A marker of methylation; treat elevated histamine and depression naturally.

Treat Elevated Histamine, Naturally

treat elevated histamine naturally

Symptoms of elevated histamine

More and more these days, people suffer from what are simply referred to simply as "allergies." Allergies are reactions by the body to exposure by foods and  other elements that cause the body to release histamine and other biochemical elements such as tryptase, heparin, serotonin and immunoglobulins. The effect of these compounds on the tissues are known as an allergic reaction.

symptoms of mcas mcad high histamine

Treat symptoms of elevated histamine naturally

To treat symptoms of elevated histamine, the best approach is to become familiar with foods and those that contain high levels of histamine or that cause the body to produce high levels of histamine.

High serum levels of histamine lead to common inflammation conditions such as hives, skin rash, diarrhea, runny nose, high stomach acid, nausea, reflux, migraines, irregular menstrual periods, red itchy eyes, etc.

foods high in histamine

Histamine Intolerance and Mast Cell Activation Disorder

Not all histamine reactions are due to allergies. There are a number of conditions that lead to an histamine intolerance. That is true whether the histamines are derived from foods or by our excessive production of, or sensitivity to histamines.

Histamine intolerance, also referred to as histaminosis or HIT or Mast Cell Activation Disorder, may be caused by an increased release or by a lack of histamine degradation enzymes. Histamine intolerance isn't a true allergic reaction. Instead, it refers to a reaction some people experience to foods that have high levels of naturally occurring histamine. The enzymes are required for breaking down ingested or naturally produced histamines.

  • DAO - diamine oxidase. This is the histamine lowering enzyme produced in the intestinal lining and by the kidneys. It circulated through the plasma and serum. Managing histamine intolerance may be addressed by supplementation with enzymes such as DAO
  • HNMT - Histamine N-methyl transferase is a histamine degrading enzyme and it is found within the whole blood cells. Supplements used for symptoms associated with high red blood cell histamine including SAMe and methionine that lower histamine levels.
how SAMe methionine lowers histamine

By treating whole blood histamine with nutrients, serotonin and dopamine levels may be corrected. 

Second Opinion Physician specializes in treating mood disorders and symptoms associated with histamine imbalance within the red blood cells. Because these cells rely on the "methyl" containing enzyme (HNMT), a whole blood histamine level is useful in establishing one's "methylation status." High whole blood histamine indicates undermethylation whereas low blood histamine indicated overmethylation. Presenting his findings at the American Psychiatric Association Conference in 2015, Dr William Walsh, PhD. describes the mood related disorders of high blood histamine and low blood histamine, referring to them as undermethylation and overmethylation respectively.

In managing depression and other symptoms affected by conditions associated with histamine levels we are not specifically treating histamine. We use whole blood histamine blood levels as a measure of over or under methylation status.

Because undermethylators have low functioning levels of serotonin and dopamine, supplementing with methionine and SAMe we can increase the activity of key neurotransmitters. In addition to reducing whole blood levels of histamine, they are important regulators of enzymes involved in serotonin and dopamine reuptake. Overmethylators who, with low whole blood histamine are typically high serotonin depressives. They more frequently benefit from supplements that reduce neurotransmitter activity.

Symptoms of Elevated Whole Blood Histamine

high histamine undermethylation symptoms

Symptoms of Low Whole Blood Histamine

symptoms of low histamine schizophrenia

Test whole blood histamine through this website.

It's a very important test!

Second Opinion Physician offers lab testing for histamine as well as consultations by phone to discuss the results of your lab test. Once ordered you will receive a requisition to take to your nearest Lab Corp.

Related Posts:

Additional Lab Tests for histamine, allergies, MCAS, histaminosis, and methylation:


Biotype Individual Tests

Histamine, Whole Blood


Other Single Item Tests

IgE Immunoglobin E, Total


40 thoughts on “Treat Elevated Histamine, Naturally

  1. Nara says:

    Hi, o have interest of knowing more about the probiotics thay increase and the others crpas that decrease histamine. Do you have the references? Thank you só much!

