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6 conditions you’d never guess are caused by allergies

Article at a Glance
  • Most people experience only traditional allergy symptoms, such as a runny nose or itchy, red eyes.
  • Sensitive people may not realize that the inflammatory response produced by allergic reactions can be to blame for conditions ranging from chronic fatigue, to depression, to interstitial cystitis.
  • When histamine levels are elevated over long periods of time, the resulting increased production of zonulin can lead to a breakdown of the gut wall, which has been linked (although not conclusively) to many autoimmune disorders.
Genes Mentioned
DAO DAOO Differences Genetics

So, you have allergies. You have a runny nose, and maybe itchy, watery eyes.

That’s where it stops, right?

For most people the answer is yes, but some experience strange symptoms and conditions in response to allergen triggers.

I’ve written before about how pollen allergies can cause anxiety. But since moving to Austin, I’ve done a ton of research on histamine, and the medical literature documents conditions arising from “allergy” that most would consider strange (not that the conditions themselves are strange, more that allergy as a cause sounds odd), so I wanted to share some of my findings in the hopes they could help a few people with as yet unexplained health issues.

For those playing along at home, with their 23andme data connected to Gene Food, the two primary histamine clearance genes are AOC1 and HNMT.

On to the list.

Interstitial Cystitis and Allergy

This is a big one, especially for women. Interstitial cystitis is a condition marked by chronic inflammation of the bladder that often leads to urinary urgency, food sensitivity and loss of quality of life.

At first blush, this seems impossible. How can allergies lead to problems in the bladder? Well, to begin, one of the commonly listed side effects of histamine intolerance is frequent urination. When you think about it, this makes sense, as the body’s allergic response is tied to the “degranulation” of mast cells, the process where immune cells release inflammatory substances (histamine, cytokines) to destroy invaders. Mast cells populate in the largest numbers around mucous membranes: the skin, sinuses, the gut, and the urogenital area (bladder). When the body’s mast cells are chronically releasing histamine from one of these localized areas, inflammation results. So, in light of where mast cells are concentrated in the body, it makes just as much sense that allergies could cause bladder problems, as it does that they would cause sinus infections.

Consider this admittedly technical, but relevant, quote from the Journal of Histochemistry and Cytochemistry (pay attention, I will refer back later):

Advances in understanding the process of mast cell activation and the effects their mediators have on the immune system revealed the complexity and multiphasic nature of allergic reactions. In addition to the acute immediate events, the allergic process includes later phases marked by leukocyte infiltration and the initiation of an acquired immune response, followed by a chronic phase that includes persistent inflammation, tissue remodeling, and fibrosis (). A role for mast cells in these various phases thus gained increased importance ().

To read more, take a look at this case study from the International Journal of Urology: Is Interstitial Cystitis and Allergic Disorder?

See also: How to cure prostatitis

Depression and Allergy

Histamine is a neurotransmitter that affects the central nervous system. (R) Viewed in this light, it’s not hard to see how some people with allergies also suffer from depression. In fact, a meta-analysis of 12 studies looking at the link between allergy and depression found that 10 of the 12 included studies linked allergy with depression.

Now, to be fair, the meta-analysis looked at studies from different countries using different criteria, so they can’t be relied on as conclusive. However, some of the findings were compelling. For example, in an analysis of over 85,000 individuals, this study reported a 1.7 times greater likelihood of depression in those with allergies.

Sensitivity to supplements

I first wrote about this one in a post I did on Lion’s Mane and Nootropic Mushrooms, and have since updated my histamine intolerance post with some tid bits as well. The bottom line is that some supplements (PQQ and Lion’s Mane are big ones) increase Nerve Growth Factor, or “NGF.” NGF is in a class of molecules, called Neurotrophic factors, which help keep neurons in the brain alive and functioning.

This sounds like a good thing, and it is, however, NGF also causes mast cells to release histamine and other inflammatory cytokines (mast cells release NGF as well), which is why you may react poorly to a supplement in a location where you have severe allergies, and have a favorable outcome in a place where your allergies aren’t triggered. Constant release of histamine, NGF and cytokines results in inflammation, especially near blood vessels, epithelial tissue (the gut) and nerves. (R)

If you’re immune system is overactive, as it can be with severe allergies, more NGF is probably not what the doctor ordered.

Candida Overgrowth and Allergy

I wrote about this in my post on Candida, but some doctors believe issues with fungal overgrowth are “secondary to allergic responses of the mucous membranes of the respiratory tract, urethra and bladder.”

The idea here is that the inflammatory process I talked about in the conditions listed above weakens the immune system locally in places where the greatest number of mast cells reside.

Candida then moves in to fill the void.

