Histamines and Adrenal Fatigue Syndrome – Part 1

By: Dr. Michael Lam, MD, MPH; Dr. Justin Lam, ABAAHP, FMNM

Histamines and Adrenal FatigueHistamines are compounds found in various parts of the body. From the brain to the gut, histamine has a variety of actions. It is both a neurotransmitter as well as an immunomodulator. Depending on where it is found in the body, and what receptor it interacts with, histamine can elicit a multitude of reactions. There are four types of receptors, numbered H1 to H4. Each are found in different parts of the body and have distinctly different effects on the body when activated.

Histamines 101

H1 receptors are found in the central nervous system (CNS) as well as the peripheral nervous system (PNS). When activated in the CNS they produce a number of effects. One such effect is the firing of hypothalamic neurons that are active when we are awake. This is why anti-histamine drugs such as Benadryl can cause drowsiness by blocking this receptor. Histamine’s effect on the PNS H1 receptor is completely different. These receptors are found on smooth muscles and on inside blood vessels. This is the receptor that gets activated when you have an allergic reaction. Histamines bind to the H1 receptor in the blood vessels to cause vasodilation and increase permeability. This is what causes hives as well as the redness and swelling seen in inflammation. It also causes smooth muscle contraction in your bronchial muscles, leading to difficulty breathing, asthma, and potentially life threatening anaphylaxis.

H2 receptors are mainly found in the gut. They are located on parietal cells, which are responsible for the secretion of gastric acid. An increase in histamines will subsequently lead to an increase in gastric acid secretion. This is why H2-antagonist drugs such as Zantac were developed. These drugs are used to decrease the release of gastric acid and help with conditions such as peptic ulcer disease and gastro-esophageal reflux disease (GERD) as well as the prevention of stress ulcers.

H3 receptors are unique in that they are inhibitory receptors. Mostly found in the CNS, they are part of a negative feedback loop that inhibits histamine synthesis and release. They have also been shown to inhibit other neurotransmitters such as dopamine, acetylcholine, GABA and serotonin. Blocking the H3 receptor in animals has been shown to increase anxiety. When the H3 receptor is blocked, histamine synthesis and release are no longer inhibited, causing an increase in histamine. Thus, histamines are thought to be related to anxiety. Although no drug has been developed and approved specifically to target the H3 receptor, many drugs still act on the receptor secondarily and produce anxiety or depression as a side effect. Due to the H3 receptor’s effect on other neurotransmitters, it has also been implicated in other mental disorders such as attention deficit hyperactivity disorder, Alzheimer’s disease, and even schizophrenia.

The fourth and final histamine receptor, H4, is found primarily in the bone marrow and on basophils. It is responsible for releasing neutrophils into the bloodstream from the bone marrow as well as mast cell chemotaxis. Mast cells are immune cells that are loaded with heparin and histamine. They play a major role in allergies and anaphylaxis. So in a chain reaction, H4 receptor modulation and chemotaxis leads to Mast cell aggregation, which upon releasing amplified amounts of histamines in a process known as mast cell degranulation, can eventually result in chronic inflammation and inflammatory disorders such as allergies or asthma.

Knowing where histamines are and what they do is half the battle. How do these chemical reactions translate to the real world though? Histamines are toxic molecules. It has a long list of negative effects on the body if left unchecked.

Elevated Histamines

Elevated HistaminesWhile histamine is a natural compound that is produced by your body and manifested at normal levels automatically elevated levels can occur. Antihistamines are common drugs prescribed by doctors and even available over the counter. Antihistamines have common side effects such as drowsiness, upset stomach, difficulty urinating, nervousness, dry mouth, and dry nose. They are typically used in an acute setting when requiring immediate symptom release such as allergic reactions and hay fever. This is fine as the receptor gets blocked for a short duration, but everything goes back to baseline soon enough. However, when taking antihistamines chronically, the body never gets back to baseline. Antihistamine drugs do not stop the production of histamine. They occupy the receptor so that histamine cannot act on it. Histamine continues to be produced in increasing amounts as the body recognizes that histamine is not functioning, as it should be. The body slowly builds a tolerance to antihistamine medication until the medicine no longer works. When antihistamines are discontinued, a rebound effect occurs and the body is flooded with histamine. The body will continue to release high levels of histamine because that is what it is used to doing. All the negative effects of histamines such as fatigue, anxiety, brain fog, and palpitations will be felt as the body is continuously overloaded with histamine.