    • Epstein says:
    • This is a tough questions. One pub med published study tested varieties of probiotics says can be referenced here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042653/ . Their research indicates probiotic lactobacilli strains Lactobacillus rhamnosus (L. rhamnosus) GG and L. rhamnosus Lc705 were beneficial however, bifidobacterium did not downregulate histamine activity. There are many genetic variations of many many gut flora. Hopefully future research will be able to map out the best probiotics for stabilizing mast cell activation.
  2. Missy Maiorano says:

    I have been suffering from high histamine issues…primarily hives and insomnia…ever since taking a round of Cipro. I’m waiting for my Dutch hormone testing but I already know my estrogen is extremely high and I have almost no progesterone. I’m taking Taurine, GABA, vitamin C, B-6, and zinc. I have a hunch I have low cortisol…I have always lived an extremely fast paced, super-stressed lifestyle. While I wait the 2-3 weeks for my Dutch results, will it hurt to take the taurine and GABA to calm my anxiety? I don’t want to lower my cortisol if it’s already too low…I can’t afford for my Histamine levels to get any worse.

    • Epstein says:

      Thanks for your question, however, it would not be appropriate for me to make medical recommendations via public chat without taking proper history and necessary labs.

    • Dee says:

      Missy if you are injured from Cipro it may be wise to take P5P instead of straight B6, B6 can make any neuropathy much worse. Im not a Dr just a fellow Floxy that learned the hard way lol.

  3. Elizabeth Keech says:

    Excellent and helpful article…Can you recommend a physician in Naples,FL who could help treat my adult daughter ? We were recently exposed to significant mold ( that she is allergic to) in our house. We are out of the house until this can be remediated next Wed. Any recommendations would be greatly aporeciated.

  4. Lee says:

    This is a great article but some of the things mentioned are things found to be high in glyphosate and glufonisate which has been found to raise histamines. They use those herbicides to dry beans and grains. Also people may want to avoid GM products because it has been found the body reacts to the BT Toxin in them the same way they would if you had food poisoning.

    • Epstein says:

      Yes, you are correct when it comes to whole foods. It is important to source organic products whenever possible to avoid glyphosates. Supplements however are not commonly available as organic. Fortunately dosages are much smaller than the source agriculture product and extracts do not likely contain glyphosates.

  5. Karlicia D. Berry says:

    This is excellent! Right on the money when it comes to explanation and advice to help. Thank you so much for publishing this.

  6. Jennifer F Jackson says:

    I find that so many who suffer with histamine problems are also sensitive to salicylates, and it is important to learn about oxalates. The best place to learn about oxalates is “Trying Low Oxalates TLO” facebook group and other groups Susan Owens is the expert. Oxalates cause kidney stones, gout, leaky gut, eye problems, joint pain, lower minerals and sulfur, if this isn’t addressed the other problems persist. Also iodine helps control histamines– and important to note meat must be very fresh (for histamines) so buy fresh and freeze right away. (No leftovers) Iodine info–https://www.youtube.com/watch?v=seymLq1ofXA– also, environmental stress is a trigger to histamine release– heat, cold, mold, … many also fine OMAD (one meal a day helps) and Intermittent fasting– at least 18 hours a day of clean fasting (Plain water only) gives the body a chance to heal — Dr. Jason Fung –“Intermittent fasting … That is the process of autophagy, where sub-cellular organelles are destroyed and new ones are …”

    • Epstein says:

      Thank you Jennifer, these are all excellent points. In regards to metals it is also important to consider copper, as it is a component of DAO. However, too much copper can also cause anxiety and ADHD, particularly if diet is inadequate or the body is low in metallothionines such as ceruloplasmin which bind free copper. Important to test copper levels prior to taking copper supplements. And a good idea to test RBC magnesium prior to taking iodine.

  7. Christine Menaged says:

    Thank you for the article. Well done.
    I have a very complex situation. I suffer from gastritis. Had my gallbladder removed do to a pancreatic attack. Everything normalized , but I continue suffering from leaky gut, gastritis, gerd post nasal drip, possible ulcers lots of burning in the gut.
    Recently developed a nagging pain that I believe may be an ulcer. I began taking Carnosine Zinc and I feel it helps my stomach, but I notice when I take carnosine the histidine makes my histamine worse. I also am gluten intolerance and recently also developed a geographical tounge which we think was a fungus infection. I was given several doses is Nystatin and Diflucan which only made it worse. I did take antibiotics a while back. I believe the Zinc carnosine can help me, but I need to balance my micro flora and control my histamine level. When I take Zinc Carnosine I get severe pain in my joints and an ache feeling as if I took gluten. My sinus are also very dry and I am always dehydrated regardless if I drink water. My E&T doctor says I have allergies but I have not suffer ed from any rashes or asthma just very dry sinus and post nasal drip. I also suffer from gerd if the acid gets out of control. Based on your article it appears I was taking the wrong probiotics.
    I would dearly appreciate any suggestion or recommendation you may have.
    Thank you,

