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The Horror of Histamine!

April 12, 2016

After a long, cold winter we are finally starting to see the early signs of spring. The snow has melted. The temperatures are warming. Birds once again tweet happily from the trees. There are lovely green buds forming on all the trees and the daffodils are once again starting to pop up their cheerful yellow splendor. Everything is perfect! Well, almost everything. That’s right; it is hay fever season again. Your eyes are itchy and watery, you can’t stop sneezing, and the congestion is driving you nuts! Sound familiar? If so, before you reach for your antihistamine let’s take a look at how our body breaks down histamine and the functional medicine way of dealing with allergies.

Histamine
Histamine is actually a neurotransmitter (brain chemical). This means that it has functions well beyond just allergies. There are four types of histamine receptors (H1R-H4R). The two types of histamine that are best understood and most relevant are histamine one (H1) and histamine two (H2). H1 is found in the intracellular pathway and is generally related to symptoms of nasal allergies, hives, and asthma. H2 is found in the extracellular pathway and is primarily found in the gut where it regulates the release of hydrochloric acid (HCL). H1 blockers are medications such as Benadryl, Zyrtec, Claritin and Allegra. H2 blockers are medications including Pepcid and Zantac.

When looking at how best to help with allergies, it is important to look at the biochemistry of histamine, particularly how it is broken down. This is true because in order to break down histamine we require specific enzymes. All enzymes require cofactors which are generally vitamins and minerals. This means that there are nutritional solutions to histamine problems.

First, let’s explore diamine oxidase (DAO). This enzyme is necessary for the breakdown of histamine in both the intracellular and extracellular pathways. This enzyme is highly polymorphic, meaning that genetic single nucleotide polymorphisms (SNPS—pronounced “snips”) sometimes referred to as mutations are relatively common (to look at your own genetics you can purchase a direct-to-consumer test such as the one offered by 23andme). When people have SNPs to this enzyme it causes histamine intolerance (HIT). Ingestion of foods that are high in histamine including alcohol, fermented foods, mature cheeses, smoked foods, shellfish, beans, nuts, chocolate, vinegar, wheat, tomatoes and citrus may exacerbate HIT. This results in symptoms including gastrointestinal complaints, migraines, fatigue, dizziness, runny nose, flushing, asthma and hives. Interestingly, elevated histamine levels also inhibit DAO causing worsening of the histamine intolerance. The DAO enzyme requires flavin adenine dinucleotide (FAD) as its cofactor. FAD requires the B-vitamin riboflavin (B2) for its synthesis. Therefore, those with this SNP require more riboflavin than the average person and therefore supplementing this vitamin may help decrease histamine intolerance. Another possible solution would be to take a supplement containing the DAO enzyme (there are several on the market).

Histamine methyltransferase (HNMT) is another enzyme that is required to breakdown histamine in the intracellular pathway. It requires S-adenosyl methionine (SAM) as its cofactor. SAM is available as a supplement, but taking it can be problematic for many as it is a strong methyl donor and will greatly increase serotonin, dopamine, norepinephrine and epinephrine which can cause anxiety. Instead, supplementing with vitamin B12 as the active methylcobalamin or folate as the active L-methylfolate can help improve methylation issues and help HNMT to work better.

Alcohol Dehydrogenase (ADH) is the final step in histamine breakdown. This is the same enzyme that breaks down alcoholic beverages. This explains why some individuals flush when they drink. It is also a good reason to perhaps skip cocktails, beer, and wine during hay fever season. This enzyme actually has four different cofactors including zinc, vitamin C, thiamine (B1) and nicotinamide adenine dinucleotide (NAD—a niacin-based flavoprotein). Therefore taking supplemental zinc, vitamin C, thiamine, and/or niacin might also improve your allergy symptoms. Vitamin in particular is often used to help with allergies. You can safely take up to 2 grams of this vitamin daily. However, it is best to take it in smaller doses (500 mg) throughout the day for better absorption.

Additional Natural Allergy Remedies
Histamine is released by mast cells, a type of white blood cell that is involved in allergy and anaphylaxis. Certain substances can help stabilize the mast cells so that they do not lose their histamine load. Pharmacologically, the medication chromolyn sodium is used in this way. However, there are several natural mast cell stabilizers. Quercetin, a natural compound found in apples, onions, and capers is a wonderful natural mast cell stabilizer. Unfortunately, it is poorly absorbed (about 1%) to increase its absorption rate it is best to take it on an empty stomach about half an hour before a meal. It may be taken up to four times per day. The herb holy basil also works as a mast cell stabilizer. This is available in capsules, tinctures and even as a tea (Tulsi Tea). It also has the benefit for helping the body cope with stress. Milk thistle, an herb often used to help improve detoxification and support the liver is another mast cell stabilizer. EGCG, a constituent found in green tea is also quite helpful in stabilizing mast cells. Ellagic acid found in raspberries, strawberries, walnuts, longan seeds, mango kernel, and pomegranate may also inhibit histamine release. Feverfew, a botanical that is both anti-inflammatory and helpful for migraines, may also be helpful for stabilizing mast cells.

When mast cell stabilizers are insufficient, H1 blockers may be helpful. If you prefer to avoid medication, the herb butterbur is a wonderful natural antihistamine. In clinical trials, this herb was found to be as effective as the over-the-counter medications Zyrtec, Claritin and Allegra. As in many H1 blocking antihistamines, butterbur may cause drowsiness. Unfortunately, if you have an allergy to ragweed, chrysanthemums, marigolds, and/or daisies you will likely find that you are also allergic to butterbur as it is in the same family.

In addition to mast cells, leukotrienes are also implicated in asthma and allergies. This substance causes contractions of smooth muscle in the respiratory tract that cause symptoms of asthma and allergic rhinitis. Medications such as monteleukast (brand name Singulair) are used as leukotriene agonists and are often used to help these symptoms. Fish oil (omega-3 fatty acids) is a wonderful natural leukotriene agonist. Not only will fish oil improve your allergies, but it is a fantastic natural anti-inflammatory.

This spring I hope that experimenting with the various vitamins, minerals, and botanicals helps to decrease your hay fever so that you may enjoy the beauty of this wonderful season. You may be amazed at just how good you feel. Consider reducing dietary histamine as well as decreasing your total histamine load is really helpful.

Jessica Pizano is the owner of Fit to You, LLC, which offers clinical nutrition and nutrigenomic counseling, as well as personalized training programs. She earned a master’s degree in human nutrition that emphasizes functional medicine at the University of Bridgeport. She is a certified nutrition specialist through the Board for Certified Nutrition Specialists. She is continuing her studies at Maryland University of Integrative Health where she is pursuing a doctor of clinical nutrition and is also an adjunct faculty member teaching nutritional genomics. A certified personal trainer and a corrective exercise specialist through the National Academy of Sports Medicine, she is also certified in mat Pilates through PHI Pilates and earned her Clinical Exercise Specialist and Longevity Wellness Specialist through the American Council on Exercise. She may be contacted at (860) 321-7234 or online at www.fittoyouct.com.

One Comment

  1. Amanda Patrick

    September 7, 2017 at 8:42 am

    This is a great article! Especially explaining the H1-H4 receptors, hard to find info on those. I have been dealing with histamine issues for years and have finally found breakthrough dealing with candida that was raising my histamine levels. I now write extensively on this, it’s helped so much. Thank you for what you’re doing. I know people will find help in this article.

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