Arthritis. Atherosclerosis. Colitis. Eczema. Psoriasis.
Q: What are two things that all of these diseases have in common?
A: Inflammation & food.
Mast Cell Activation, Histamines, and Inflammation
Mast cells, or granulated immune cells that are located at barrier sites on the body such as the skin and gastrointestinal tract,1 are known for their role in defense against pathogens (particularly bacteria), for neutralization of venom toxins, and for triggering allergic responses and anaphylaxis.2 Activated mast cells also recruit other innate and adaptive immune cells and can participate in tuning the immune response,2 and are considered the major effector cells in allergic disorders.3 Mast cell stabilization is also the basis for medications that may help reduce symptoms of allergic/inflammatory conditions.
In recent years, low grade inflammatory infiltration, often rich in mast cells, in both the small and large bowel has been observed in patients with irritable bowel syndrome (IBS).4,5 Mast cells can be activated in the gut in an IgE-dependent way via the high-affinity receptor Fc epsilon RI, which plays a key role in allergic reactions.4 IgG, IgA, Ig-free light chains, and even complements (C3a and C5a) might also play a role via binding to the related receptors expressed on mast cells.4 When activated, mast cells release bioactive substances preformed in granules (histamine, enzymes, and heparin) and newly synthesized cytokine, chemokines, and lipid metabolites.4
These mediators may participate in disease processes beyond allergy and IBS, including functional dyspepsia, inflammatory bowel disease, and intestinal infections.4,6
Biochemical and nutritional inadequacies contribute to immune response. Diamine oxidase (DAO) is an enzyme that’s responsible for breaking down histamine. Low levels of DAO can cause histamine levels to rise and potentially lead to histamine sensitivity, chronic inflammation, or idiopathic mast cell activation syndrome—a condition in which the patient experiences repeated episodes of the symptoms of anaphylaxis—allergic symptoms such as hives, swelling, low blood pressure, difficulty breathing, and severe diarrhea. High levels of mast cell mediators are released during those episodes.
Some patients with functional gastrointestinal disorders have also been diagnosed as histamine intolerant, based on low DAO values and improvement of symptoms with a histamine-reduced diet.7 In a 2019 study, a significant increase of serum DAO levels was found in patients with strict and occasional low-histamine diet compliance.7 Another recent study found that vitamin D may be required to maintain the stability of mast cells, and a deficiency of vitamin D may result in mast cell activation.3 Increasing evidence indicates that mast cells are involved in many diseases.8 Research suggests that psoriasis, atopic dermatitis, interstitial cystitis, and asthma have strong associations with mast cells; cancer, arthritis, IBS, multiple sclerosis, coronary artery disease, and obesity have a medium association; and prostatitis, ulcers, infections, inflammatory bowel disease, migraines, autism, and periodontitis have weak associations.8
Research also suggests that patients with urticaria, a common skin condition that can be caused by a release of mediators such as histamine, have also shown improvement on a histamine-free diet.9 Study participants restricted foods with high histamine levels for four weeks, including foods such as tuna, mackerel, pork, and spinach, as well as fermented foods such as sauerkraut, yogurt, cheese, wine, and beer; there were significant clinical improvements in urticaria severity, and plasma histamine levels were significantly reduced after the histamine-free diet.9 In 2018, a randomized double-blind placebo-controlled study suggested that DAO may be involved in the pathogenic cascade of chronic spontaneous urticarial and migraine, and that DAO supplementation could be effective for symptom relief in patients with low DAO levels in serum.10
Anti-Inflammatory Foods to Support Immune Health
Rather than focusing entirely on removing foods, functional medicine also seeks to support immune health. What foods are known to fight inflammation and stabilize mast cells naturally? The following list is a selection of anti-inflammatory foods, in no particular order, with associated clinical references:
Watercress is a cruciferous vegetable that is considered one of the most nutrient-dense plants commonly available. A study showed that watercress inhibits 60% of all histamines released from mast cells. Of the 15 compounds isolated, flavonols and megastigmanes significantly inhibited histamine release.11
Onions (including the spring onion) are an important prebiotic food. Onions have been shown to inhibit histamine release, stabilize mast cells, and even lower histamine levels extracellularly in blood plasma.12 One study suggests that quercetin, found in onions, is a promising candidate as an effective mast cell inhibitor for allergic and inflammatory diseases.13 In two pilot open-label clinical trials, quercetin significantly decreased contact dermatitis and photosensitivity, skin conditions that do not respond to conventional treatment.13
Moringa is a “super-food” that has found its way onto health food shelves. It is so nutrient dense that it has historically been used to treat malnutrition. A study in pigs suggests that moringa inhibits 72% of all histamines released, making it almost as effective as ketotifen.14 The results of a 2016 study, in vitro and in vivo, strongly suggest the beneficial effects of moringa on atopic dermatitis via the regulation of inflammatory responses.15
Chamomile is typically consumed as a tea. Fresh flowers are frequently available and are preferable to dried. One study suggests that, in mast cell–mediated allergic models, chamomile acted in a dose-dependent manner to inhibit histamine release from mast cells.16
Nettle is typically consumed as a tea. In vitro, it has been shown to be a potent antihistamine (working at the H1 receptor) and mast cell stabilizer.17
Galangal is also called “Thai ginger” and is readily available at Asian grocers. Research using in vitro and in vivo models suggests that a compound of galangal, called galangin, downregulates mast cell–derived allergic inflammatory reactions by blocking histamine release and expression of pro-inflammatory cytokines and could be a beneficial anti-allergic inflammatory agent.18
Turmeric has powerful anti-inflammatory and anti-oxidant properties. Curcumin, an active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. A 2003 study suggests that curcumin inhibits protease-activated receptors (PAR), which play a role in inflammation and PAR2 and 4-mediated human mast cell activation.19
Apples are not so much rich in one nutrient but instead have a wide range of flavonoids and polyphenols. A randomized double-blind placebo-controlled study in 33 patients suggests that apple polyphenols (found in the apple peel) are effective in alleviating symptoms of persistent allergic rhinitis.20
Peaches. A 2010 study suggests that peaches inhibit mast cell–derived allergic inflammation.21 The inhibitory effect of peaches on pro-inflammatory cytokines was nuclear factor (NF)-kappaB dependent.21
Brazil nuts have an extraordinary selenium content. The trace mineral selenium is an antioxidant, and a single Brazil nut can provide more than twice the recommended dietary allowance of selenium. A 2013 study showed that selenium-treated mast cells revealed significant decrease in concentration of histamine and prostaglandin D2 and beta-hexosaminidase.22 In addition, a slight reduction of histamine release by the selenium-treated cells was observed, based on the study’s intracellular and extracellular assessments. The study demonstrated the beneficial effects of supplemental selenium in attenuating clinical manifestations of allergy and asthma.22
Fiber. Consistent with the reported health benefits on other immune cells, studies suggest that dietary fiber (especially polysaccharides and oligosaccharides) and metabolites can regulate mast cell function. Mast cell function has been shown to be susceptible to the immunoregulatory effects of dietary fiber and butyrate.23
Personalized nutritional intervention strategies are just one functional medicine tool used to combat chronic inflammation and support a patient’s immune health. Learn more from field experts at IFM’s Immune Advanced Practice Module (APM).
- Lorentz A, Sellge G, Bischoff SC. Isolation and characterization of human intestinal mast cells. Methods Mol Biol. 2015;1220:163-177. doi:10.1007/978-1-4939-1568-2_11