    • Epstein says:

      Christine, thanks for your comment. It would be difficult to assess your situation from this information alone, and it would not be appropriate for me to do so in this comment section. Suggest that you have a Comprehensive Digestive Stool Analysis x 3 (I use Doctors Data) completed and start with identifying status of your digestive tract flora, parasites, yeast and food digestion. Nasal drip will disrupt the protective gastric mucosa and lead to leaky gut and a worsening of the sinus drainage. You might ask your doctor about chromalyn sodium, aka Nasalchrome. A low carb, low fruit, paleolithic diet along with a broad spectrum probiotic and other digestive support supplements should also give you some relief.

  8. Pingback: Histamine Intolerance

  9. Amanda Drake says:


    I was looking at the information on your website as I am researching to help with issues my 8yo son is suffering from…..chronic infections, chronic fatigue, rashes, chronic abdominal pain and vomiting. After much begging, we did additional blood work.

    Histamine Level= 4913 nmol/L
    Zinc= 77 ug/dl
    Copper= 115 ug/dl
    Cortisol (9am)= 5.4 ug/dl
    Ferritin= 21 ng/ml

    Any recommendations?


    • Epstein says:

      I cannot provide specific medical recommendations by open forum, however, the histamine we use in determining methylation status is from Whole Blood; this test was for plasma or serum. Judging from these labs there is a sufficient copper imbalance to suggest supplementation will be helpful for various mood disorders (none indicated in your comment). Whether or not the histamine or oxidative stress is contributing to rashes, pain, vomiting etc would have to be determined through more detailed assessment and supplements trial.

    • Epstein says:

      The histamine is not a whole blood histamine fraction. Evidently the sample was a plasma or serum specimen. Suggest retesting that for methylation status. We like to see a range of 40-70 for normal, assuming no antihistamines (including histamine lowering anti-depressants) were taken within a month prior to the labs. Higher levels of histamine suggest undermethylation, lower suggest overmethylation. Remember, it is not advisable to take folates for undermethylation or for high histamine when addressing mood disorders, because they increase the reuptake of serotonin and dopamine, lowering the action of these neurotransmitters. Zinc and copper levels should be flipped Zinc/Copper ratio of 1.25 is ideal. In this case the Copper/Zinc ratio is too high. Use caution when treating low zinc/high copper. Testing ceruloplasmin when testing copper is needed to determine free copper.

  10. Mary Holladay says:

    I have a history of Paroxysmal Atrial Fibrillation. A cardiologist said that he would normally do an ablation because of the number of episodes I had had but considering that I was on a blood thinner and have a high BMI he felt that proper pressure could not be applied at the catheter insertion site and that I could bleed and bruise excessively post ablation. So in spite of an anti arrhythmic I still had episodes. I read as much as I could and found that histamine excess due to a decrease in DAO production in older people can trigger A Fib. I have modified my diet to reduce histamine producing foods and rarely have break through A Fib. My cardiologist is skeptical. Is there a peer reviewed article that mentions excess histamine as an A Fib trigger that I can share with her?

  11. Pete says:

    They have several benefits and I would like to try some of them. I didn’t know they have this excellent benefits other than they are nutritious.

  12. Katie says:

    Do you think rosacea can be linked to histamine and Mast Cell Activation Disorder? I’m wondering what test and/or supplement I could take to see if there is a correlation?

  13. Dan says:

    Where is the published research or Pubmed study or studies that show methionine lowers histamine levels. Thanks in advance.

    • Epstein says:

      You may wish to peruse the studies that indicate SAMe is the rate limiting factor behind 220 of 230 known methyltransferase activities. Histamine methyl transferase is the enzyme that lowers histamine within the red blood cells. By deduction, it is strongly argued that that reduced SAMe (methionine source) or low methylation will result in higher whole blood histamine. Here’s a usedful link: https://www.sciencedirect.com/topics/neuroscience/methyltransferase “3.1 Assay Formats – Methyltransferases utilize SAM as a methyl donor, regardless of their substrates as proteins, nucleic acids, or small-molecule substrates, and with the formation of SAH as a by-product (Carmel, Jacobsen, & Hajjar, 2001).”

      • Dan says:

        Hey thanks for your reply, and sorry for my delayed response. That makes sense, especially with SAM-e. But if one doesn’t have enough methylcobalamin or other methyl-groups, then I’m guessing methionine won’t work quite as well as SAM-e.