Read Part 2 Now!

© Copyright 2015 Michael Lam, M.D. All Rights Reserved.

Dr. Lam’s Key Questions

Hives can be due to many reasons, the most common of which is some form of sensitivity that leads to excessive histamine release. This can be associated with AFS.

You could have allergies from the environment, chemical or food. Keep a journal and find out what is causing your allergies. Allerdim has quercetin that is a natural antihistamine. Allergic (food or chemicals or sensitivities) and asthma reactions usually have strong adrenal components. Many allergies involve the release of histamine and other pro-inflammatory substances. The body’s response is to produce cortisol, a strong anti-inflammatory hormone. The weaker the adrenals, the higher the frequency of allergies. This is because the more histamine is released, the more cortisol it takes to control the inflammatory response and the harder the adrenals have to work to produce more cortisol. When the adrenals are eventually exhausted, cortisol output is compromised, allowing unopposed histamine to inflame the bodily tissues more. This vicious circle can lead to progressively deepening adrenal exhaustion and producing more severe allergic reactions.


5 stars –Hi,Hi,

Thank you for great articles. They have been very helpful to me and I am definitely going to share this website with other people I know are suffering from the same condition as I am.

Histamines and Adrenal Fatigue

5 - "My rushed pace to find" My rushed pace to find definitive answers and solutions I forgot to thank you for your website and your personal reply to my questions. My friend's symptoms are grossly improving? Thank you.

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  • Mike says:

    In your article you state the body “never gets back to baseline” after stopping antihistimines. So does that mean I will not ever improve after stopping hydroxyzine after taking a few years? I am currenlty feeling dizzy, nauseated, foggy headed, anxious and I have insomnia. I started to take 1000 mg of vitamin C along with tryptophan to offset the serotonin affects of hydroxyzine. I am 6 days from my last dose. I was taking 25 mg a day (50 mg sometimes).

  • Brandon says:

    Is the way the body swells in an allergic reaction different depending on whether it’s an inhaled allergen or an ingested one?

  • Lindsay Parkinson says:

    Thank you for this article, I need help! I was diagnosed Celiac, took gluten out of my diet then developed what seems to be a histamine intolerance. It’s been about 4 months of daily redness, inflammation, fatigue, brain fog. Gluten makes the brain fog worse but actually decreases the redness and swelling.
    I found histamaid (DAO enzyme) which helps to take before eating and have reduced my daily intake of Claritin to like 2 out of 3 days, then I take quercetin at night and l-methionine, sometimes benadryl – but I can barely get out of bed in the mornings. I’m not depressed, the anxiety has actually gone down since taking out gluten and when the histamine response gets lowered (high anxiety when there is a response) but I just don’t know what to do now. I’m sleeping like 12 hours a day. I’ve been taking 10mg of Adderall which usually helps to wake me up and concentrate but that isn’t even working anymore, and thinking of trying L-Tyrosine instead. Any suggestions?

    • Dr.Lam says:

      Adding more stimulant can give you some temporary relief at best, but the longer term can be very problematic. You need to get to the root of the problem and not patch the symptoms. What you experienced is not unusual. So that is the good news.


  • Peter says:

    Oh, I didn’t know antihistamines can cause dry nose. That makes perfect sense because they put it in allergy medication for symptoms like runny eyes and nose. Maybe I should be more careful with this stuff.

  • Katerina says:

    Is it true that bromelain and quercetin can act as a natural antihistamine?

  • JB says:

    A woman with a son with PANDAS has an MTFHR defect and histamine intolerance. He is experiencing adrenal fatigue and has been given hydrocortisone. His tics and grimaces have gotten worse. Why would this steroid increase histamine, not suppress it?

    • Dr.Lam says:

      Not being able to tolerate steroids is not unusual. This reflects upon deeper underlying problems which require a detailed history to figure out

      Dr Lam

  • Hugo says:

    Are asthma inhalers used for anti-histamine ?

  • Tara says:

    I can’t seem to stop hydroxyzine without terrible symptoms. I get palpitations, anxiety, stomach pain, irritability, foggy headed, pain, and very dizzy. I don’t know what to do. I was told this medication isn’t addictive.

    • Dr.Lam says:

      Rebound and withdrawals can happen in certain people, especially if you have been on it for some time. It is also dose dependent to a certain degree.

      Dr Lam

  • Precious says:

    I’ve heard that pineapple contains bromelain, a natural antihistamine. How much pineapple would I need to have to help with infammation?

