~ Drinking alcohol is often a problem for people with histamine intolerance.
~ Two different genetic pathways are at play here: histamine degradation and/or alcohol metabolism pathways.
~ Understanding these pathways may help people with histamine sensitivity avoid alcohol-induced reactions.
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Why does alcohol increase histamine levels?
Drinking alcohol can trigger histamine reactions via several pathways.
- Alcoholic beverages often contain a lot of histamine. For people who don’t break down histamine well, this can cause a reaction.
- The breakdown of alcohol into acetaldehyde can trigger histamine release under certain conditions.
- Alcohol also inhibits the enzyme that breaks down histamine
First, I’ll explain a little of the background science on these pathways. Then, I’ll show you how you can use your genetic data to see which pathway is likely causing you problems.
What is histamine intolerance?
Histamine intolerance is a condition caused by the body’s inability to break down the histamine contained in foods and drinks. Normally, histamine from foods is broken down in the intestines.
Symptoms of histamine intolerance include headaches, itching, hives, sinus drainage, digestive issues, rapid heartbeat, anxiety, flushing, and (rarely) anaphylaxis.
How is histamine metabolized?
There are two ways your body clears histamine: the DAO enzyme or the HMNT enzyme.[ref]
- Diamine oxidase (DAO) enzyme:
Histamine from foods or bacteria in your gut is broken down or metabolized using the DAO (diamine oxidase) enzyme. The DAO enzyme is produced in the villi lining the small intestines and is released to metabolize histamine.[ref]
- Histamine methyltransferase (HMNT) enzyme:
The HMNT enzyme works throughout the body, including in the brain, to deactivate and break down histamine created by your cells.[ref]
Too much histamine can result in allergy-like symptoms, including the histamine intolerance symptoms listed above.
Genetics comes into play here. Not producing enough DAO in the intestines can cause excess histamine throughout the body. Similarly, not enough HNMT enzyme can cause excess histamine in certain tissues.
Which foods are high in histamine? Fermented and aged foods are high in histamine — e.g., wine, aged cheeses, sausages, and processed meats. Other foods, such as strawberries, spinach, and chocolate, are also naturally higher in histamine. There’s a complete list in the Lifehacks section.
Histamine and biogenic amines in fermentation
Alcoholic beverages are made by fermentation, and histamine levels are generally high in fermented foods. For example, a 2009 study found all beers tested contained histamine.[ref]
Biogenic amines include histamine as well as tyramine, putrescine, cadaverine, and β-phenylethylamine. These biogenic amines can be produced by bacteria – specifically lactic acid producing bacteria used in fermentation.
Side note: Researchers think that lactic acid bacteria produce biogenic amines as a defense mechanism in order to withstand acidic environments.
Wine is fermented and is often very high in biogenic amines, including histamine. Levels of biogenic amines depend on the bacteria strains used in the fermentation process.[ref]
A recent Danish study found that 8% of the population had hypersensitive reactions to wine, including sinus drainage, sneezing, lower respiratory problems, or skin reactions (itching, hives).[ref]
However… Not all alcoholic beverages are high in histamine, so it isn’t as simple as all alcohol causes reactions due to containing histamine.
Alcohol exacerbates a lack of DAO
It is important to understand how alcohol can exacerbate symptoms if you suffer from histamine intolerance.
There are two ways alcohol can increase histamine:
- The DAO enzyme, which breaks down histamine, is inhibited by alcohol.[ref]
- Additionally, both alcohol and acetaldehyde can trigger mast cells and basophils to release histamine in the periphery. This increases histamine levels in different tissues, such as in the skin, causing itching and hives.[ref]
Metabolism of alcohol: creating acetaldehyde
I’ve mentioned acetaldehyde a couple of times without really explaining it…
Alcohol goes through a multistep process to be broken down and eliminated by the body.[ref]
- Alcohol is first metabolized by alcohol dehydrogenase (ADH genes) into acetaldehyde, which is toxic.
- Acetaldehyde is metabolized by acetaldehyde dehydrogenase (ALDH genes) into acetic acid, which is non-toxic.
In addition to alcohol-containing beverages, the alcohol dehydrogenase enzyme also breaks down alcohols produced by bacterial fermentation in the intestines. Retinol (vitamin A) and bile acids are also metabolized by alcohol dehydrogenase.[ref]
When alcohol is turned into acetaldehyde more quickly than the body can handle, there can be a buildup of acetaldehyde (toxic). Genetics plays a significant role in how quickly you turn alcohol into acetaldehyde.
Acetaldehyde needs to be quickly converted to acetic acid. Genetic variants that slow down this process cause a buildup of acetaldehyde.
As I mentioned above, excess acetaldehyde can trigger histamine release from mast cells and basophils.[ref]
Doctors define alcohol hypersensitivity as an “exacerbation of respiratory symptoms in response to alcohol”.
A recent study of chronic rhinosinusitis patients with alcohol hypersensitivity found they also had higher platelet counts. In these patients, red wine extract activated the platelet-adherent basophils. This is important because basophils release histamine when activated.[ref]
Alcohol can also trigger asthma reactions in some people. Asthma is an airway hyperactivation involving histamine.
