Copper Zinc Balance and Migraine

• Migraine is a mineral imbalance issue which leads to enzymatic deficiencies and inability to properly break down histamine, glutamate, and tyramine – – ie, it is a metabolic disorder.
• High estrogen levels at ovulation affect histamine, while low estrogen and progesterone levels raise glutamate levels and contribute to migraine around menstruation.

While metabolic processes require many nutrient cofactors to take place, I will focus on copper and zinc in this article, as balancing these two minerals is the biggest leverage point in transforming migraine.

From my studies into migraine and mineral balancing, I have come to believe that there are at least two important things to consider in regard to copper zinc balance as it relates to glutamate, histamine, and hormone imbalances:

• Excesses of histamine and glutamate in the body from food and gut flora imbalances place a greater demand on mineral stores of copper and zinc which are also needed for hormonal balance.  This means that even if someone has copper and zinc levels within the “normal” range, there may insufficient amounts to meet the increased demand.
• Insufficient amounts of these two minerals will result in a reduced ability to regulate hormones at key times throughout the cycle, lower levels overall of estrogen and progesterone, and higher levels of histamine and glutamate. 
• As a result, women will be more prone to food triggers from an overload of these two amino acids at key times during their menstural cycle – right after ovulation, 2 days prior to menstruation, and on day 3 of menstruation.

A quick recap from part 1

Women with migraine have less bio-available copper needed to make the enzymes that break down histamine and tyramine – and which make estrogen. They have less copper because their digestive, kidney, adrenal and liver function is more compromised, which in turn makes it harder for them to absorb and retain minerals and efficiently detoxify pollutants, convert amino acids, or make hormones as efficiently as women who are not compromised in these organ systems.

Ditto with zinc. When major organ systems like the kidney and liver aren’t working optimally, zinc will not be assimilated or optimally utilized for glutamate or progesterone (or serotonin), or for the removal of heavy metals in the body. Once heavy metal buildup occurs (usually in the very organs that are already strained), these heavy metals will further disrupt mineral balance by displacing zinc and copper.

It is true that copper toxicity in the form of biounavailable copper built up in tissues contributes to migraine, and it is true that many women have an excess of estrogen in relation to progesterone (ie, an excess of copper in relation to zinc) – nevertheless, the following is also true: too little copper, too little zinc, too little estrogen, and too little progesterone all lead to migraine. 

It isn’t helpful to demonize estrogen or copper. Both estrogen and copper are vitally needed to be free from migraine.  So are zinc and progesterone.  Copper zinc balance is the key.

Copper zinc balance and migraine

Zinc and copper are both synergistic and antagonistic – I like to think of them as like husband and wife, with copper (estrogen) as the wife and zinc (testosterone) as the husband. Of course, both men and women need copper and zinc because both men and women have estrogen and testosterone. 

Copper and zinc compete for absorption in the intestine and are very close in atomic weight, so are easily swapped out for each other in various metabolic functions. This is why too much of either mineral can cause a deficiency in the other, and why maintaining a good balance and harmony between them is crucial for physical health. 

Copper zinc balance can’t be accomplished by just fixing deficiencies in copper and zinc, or assuming that if you are within normal range on a blood serum test that your copper and zinc are fine. Copper zinc balance has to do with looking at optimal ratios of zinc to copper, and not just the total amount of copper or zinc. 

A relative imbalance can exist in this ratio even when there is a sufficient level of both minerals on an absolute level. The converse is also true: in the case of someone who is deficient in both copper and zinc, a copper excess can still occur from too much copper in relation to zinc, or vice versa.

A deficiency of copper in relation to zinc can lead to connective tissue problems, especially connective tissue in the lining of the endothelium of the blood vessels so needed for blood flow to the brain.  A deficiency of zinc in relation to copper can lead to low stomach acid, depression and heavy metal buildup.

Most migraineurs are deficient in both minerals. In a study done in Turkey measuring blood serum levels for various minerals and heavy metals, researchers found that

There were 25 migraine patients with an average age of 36.4±8.9 years and 25 healthy controls with a mean age of 42.4±9.5 years. Cadmium, iron, manganese and lead levels were significantly elevated in the patients compared to the controls (p<0.05 each), while copper, magnesium and zinc were decreased and cobalt demonstrated no change. (Source)

Copper basics

Copper is needed for hundreds of enzymatic processes in the body, but most importantly for migraineurs, it is needed for DAO (diamine oxidase) in the breakdown of histamine and in the breakdown of tyramine, as well as for enzymes needed to synthesize estrogen.

