Mitochondrial Health: A Key to Combat Long COVID

In the wake of the COVID-19 pandemic, a new health concern has emerged: Long COVID. This condition, characterized by lingering symptoms long after the acute phase of the virus, has left many searching for answers. One area of focus is mitochondrial health. Mitochondria, the powerhouses of our cells, play a crucial role in overall health and well-being. Research shows a potential connection between the SAR-CoV-2 virus and mitochondria dysfunction. Here we explore the importance of mitochondrial health in relation to Long COVID as well as how certain supplements can support mitochondrial function.

What are Mitochondria?

Mitochondria play a pivotal role in the body, serving as the primary source of energy production at the cellular level. The mitochondria have four steps to energy production. Electrons flow through the four steps to eventually make adenosine triphosphate or ATP. ATP is the fuel of the cell and responsible for the necessary energy our bodies need to function.

Beyond energy production, mitochondria are involved in a range of other important processes. They play a key role in cellular signaling, helping cells communicate and respond to their environment. They also contribute to the regulation of the cell cycle, including cell growth and death.

Moreover, mitochondria are involved in maintaining the body’s overall metabolic balance. They help regulate lipid metabolism, which is essential for the production of hormones and other vital substances. They also play a role in the metabolism of carbohydrates and amino acids.

In the context of the immune system, mitochondria contribute to the body’s defense against infections. They participate in the production of reactive oxygen species (ROS), which can destroy invading pathogens.

Lastly, mitochondria are crucial for maintaining calcium homeostasis in cells, which is essential for various cellular functions, including muscle contraction, nerve impulse transmission, and hormone secretion.

Mitochondria are not just the powerhouses of the cell, but they also play a central role in numerous biological processes that are vital for the body’s overall health and functioning.

Energy Production in the Mitochondria

Energy production in the mitochondria, also known as cellular respiration, involves several steps:

1. Glycolysis – This process occurs in the cytoplasm, outside the mitochondria. It involves the breakdown of glucose into two molecules of pyruvate. This process produces a small amount of ATP (Adenosine Triphosphate) and NADH (Nicotinamide Adenine Dinucleotide).
2. Pyruvate Decarboxylation – The pyruvate molecules enter the mitochondria and are converted into Acetyl CoA. This process also produces NADH.
3. Citric Acid Cycle (Krebs Cycle) – The Acetyl CoA enters the citric acid cycle, where it is broken down into carbon dioxide. This process produces ATP, NADH, and FADH2 (Flavin Adenine Dinucleotide).
4. Oxidative Phosphorylation (Electron Transport Chain) – This is the final stage of energy production in the mitochondria. The NADH and FADH2 produced in the previous steps are used here. They donate their electrons to the electron transport chain, which powers the creation of a large amount of ATP. Oxygen is the final electron acceptor in this process and combines with hydrogen to form water.

These steps together constitute the process of cellular respiration, which is how mitochondria produce energy for the cell. If any step in this process is disrupted, it can lead to a decrease in ATP production, which can impair the cell’s ability to perform its functions. This can manifest in a variety of ways, depending on the type of cell and the severity of the disruption.

Mitochondrial Health and Long COVID: An Intricate Connection

The connection between mitochondria and COVID-19 is an area of active research, with several key links emerging.

• Mitochondria play a crucial role in the body’s immune response. They produce energy needed for immune cells to function effectively and generate reactive oxygen species (ROS) that can help combat pathogens. However, COVID-19 can disrupt these processes. The virus can cause mitochondrial stress and dysfunction, leading to an impaired immune response.
•  COVID-19 can cause a ‘cytokine storm’, an overactive immune response that can lead to severe inflammation and organ damage. Mitochondria are involved in regulating inflammation and apoptosis (cell death), so their dysfunction can contribute to the severity of this response.
• The SARS-CoV-2 virus, which causes COVID-19, can directly impact mitochondria. Some research suggests that the virus can hijack mitochondrial machinery to replicate itself, leading to further mitochondrial damage and dysfunction. In research conducted on mice and human mitochondria, viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. OXPHOS is the process whereby 90% of ATP is created in the body. Even when the virus was cleared and lung mitochondrial function regained, mitochondrial function in the heart, kidney, liver, and lymph nodes remained impaired. 
• The connection between mitochondria and COVID-19 may also be relevant in the context of Long COVID, where symptoms persist for weeks, months, or even years after the acute phase of the infection. In this study, SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia, we see that the SARS-CoV-2 virus inhibits the first step in mitochondrial energy production.  
• In a recent study published in Nature, researchers looked at the connection between Long COVID, post-exertional malaise, muscle abnormalities, and mitochondrial dysfunction.

While more research is needed, it’s clear that mitochondria play a significant role in the body’s response to SARS-CoV-2 and the potential long-term impacts of the virus.

