CoQ10 Deficiency: Mitochondrial energy

Key takeaways:
~ CoQ10 is essential for mitochondrial energy (ATP) production.
~ In addition, CoQ10 acts as an antioxidant, protecting against neuroinflammation and cell death.
~ CoQ10 levels decrease with age.
~ Genetic variants can also impact CoQ10 levels and the efficacy of supplementation.

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What is Coenzyme Q?

Coenzyme Q (CoQ10 or ubiquinone) is a fundamental part of how your cells make ATP for energy. From plants to yeast to all animal cells, coenzyme Q is essential for life.

Within cells, mitochondria produce most of the ATP through the electron transport chain (ETC).

The ETC is a series of protein complexes, called complexes I through IV, that transfer electrons via redox reactions. This process creates a proton gradient across the mitochondrial membrane, which is used for ATP synthesis.

CoQ10 plays a key role in the ETC as an electron carrier, shuttling electrons from complexes I and II to complex III. Chemically, CoQ10 is classified as a quinone.[ref]​

Coenzyme Q is also known as ubiquinone. This name refers to its ubiquitous presence in all animal cells. In humans, CoQ10 is the most common form of coenzyme Q, referring to its 10 isoprenyl subunits. Other animals have different numbers of subunits, such as mice, which primarily produce CoQ9.

Beyond ATP: Other roles for CoQ10

CoQ10 is an essential part of energy production, and you literally can’t live without it.

Like many molecules in the body, CoQ10 is used by cells for multiple purposes. Being able to move electrons and act in redox reactions lets it function in several ways — limiting free radicals and linking several processes of aging.

Here are some of the roles CoQ10 plays:

Antioxidant:
In its reduced form, CoQ10 acts as a lipid-soluble antioxidant, which allows it to neutralize oxidative stress within cells.[ref] Importantly, as a lipid-soluble antioxidant, CoQ10 can help to prevent the oxidation of LDL cholesterol.[ref][ref]

Ferroptosis:
A type of regulated cell death, ferroptosis involves the accumulation of iron and ROS in a cell to cause apoptosis (cell death). CoQ10 is one of the ways that cells stop ferroptosis and regulate cell death.[ref]

Regulation of NAD+:
CoQ10 is also a cofactor that regulates the NAD+ to NADH ratio within the plasma membrane redox system.[ref]

Anti-inflammatory:
CoQ10 plays a role in the modulation of inflammation through the regulation of IL-1 and TNF-alpha. Studies show that supplemental CoQ10 also reduces CRP and IL-6.[ref]

Infectious disease:
Research shows that supplemental CoQ10 helps the immune response against pathogens, such as in sepsis and viral myocarditis. It takes a lot of energy to mount an immune response, so one role CoQ10 plays is to provide mitochondrial energy to immune system cells. In addition, as a lipid-soluble antioxidant, CoQ10 helps protect cells from cellular destruction caused by high levels of ROS in the immune response. Studies also show that in elderly patients with influenza, CoQ10 (200mg/day) reduces the severity and duration of illness. [ref]

In a large population study (4.5 million people), researchers investigated which current medications or supplements were associated with reduced severity and reduced risk of Covid-19. One of the strongest associations was CoQ10 supplementation, which reduced the risk of hospitalization by 85% in COVID patients.[ref]

Neuroinflammation:
Oxidative stress in the brain can cause neuroinflammation, and CoQ10 is a potent antioxidant. Patients with epilepsy have lower serum CoQ10 levels, on average, and CoQ10 plus seizure medications are more effective in reducing the frequency and duration of seizures. In Parkinson’s, though, clinical trials have shown mixed results.[ref][ref][ref]

CoQ10 deficiency or insufficiency:

CoQ10 is essential for life, so severe deficiency is rarely seen. In other words, CoQ10 is something you literally can’t live without, and people with low or insufficient levels of CoQ10 may experience effects on the heart, brain, and more.

