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 target in research for conditions like cancer, cardiac protection, and alzheimer’s so I think in the next decade or so, we will begin to see some talk about low histamine and not just high histamine. Histamine is there for a reason and present in different levels in different humans, so it is equally likely that there are problems from low levels just like there are from high levels.

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, allergies, and the action of your basophils, which are one of your 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 an incredibly 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.

Thank you so much for listening today, and be sure to check out courses.tohealthwiththat.com for the Free MTHFR Basics class and to sign up so you’re the first to know about beta testing opportunities with the MTHFR for life class at 1/4 of the usual price.

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High Histamine, gene SNPs, and MTHFR

Histamine and MTHFR are bound together for so many reasons. One, is because just like MTHFR, histamine has its fingers in so much more than just allergies.

Histamine is involved in:

  • Allergic reactions – this is the part everyone knows about.
  • Immune response
  • Opening blood vessels (or vasodilation)
  • It’s a neurotransmitter!
  • Signaling within your stomach

Histamine levels in your body depend on two factors.

  1. How much histamine is being produced – this depends on your gut microbiome, how easily your mast cells degranulate, and allergies and the action of your basophils, which are one of your 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 is mostly formed in your mast cells, which are immune cells that protect sites vulnerable to injuries like mucus membranes in your nose and mouth, your internal body surfaces, and the insides of your blood vessels. Also, in your basophils, which are white blood cells in your immune system that respond to allergins. It is also scattered throughout your body tissues and has an incredibly diverse range of effects including:

  • Promoting wakefulness (otherwise known as stopping a good night’s sleep)
  • Constricting airways
  • Increasing stomach acid secretion
  • Modulating pain signals
  • Itch perception

Histamine is important with MTHFR for a couple of other reasons as well. Histamine breakdown is dependent on healthy methylation just like other monoamine neurotransmitters, and the HNMT enzyme needs a methyl group from SAMe in order to function. That means if you have a sluggish MTHFR, then it is much harder to break down histamine and you are more likely to have a high histamine picture.

Keep in mind that high histamine states are one of the characteristics of the “undermethylation” (legacy term) basic state – these are the folks I like to call the Achievers. Of course more than just your MTHFR status goes into high histamine – there are several gene SNPs that can affect it including DAO and HNMT – the two major histamine breakdown pathways – but it is still really useful for us MTHFR folks to know. I believe this simply because the general patterns between over- and under-methylators (again, that’s a legacy term handed down from the Walsh Research Institute and doesn’t necessarily describe what is happening physiologically) are still really useful.

The most useful aspect, in my opinion, is the drug and supplement reactions in each group, which I find to be shockingly accurate.

Gene SNPs That Affect HIstamine

  1. MTHFR and other genes in the methylation pathway – especially MTR (or MTRR which affects MTR’s ability to function. Remember that MTHFR is dependent on riboflavin as well, so low riboflavin status can look like difficult methylation.
  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.

High Histamine Symptoms Include

  • Seasonal allergies that present as hayfever type allergies – sneezing, watery eyes and runny nose, itching, hives, itchy nose, sudden symptoms.
  • Headaches and migraines
  • Shortness of breath
  • Skin itching for no apparent reason, or because of any and everything that happens, and low pain tolerance
  • Digestive symptoms including cramping, diarrhea, and bloating
  • Wakefuless, insomnia, anxiety
  • Drop in blood pressure, dizziness on change of position, or irregular heart beat.

Managing High Histamine Naturally

HIgh histamine can be seasonal, or it can be constant in the case of something called Histamine Intolerance. Either way, here are some steps you can take toward managing high histamine levels.

  • Eat a low histamine diet – some foods are extremely high in histamine including alcohol, fermented foods, processed or smoked meats, aged cheeses, and shellfish. Avoid these and focus on fresh unprocessed foods.
  • Ditch the leftovers – food that sits for a while, like leftovers, accumulates histamine while it sits so if you generally have a high histamine picture then leftovers may not be your friend. Make enough food for one sitting and cook fresh each time.
  • Vitamin C – vitamin C helps to prevent mast cell degranulation, which is the histamine-release event. In my own clinical experience, it is quite often a larger than average dose of vitamin C, and a buffered vitamin C product like Ester-C can be most effective.
  • Calcium – calcium helps to lower histamine levels in brain tissues and has a generally complicated relationship with histamine in mast cells – stimulating histamine release in some circumstances and regulating it in others. Some people seem to feel a direct and clear improvement in their symptoms with calcium supplementation and some people don’t notice anything.
  • Watch your folate levels – histamine increases with increasing folate, and often people with folic acid toxicity have problems with high histamine levels. Also, people who are supplementing with too much folate in any form – even the good ones like 5-LMTHF – can experience high histamine symptoms.
  • DAO enzyme – DAO, remember, is one of your main histamine breakdown pathways and a DAO supplement can help tremendously, especially if you experience a lot of histamine release directly related to foods. Still eat a low histamine diet if possible, but supplement a DAO enzyme to help your body calm down.
  • Try Quercetin – quercetin is well known and well researched to inhibit histamine production and to reduce pro-inflammatory mediatiors. For allergies it should be taken in a higher dose. Around 400 mg twice daily away from food is most common.

