Copper dysregulation is a hot topic and rightly so! It seems to be a very critical root cause for so many ailments I see in clinical practice.
I am going to present copper over a 3 part series to help you become familiar with it, why it is important and why you should test the HTMA if you are dealing with relentless symptoms that may be associated with copper dysregulation.
In this blog, I am going to dive deep into Copper- reviewing both deficiency and toxicity. In both cases we have copper dysregulation. And there is another concept you probably are not aware of- a hidden toxicity.
The good news is, we can explore much of this copper dysregulation with our HTMA Supercharged program.
Review of Copper
Let’s start by doing a quick review of copper and copper dysregulation. Copper is important in the electron transport chain. It’s important for hemoglobin synthesis. Copper is therefore very important for iron utilization.
It’s needed for:
immune system health
synthesis of collagen and elastin
it is the body’s primary antifungal, anti-mold, and antibacterial.
The highest level of copper is found in the liver and the brain.
We’re going to dig into it more, but oftentimes copper toxicity is hidden, so you can’t just look at the copper level to assess for copper toxicity.
Copper is required for over 30 metalloproteins involved in oxidation-reduction reactions; neurotransmitter, myelin and, energy, bone and connective tissue production; immune function; and hematopoiesis.
Cuproenzymes (enzymes that use copper), have key roles in antioxidant defense systems, including superoxide dismutase (SOD), which reduces the free radical superoxide to hydrogen peroxide and water. Similar to iron, copper’s ability to transfer electrons makes it critical for metabolic pathways, yet also contributes to its potential toxicity.
Copper is a double-edged sword!
Let’s dive into the science of copper a bit more
Copper toxicity is kept in check by homeostatic mechanisms, which include transport, chaperone, and storage proteins such as cuprometallothionein. Metallothionine (MT) has metal binding properties and is a key player in copper (as well as zinc) homeostasis.
Zinc will be discussed in another blog.
MT can bind up intracellular copper to help minimize the presence of free copper ions. The synthesis of MT is upregulated in states of excessive copper to sequester cellular Cu2+ thereby decreasing copper and in deficiency to increase absorption.
MT is capable of binding multiple elements including toxic metals. It has a high affinity for Cadmium and Mercury. As a result, deficiency copper and zinc states can increase MT and result in increased uptake of toxic metals such as Cadmium. Cystine residues in MT must be reduced by selenoproteins so that MT can bind metals. Thus in selenium-deficient, oxidative environment, elements are released from MT which also can contribute to metal toxicity.
Selenium is another common mineral deficiency I see in clinical practice. This often goes hand in hand with copper dysregulation.
The problem with excess or deficient copper
Excess copper intake or dysregulation can lead to the presence of free copper ions causing pro-oxidative events such as the Fenton reaction. I talk about the Fenton reaction here.
Copper deficiency can also lead to oxidative damage due to insufficient cuproenzyme activity. Thus copper levels must be maintained in quite a narrow range for optimal function. For example, refractory anemia is the most common copper deficiency presentation, and subclinical deficiency is often difficult to diagnose.
Copper deficiency and copper excess often present with similar symptoms since both states can contribute to oxidative stress.
An extensive body of evidence exists for copper deficiency associated with cardiovascular disease: aortic fissures and rupture, arterial foam cells and smooth muscle migration, cardiac enlargement and rupture, coronary artery thrombosis, and myocardial infarction. Mild deficiency can contribute to elevated cholesterol, impaired glucose tolerance, and anemia, neutropenia, thrombocytopenia, peripheral neuropathy, defective elastin and bone demineralization.
Chronic copper exposure can occur with copper popping or cooking utensils that can lead to poisoning. Symptoms include nausea, vomiting, diarrhea. Long term exposure can lead to liver cirrhosis.
You may have heard of Wilson’s disease. This is a condition of copper excess- as an autosomal recessive metabolism disorder resulting from insufficient copper excretion via hepatocytes into bile due to defect in copper transport enzymes. It can accumulate and produce neurodegeneration and cirrhosis.
Excessive copper can behave as free radicals- resulting in cancer and heart disease.
Both zinc and molybdenum are often used to treat these conditions. The competition of zinc and molybdenum with copper for binding sites on proteins is used to treat copper toxicity conditions, cancer and other inflammatory conditions.
The elderly are also more likely to have insufficient copper homeostatic mechanisms producing elevated free serum copper, which can lead to oxidative stress. Both excess and deficiency are associated with Alzheimer’s disease and other conditions such as ALS, Parkinson’s disease, Down’s syndrome, and seizure. Copper binding therapies inhibit angiogenesis, fibrosis and inflammation an d are used to treat conditions such as RA, diabetic neuropathy and heart disease indicating the toxic effects of excess copper and other metals.
Many of my patients will run my custom blood chemistry panel, and ceruloplasmin is on this panel. This enzyme, referred to as ferroxidase, is a multicopper oxidase essential for normal iron homeostasis and copper transport. The metabolic fates of copper and iron are intimately related, and deficiency of copper or ceruloplasmin result in cellular iron deficiency and eventually anemia.
Anemia will compromise your immune system greatly! It is associated with chronic UTI’s, chronic infections but also can affect your brain and is a big contributor to depression and anxiety states!
Elevated zinc can decrease copper absorption and lead to iron-deficiency anemia. The RDA recommends a zinc : copper ratio 9:1. In my practice, I like to see this ratio 0.7-1.0.
CP contains 6 atoms of copper, 3 of which provide active binding sites for electron transfer. It is a powerful antioxidant, scavenging hydrogen peroxide and other reactive oxygen species while inhibiting lipid peroxide and DNA damage caused by free copper and iron atoms. CP is also an acute phase reactant protein and may elevate in inflammation.
Copper for electron transport chain
At least 4 atoms of copper are required for the structure of cytochrome-c-oxidase, the final and rate limiting electron transport in mitochondrial ATP. So you can see, if you have copper dysregulation, you can impair your ATP and energy production! This is the final gateway for energy flow and could be the most important enzyme in mammals.
Copper for neurotransmitters
Copper acts as a modulator of neuronal transmission in the CNS neurons, being involved in NDMA receptor modulation and catecholamine biosynthesis.
In my practice, the first line I use to assess Copper is a combination of the HTMA and the Copper toxicity checklist, along with patient symptom presentation.
The HTMA is included in our HTMA Supercharged program.
Here is a link for you to check it out
Common symptoms include:
- Panic attacks
- Brain fog
- Racing mind
- Low libido
- Low immunity
- Weight gain
- Chronic candida
Other supporting tests I can do include:
- Serum ceruloplasmin
- Serum or RBC copper
- Plasma zinc
- Zinc/Copper ratio
- Calculation of bound and unbound copper
- Urinary HVA/VMA ratio
- Urine testing (for excessive copper- often done on metabolomix)
Please note these tests are not included in the HTMA Supercharged, but you can consider running them with me if you become a patient of our Root Cause Investigation Program.
When it comes to assessing copper, is important your practitioner is trained appropriately. As you can see, there are a lot of nuances when it comes to Copper and just looking at the HTMA for face value can actually make you worse!
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