Supplements for Mitochondrial Health: A Potential Ally Against Long COVID

Several supplements have been identified as beneficial for mitochondrial health and have the potential to help those with symptoms of Long COVID. These include:

Ubiquinol CoQ10

Coenzyme Q10 (CoQ10) plays a crucial role in the process of oxidative phosphorylation, which takes place in the mitochondria and is responsible for producing adenosine triphosphate (ATP), the primary energy currency of cells. CoQ10 is a component of the electron transport chain, which is a series of protein complexes embedded in the mitochondrial membrane. These complexes facilitate the transfer of electrons, driving the production of ATP.

When there are defects or damage in the steps of oxidative phosphorylation, it can lead to a decrease in ATP production and an increase in the production of reactive oxygen species (ROS), which can cause further damage to cellular structures.

1. Antioxidant function – CoQ10, in its reduced form (CoQ10H2), acts as an effective antioxidant. It can protect mitochondrial proteins and DNA from the oxidative damage that accompanies lipid peroxidation. This antioxidant function can help mitigate the damage caused by ROS, which is often elevated when there are defects in oxidative phosphorylation.
2. Energy production – CoQ10 plays a central role in mitochondrial ATP synthesis. By supplementing with CoQ10, it may be possible to enhance the efficiency of ATP production, even when there are defects or damage in the oxidative phosphorylation process.
3. Mitochondrial protection and biogenesis – CoQ10 has been shown to promote mitochondrial biogenesis. This means that CoQ10 could potentially help to maintain the number and health of mitochondria, which is particularly important when oxidative phosphorylation is impaired.
4. Cardiovascular health – Higher plasma levels of CoQ10 have been associated with reduced risk of cardiovascular disease, which can be a consequence of impaired energy production in heart muscle cells due to defects in oxidative phosphorylation.
5. Neuroprotection – CoQ10 has been shown to protect against mitochondrial dysfunction, prevent apoptosis, and maintain mitochondrial membrane potential. This is particularly relevant in neurodegenerative diseases, where oxidative phosphorylation can be impaired.

In terms of COVID-19, Long COVID, and CoQ10, research shows that the SARS-CoV-2 virus causes a reduction in oxidative phosphorylation and platelet mitochondrial respiration, but that supplemental CoQ10 may play a vital role in the recovery of mitochondrial health in those with post-COVID symptoms. 

Liposomal Glutathione

Liposomal glutathione supplementation aids with oxidative phosphorylation by enhancing the body’s antioxidant defense system. Glutathione (GSH) is a potent antioxidant that plays a crucial role in maintaining cellular redox balance, neutralizing free radicals, detoxifying harmful substances, and regenerating other antioxidants like vitamins C and E.

In the context of oxidative phosphorylation, a process that occurs in the mitochondria to produce ATP (the energy currency of the cell), glutathione’s role is particularly significant. The process of oxidative phosphorylation, while essential for energy production, can generate reactive oxygen species (ROS) as by-products. These ROS can cause oxidative stress if not adequately neutralized, leading to cellular damage and dysfunction.

Glutathione helps to neutralize these ROS, thereby protecting the mitochondria and ensuring the efficient functioning of oxidative phosphorylation. It also appears to regulate apoptosis (programmed cell death) within the mitochondria, further contributing to cellular health and function.

Liposomal glutathione supplementation is thought to enhance the bioavailability of glutathione. The liposomal form allows glutathione to be encapsulated in a lipid layer, protecting it from degradation in the digestive system and facilitating its absorption into the bloodstream and cells.

L-carnitine

L-carnitine is an amino acid derivative that plays a pivotal role in energy metabolism and mitochondrial health. Its primary function is to transport long-chain fatty acids into the mitochondria, where they are oxidized to produce adenosine triphosphate (ATP), the primary energy currency of cells. This process, known as beta-oxidation, is a major source of energy, particularly for the heart and skeletal muscles. By facilitating the entry of fatty acids into the mitochondria, L-carnitine ensures that these organelles have the necessary fuel to generate energy efficiently. In addition, L-carnitine helps to remove toxic compounds from within the mitochondria, which can accumulate as a result of normal metabolic processes. 

Post-COVID, mitochondrial health can be compromised due to the virus’s impact on cellular function. Research suggests that L-carnitine could potentially aid in the recovery process. It may help restore normal mitochondrial function by reducing oxidative stress, inflammation, and cell death, which are common in severe COVID-19 cases. Furthermore, L-carnitine’s role in lipid metabolism could help manage dyslipidemia, a common condition seen in Long COVID. However, while these potential benefits are promising, more extensive clinical trials are needed to confirm the efficacy and safety of L-Carnitine supplementation in post-COVID care.