  • Mike says:

    What are the symptoms of histamine rebound? How long does this affect occur after stopping an antihistamine after usage for about a year?

  • Erica P. says:

    I am a 49 year old woman and I have struggled with many phases of adrenal fatigue over the last 10 years. I have seen an holistic M.D. to deal with my issues and have had some success. I started twice weekly allergy shots two months ago in an effort to reduce seasonal allergies and the adrenal stress they cause. I have since experienced severe hot flashes and night sweats which don’t seem related to perimenapause because they are preceeded by an adrenaline rush. After some research I see that the increase in histamine caused by the allergy shots could be causing my symptoms. I read tat you don’t recommend antihistimes so I’m not sure what to do. My allergist suggests daily Zyrtec and Singulair while taking shots. Currently I only take Zyrtec on my sot days. If I take a daily antihistime while I am getting shots will this make my adrenal fatigue worse? Should I stop the shots? Is there anythhing I can do?

  • Elysa says:

    Is it possible to get specific anti-histamine supps depending on whether it’s for an H1, H2, H3?

  • Mary says:

    You had a high all day timed urine cortisol. So I suppose that makes me stage 2. I have also been taking low dose visteral for about a year. I seem to get increased anxiety and my skin feels like it’s burning if I try to stop. Is this typical? Can I switch to the natural bromelin and quercenlin and avoid the rebound effects?

    • Dr.Lam says:

      Visteral can have a rebound effect. Switch to natural compound can be considered, but the dosage needs to match the clinical effect, and may be high. Urine cortisol for staging is not very accurate. Be careful.

      Dr Lam

      • Mary says:

        Do you mind telling me an effective way to stop the visteral? Taper? Switch to one of the newer ones (claritin, zyrtec)?

        • Dr.Lam says:

          You have to talk to your doctor because everyone is different. Some people can go off cold turkey while others need a substitute in place for some time before attempting to taper off.

          Dr Lam

  • Alex says:

    Hey Dr. Lam, I’ve heard of some people having good luck with capsaicin for allergies. Is this okay to try with mild Adrenal Fatigue?

    • Dr.Lam says:

      Its anti-inflammatory properties can be helpful in AFS provided that you are not very sensitive and not in late stages

      Dr Lam

  • Megan says:

    What are we supposed to do instead for allergy symptoms?

    • Dr.Lam says:

      eAnti-histamine is useful short term, but the long term approach is quite different. Supporting the adrenals can be very helpful provided that you do it right because the adrenals control imflammation to a large degree thorough cortisol.

      DR Lam

  • Michelle Lana says:

    Is it okay to be on anti-histamines for a long time ? Should I be changing them around ?

  • Sylvia says:

    I take 75mg of benadryl at night. I titrated up to that amount in order to sleep at least six hours through hot flashes. I was just diagnosed with secndary adrenal Insufficiency . Did I cause this? I also take melatonin 5mg time released to quiet my run away thought at bedtime. Did I do this to my self?

    • Dr.Lam says:

      hot flashes is a reflection of hormonal imbalance. It can happen in AFS or can be independent event. Melatonin is a temporary sleep aid.
      There is much more to be known before I an give you an accessment. Click Estrogen Dominance for more information. Click Adrenal Exhaustion for more information.

      Dr Lam

  • Johnny says:

    Can Adrenal Fatigue make you have hyper-histamine reactions such as extreme sensitivity to bug bites? I have always swollen extremely bad from flea bites while others around me don’t even have a bump come up!

    • Dr.Lam says:

      Yes it can. when the adrenals are weak and cortisol production goes down, the body tend to be easily inflamed.

      Dr Lam

  • Elysa says:

    What are ways to relieve the body of built up histamine in the body?

  • Becky says:

    So if we have been taking antihistamines, such as visteral, for the anxiety symptoms of AFS.. How long will it take the body readjust if we stop? I cannot seem to go more then 2 days without feeling I’m in withdraw from this. I am trying not to take anything for this debilitating wired/anxious feeling but I need to function.

    • Dr.Lam says:

      For no normal people, no adjustment is needed. For those with AFS, it can range from zero to months. It really depends on the body.Remember that I deal with the most severe of cases so my perspective may be different. Without knowing each person specific state in real time, my reply can only be very general.

