulty remembering things? Starting to think Alzheimer’s is setting in? Don’t worry just yet. It may have nothing to do with the number of candles on your birthday cake. Those with mast cell disorders and histamine intolerance often report a lack of mental clarity and focus, as well as varying levels of forgetfulness.

This is all likely due to a combination of chronic inflammation, oxidative stress/free radicals, and the body being kept in a chronic state of stress. Studies show histamine levels have a direct effect on the formation of memories. Something I frequently refer to as “goldfish brain”.

While a certain level of histamine is necessary for brain function (and even critical), including learning and memory, too much is detrimental. Out of control histamine levels are a recipe for cognitive catastrophe. And that’s where those of us with mast cell disorders live…

In animal studies, disturbances in the brain’s histamine system causes an inability to retrieve memories. In some studies, histamine itself was shown to decrease memory retention, while blocking the histamine receptors was shown to increase memory retention. However, other studies demonstrate the opposite — with histamine increasing memory.

It’s probably better to focus on other factors, like oxidative stress, inflammation, and the chronic fight-or-flight stress response.


Oxidative Stress

Histamine can cause a number of issues with cognitive function due, in part, to the oxidative stress (free radicals) it produces. One of the main free radicals produced by mast cells is superoxide, which is deployed by the immune system as a defense against threats — particularly harmful microorganisms. While superoxide is there for our benefit– to protect us– it also is toxic to the body and damages our tissues, including brain tissue. Oxidative stress in the hippocampus in the brain leads to memory issues.


Inflammatory Cytokines

The inflammatory cytokines which are increased in the presence of high histamine have also been shown to break down the hippocampus, the memory center of the brain.

A study published in the journal, Neuroscience and Biobehavioral Reviews, found that the cytokines produced by mast cells, IL-1beta, IL-6, and TNF-alpha, play a role in the brain’s ability to make new connections and grow new brain cells. This has huge implications for learning and memory.

TNF-alpha is especially bad for memory because it suppresses orexin, a neurotransmitter in the brain that is important for the acquisition and consolidation of new memories, as well as for long-term memory storage.

It’s interesting to note that TNF-alpha levels are high in Traumatic Brain Injury (TBI) patients as well as in post-chemotherapy brains — Hence “Chemo Brain.”

IL-1beta, which tends to accompany TNF-alpha, has many similar functions, including the tendency to induce IL-6. TNF-alpha and IL-1 also induce each other, keeping the inflammatory cycle going.

Since IL-1beta suppresses the brain’s production of Brain-Derived Neurotrophic Factor (BDNF), another chemical critical for memory, the brain receives yet another hit in the memory department.

IL-6 is another cytokine that decreases BDNF and has been associated with cognitive decline in human studies.

Chronic state of Stress

The limbic system is the emotional area of the brain, which deals with stressors, and the hippocampus is within its jurisdiction. The hippocampus is critical for long term memory storage. When it is impaired with inflammation and degeneration, memory may be compromised; this is seen in extreme form with the diagnosis of dementia.


Luteolin-rich Foods

According to Dr. Theoharides at Tufts University, brain fog (often resulting in memory loss) may be due to inflammatory molecules and histamine released from mast cells, causing brain inflammation. AND naturally occurring flavonoids, like luteolin (and quercetin to an extent), can help. Quercetin and luteolin rich foods include: broccoli, parsley, artichoke, butternut squash, and all the foods in my Histamine Reset program.

  • Neuroprotek

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.


Curcumin is powerful against both oxidative stress and inflammation. It specifically inhibits the release of cytokines IL-1beta, IL-6, TNF-alpha mentioned earlier that are behind chronic inflammation, suppression of orexin, and memory problems.

Increase Orexin

Strategies to boost orexin include using red light therapy (I use the Joovv light), getting outside for some sunshine, interval training, takeing it easy on sugars, and lightly restricting calories.

