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• Copper is essential for brain health, but having too much also leads to neurodegeneration and neurological disorders; maintaining balanced copper levels is essential to prevent oxidative stress and maintain cellular health
• Copper deficiency disrupts iron recycling and mitochondrial function, affecting enzymes crucial for glucose and antioxidant metabolism
• Mitochondrial dysfunction is a key factor in copper-induced neurotoxicity, with copper overload disrupting mitochondrial fusion and fission, leading to impaired energy production and increased oxidative stress
• Proper copper and iron balance is vital for overall metabolic health, as imbalances disrupt iron homeostasis and contribute to mitochondrial dysfunction and neuronal damage
• Strategies for addressing copper-related disorders include using mitoprotective agents to prevent copper neurotoxicity and ensuring adequate copper intake through diet or supplements to support mitochondrial function and iron metabolism

Copper's dual role in brain health and neurotoxicity is a fascinating yet complex topic. While copper is necessary for brain development and function, having excessive amounts also leads to serious issues. In this article, we'll discuss the benefits of copper and how it's used in your body, but why an overload is also dangerous to your health, especially your brain.

Having Low Copper Levels in the Brain Is Linked to Parkinson's Disease Dementia

Parkinson's disease dementia (PDD) is a debilitating neurodegenerative disorder characterized by a decline in cognitive function alongside the classic motor symptoms of Parkinson's disease, such as tremors, rigidity and bradykinesia (slowness of movement). This condition, which affects 1% of the world's population above age 60,1 significantly impacts daily living, making simple tasks increasingly challenging and reducing overall quality of life.

Around 80% of people diagnosed with Parkinson's disease end up developing dementia within 20 years after the onset of their symptoms.2 As the disease progresses, individuals experience severe memory loss, impaired judgment and difficulties with language, further complicating their ability to communicate and interact with others.

Research published in the Frontiers in Aging Neuroscience journal highlights a critical imbalance in essential metals within the brains of those suffering from PDD. In particular, the researchers looked at how low copper (Cu) levels in certain brain areas contribute to the development of this condition.3

The participants were composed of nine patients that have been diagnosed with PDD and a control group composed of nine healthy individuals. Tissue samples were taken from the different brain regions of the participants, and their levels of essential metals were studied.

The researchers found that in PDD patients, seven out of nine brain regions exhibit reduced copper concentrations compared to the control group. The widespread decreases were observed in the cingulate gyrus (CG), substantia nigra (SN), hippocampus (HP), medulla oblongata (MED), primary visual cortex (PVC), middle temporal gyrus (MTG) and motor cortex (MCX).4

"The widespread decreases in Cu in the MCX, CG, HP, and MTG were the most striking similarity between the PDD and AD [Alzheimer's disease]. Cu was also decreased in the SCX, ENT, and CB of AD brains, and in the SN, MED, and PVC of PDD brains.

CB was the only region with dissimilar Cu concentration, with decreases in AD and no change in PDD brains. Several perturbations including decreased Mg, K, Mn, Zn, and Se were found in the CB of AD brains but no changes were found at all in the PDD CB, indicating a relative sparing of the CB in PDD compared to AD," they reported.5

This significant reduction in copper is not only prevalent in PDD but also mirrors similar patterns found in Alzheimer's disease dementia, suggesting a common underlying mechanism related to metal homeostasis in neurodegeneration.

Additionally, decreases in other essential metals such as manganese and potassium were noted in several regions, further indicating a disruption in the brain's metal balance.6 These alterations impair vital physiological processes, including mitochondrial function and antioxidant defenses, which are crucial for maintaining neuronal health and preventing oxidative stress. The researchers concluded:

"The observations from this study confirm that PDD is driven by increased oxidative stress and mitochondrial dysfunction due to a loss of antioxidative and ETC enzyme metallomic co-factors including Cu, Mn, Zn, Se, K and Mg. This includes widespread Cu decreases in PDD brains, reported for the first time here, affecting seven of the nine regions investigated …"7

Study Reveals How Excess Copper Disrupts Mitochondrial Function in the Brain

Another recent study, published in Frontiers in Aging Neuroscience, investigated how excessive copper affects brain cells, particularly focusing on the mitochondria, which are the cell's energy factories. The researchers sought to determine the exact ways in which copper imbalance leads to neurological problems. They examined brain cells exposed to high levels of copper and discovered that excess copper disrupts essential functions within the mitochondria.8

The mitochondria are responsible for producing adenosine triphosphate (ATP), the energy currency of cells; copper is necessary for this process. However, when copper levels become too high, it hampers the mitochondria's ability to generate sufficient energy, leading to cellular fatigue and impaired brain function.9

