What Is Histamine ?

Clipart of cheese with holes in it. A source of histamine and tyramine.
Clipart by OpenClipart Vectors, c/o Pixabay.

Histamine is found in many food products especially, cheese, fish, some fermented vegetables, fermented sausages and salamis, and some alcoholic beverages. It appears to accummulate in fermented or spoiled foods particularly. Its presence is often a marker of food safety. In fish it is the basis behind scombrotoxin food poisoning.

Histamine is a low-molecular weight nitrogenous compound, a biogenic amine which has a basic reaction chemistry. It is formed by the decarboxylation of histidine and is usually generated by bacteria which produce histamine (Diaz et al., 2015). 

The production of histamine and its accumulation in high protein food products depends on many factors. Most of these physicochemical ones associated with the condition of the food and the manner of its storage:-

  • pH
  • moisture content
  • rawness and quality
  • method of processing
  • manufacturing equipment
  • substrate concentrations of histidine
  • presence of histamine producing bacteria in the food product or in the starter cultures


Histamine has a number of important roles in the body. Notably, it plays a part in human memory and learning, regulating body temperature and responsiveness to immunological challenges.

Normally, ingested histamine is degraded by catalysis using histamine oxidases. if detoxification is inadequate because of illness or the initial concentration is too high, then histamine intolerance and poisoning occurs (Linares et al., 2012).

Histamine intolerance in the wider human population is 1% and is especially prevalent in the middle aged (Kovacova-Hanuskova et al., 2015).

Histamine Producing Micro-organisms

The production of histamine by microbial decarboxylation of histidine is a survival mechanism for use in acidic environments (Trip et al., 2012). The histamine-producing microorganisms in fermented products are mainly lactic acid bacteria (LAB) which have the histidine decarboxylase gene cluster either on a the bacterial chromosome or in a plasmid.

When it comes to cheeses, the LAB are usually present in the vat milk, are part of the starter culture or contaminate the food during manufacturing. The presence of these bacteria is virtually impossible to avoid if very low-quality or a poor supply chain is managed. 


If too much histamine is consumed then a number of symptoms of poisoning occur. these are headache, urticaria, rashes and dizziness (Ladero et al., 2010). The cytotoxic actions acts synergistically with tyramine which is another biogenic amine. The cytotoxic threshold is 440 mg/kg and can often be exceeded in all the produce described so far if spoilage is really bad (Alvarez & Moreno-Arribas, 2014).

Some cheeses such as blue cheese and long-ripened cheese can have histamine levels at 1g/kg (Fernandez et al., 2006, 2007). Consuming these cheeses have been associated with some of the most serious food poisoning cases – even more so than suffering scombrotoxicosis.


Histamine poisoning is more commonly associated with fish spoilage or spoilage of fish based products like pate. Only levels in fish are currently regulated and the limits are 200 to 400 mg/kg according to  European Union Commission Directives 2073/2005 and 1019/2013. The US FDA states  a maximum of 50 mg/kg.


Alvarez, M.A. & Moreno-Arribas, M.V. (2014). The problem of biogenic amines in fermented foods and the use of potential biogenic amine-degrading microorganisms as a solution. Trends in Food Science & Technology, 39, pp. 146–155.
Diaz, M., del Rio, B., Ladero, V. et al. (2015). Isolation and typification of histamine-producing Lactobacillus vaginalis strains from cheese. International Journal of Food Microbiology, 215, pp. 117123
Fernandez, M., del Rio, B., Linares, D., Martın, M.C. & Alvarez, M.A. (2006). Real-time polymerase chain reaction for quantitative detection of histamine-producing bacteria: use in cheese production. Journal of Dairy Science, 89, pp. 3763–3769.
Fernandez, M., Linares, D.M., del Rio, B., Ladero, V. & Alvarez, M.A. (2007). HPLC quantification of biogenic amines in cheeses: correlation with PCR-detection of tyramine-producing microorganisms. Journal of Dairy Research, 74, pp. 276–282.
Kovacova-Hanuskova, E., Buday, T., Gavliakova, S. & Plevkova, J. (2015). Histamine, histamine intoxication and intolerance. Allergologia et Immunopathologia, 43, pp.  498506.
Ladero, V., Sánchez‐Llana, E., Fernández, M. & Alvarez, M.A. (2011). Survival of biogenic amine‐producing dairy LAB strains at pasteurisation conditionsInternational Journal of Food Science & Technology46, pp. 516–521 https://doi.org/10.1111/j.1365-2621.2010.02508.x
Linares, D. M., del Rıo, B., Ladero, V. et al.(2012). Factors influencing biogenic amines accumulation in dairy products. Frontiers in Microbiology, 3, https://doi.org/10.3389/fmicb.2012.00180.x
Schirone, M., Visciano, P., Tofalo, R. et al. (2016). Histamine Food Poisoning. Histamine and Histamine Receptors in Health and Disease. Pp. 217 235 Cham, Switzerland: Springer.
Trip, H., Mulder, N.L. & Lolkema, J.S. (2012). Improved acid stress survival of Lactococcus lactis expressing the histidine decarboxylation pathway of Streptococcus thermophilus CHCC1524. Journal of Biological Chemistry, 287, pp. 11195–11204. .

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