      Dr Lam

      • Becky says:

        I have just signed up and am terrified. I might just be reading to much but I am hypothyroid, on levothyroxine 23 years, I am surgically post menopausal, on estrogen for 3 years, I have recently (2012) withdrawn from cymbalta and klonipin (Feb 2016), I have the MTHFR gene, I have pyroluria and late stage AFS. I feel like I’m not fixable with all my problems which terrifies me. I have a hard time eating because of the gnawing stomach pain and I am losing weight pretty fast. I am doing the breathing exercises and doing gentle walking (where I used to workout almost daily) but it’s only temporary. I am afraid

  • Phil says:

    how long should i take antihistamines for? as histamine reactions improve should i continue taking antihistamines?

  • Joseph Campochiaro, ND says:

    I would like to download and print some of this wonderful material, so that I could study it all more carefully, priort to my effort as to which of your products I ought purchase.

    My problem is , all the your ” Enjoy Free Access To all we have to offer , right side bar….I do not need to copy all of that. How might I remove it temporarily, so that I might be able to copy just your words.

    • Dr.Lam says:

      I believe there is print copy function icon on top to allow you to print the material for personal use.

      Dr Lam.

  • Esther says:

    Hi Dr Lam, I had been prescribed with promethazine (daily 25-75 mg) for 3 months. But since I started taking them my body condition grew progressively worse, with nausea, unusual weakness (have to be bed bound), and fainting if I exert myself. The doctor didn’t realise I had an adverse drug reaction and did not tell me to stop taking the drug, but after I did online research I decided to quit cold turkey 2 weeks ago.

    Since I stopped the medication, I suffered major withdrawal symptoms like nausea, stomach cramps, insomnia. Good thing is my energy level is slowly rising, and the insomnia seems to be letting up. However I still have nausea, stomach cramps, and muscle weakness from time to time.

    May I know would I continue to suffer these symptoms forever? Or would they get better eventually? About how long does it take for my body to balance the histamine level?

    Thanks for your attention!

    • Dr.Lam says:

      Abrupt stoppage reactions can last from a few days to a few months. The stronger your body , the shorter it is. Without knowing your history and constitution I am not able to be specific as much as I like to as I could be totally wrong.

      Dr Lam

      • Esther says:

        Thanks for your prompt reply!

        I had no major illnesses all along in the past, and I was prescribed promethazine for my nausea due to morning sickness of pregnancy. Anyhow I hope these symptoms can be settled asap.

        Is there anything I can do to speed up this recovery process?

  • Don says:

    When my adrenals start to heal will my histamine intolerance get better?

    • Dr.Lam says:

      Generally speaking, yes, but there are many variables and usually the recovery is not straight forward with frequent relapses.

      Dr Lam

  • cindy says:

    Well, this is a troubling column to read. I have been diagnosed with Adrenal Fatigue as all my cortisol levels were low on a saliva test, and was told to take Adrenomend. The result after several months was that my cortisol levels came back to the proper level for the 4 times a day tested. I still take a couple of adrenomend a day, or 3 if there is a lot of stress going on. However, I have chronic allergic rhinitis and the symptoms are much worse at night than day. I have had food sensitivities that cause stuffiness and also positive allergy tests to mold, etc in the environment. I live in S Florida where it is humid and the mold count gets high at night, so I always suspected that was the cause of my stuffiness, which interrupts sleep frequently, sometimes for hours. So I use Flonase nasal spray and also take Benadryl at bedtime. I am concerned after reading this because I have been taking Benadryl (25 or 50 mg) at bedtime for YEARS! Should I request a histamine level with my next labwork before getting alarmed about it? And I wonder if histamine is chronically elevated, what that does to your adrenals? Now I remember why I hated neurology in nursing school.

    • Dr.Lam says:

      there is no histimine test that is relevant to your situation. The best thing to do is to avoid inflammatiohn and histamine type food to start. Taking benadryl long term is very problematic but you may not be able to stop due to withdraw reactions. The higher the histamine, the more strain on your adrenals. REmember that just because your cortisol curve normalized does not mean you are clear of AFS . When you use glandulars /herbs to normalize curve, it is more often than not a temporary patch. Click Adrenal Fatigue Glandular & Herbal Therapy for more information. Take some time to further study and trace to the root issue.