In people with reduced ALDH2 levels (and thus more acetaldehyde), alcohol is more likely to induce asthma.[ref]
One study explains: “Impaired ALDH2 activity leads to high peak levels of acetaldehyde and to histamine release.” Studies show that inhaling acetaldehyde induces histamine-mediated airway constriction, such as is seen in asthma.[ref]
Hangovers and histamine
A recent animal study sheds light on the age-old question of what causes hangover symptoms.
Researchers found some hangover symptoms (headache, behavioral inhibition, dizziness, movement imbalance) are caused by high histamine levels. Treating the high histamine levels resulted in decreasing levels of specific migraine-related neurotransmitters.[ref]
Histamine and Alcohol Genotype Report
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Histamine reactions can occur when acetaldehyde is hanging around too long. Acetaldehyde can trigger the release of histamine from mast cells and basophils. There are two paths here: accelerated alcohol metabolism into acetaldehyde -or- decreased acetaldehyde clearance.
ADH1B gene: encodes alcohol dehydrogenase, which converts alcohol to acetaldehyde. When this enzyme works more quickly, it results in higher amounts of acetaldehyde than the body can clear out.
Check your genetic data for rs1229984 (23andMe v4, v5):
- TT: faster metabolism of alcohol to acetaldehyde[ref], causes a build-up of acetaldehyde, known as ADH1B*2 and more common in Asian populations, decreased alcohol consumption (on average)[ref]
- CT: faster metabolism of alcohol to acetaldehyde, causing a build-up of acetaldehyde, known as ADH1B*2 and more common in Asian populations, decreased alcohol consumption
- CC: typical, higher alcohol consumption compared to T allele[ref]
Members: Your genotype for rs1229984 is —.
Check your genetic data for rs2066702 (23andMe v4 only; AncestryDNA):
- G/G: typical
- A/G: faster metabolism of alcohol to acetaldehyde, causing a build-up of acetaldehyde, known ad ADH1B*3 and more common in African populations[ref][ref]
- A/A: faster metabolism of alcohol to acetaldehyde, causing a build-up of acetaldehyde, known ad ADH1B*3 and more common in African populations[ref]
Members: Your genotype for rs2066702 is —.
ALDH2 gene: enzyme needed for the elimination of acetaldehyde through conversion to acetic acid
Check your genetic data for rs671 (23andMe v4, v5; AncestryDNA):
- A/A: slower elimination of acetaldehyde[ref]; Alcohol flush reaction[ref], a much higher risk of lung cancer from smoking, decreased alcohol consumption (on average)[ref]
- A/G: slower elimination of acetaldehyde; Alcohol flush reaction,
- G/G: typical acetaldehyde metabolism
Members: Your genotype for rs671 is —.
Breakdown of histamine:
DAO (diamine oxidase) is the enzyme produced by the intestines, breaking down histamine from foods. The AOC1 gene codes for the production of the DAO enzyme. Genetic variants in AOC1 can increase or decrease the production of the enzyme.
Note: Rare mutations influencing DAO production are not included in most genetic data.[ref][ref]
AOC1 gene: encodes diamine oxidase (DAO):
Check your genetic data for rs10156191 (23andMe v4; AncestryDNA):
- C/C: typical
- C/T: reduced production of DAO, increased risk of migraines due to histamine[ref]
- T/T: reduced production of DAO[ref][ref][ref], increased risk of migraines due to histamine[ref]
Members: Your genotype for rs10156191 is —.
Check your genetic data for rs2052129 (23andMe v5 only):
- G/G: typical (most common genotype)
- G/T: reduced production of DAO, increased risk of migraines due to histamine[ref]
- T/T: reduced production of DAO[ref], increased risk of migraines due to histamine[ref]
Members: Your genotype for rs2052129 is —.
Check your genetic data for rs1049742 (23andMe v4):
- C/C: typical
- C/T: reduced production of DAO
- T/T: reduced production of DAO[ref]
Members: Your genotype for rs1049742 is —.
HNMT gene: Histamine n-methyltransferase (HMNT) is the enzyme that regulates histamine in the body via converting it from histamine into N-methylhistamine, which can then be eliminated from the body. HNMT is responsible for eliminating 80% of histamine in the body.[ref]
Check your genetic data for rs1050891 (23andMe v4, v5):
- G/G: typical[ref]
- A/G: reduced breakdown of histamine compared to G/G
- A/A: reduced breakdown of histamine compared to G/G[ref]
Members: Your genotype for rs1050891 is —.
Check your genetic data for rs11558538 C314T (23andMe for i3000469, v4; AncestryDNA):
- T/T: reduced HNMT activity[ref][ref] higher histamine levels, increased relative risk of asthma[ref]
- C/T: somewhat reduced breakdown of histamine
- C/C: typical[ref]
Members: Your genotype for rs11558538 is — or for i3000469 is —.
Let’s talk about some ways of avoiding histamine reactions from alcohol!
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