"[S]trong support exists for mitochondria as a primary target of Cu neurotoxicity. Alterations of mitochondrial dynamics and dysregulation of mitophagy may play a significant role in Cu-induced mitochondrial dysfunction, thus contributing to neuronal death and neuroinflammation," the researcher said.10

One of the key findings was that excessive copper triggers the production of reactive oxygen species (ROS), which are harmful molecules that cause oxidative stress. Oxidative stress damages neurons and glial cells, which support and protect neurons, ultimately leading to cell death. This process not only weakens individual neurons but also disrupts the overall communication network in the brain.11

The study also found that high copper levels promote the clumping together of proteins like amyloid beta and alpha-synuclein. These proteins are known to form plaques in the brains of individuals with Alzheimer's and Parkinson's diseases, respectively.12

Furthermore, the research highlighted that excess copper affects mitochondrial dynamics by increasing fission (splitting) and decreasing fusion (merging) of mitochondria. This imbalance leads to fragmented mitochondria, which are less efficient at producing energy and more prone to generating ROS.13

Additionally, the study showed that copper overload induces mitophagy, a process where damaged mitochondria are removed from the cell. However, prolonged exposure to high copper levels overwhelms this system, resulting in the accumulation of defective mitochondria that cannot sustain healthy cell function, ultimately contributing to neurodegeneration.14

Another critical discovery was the role of cuproptosis, a type of programmed cell death triggered by copper-induced stress in mitochondria. Cuproptosis contributes to the loss of neurons, exacerbating conditions like depression, anxiety and various neurodegenerative diseases. By understanding how high copper levels induces cuproptosis, researchers will be able to explore new treatments that protect neurons from copper-induced death.15

The study also revealed that excess copper interferes with iron metabolism in the brain. Copper and iron are both essential for various cellular processes, but their imbalance leads to toxic interactions.

High copper levels interfere with mitochondrial dynamics and mitophagy, leading to mitochondrial dysfunction and neuronal damage, which are crucial for maintaining cellular energy production and brain health. This disruption further contributes to mitochondrial dysfunction and neuronal damage.16

The study findings underscore the importance of maintaining proper copper levels for brain health, and that treatments aimed at restoring copper balance and protecting mitochondrial function could be effective in preventing or slowing down the progression of neurodegenerative diseases. Strategies include using agents that chelate excess copper, antioxidants that neutralize ROS and compounds that enhance mitochondrial resilience.17

Copper Deficiency Disrupts Iron Recycling

Download Interview Transcript | Video Link

In my interview with Morley Robbins, MBA, CHC, we discussed how having insufficient copper seriously messes up how your body handles iron and how your cells produce energy. Robbins is the founder of the Magnesium Advocacy Group and author of "Cu-RE Your Fatigue: The Root Cause and How to Fix It on Your Own."

People often think iron deficiency is common, but true iron deficiency is rare; it usually only happens after significant blood loss, and is not related to conditions like menstruation. Instead, what's commonly misdiagnosed as iron deficiency is often a result of not having enough copper, which is crucial for recycling iron properly.

"We have the myth of iron deficiency. We have the myth that iron regulates itself. It does not. It is entirely copper dependent. When you get into the real deep research, you're going to find that copper is the General, iron is the foot soldier," Robbins said.

The imbalance caused by copper deficiency leads to poor iron recycling, meaning your body can't efficiently reuse iron from old red blood cells. This inefficiency forces the body to rely more on iron stored in other places, leading to iron overload in certain tissues; at the same time, iron becomes unavailable where it's needed, such as for functions like oxygen transport.

This mismanagement of iron contributes to overall metabolic distress and exacerbates conditions related to both iron overload and mitochondrial dysfunction.

Robbins adds that when you have copper deficiency, several important genes don't work as they should. This includes aldose reductase-1, which helps break down sugars like glucose and fructose, and glutathione peroxidase, a key enzyme that protects your cells from damage caused by harmful molecules called free radicals.

Without enough copper, these genes are down-regulated, making it harder for the body to process sugars and defend against oxidative stress — it's like rust forming inside your cells from too many reactive molecules.

Another important gene affected by copper deficiency is the one responsible for encoding transferrin, a protein that transports iron throughout your body. When copper levels are low, the body tries to compensate by making more transferrin, but without enough copper, this extra transferrin can't do its job effectively.

As a result, iron gets stuck in certain cells called RES macrophages, preventing it from being reused and distributed where it's needed. This buildup disrupts the balance, even if your blood tests might misleadingly show normal iron levels.