      Dr Lam

      • cindy says:

        Ok, thanks, will look into all your suggestions. Regarding inflammation, I did not mention that my CRP used to be really elevated and now is WNL. Does that mean I have gotten rid of most of my inflammation?
        I think this mostly happened by the elimination diet for food sensitivities- my arthritis symptoms went away as well. Thank you~

    • Maddy says:

      You may try a nasal spray called NasalCrom. It is not an antihistamine, it is a mast cell stabilizer. Prevents mast cells in nasal passages from degranulating and releasing histamine.

  • Sally says:

    Do I treat the inflammation first or the adrenal fatigue?

    • Dr.Lam says:

      The best is to do both concurently in a graded approach that is comprehensive and take into consideration both components. The degree and approach will ultimately have to be personalized as each person is different. What works for one person may backfire for another if AFS is advanced.

      Dr Lam

  • Tia says:

    I’d been taking a sleep aid with diphenhydramine in it for almost seven months. I am able to sleep without it now that I’ve quit. I still feel a bit jittery and distracted, plus my allergies are in high gear…. do you suppose it’s a rebound effect? I feel no need to take it ever again, but I’m hoping the effects lessen.

    • Dr.Lam says:

      That is a strong possibility, but there are other reasons as well . If it is rebound, the trend is to improve over time, though for some people that can take weeks. Generally its a matter of days, depending on your constitution. The drug is anti-inflammatory, so no surprise now that remove, your histamine level is unopposed. Click Histamine & Adrenal Fatigue Syndrome for more information. These are signals the body is sending you on the need to fortify your adrenal function.

      Dr Lam

  • Mario says:

    I’ve been diagnosed with chronic urticaria & angioedema by an allergy MD; also a naturopathic MD had no answer for me after several visits, blood tests, & a skin panel test… I’ve had hives for 6 months & tried a variety of natural & diet approaches. Nothing worked. Antihistamines made things bearable. I took a kenalog (corticosteroid) shot & they went away for 6 weeks, then slowly returned. I’m 8 weeks out from that shot and needing to take 1 or 2 Zytec daily again. I was told this could be genetic. I’m not wanting to give up yet. Perhaps it’s related to adrenals, or do you have a thought?

    • Dr.Lam says:

      It is possible to be associated with AFS. When the adrenals are weak, the body is inflamed Click Chronic Inflammation and Adrenal Fatigue for more information. , with high histamine being a key pathway. Good news is that this often gets better provided that the adrenals are well supported. Conventional medcicine unfortunately understand some but not the complete picture. the use of meds is good short term but should be used only as last resort. Each person is different as there are so many variables. do not give up. continue your search for doctors who understand, and if you have further questions, call my office and i will explain to you your options.

  • Jayne says:

    Would you suggest a low histamine diet or a moderate histamine diet with natural antihistamines such as quercetin? My cortisol and dhea are low. Trying to figure out what diet may help. Other symptoms are severe depression and anxiety.

    • Dr.Lam says:

      That is a good question. Its hard to give you a specific answer because when you have low adrenal function with low cortisol, the body can go into a variety of reactions that is not ordinary. that is why a detailed history is critical and we do that before able to recommend specific diet as what works for one person in theory does not necessarily work for others.

  • Tiffany Bayer says:

    I Live in an area where all Dr’s are uneducated on looking for a root cause. What can I do as a pregnant woman to combat this without harming the baby? I have been on zyrtec for a sudden cat allergy that caused me to have sudden asthma. Never in life have I had ANY allergies..now all this.

    • Dr.Lam says:

      When you are pregnant, the body’s reaction is very different. You need to talk to your ob doctor. natural compounds such as quercetin and bromaline are good as natural anti-histmaine, but your doctor needs to approve because you are pregnant.

      Dr Lam

  • Estelle says:

    My adrenals are low. I’ve got skin burning and tingeling aswell as muscle spasms from time to time. Can it be that ny histamine are yoo much?

  • Cassandra says:

    I’ve been having terrible heart pounding in my head for months. It’s adrenal and histamine I think but I don’t know what to do about it.

  • mike says:

    I have decided that it’s probably safer to start using tobacco again and get help from a natural medicine doctor to strengthen my adrenals before quitting again, I was getting worse every day for a month straight

  • dan says:

    when my adrenals get better will my histamine reaction improve?

    • Dr.Lam says:

      Generally speaking it does if you are able to get to the root and reduce histamine release. Simply suppressing histamine and reducing sypmptoms as a patch will not help the adrenals but in fact can make it worse.

      Dr Lam

  • Lotti says:

    How would you improve your histamine reactions without taking anti-histamines?