What is histamine intolerance?
Some people have a deficiency in the enzyme diamine oxidase (DAO) that normally breaks down histamine, so they cannot tolerate fermented foods high in histamine such as aged cheese. Histamine is a breakdown product from the amino acid histidine by lactic acid bacteria.
“Histamine intolerance (HIT) is a proposed condition caused by an inability to digest histamine in your diet, leading to gastrointestinal and allergy-like symptoms. Histamine is also produced by our own body, especially in mast cells that can activate inflammatory responses (which is why we take “anti-histamines” to block allergies). This may explain why an excess of dietary histamine can trigger an allergy-like response. The American Academy of Allergy and Immunology doesn’t currently recognize histamine intolerance as a condition. It’s a controversial issue.” - https://my.clevelandclinic.org/health/diseases/histamine-intolerance
“Most people can tolerate foods high in histamines, but approximately 1% of the population has histamine intolerance. It tends to be more common in middle age. When you have this condition, you can’t break down histamine correctly, causing it to build up in your body. Although it can lead to allergy-like symptoms, it’s not considered a food allergy.” - https://my.clevelandclinic.org/health/diseases/histamine-intolerance
Many foods are naturally high in histamines (From: General trend of histamine levels in various food products. These numbers come from the European Food Safety Authority (EFSA) Scientific Opinion on risk based control of biogenic amine formation in fermented foods.)
Alcohol (wine - 3.0 - 4.0 ppm)
Swiss Cheese (0 - 1000 ppm)
Blue Cheese (22 -64 ppm)
Washed Rind Cheeses (15 - 54 ppm)
Fermented vegetables (39 - 43 ppm)
Fish Sauce (196 - 197 ppm)
Dried Anchoives (~350 ppm)
Fermented Sausages (23 - 24 ppm)
In cheese it is microbes which can contribute to the ripening flavor that produce the histomines, similar to other fermented foods. Many different types of microbes can create histamine byproducts including: Oenococcus oeni (wine), Pediococcus damnosus (beer), and Lactobacillus buchnerii (cheese).
Histamine is derived from the decarboxylation of the amino acidhistidine, a reaction catalyzed by the enzymeL-histidine decarboxylase.
DAO metabolizes histamine into imidazole-4-acetaldehyde. Imidazole-4-acetaldehyde is then further oxidized by a NAD-dependent aldehyde dehydrogenase, leading to imidazole-4-acetic acid.[5]
Histamine N-methyltransferase (HNMT) also plays a role in the inactivation of histamine.
Is it possible to engineer around the histamine in cheese? We discussed three possible pathways for further research:
Could we replace all or most histidines in caseins? The two major caseins in cow’s milk - alpha S1 and beta - have 5 histidines each (see Molecular Biology). Interestingly, the “good” A2 form of beta casein has a proline at position 67 where the more common A1 and B forms have a histidine. Do any of the histidines contribute more to histamine production in aged cheeses? We definitely don’t understand caseins well enough to guarantee that replacing the histidines won’t destroy their function as a casein.
Could we build histamine-degrading enzymes into the cheese? This paper shows that supplementing DAO enzyme in pill form helps patients - so at least porcine DAO is somewhat stable. Another major histamine degrading enzyme is Histamine N-methyltransferase. Do the degradation products of histamine (Imidazole-4-acetaldehyde or imidazole-4-acetic acid from DAO, or N-methylhistamine from HNMT) still have the same flavor in cheese?
Use cheese ripening bacteria that either do not have histidine degrading enzymes OR contain a histamine-degrading pathway.
This is a novel concept and much as when we have discussed engineering around protein allergies a continued deep dive on the topic is required but we continue to learn and share more cheese science facts.