Low Histamine, Gene SNPs, and MTHFR

Low histamine is generally not recognized as a problem within the medical community or even in the media, but histamine is emerging as a research target for conditions like cancer, cardiac protection, and alzheimer’s so I think soon we will begin to see some talk about low histamine and not just high histamine. 

Histamine is vital for functioning and is present in different levels in different humans, so it stands to reason that low levels could create problems just like high levels do.

Histamine is involved in so many things beyond the allergies we usually attribute to it.

Histamine is involved in:

• Allergic reactions – this is the part everyone knows about.
• Immune response
• Opening blood vessels (or vasodilation)
• Neurotransmission
• Signaling within your stomach

Histamine levels depend on two factors.

1. How much histamine is being produced – this depends on your gut microbiome, how easily your mast cells degranulate (white blood cells typically associated with allergic response), allergies, and the action of your basophils, which are another type of white blood cells.
2. How much histamine is being broken down – this depends on MTHFR, and two histmine-specific enzymes called DAO and HNMT.

Histamine has a diverse range of effects including:

• Promoting wakefulness, or stopping you from sleeping all the time.
• Constricting airways
• Increasing stomach acid secretion
• Modulating pain signals
• Itch perception

Histamine interconnects with MTHFR in a couple of ways. Histamine breakdown is dependent on healthy methylation just like other monoamine neurotransmitters. Also, the HNMT enzyme needs a methyl group from SAMe in order to function. That means if you have an overactive methylation cycle, then you break down histamine more quickly than average and you are more likely to have a low histamine picture.

Keep in mind that low histamine states are one of the characteristics of the “overmethylation” basic state – these are the folks I like to call the Black Sheep. Of course, far more than just your MTHFR status goes into your histamine levels but it is still really useful for us MTHFR folks to know which side of the basic state picture we fall on. I believe this simply because the general patterns between over- and under-methylators, especially as it pertains to probable drug and supplement tolerances, are surprisingly accurate..

Gene SNPs That Affect Histamine

1. MTHFR and other genes in the methylation pathway – including MTR and MTRR. Also, even if these gene SNPs are “wild type” (or “normal”), this can look impaired if your folate status is low, your folic acid intake is too high, or your riboflavin levels are too low.
2. DAO – DAO is one of the major breakdown pathways of histamine and gene SNPs can cause problems.
3. HNMT – HNMT is the other major breakdown pathway and it needs a SAMe (from the methylation cycle) in order to function.

Low Histamine Symptoms Include

• Seasonal allergies that present as general symptoms for a season but aren’t the typical allergy picture. This could include a seasonal headache, body pain, muscle tightness, brain fog, and more long-term, non-specific symptoms. If your allergies don’t look like hay fever, but repeat seasonally and don’t feel any better with antihistamines, you might fall into this category.
• Fatigue, lack of alertness, and difficulty feeling awake in the morning. Keep in mind there are a number of other factors involved here like the MAOA or COMT gene SNP which may lower dopamine, epinephrine and norepinephrine and that will also feel like fatigue and lack of alertness in the morning.
• Digestive symptoms including low stomach acid and reflux related to low stomach acid, cramping, and bloating
• High blood pressure
• Alzheimer’s disease – this is not actually a symptom of low histamine, but an interesting association has been found specifically with low brain levels of histamine and the progression of Alzheimer’s. Raising brain levels of histamine is being explored as a new treatment strategy.
• Increased heart damage in heart attack – new research is showing that histamine levels rise sharply in the first moments of a heart attack, and that if they don’t rise appropriately then the level of damage the heart sustains is likely to be worse.

Managing Low Histamine Naturally

Low histamine isn’t typically regarded as a problem by the medical community, but balancing histamine levels can make you feel better on a day to day basis, especially if you struggle with lack of alertness, high blood pressure for no clear reason, or low stomach acid and digestive power. If you find, like I do, that you generally feel better with high-histamine foods like aged cheeses, smoked meats, bone broth, and leftovers, then your histamine might be on the lower end of normal.

• Eat a higher histamine diet – some foods are extremely high in histamine including alcohol, fermented foods, processed or smoked meats, aged cheeses, and shellfish. Adding those into your diet can help to boost histamine levels
• Embrace the leftovers – food that sits for a while, like leftovers, accumulates histamine while it sits so if you generally have a low histamine picture then leftovers are great for you. Batch cook your favorite foods and enjoy for a few days.
• Exercise – exercise has been shown to boost histamine levels, which is part of your body’s mechanism to increase blood flow to muscles and to decrease pain perception. If you tend to have low histamine symptoms, exercise can be a great way to boost your numbers.
• Boost your folate levels if you can tolerate it – histamine increases with increasing folate, and so boosting your folate levels can help to boost a flagging histamine. Just don’t flip over into a too-high histamine picture.

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