Copper is needed for:

• reducing histamine via DAO
• blocking glutamate receptors, reducing excitotoxicity (Source)
• ATP production in the cell (ie, energy)
• nerve conduction
• fatty acid metabolism (and by extension, brain health)
• neurotransmitter function (norepinephrine)
• liver health (and by extension, detoxification)
• bile flow (and by extension, gallbladder health)
• connective tissue health of blood vessels, bone, skin, and tooth enamel in the formation of elastin (via the lysyl oxidase enzyme)
• combating oxidative stress
• release of luteinizing hormone follicle-stimulating hormone (Source)
• signalling in the anterior pituitary (Source)

Copper and estrogen

Copper is so closely linked to estrogen as estradiol that most sources state that copper mirrors it’s fluctuations (Source) – ie, that when estrogen levels rise, so does copper.  If this is true, then it could be that the body regulates copper levels alongside estrogen as an adaptive mechanism to help protect the body from too much histamine (since copper is needed for DAO, an enzyme that breaks down histamine).

I began to get confused about this because I was not seeing this reflected in blood serum tests for copper, zinc, and ceruloplasmin, which I have clients test at ovulation and menstruation.

Biounavailable copper and copper “toxicity”

Many people avoid copper because of fear of copper toxicity.  Common factors which can contribute to copper toxicity aside from having a slow metabolism include the use of (or historical use of) hormonal birth control, hormone replacement therapy, heavy metal toxicity – especially mercury toxicity – or the use of a copper IUD. Copper water pipes contribute to excessive copper intake when water is acidic, and Wilson’s disease is a rare example of genetic copper toxicity. 

The body regulates copper levels by eliminating excess copper through the bile where it is then excreted in the stool. 

In order for copper to be bioavailable to cells, it must be carried by the protein enzyme ceruloplasmin, which is manufactured in the liver.  This is why liver health is so important, and why simply getting the right supplements and minerals is not always enough to heal migraine if the woman’s liver is being challenged by pharmaceutical medications or heavy metal toxicity. 

Many things can help to trigger ceruloplasmin production (including copper and estrogen) but ultimately the signal for the liver to produce ceruloplasmin comes from the adrenal glands.  Therefore adrenal gland health is crucial for healthy copper metabolism and balance. The thyroid also plays a role in signaling the liver to make ceruloplasmin.

A woman’s metabolic type plays a huge role in how her body utilizes or stores copper. Slow oxidizers (as compared to fast oxidizers, who burn up copper more quickly) tend to accumulate copper in biounavailable form in different parts of the body.  This is a simultaneous copper toxicity AND copper deficiency, as this biounavailable copper is not able to make it inside the cells for enzymatic processes including the breakdown of histamine and the synthesis of estrogen. 

The strategy here is to make the copper bioavailable with the appropriate nutrient cofactors, including whole food vitamin C, vitamin A as retinol, and boron. 

A Hair Tissue Mineral Analysis and/or a blood test checking serum ceruloplasmin, copper, and zinc is the best way to determine if someone is “copper toxic” or not. Copper toxicity is often indicated on a hair tissue mineral analysis by a high tissue calcium level or mercury toxicity.

I believe that for many of those with migraine (though not all), copper deficiency may be playing a greater role than copper toxicity. For most people some level of tissue copper buildup and simultaneous cellular deficiency is probably going on, and this is why increasing ceruloplasmin will benefit both fast and slow oxidizers. 

Zinc basics

Zinc is also critical, as it is needed to

• break down glutamate
• make progesterone and testosterone AND estrogen
• remove heavy metals from the body
• make serotonin
• diversify gut flora
• make stomach acid
• transcription of DNA
• oocyte maturation and reproduction
• regularity of menstrual cycle (Source)

Zinc is easily lost through stress.  Vegetarians and vegans tend to be low in zinc. 

Supplementing with zinc can be much more dangerous than supplementing with copper is, unless you have a genetic condition or pyrrole disorder which predisposes you to excessive zinc loss.

As it relates to migraine, zinc’s ability to convert glutamate and prevent its buildup in the brain is especially important.

The higher glutamate concentration that is found in zinc deficiency is thought to be due to enhanced activation of the hypothalamic-pituitary-adrenal (HPA) axis, the main mechanism involved in the stress reaction. Rodents receiving a zinc-deficient diet had significantly elevated corticosterone concentrations. It is thought that cortisol/corticosterone may mediate the blocking of glutamate transporter activity under zinc-deficient/stress conditions, leading to the accumulation of excess glutamate. (Source)

While zinc is clearly crucial for those with migraine (especially since it too is needed to make estrogen), it is extremely important to supplement zinc cautiously.  This is because zinc depletes copper more readily than copper depletes zinc.

High dietary zinc intakes increase the synthesis of an intestinal cell protein called metallothionein, which binds certain metals and prevents their absorption by trapping them in intestinal cells. Metallothionein has a stronger affinity for copper than zinc, so high levels of metallothionein induced by excess zinc cause a decrease in copper absorption. In contrast, high copper intakes have not been found to affect zinc nutritional status. (Source)