Medicines That Cause Histamine Intolerance

August 10, 2018 | Blog

The realization that Metformin blocks the diamine oxidase enzyme led me to research the medicines that cause histamine intolerance.

Diamine oxidase is the enzyme within the intestine which breaks down biogenic amines (including histamine). When the level of histamine consumption exceeds the capacity of diamine oxidase to break it down histamine intolerance occurs.

By blocking diamine oxidase Metformin can cause histamine intolerance. It did for me.

Let me make it clear from the outset I am not a medical doctor and you should not stop any medicines without talking to your doctor.

All medicines have risks and benefits.

I am providing this information so that you can partner with your doctor about those risks and benefits and make an informed choice. It may be that on balance it may be best to take the medicine and manage the histamine intolerance.

Also, there are many reasons that a medicine might be acting promiscuously.

In this blog post, I am simply addressing one aspect which is medicines that block the diamine oxidase enzyme and those that release histamines.

I have previously written about pharmacogenomics.

And finally, whilst there has been some research into medicines that block the diamine oxidase enzyme or release histamines, this is not a requirement prior to listing medicines with the regulatory authorities.

Simplistically, medicines when listed only are required to demonstrate what problem they solve not necessarily all the unintended problems if any they may create. This means that despite my best efforts this information may be incomplete.

With that said, drug allergies are a common cause of histamine intolerance type symptoms, at least in my client base, and the role that medicine plays in both optimizing health, and causing unwanted side effects is worth considering.

How Medicines Cause Histamine Intolerance

Metformin is a good example of how medicines cause histamine intolerance. It did for me.

Metformin is the first-line treatment for patients with type 2 diabetes, however, adverse reactions have limited its use. This discontinuation rate led to research that identified that it unknowingly blocked diamine oxidase.

Speaking personally, it dramatically escalated my food intolerances, and histamine intolerance symptoms, and also my reactivity to histamine releasing medicines and even led to severe IgE (allergic) reactions to drugs. On one drug my IgE was 3,000!

My working hypothesis is that in some genetically vulnerable people, the intermittent use of diamine oxidase blocking or histamine releasing medicines do not cause a long-term destabilization of the histamine system.

Rather, the issue is with daily and repeated use, which may destabilize the histamine system, and may even escalate to the propensity to IgE reactions to medicines.

This hypothesis fits with the emerging hypothesis that the anti-histamine system is normally a tightly controlled process. The long-term use of anti-histamines, for example, is thought to alter the equilibrium of this tightly controlled immune system. Chronic anti-histamine use is also thought to trigger IgE allergies and food sensitivities.

Interestingly, recent research suggests that a low histamine diet plays a role in restoring diamine oxidase and therefore histamine tolerance.

This is certainly my experience.

Once all medicine was withdrawn it took about two years for my histamine system to stop hyper-responding and find its equilibrium. During this time a low histamine diet and avoidance of common allergens was a critical part of my strategy to reset my histamine system.

So here is the available research.

Diamine Oxidase Blocking Medicines

These medicines have been shown in the scientific literature to block the histamine degrading enzyme diamine oxidase and in so doing limit the ability of the body to degrade excess histamine.

Where the research indicates the degree to which the enzyme is blocked I have provided that information. I have not included any weak (that is less than 20%) inhibitors. The actual function would also depend on a person’s genetic function.

Here is the list:

Active Ingredient	Medicine Type	% Blocked
Acemetacin	Anti-rheumatic	42
Acemetacin	Anti-rheumatic	42
Acetylcysteine (NAC)	Mucolytic	29
Alcuronium	Muscle Relaxer	*
Ambroxol	Expectorant	*
Amiloride	Diuretic	*
Aminophylline	Anti-asthma/bronchitis	40
Amitriptyline	Anti-depressant	33
Carbocromene	Anti-hypertensive	65
Cefotiam	Antibiotic	29
Cefuroxime	Antibiotic	34
Chloroquine	Antimalarial	90
Chlorphenoxamine	Anti-histamine	28
Ciclacillin	Antibiotic	27
Cimetidine	Anti-histamine	37
Clavulanate (Clavulanic Acid)	Antibiotic	90
Clomipramine	Anti-depressant	23
Clonidine	Other	Strong
Colistin (Mesilate)	Antibiotic	54
Cycloserine	Antibiotic	100
Dalfampridine	Potassium Channel Blocker	Strong
Diazepam	Tranquilizer	*
Dihydralazine	Anti-hypertensive	100
Dobutamine	Anti-hypertensive	*
Dopamine	Dopamine	34
Doxycycline	Antibiotic	*
Framycetin (Neomycin)	Antibiotic	34
Furosemide	Diuretic	*
Guanabenz	Anti-hypertensive	Strong
Guanethidine	Anti-hypertensive	Strong
Haloperidol	Anti-psychotic	*
Isoniazid	Antibacterial	47
Metformin	Anti-hyperglycemic	Strong
Metoclopramide	Dopamine Antagonist	36
Orciprenaline	Anti-asthma/bronchitis	39
Pancuronium	Muscle Relaxer	88
Pentamidine	Antiprozal	100
Pirenzepine	Anti-asthma/bronchitis	55
Promethazine (Phenergan)	Anti-histamine	23
Propafenone	Calcium Channerl Blocker	*
Proxyphylline (Theophylline, Pramiverine)	Anti-asthma/bronchitis	26
Quinidine	Sodium & Potassium Blocker	*
Sulfapyridine	Antibiotic	21
Sulfasalazine	Analgesic	21
Tegaserod	Other	Strong
Tetroxoprim	Antibiotic	54
Tranylcypromine	Anti-depressant	*
Tubocurarine	Muscle Relaxer	95
Verapamil	Anti-hypertensive	50
* % Not Disclosed		50

Interestingly, some anti-histamines blocks diamine oxidase.

If an anti-histamine is being used to manage the use of any of these diamine oxidase blocking medicines that an alternative anti-histamine should be used.

This is something that personally went wrong for me.

Histamine Releasing Medicines

Certain whole classes of medicines are also known more generally to stimulate the release of histamine. This includes:

Non-steroidal anti-inflammatory agents like aspirin
Antibiotics (which also often block diamine oxidase are twice as problematic)
Opioids
Contrast Agents
Muscle Relaxants
Local anesthetics.

Medicine Type	Low Risk	High Risk
Tranquilizers	Diazepam
	Flunitrazepam
	Midazolam
Analgeasics	Acetaminophen	Acetylsalicylic Acid
	Alfentanil	Codeine
	Fenbufen	Diclofenac
	Fentanyl	Flubiprofen
	Ibuprofen	Indomethacin
	Levamisol	Ketoprofen
	Naloxone	Meclofenamic Acid
	Remifentanil	Mefenamic Acid
	Sufentanil	Metamizole
		Morphine
		Naproxen
		Novaminsulfon
		Pethidine
		Sulfasalazine
		Tramadol
Hypnotics	Ketamine	Phenobarbital
	Propofol	Propylene glycol (as filler)
		Thiopental
Muscle Relaxants	Cisatracurium	Atracuronium
	Vecuronium	Mivacurium
		Pancuronium
		Rocuronium
		Succinylcholine
		Tubocurarine
Local Anesthetics	Bupivacaine	Chloroprocaine
	Mepivacaine	Lidocaine
	Prilocaine	Pontocaine
	Ropivacaine	Procaine
		Tetracaine
Anesthetics	Enflurane
	Isoflurane
	Sevoflurane
Other		Atropine
		Gelatine
		Hydroxyethyl starch
Contrast Medium		All MRI contrast agents
		Iodinated contrast media
		X-ray contrast media
Source: Jarish (NSAIDS), Interdisciplinary Mastocytosis Centre

These medicines may or may not be a problem depending on the individual’s ability to degrade that histamine.

Fluoroquinolone Antibiotics

Whilst I have not been able to find it in the research, in clinical practice there appears to be a high correlation between fluoroquinolone antibiotics, and mast cell activation or histamine intolerance.

What can be said, however, is that there are now FDA warnings on the effects of fluoroquinolone antibiotics on the central nervous system, making it a high-risk alternative when compared to other antibiotics.

Antidepressants

Many anti-depressants, appear to work through the histamine system, and in clinical practice appear to be highly correlated with histamine intolerance and mast cell activation.