  14. Carrie Rogers says:

    So you mention that in under methylation one should not take folates in mood disorder because it lowers serotonin. I’m confused by this, if I was under myth elating wouldn’t I need folate? What about b vitamins that are already methylated?

    • Epstein says:

      ‘Methylated’ B Vitamins are not a factor in contribution of total methyl compounds. They are advisable when genetic test suggests need for methylated, assuming one does not have low serotonin ACTIVITY, based on Walsh test measure of whole blood histamine. This is key, methylation may increase the production of serotonin, but folates lower the activity. The same goes for persons with chronic low levels of zinc or vitamin B6, common with pyroluria. These are considered to be low serotonin ‘level’ conditions. If low levels or low activity exists then folates, like niacin and DMAE are discouraged when patients are suffering from low serotonin or low dopamine mood and/or behavior disorders. If there is reason to believe the need to supplement with folates (pregnancy planning, macrocytosis, etc) outweighs the risk of lowering serotonin activity then this information must be reconsidered, case by case.

  15. Sam says:

    Thank you for this information, it has helped me immensely.

    My whole blood histamine is elevated 1,722 nmol/L/191.4 ng/mL (serum was recently 0.29 ng/mL). I’ve been working on it over a year and have gotten it down from 2,541 nmol/L.
    Copper is 1.2 ug/mL (120 ug/dL),
    Ceruloplasmin 24 mg/dL,
    rbc zinc 10.8 mg/L
    Eosinophil % 7 (was 17 – shot up suddenly 11/2018)

    This started after I had surgery and the doc recommended a vegan diet and prescribed Metformin for my A1C of 6%. I followed the diet but became sick from the Metformin and then malnourished from the diet and the messed up gut from the Metformin. She also advised me to take probiotics. Unfortunately, I believe many were high histamine probiotics. I have since stopped listening to her (and ditched the vegan diet for a mainly plant based with salmon/eggs/low histamine cheese) and have done my own research. I followed the plan of methionine (zinc methionine that also had b6), C, Magnesium and low histamine diet. I’ve stopped taking probiotics. Right now my b is too high 140 ug/L from the methionine supp. Need to find one where b6 is not included.
    My main symptom now is runny nose. I have treated the insomnia with GABA and magnesium (CALM)
    Does activated charcoal (coconut based) sop up extra histamine?

    Do you have any suggestions? I’m starting to get frustrated at the slow pace.
    Thank you,

    • Epstein says:

      Eosinophilia is commonly elevated with intestinal parasites. This is another pandemic that is hardly discussed. It does appear that you are undermethylated, though it is best to look at a history and review full Walsh Panel before treating. For instance treating methylation prior to proper evaluation of “plasma” zinc and copper overload status can be problematic. Some of the worst behavior disorders come from overmethylation (and overmethylating) plus elevated free copper. Suggest proper test of plasma zinc and then treat your copper overload, THEN work on methylation. Meantime, you’ll need a good natural protocol for intestinal parasites. These, worms in particular, are a major source of intestinal dysbiosis, skin rashes, back pain, sleep disorders, and mood problems.

  16. Gin says:

    My husband can’t function without daily anti-histamine drugs, namely Zyrtec. He’s been suffering terrible allergies all his life, and even with allergy shots he is still dependent on daily Zyrtec so it seems futile to order a whole blood histamine test since he can’t go off for a month duration. Does this pretty much mean that he is an under-methylator who needs to avoid folic acid? I recently gave him some organic celery juice (high in folate) and he definitely feels ill immediately after and did not feel well besides the juice causing acute diarrhea every single time. Within last few days, he’s been noticing muscle spasms and fatigue, and I’m trying to understand his methylation status especially because his stress/anxiety is sky high.

    • Epstein says:

      There’s a pretty good chance he’s an undermethylator. Best to test with another panel that is not affected by anti-histamines. This is the Methylation Panel by Doctor’s Data that measures SAMe, methionine, homocysteine, SAH and adenosine. That is the gold standard for methylation evaluation. But it is not a good test for overmethylators and it is not useful if someone has been taking SAMe and methionine.

    • Epstein says:

      This depends on symptoms and weight, plus history and current medications. We don’t treat all undermethylators wwith SAMe, for instance Bipolar Disorder or those with high copper do not do well with SAMe or until copper and zinc levels are first corrected.

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