Vitamin B Complex

Vitamin B complex, a group of eight essential vitamins, plays a crucial role in maintaining overall health, including the health of mitochondria. These vitamins, particularly B1 (thiamine), B2 (riboflavin), and B3 (niacin) are integral to the process of energy production within the mitochondria. They act as coenzymes in the metabolic pathways that convert nutrients into ATP, the primary energy currency of the cell.

Post-COVID, mitochondrial health can be compromised due to the virus’s impact on cellular function. The virus can cause mitochondrial stress and dysfunction, leading to fatigue and other long-term symptoms. Supplementing with a B complex can support mitochondrial health during recovery by ensuring the energy production pathways function optimally. This can help alleviate some of the fatigue and other symptoms associated with Long COVID.

Pyrroloquinoline Quinone (PQQ)

Pyrroloquinoline Quinone (PQQ) is a small molecule with antioxidant and B-vitamin-like activity, known for its involvement in cellular processes including growth and development. It’s particularly significant for its role in supporting mitochondrial health. PQQ has been shown to stimulate mitochondrial biogenesis, the process by which new mitochondria are formed in the cell. This can help restore energy production, reduce oxidative stress, and promote recovery.

Additionally, PQQ’s antioxidant properties can help protect mitochondria from damage, further supporting their function and overall cellular health. PQQ could play a beneficial role in the recovery process post-COVID by supporting mitochondrial health and function, though additional research is needed.

Alpha-lipoic acid (ALA)

Alpha-lipoic acid (ALA) is a naturally occurring compound that’s made in the body and found in several foods. It plays a crucial role in metabolism and energy production, as it helps enzymes turn nutrients into energy. Post-COVID, ALA has been studied for its potential to improve mitochondrial health. 

ALA is a potent antioxidant that can neutralize harmful free radicals and reduce oxidative stress, which is beneficial for mitochondrial health. It also can regenerate other antioxidants, like vitamins C and E, enhancing the body’s overall antioxidant defenses.

Furthermore, ALA can improve mitochondrial function by enhancing glucose uptake and utilization, which is particularly beneficial for cells with high energy demands. Therefore, supplementing with ALA could potentially help alleviate some of the symptoms seen with Long COVID.

N-Acetyl Cysteine (NAC)

NAC plays a crucial role in replenishing the body’s primary antioxidant, glutathione, which is essential for maintaining mitochondrial health. In the context of Long COVID, where mitochondrial dysfunction is suspected, NAC’s antioxidant properties can help mitigate oxidative stress, a condition that can damage mitochondria and impair their function. Furthermore, NAC, when administered in high doses, can improve situations of oxidative stress, which is often seen in viral infections like COVID-19.

Nicotinamide Adenine Dinucleotide (NAD+)

Nicotinamide Adenine Dinucleotide (NAD+) may help some of the processes that are deficient in long COVID.  NAD+ is required in the 3 steps of Kreb’s cycle which produces the NADH and FADH2 required by the mitochondria to make ATP.  By supplementing, NAD+ (which also catalyzes the conversion of Pyruvate to acetyl-CoA) perhaps this is driving the cycle forward to produce the substrates that the mitochondria need to make energy. 

Oxaloacetate (OAA)

Oxaloacetate (OAA), also known as oxaloacetic acid or Anhydrous Enol-Oxaloacetate, is a four-carbon molecule that plays a crucial role in various metabolic processes within the body. It’s a key intermediate in the citric acid cycle, also known as the Krebs cycle or the tricarboxylic acid (TCA) cycle, which is the primary energy-producing process that occurs in the mitochondria of cells.

In the citric acid cycle, OAA combines with acetyl-CoA, a product of the breakdown of carbohydrates, fats, and proteins, to form citrate. This reaction initiates the cycle, which ultimately leads to the production of ATP, the primary energy currency of cells. After several steps in the cycle, OAA is regenerated and ready to combine with another molecule of acetyl-CoA, allowing the cycle to continue.

Research has suggested that OAA may have additional benefits for mitochondrial health. For instance, one study looked at the effects of Anhydrous Enol-Oxaloacetate supplementation in those with ME/CFS and Long COVID. Those taking the supplement experienced significant improvement in physical and mental fatigue. However, these potential benefits are still under investigation and more research is needed to fully understand the role of OAA supplementation in mitochondrial health.

Supplementation for Mitochondrial Health with Long COVID

Maintaining mitochondrial health can play a vital role in managing Long COVID. The supplements listed above are just some of the tools used by RTHM clinicians to help support mitochondrial function and, in turn, help alleviate symptoms. RTHM clinicians believe that every step towards better mitochondrial health may be a step towards a healthier, more energetic you, even as you face the challenges of Long COVID.

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