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Histamine Intolerance and The Paleo Diet

By Casey Thaler, B.A., NASM-CPT, FNS
June 10, 2014
Histamine Intolerance and The Paleo Diet image

Do you suffer from headaches or migraines? Low blood pressure? Maybe a runny nose? All of these symptoms could be resultant of a histamine intolerance. This vastly overlooked condition can derail many who would otherwise greatly benefit from The Paleo Diet. But what exactly is histamine and what does it mean to be intolerant to it?

Histamine is a biogenic amine that occurs (in differing amounts) in many foods.1 In a person without an intolerance, exogenous histamine obtained via food can be rapidly detoxified by amine oxidases.2 In subjects with an intolerance, there is usually low amine oxidase activity. Diamine oxidase (DAO) is the primary enzyme which metabolizes dietary histamine.3 Below is a comprehensive list detailing the kinds of foods that may cause reactions in individuals with low amine oxidase activity or commonly referred to as histamine intolerance.

Histamine-Rich & Histamine-Releasing Foods
Aged cheese
Artificial preservatives
Citrus fruits
Goat cheese
Hot dogs
Smoked fish
Sour cream
Sour milk
Soy Sauce


Wheat germ

Astute readers will note this list contains histamine-rich foods, as well as histamine-releasing foods. There are other causes of histamine intolerance, besides having low DAO activity4 including ‘leaky gut’,2,3 among other commonly exhibited symptoms as seen in the second table.

Symptoms of Histamine Intolerance
Acid reflux
Asthma-like symptoms
Chest pain
Chronic headache
Digestive tract upset
Nasal congestion
Runny nose



Diagnosing a histamine intolerance can be a bit tricky in that you can be tested for allergies, and have negative test results across the board, yet still be histamine intolerant.7 This is a case where the best method of action, is to follow a low histamine diet for a period of time, and then slowly re-introduce foods which provoke a histamine response.

Since your body produces histamine8 it is best to think of histamine intolerance as an ‘overflow’ type of situation. Exogenous sources of histamine put your body over the edge. Other causes of histamine intolerance include: allergies, GI bleeding, and small intestinal bacterial overgrowth (SIBO). Endogenous histamine is so important that histaminergic neurons may form part of a “flip–flop switch” hypothesized to regulate sleep and wakefulness9 It is also important to note that antipsychotic drugs can interact with H1 histamine receptors, and may lead to weight gain10 In cases of asthma, histamine can modulate the cytokine network through up regulation of prostaglandin E and nitric oxide11 Then there is the case of atopic dermatitis, which can be improved via a low histamine diet.12 There are also studies, which show that modulation of histamine receptors (specifically H1 receptors) can affect actual dietary intake.13

Histamine-induced food intolerance is not IgE-mediated.14 This means, again, that the best way to improve a histamine intolerance is to follow a low histamine diet, which can easily be done within The Paleo Diet framework. Diamine oxidase cannot be supplemented; so lowering your histamine intake via food is the best method of action. As stated in this study,15 the only effective long-term therapy for a histamine intolerance is the avoidance of histamine-containing food.

Histamine Intolerance and The Paleo Diet image


1. Naila A, Flint S, Fletcher G, Bremer P, Meerdink G. Control of biogenic amines in food--existing and emerging approaches. J Food Sci. 2010;75(7):R139-50.

2. Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007;85(5):1185-96.

3. Kusche J, Lorenz W, Schmidt J. Oxidative deamination of biogenic amines by intestinal amine oxidases: histamine is specifically inactivated by diamine oxidase. Hoppe-Seyler's Z Physiol Chem. 1975;356(10):1485-86.

4. Rosell-camps A, Zibetti S, Pérez-esteban G, Vila-vidal M, Ferrés-ramis L, García-teresa-garcía E. Histamine intolerance as a cause of chronic digestive complaints in pediatric patients. Rev Esp Enferm Dig. 2013;105(4):201-6.

5. Fasano A. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol. 2012;42(1):71-8.

6. Andriopoulou P, Navarro P, Zanetti A, Lampugnani MG, Dejana E. Histamine induces tyrosine phosphorylation of endothelial cell-to-cell adherens junctions. Arterioscler Thromb Vasc Biol. 1999;19(10):2286-97.

7. Götz M. [Pseudo-allergies are due to histamine intolerance]. Wien Med Wochenschr. 1996;146(15):426-30.

8. Marieb, E. (2001). Human anatomy & physiology. San Francisco: Benjamin Cummings. p. 414. ISBN 0-8053-4989-8.

9. Williams RH, Chee MJ, Kroeger D, et al. Optogenetic-mediated release of histamine reveals distal and autoregulatory mechanisms for controlling arousal. J Neurosci. 2014;34(17):6023-9.

10. Kroeze WK, Hufeisen SJ, Popadak BA, et al. H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology. 2003;28(3):519-26.

11. Packard KA, Khan MM. Effects of histamine on Th1/Th2 cytokine balance. Int Immunopharmacol. 2003;3(7):909-20.

12. Chung BY, Cho SI, Ahn IS, et al. Treatment of Atopic Dermatitis with a Low-histamine Diet. Ann Dermatol. 2011;23 Suppl 1(Suppl 1):S91-5.

13. Mercer LP, Kelley DS, Humphries LL, Dunn JD. Manipulation of central nervous system histamine or histaminergic receptors (H1) affects food intake in rats. J Nutr. 1994;124(7):1029-36.

14. Wantke F, Götz M, Jarisch R. Histamine-free diet: treatment of choice for histamine-induced food intolerance and supporting treatment for chronic headaches. Clin Exp Allergy. 1993;23(12):982-5.

15. Schwelberger HG. Histamine intolerance: a metabolic disease?. Inflamm Res. 2010;59 Suppl 2:S219-21.

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