Histamine, copper, hives and leaky gut

In our Q & A series on histamine intolerance Dr Janice Joneja was asked whether histamine and excess copper could be implicated in her severe and chronic hives. Dr Joneja's answer ranges over a number of food intolerance related conditions including the excessive intake of supplements without medical advice.


What is the relationship between histamine levels and copper levels?  Does a C677t MTHFR defect impact histamine tolerance in any way?

I have severe chronic hives. In addition, I have a single C677T MTHFR defect. And I appear to have very low bound copper levels and very high unbound copper levels. Are all of these conditions related in any way?  If so, what is the best way to get all of them under control?  I already take lots of digestive enzymes and probiotics and other things to address any leaky guy issues I might have.

Dr Joneja says:

When several different conditions are present it is understandable that one looks for a connection or a common cause.  However, it is quite possible, sometimes probable, that each is autonomous and unconnected, even though occurring in the same body.  So, looking at your list of medical problems, I would conclude that you are dealing with at least three distinct conditions.

The genetic issue

First, let us look at the C677T MTHFR defect.  Now we have genetic analyses available to detect possible anomalies in our DNA, being human we look for an effect (symptoms) from the seeming cause (a genetic code defect).  However, it is very important to realise that we are far from being able to predict outcomes from genetic codes, because possessing a genetic marker does not necessarily mean that the person will develop the disease or fault that the gene may code for.  There are many factors in addition to the gene that determine the expression (the protein it codes for and its effects on the body) of that gene. 

In this specific case, the enzyme methylenetetrahydrofolate reductase (MTHFR) directs folate (a water-soluble B vitamin, known as B9) either to making DNA or to homocysteine (Hcy) remethylation. People with a defect in the gene tend to have higher than normal levels of homocysteine in their system.  It is the high homocysteine that can cause problems such as an increase in the risk for neural tube defects and vascular disease. Because of the high prevalence of this defect in most populations, it has been suggested that the variant might represent an ancestral genetic adaptation to harsh living conditions such as tissue injury or unbalanced vitamin intake.  Although this would make your ancestors the survivors, in modern times it may (but not definitely) cause problems for you.


You do not provide details of your age, nor do I have any information about your medical history, so I can only discuss copper in general terms.  Abnormal copper results are not diagnostic of a specific condition; they indicate the need for further investigation.

Copper is an essential element but when in excess, it can be toxic. A dramatic example of copper toxicity is Wilson disease (WD), a treatable but potentially fatal condition that is difficult to diagnose and monitor.  You must consult your doctor about this.  Furthermore, copper test results must be evaluated in context and are usually compared to ceruloplasmin levels. Ninety five percent of the copper in human plasma is linked to the protein ceruloplasmin.  Interpretation can be complicated by the fact that ceruloplasmin is produced when there is increased immunological activity.  It may be elevated whenever inflammation or severe infections are present. For example, ceruloplasmin, and therefore copper levels tend to be elevated in rheumatoid arthritis.  Both ceruloplasmin and copper are also increased during pregnancy and with oestrogen and oral contraceptive use. 

Chronic hives and histamine

The severe chronic hives can be the result of a variety of conditions; I would need to know your medical history in order to provide any specific directive for management.  The underlying cause would need to be addressed before you could expect any long-term relief.  The problem may be allergy to food ingredients, environmental allergens, contact allergy, autoimmune conditions, inflammation for any number of reasons, among others.  I would suggest that you seek the advice of an allergist, if you have not already done so.

However, whatever the underlying cause, histamine will be involved.  You will be able to reduce the severity and incidence of the hives by following a histamine-restricted diet which will eliminate most if not all of the histamine that is entering your body from the outside (extrinsic histamine).  You will find an outline of my histamine-restricted diet here and the specific foods to avoid and those allowed in my publication, The Health Professional’s Guide to Food Allergies and Intolerances, Consumer Factsheets.

Leaky gut and digestive enzymes

Finally, I am greatly concerned by your statement “I already take lots of digestive enzymes and probiotics and other things to address any leaky guy issues I might have.”  My primary question would be, “Why?”  First of all, do you actually have a diagnosis of “leaky gut”?  You state “….might have” which leads me to believe that you have reached this conclusion, perhaps from reading, without any real basis.  There are fairly reliable tests available, such as the mannitol and lactulose test, which will determine whether you do indeed have this problem.

It would appear that you are consuming many different types of supplements without any real understanding about their need or method of action.  Many readily available compounds sound as if they are beneficial when reading the literature put out by their manufacturer.  However, without a thorough understanding about how they impact the body, the effects of different formulations interacting with others, as well as disrupting the natural checks and balances within the body, you can cause yourself much more harm than good.  When attempting to reduce histamine, for example, it is very important that no probiotics are taken because there are micro-organisms in some formulations that can actually increase the histamine in your body as they convert histidine from food residue to histamine. Furthermore, indiscriminate consumption of supplements without knowledge of the way they impact the body can cause imbalances that can make a histamine excess considerably worse.

After all that discussion it should have become clear that for each of your questions you must seek the help of a qualified professional for a definitive diagnosis and appropriate management plan.  Here I can only point you in the appropriate direction.  I do not know your medical history, the results of any tests you may have undergone, and the medical practitioners who have been involved in your care.  So, I want to emphasise my message to you, and to anyone in a similar predicament with apparently multiple conditions revealed by a variety of testing modalities: do not try to self-diagnose.  Obtain definitive diagnoses from qualified practitioners and definitely do not attempt any therapy on your own without proper medical supervision.

March 2015

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