"When people are told they have low iron in the blood, the practitioner doesn't know that iron is high in the tissue, and then they give them more iron, and what's the iron going to do? It's going to find its way to the cell, and then it's going to find its way to the mitochondria, and then, there's this collapse in energy production," Robbins explains.

Copper's Role in Optimal Mitochondrial Function

Copper and its master protein, ceruloplasmin, are instrumental for mitochondrial function. Ceruloplasmin is what drives the copper into the mitochondria, and each mitochondrion needs about 50,000 atoms of copper to do its work.

Your mitochondria membranes have five cytochrome complexes embedded in them that are essential for producing energy; these complexes rely on copper to work correctly. Their purpose is to shuttle electrons created from the food you eat that is ultimately converted to acetyl-CoA to produce ATP. When they're deficient in key minerals like copper, these complexes can't function as they should, leading to less energy being produced and more oxidative stress in your cells.

Copper deficiency affects the enzymes involved in iron metabolism within the mitochondria. Specifically, enzymes like mitochondrial aconitase, which help manage iron within the mitochondria, are impacted. Without sufficient copper, these enzymes can't do their job, leading to problems with how iron is handled inside your cells.

This disruption not only affects energy production but also increases the risk of oxidative stress, as iron participates in reactions that produce harmful free radicals when not properly managed.

Addressing copper deficiency involves ensuring adequate intake of copper through diet or supplements. Foods rich in copper include grass fed beef liver, oysters, shrimp (from safe, sustainable sources) and acerola cherries. For those who might not get enough copper from their diet, supplements like copper bisglycinate, which is highly absorbable, is beneficial.

Additionally, managing iron levels through methods like donating blood will help if there is excessive iron due to poor recycling caused by copper deficiency. By correcting copper levels, the body will restore proper iron metabolism and mitochondrial function, promoting overall health and preventing the complications associated with copper and iron imbalances.

Balancing Your Body's Copper Levels for Optimal Brain Health

Maintaining proper copper levels is crucial for optimal brain function. Imbalances lead to significant health issues. Here's how to achieve and sustain the right balance:

1. Adopt a balanced diet tailored to your microbiome — Embrace a diverse range of whole foods that support your body's natural regulation of copper. Incorporate a minimum of 200 to 250 grams of targeted carbohydrates daily, adjusting based on activity levels and individual microbiome profiles.

Include copper-rich foods such as grass fed beef liver, organ meats and bee pollen to ensure adequate copper intake. Additionally, use whole food vitamin C to enhance copper absorption. You also want plenty of saturated fats in your diet, as copper is a fat-soluble mineral. If you don't have fat in your diet, your ability to absorb copper plummets.

However, if you have elevated copper levels, it's best to avoid these copper-dense foods and consult with a healthcare professional before making dietary adjustments.

2. Ensure adequate protein intake to support copper metabolism — Aim for 0.8 grams of protein per pound of lean body mass to address copper deficiencies. Focus on high-quality protein sources like pasture-raised animal products, which provide essential amino acids necessary for regulating copper levels effectively. Incorporate collagen as one-third of your daily protein intake to facilitate healthy metabolism and cellular function.

3. Manage copper overload — If you have excessive copper levels, reduce the intake of copper-rich foods. Enhance your body's natural copper-binding capabilities by taking 3 to 4 milligrams of copper bisglycinate supplements as directed by a healthcare professional. Support optimal methylation through targeted nutrition, as undermethylation often accompanies copper dysregulation.

Ensure adequate magnesium levels by supplementing with magnesium threonate and avoid processed vegetable oils to maintain cellular energy production and reduce copper-related mitochondrial stress.

4. Enhance mitochondrial health for efficient energy production — Support your mitochondria by consuming a diet rich in balanced carbohydrates and high-quality proteins while avoiding processed vegetable oils that impair energy production.

Engage in regular, safe sun exposure to promote cellular energy production, but avoid harsh sunlight until you've been off vegetable oils for at least six months. This is because the linoleic acid (LA) in these oils migrate to your skin and oxidize when exposed to sunlight.

Incorporate grounding practices, such as spending time in ocean environments, to mitigate reductive stress and enhance overall cellular health. Additionally, use pharmaceutical-grade methylene blue in capsule or tablet form, as prescribed by a healthcare professional, to further support mitochondrial efficiency.

Sources and References

• 1, 2, 3, 4, 5, 6, 7 Front. Aging Neurosci., 02 March 2021, Volume 13
• 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Front. Mol. Neurosci., 05 December 2024, Sec. Molecular Signalling and Pathways, Volume 17 - 2024