Chronic Fatigue and Allergy

This one is fascinating, albeit a bit alarming as well. There is a whole community of people with a rare condition called Myalgic encephalomyelitis, otherwise known as chronic fatigue syndrome (CFS), who swear that their symptoms improve significantly based on their location. This change in condition brought on by physical location is known as the “Locations effect.” I don’t suffer from fatigue, but I can relate on some level here, as I’ve written about how different supplements and foods impact me differently based on the location I find myself in. Dr. Janice Joneja, one of the leading online commentators on histamine intolerance, has said that symptoms of histamine overload can vary greatly by location because, in places where allergies trigger a histamine release, even the smallest amount of histamine in food will cause histamine levels to spill over.

The chronic fatigue community places the blame for many of their symptoms on mold sensitivity rather than pollen. Is the flare up they describe in certain locations brought on by mold allergy, or mold colonization? It’s impossible to say for sure, however, I list chronic fatigue in this post because it’s a condition that can be impacted by location and allergy, both anecdotally in groups discussing the Locations effect, as well as in the medical literature.

From the University of Maryland Medical Center:

Allergies. Some studies have reported that a majority of CFS patients have allergies to foods, pollen, metals (such as nickel or mercury), or other substances. One theory is that allergens, like viral infections, may trigger a cascade of immune abnormalities that lead to CFS. However, most allergic people do not have CFS.

Leaky gut and Allergy

The blogosophere is full of tips for beating allergies with nutritional supplements. You may have come across articles discussing quercetin’s ability to act as a mast cell stabilizer, or read our post on how L-theanine can boost the immune system. However, if you’re having severe allergic reactions to your environment, my focus would be on gut health, labs, and diamine oxidase (DAO), which is the enzyme that breaks down “extracellular histamine,” such as the histamine found in food.

It really does seem that many chronic conditions faced by Americans today, including depression, come back to gut health.

Aaron has written previously about zonulin, a protein that breaks down the lining of the gut. Wheat has been identified as one of the major culprits in producing zonulin, but histamine can as well, which is why histamine issues and gut issues often go hand in hand.

How does this work?

When the immune system is activated, as it can be by a pollen or mold, histamine is released.  Normally DAO breaks down the histamine so your body can go back to normal.

However, with chronic allergies normal never arrives. The body is assaulted by constant irritation from a foreign invader, such as grass pollen, which results in allergy symptoms like too much mucus, redness and itch (blood vessels enlarged and immune cells/nerve cells stimulated), and in some rare cases, the conditions I list in this post.

Mutations in AOC1 gene, as well as lifestyle factors, lead to a reduction DAO activity. Some people with these SNPs, or who have recently engaged in a behavior that reduces DAO levels, won’t clear histamine as well. For example, let’s say the “wild type” for AOC1 clears histamine in 5 mins, whereas someone who inherited risk alleles will take 60 minutes to clear (I made those numbers up as no one has a handle on the exact time, just that it’s slower is the main point to illustrate here). The mechanism I describe is technically not an allergy but it has a very similar effect.

For the impact on the gut, think of how your nose feels if it’s been runny. Sore and red, with some people even getting nose bleeds. The same principle applies with the gut. With repeated immune cell activation of the epithelium (gut lining), the gut grows raw and loses its function. This decrease in DAO causes an increase in histamine, which can then lead to an increase in zonulin and a compromised “leaky” gut. (R)

Lifestyle factors, such as NSAID use, antibiotic use, and drinking alcohol, all cause a reduction in DAO.

Closing thoughts

Well, there you have it – allergic reactions can show up in places, and as conditions, that you wouldn’t have guessed.  If some of what I am talking about in this post resonates with you, and you want to dig further, my understanding is that it’s very difficult to have serum DAO levels tested as there aren’t many labs that run this test.

To rule out mast cell activation disorder, most doctors will measure serum tryptase, which is released by mast cells when they degranulate along with histamine. Tryptase, if normal, will rule out mast cell activation disorder for most allergists.

John O'Connor

John O'Connor is the founder of Gene Food. He is passionate about nutrition, genetics, and wellness and uses this blog to publish self experiments as well as some of the research that the Gene Food team does internally to highlight stories of bio-individuality.

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  1. Michael Jacob says:

    Very great soothing and calming article that is rarely published. Your article has brought my concerns about frequent urination especially at nights and cold/cool environment/exposure during the periods of allergy to rest. In fact, apart from frequent urination, I am always unable to sleep at nights. Interestingly, however, I am active in the day time without fatigue or sleepiness that is common with people who lost sleeps at night.

    As Michael asked above, “are there supplement regimens” or any known solutions to this issues?

  2. Michael says:

    Great article I have realized i have a histamine issue for some time. I am on a roller coaster as far as intensity and was wondering what would be the best was to enhance DOA. Your article explains why I urinate more when I have issues. Do you have a supplement regiment


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