Thank you so much for listening today and it’s official – a free MTHFR Basics course has launched at courses.tohealthwiththat.com and an in-depth MTHFR for Life course is coming soon. That one will need beta testers who will be able to attend the course for 1/4 of the usual price, so please do sign up for the mailing list at tohealthwiththat.com, or on the courses page.

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MTHFR and Allergies or Sensitivities – We’ve All Got Them.

MTHFR and sensitivities are intimately linked and for better or for worse, this is part of the MTHFR experience that makes having an MTHFR community so important. Let’s face it – we need someone to talk to who also can’t use normal face cream and can’t eat wheat without feeling like we’re insane. Sensitivities come in four flavors and we’re only beginning to understand why.

MTHFR and Allergies

Allergies and atopic illness in general (this includes asthma, migraines, skin sensitivities, interstitial cystitis, and any other condition that is linked to over-responding to some irritant) are a huge problem for MTHFR folks. The reasons are multifaceted, but mostly, it centers around histamine. Histamine is the main mediator of conventional allergic reactions. There are a few concrete links, and also some logical connections.

MTHFR and Food Sensitivities

Food sensitivities have been increasing in the last few years – hence the rise of the “gluten free” industry and the implementation of food allergy labeling. Nobody really knows why this problem has become so pervasive, although I’ve heard theories about vaccine ingredients, genetic modification and selective breeding of crops, and gut bacteria. More than likely, the truth is some combination of all of those things. One other factor exists, and that is, of course, genetics. Food sensitivities certainly seem more common within the MTHFR community, and much of that could be attributed to the histamine problem. Also, because of the tendency toward higher resting histamine, there is also a tendency toward something called “histamine intolerance” within the MTHFR community.

Histamine intolerance shows up as food sensitivities in combination with a host of other issues (we’ll go over it in a whole post because it’s too much to condense here) and can be treated with a low-histamine diet that is absolutely life-changing for some people.

Histamine intolerance or no, food sensitivity elimination is crucial for MTHFR folks and for many of us, will knock a big chunk of symptoms out even before we’ve got our methylation balanced. For me, eliminating wheat and gluten from my life has been life changing.

MTHFR and Chemical Sensitivities

Chemical sensitivities can be seen as a combination of allergic issues related to high histamine, and detox issues related to the toxin buildup that can happen with MTHFR because we have a hard time methylating. This toxic buildup isn’t just with toxins that need to be methylated because as the system becomes overburdened and overloaded, all other detoxification pathways are slowed as well. In general, to have a good MTHFR lifestyle it is important to limit chemical exposure to every degree possible so that you can reduce the burden on your system.

MTHFR and Emotional Sensitivity

To put a general disclaimer out there – this comes entirely from my own clinical observations and hasn’t been seen in research (although, to be fair, this isn’t the type of topic that is often researched anyway because who would profit from it?)

I have seen a clinical correlation between MTHFR mutations and emotional sensitivity and I don’t mean delicate-flower-not-coping with real emotions, sensitivity, I mean actual sensitivity to emotions in oneself and in other people. I would call it a higher level of emotional awareness. In people on the autistic spectrum this might mean feeling the emotions in the room as physical sensations or finding other people’s emotions so distracting that they almost overwhelm that person’s own internal state. In lesser forms, it might just be a heightened awareness of internal or external emotional states that van impact mood and also decision making.

This is a trait that I see over and over again in my MTHFR community and I find it to be such a double-edged sword. On one hand, higher awareness of emotions allows for greater empathy, greater emotional intelligence and greater performance in relationships. On the other, it can come with the fallout of increased moodiness, greater tendency toward overwhelm, and greater need for buffer time between interactions with people and the outside world.

It isn’t something I have a solution for, outside of implementing more careful self-care, as I have done in my life, but it is a situation I want to bring awareness to and get people talking about. I do think this is a strength as much as it’s a weakness, if we understand how to harness it.

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