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

Use it or lose it

Let’s not overlook that our brain needs exercise too: scientists suggest learning a new language, take a different route to work, brush your teeth with the non-dominant hand, anything to take the brain out of auto pilot.

———- REFERENCES ————

Cristiano André Köhler, Weber Cláudio da Silva, Fernando Benetti, and Juliana Sartori Bonini, “Histaminergic Mechanisms for Modulation of Memory Systems,” Neural Plasticity, vol. 2011, Article ID 328602, 16 pages, 2011. doi:10.1155/2011/328602

Clark, I. A., & Vissel, B. (2014). Inflammation-sleep interface in brain disease: TNF, insulin, orexin. Journal of Neuroinflammation, 11, 51. http://doi.org/10.1186/1742-2094-11-51

Eidi, M., Zarrindast, M. R., Eidi, A., Oryan, S., and Parivar, K. (2003). Effects of histamine and cholinergic systems on memory retention of passive avoidance learning in rats. European Journal of Pharmacology, 465(1-2), 91-96.


Henderson, W. R. and Kaliner, M. (1978). Immunologic and nonimmunologic generation of superoxide from mast cells and basophils.

Journal of Clinical Investigation, 61(1), 187-196. doi:10.1172/JCI108917.

Klein, B., Mrowetz, H., Thalhamer, J., Scheiblhofer, S., Weiss, R., and Aigner, L. (2016). Allergy enhances neurogenesis and modulates microglial activation in the hippocampus. Frontiers in Cellular Neuroscience, 10(169), n. p.  https://doi.org/10.3389/fncel.2016.00169

McAfoose, J. and Baune, B. T. (2009). Evidence for a cytokine model of cognitive function.Neuroscience Biobehavioral Review, 33(3), 355-66. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/18996146

Rada, B., Boudreau, H. E., Park, J. J., & Leto, T. L. (2014). Histamine Stimulates Hydrogen Peroxide Production by Bronchial Epithelial Cells via Histamine H1 Receptor and Dual Oxidase. American Journal of Respiratory Cell and Molecular Biology, 50(1), 125–134. http://doi.org/10.1165/rcmb.2013-0254OC

Rajmohan, V., & Mohandas, E. (2007). The limbic system. Indian Journal of Psychiatry, 49(2), 132–139. http://doi.org/10.4103/0019-5545.33264

Silva, R. H. et. al. (2004). Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Neuropharmacology. 46(6): 895-903. https://www.ncbi.nlm.nih.gov/pubmed/15033349

Sikora, E., Bielak-Zmijewska, A., Mosieniak, G., Piwocka, K. (2010). The promise of slow down ageing may come from curcumin. Current Pharmaceutical Design, 16(7), 884-92. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/20388102

Singh-Manoux, A., Dugravot, A., Brunner, E., Kumari, M., Shipley, M., Elbaz, A., & Kivimaki, M. (2014). Interleukin-6 and C-reactive protein as predictors of cognitive decline in late midlife. Neurology, 83(6), 486–493. http://doi.org/10.1212/WNL.0000000000000665

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., Alysandratos, K.-D., Angelidou, A., Delivanis, D.-A., Sismanopoulos, N., Zhang, B., … Kalogeromitros, D. (2012). Mast cells and inflammation. Biochimica et Biophysica Acta, 1822(1), 21–33. http://doi.org/10.1016/j.bbadis.2010.12.014

Tong, L., Balazs, R., Soiampornkul, R., Thangnipon, W., & Cotman, C. W. (2008). Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction. Neurobiology of Aging, 29(9), 1380–1393. http://doi.org/10.1016/j.neurobiolaging.2007.02.027

Cohen, J. (2017, December 07). 30 Ways To Naturally Increase Orexin/Hypocretin (and Wakefulness). Retrieved January 31, 2018, from https://www.selfhacked.com/blog/how-to-increase-orexin-and-decrease-fatigue-naturally/?_ga=2.48436262.1893799168.1516943742-2092241840.1515423537#1Get_Rid_of_Inflammation