Professor Healy, a leading expert on psychopharmacology, concludes that many anti-depressants are not “clean” but interfere with the histamine system.

He states that SRI withdrawal can be viewed as a “histamine over-activity (semi-allergic) state brought around by the fact that the person has been on anti-histamines chronically.”

Please consider consulting professor Healy if you are struggling with antidepressant withdrawal. He consults with patients remotely.

Estrogen

And finally, estrogen supplementation, and specifically when there is estrogen dominance, relative to progesterone in women and testosterone in men, is histamine releasing.

Fillers

Fillers should also be checked for a history of allergic reaction. For this reason, compounded medicines are often better tolerated.

Basic Strategies

If you have histamine intolerance, then you may like to consider the role of medicine, in causing histamine intolerance, and also develop a strategy for managing any histamine intolerance symptoms with any essential medicine.

Here are a few strategies I have personally found helpful.

Step 1: Keep a Good History

History is really important.

Historically, I have outsourced my medical records, to my general practitioner. But I have also moved countries, cities, and doctors.

I have had severe adverse reactions to medicines throughout my life but I cannot remember which ones and I did not take a note of them. I’ve also taken medicines without incident and cannot remember which ones.

I now keep a folder with an accurate up to date history and family history.

Step 2: Evaluation of The Risks and Benefits

A common assumption amongst my clients is that all medicine is safe and that their symptoms may be due to some unknown chronic disease.

In fact, all medicine has risks and benefits. Australians for Safe Medicines have the questions to ask your doctor or community pharmacist to determine what is right for you.

In my case, I try to manage my preventative health strategies through lifestyle interventions, including diet, exercise, and stress management, and this has included reversing insulin resistance. I did not need Metformin to reverse insulin resistance.

When lifestyle interventions have not worked, I have used targeted natural supplements to support my body’s own innate function. For example, I use a high dose of Liposomal Vitamin C to knock flu on its head.

Only with an irreversible disease process do I used medicine. I focus on medicines with a long history of safe use rather than the latest new shiny medicine.

And yes I do use medicine when the benefits outweigh the risks. I then manage any short-term symptoms with a low histamine diet and/or diamine oxidase enzymes or anti-histamines.

That’s what works for me. There are no absolutes and no right or wrongs. Your approach may be different but these are some of the basic principles that work for me.

Step 3: Partner with Experts

In my experience, which is based on the Australian medical system, doctors are trained in a “one size fits all” model. This means if you don’t fit the mold then your doctor may need to refer you to a specialist.

I personally have partnered with a specialist clinical pharmacologist (who specializes in pharmacogenomics), immunologist (who specializes in drug allergies), community pharmacists, and a functional nutrition practitioner (I don’t coach myself!).

Step 4: Plan for An Emergency

Another common issue amongst my clients is that they wait until they are in crisis before getting a plan in place, or they turn up with lists of medicines, and detailed explanations of mast cell activation and histamine intolerance, too overwhelming to wade through, in a crisis.

I have a medic alert and an advanced health care directive in place which is a simple legal document that outlines in the case of an emergency

That I have “drug allergies” which is a simple universal term,
What medications I CAN have for key categories of essential medicines,
Requests the concurrent treatment with anti-histamines (diamine oxidase enzymes are not readily available in Australia), and
Who to call with any questions.

It’s a simple plan that gives me peace of mind and gives the doctor confidence.

It’s also a plan which has seen me successfully have emergency surgery without adverse reactions in circumstances where I previously had repeated hospitalizations.

Conclusion

I am not a doctor and I don’t ever tell a person to stop taking medicines. And yes I do take essential medicines where the benefits outweigh the risks.

I am simply providing you with this information, so that you can partner with your health professionals, about the role that medicines are playing if any in your symptoms.

All medicines have risks. Some medicines are very effective for some people. Some provide little benefit. In other cases, they may even cause severe histamine intolerance, drug allergies, and even severe harm.

In some cases, it is as simple as switching medicines. In others, it might be about managing the symptoms including with a low histamine diet. And in other cases, lifestyle interventions may be a better alternative.

What if rather than an additional disease process our prescribed medicines were the cause or our histamine intolerance?