- DeBruin EJ, Gold M, Lo BC, et al. Mast cells in human health and disease. Methods Mol Biol. 2015;1220:93-119. doi:10.1007/978-1-4939-1568-2_7
- Liu ZQ, Li XX, Qiu SQ, et al. Vitamin D contributes to mast cell stabilization. Allergy. 2017;72(8):1184-1192. doi:10.1111/all.13110
- Zhang L, Song J, Hou X. Mast cells and irritable bowel syndrome: from the bench to the bedside. J Neurogastroenterol Motil. 2016;22(2):181-192. doi:10.5056/jnm15137
- Krammer L, Sowa AS, Lorentz A. Mast cells in irritable bowel syndrome: a systematic review. J Gastrointestin Liver Dis. 2019;28(4):463-472. doi:10.15403/jgld-229
- Wilder-Smith CH, Drewes AM, Materna A, Olesen SS. Symptoms of mast cell activation syndrome in functional gastrointestinal disorders. Scand J Gastroenterol. 2019;54(11):1322-1325. doi:10.1080/00365521.2019.1686059
- Lackner S, Malcher V, Enko D, Mangge H, Holasek SJ, Schnedl WJ. Histamine-reduced diet and increase of serum diamine oxidase correlating to diet compliance in histamine intolerance. Eur J Clin Nutr. 2019;73(1):102-104. doi:10.1038/s41430-018-0260-5
- Theoharides TC, Alysandratos KD, Angelidou A, et al. Mast cells and inflammation. Biochim Biophys Acta. 2012;1822(1):21-33. doi:10.1016/j.bbadis.2010.12.014
- Son JH, Chung BY, Kim HO, Park CW. A histamine-free diet is helpful for treatment of adult patients with chronic spontaneous urticaria. Ann Dermatol. 2018;30(2):164-172. doi:10.5021/ad.2018.30.2.164
- Yacoub MR, Ramirez GA, Berti A, et al. Diamine oxidase supplementation in chronic spontaneous urticarial: a randomized, double-blind placebo-controlled study. Int Arch Allergy Immunol. 2018;176(3-4):268-271. doi:10.1159/000488142
- Goda Y, Hoshino K, Akiyama H, et al. Constituents in watercress: inhibitors of histamine release from RBL-2H3 cells induced by antigen stimulation. Biol Pharm Bull. 1999;22(12):1319-1326. doi:10.1248/bpb.22.1319
- Kaiser P, Youssouf MS, Tasduq SA, et al. Anti-allergic effects of herbal product from Allium cepa (bulb). J Med Food. 2009;12(2):374-382. doi:10.1089/jmf.2007.0642
- Weng Z, Zhang B, Asadi S, et al. Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans. PLoS One. 2012;7(3):e33805. doi:10.1371/journal.pone.0033805
- Mehta A, Agrawal B. Investigation into the mechanism of action of Moringa oleifera for its anti-asthmatic activity. Orient Pharm Exp Med. 2008;8(1):24-31. doi:10.3742/OPEM.2008.8.1.024
- Choi EJ, Debnath T, Tang Y, Ryu YB, Moon SH, Kim EK. Topical application of Moringa oleifera leaf extract ameliorates experimentally induced atopic dermatitis by the regulation of Th1/Th2/Th17 balance. Biomed Pharmacother. 2016;84:870-877. doi:10.1016/j.biopha.2016.09.085
- Chandrashekhar VM, Halagali KS, Nidavani RB, et al. Anti-allergic activity of German chamomile (Matricaria recutita L.) in mast cell mediated allergy model. J Ethnopharm. 2011;137(1):336-340. doi:10.1016/j.jep.2011.05.029
- Roschek B Jr, Fink RC, McMichael M, Alberte RS. Nettle extract (Urtica dioica) affects key receptors and enzymes associated with allergic rhinitis. Phytother Res. 2009;23(7):920-926. doi:10.1002/ptr.2763
- Kim HH, Bae Y, Kim SH. Galangin attenuates mast cell-mediated allergic inflammation. Food Chem Toxicol. 2013;57:209-216. doi:10.1016/j.fct.2013.03.015
- Baek OS, Kang OH, Choi YA, et al. Curcumin inhibits protease-activated receptor-2 and -4-mediated mast cell activation. Clin Chim Acta. 2003;338(1-2):135-141. doi:10.1016/j.cccn.2003.08.015
- Enomoto T, Nagasako-Akazome Y, Kanda T, Ikeda M, Dake Y. Clinical effects of apple polyphenols on persistent allergic rhinitis: a randomized double-blind placebo-controlled parallel arm study. J Investig Allergol Clin Immunol. 2006;16(5):283-289.
- Shin TY, Park SB, Yoo JS, et al. Anti-allergic inflammatory activity of the fruit of Prunus persica: role of calcium and NF-kappaB. Food Chem Toxicol. 2010;48(10):2797-2802. doi:10.1016/j.fct.2010.07.009
- Safaralizadeh R, Nourizadeh M, Zare A, Kardar GA, Pourpak Z. Influence of selenium on mast cell mediator release. Biol Trace Elem Res. 2013;154(2):299-303. doi:10.1007/s12011-013-9712-x
- Folkerts J, Stadhouders R, Redegeld FA, et al. Effect of dietary fiber and metabolites on mast cell activation and mast cell-associated diseases. Front Immunol. 2018;9:1067. doi:10.3389/fimmu.2018.01067