Rare genetic mutations that cause partial CoQ10 deficiency can result in encephalopathy, stroke, cerebral ataxia, spasticity, deafness, retinopathy, or intellectual disability. Less severe CoQ10 genetic deficiency can cause exercise intolerance, muscular weakness, and ataxia later in life. Some genetic CoQ10 deficiency syndrome can be treated with high doses of supplemental CoQ10.[ref]

In aging, levels generally decline due to a reduction in CoQ10 synthesis. Another study found that older adults (both sexes) often had lower serum CoQ10 concentrations and a decrease in CoQ10 redox capacity.[ref]

Animal studies show that CoQ10 restoration in older mice helps reverse the loss of B-cell and T-cell function which is a part of aging and immunosenescence.[ref]

A 4 year clinical trial in elderly adults showed that CoQ10 plus selenium supplementation was associated with decreased days in the hospital and better physical performance and vitality. [ref]

Genetic studies suggest that CoQ10 may play a significant role in neurodegenerative diseases. A genome-wide association study identified several genes that are linked to slightly lower serum CoQ10 levels. These genes are also implicated in Alzheimer’s disease and dementia.[ref]

Most people associate supplemental CoQ10 with heart disease, and the heart does need a lot of CoQ10 for energy production. The anti-inflammatory effects of CoQ10 are thought to protect against cardiovascular disease.[ref]

Statins are the most prescribed class of drug in the U.S., and statins act to block the pathway involved in both LDL and CoQ10 production.[ref] A meta-analysis that involved data from 12 RCTs found that statins clearly reduce circulating CoQ10 levels. This reduction of CoQ10 was seen with all statin types and with using low, medium, or high-intensity statins.[ref]

Related article: Statins and Brain Fog

People with migraines have lower levels of CoQ10, and a small placebo-controlled clinical trial showed that CoQ10 reduced migraine frequency, severity, and duration.[ref]

Studies of chronic fatigue syndrome (ME/CFS) patients show a decrease in ATP synthesis and an increase in oxidative stress. Randomized, controlled trials of CoQ10 in ME/CFS show promise with decreased fatigue. However, it appears that CoQ10 helps a little, but doesn’t cure ME/CFS.[ref]

In Parkinson’s disease, the study results for CoQ10 are mixed. Trials with high doses, such as 1000 – 1200 mg/day, seem to show benefit.  This would be a ‘talk to your doctor’ situation for someone with Parkinson’s.[ref]

In women with PCOS, CoQ10 supplementation lowers triglycerides, and a combination of CoQ10 and vitamin E reduces other lipid and hormonal levels.[ref]

Insulin resistance may also tie into low CoQ10.  The inflammation and hyperinsulinemia is thought to prevent the expression of CoQ10 synthesis enzymes and reduce biosynthesis. This then leads to mitochondrial changes with excess ROS.[ref] A study in adults with pre-diabetes showed that 8 weeks of CoQ10 significantly reduced HOMA-IR levels, a marker for insulin resistance. However, there was no effect on HbA1c or fasting glucose.[ref]

More on clinical trials with CoQ10 in the Lifehacks section below. This molecule truly touches many aspects of health.

Aging, decreased CoQ10, and mitochondrial health:

I want to circle back to something I mentioned above: CoQ10 levels decline with aging.

One theory of aging is that mitochondrial dysfunction and excessive production of reactive oxygen species (ROS) are integral causes of aging and age-related diseases. As we age, mitochondria in cells have decreased functionality and decreased proliferation. Overall, this would lead to a decrease in cellular health and bioenergetics.[ref]

CoQ10 is essential for mitochondrial energy production and acts as a lipid-based antioxidant within cells.  The decline in CoQ10 synthesis in aging affects both oxidative stress levels as well as mitochondrial health.

Exercise is important in aging in part because physical activity increases CoQ10 levels. It is a two-way street here, with low CoQ10 levels causing decreased muscle strength and energy levels – and thus decreased ability to exercise.[ref]

How is CoQ10 produced in cells?

The synthesis of coenzyme Q10 within cells is a complex process that involves multiple steps and genes.

1) The first step is the synthesis of benzoquinone from a derivative of either tyrosine or phenylalanine.  Phenylalanine is an essential amino acid that we get from foods containing protein, and tyrosine is an amino acid that the body makes from phenylalanine.

2) A polyisoprenoid side chain is synthesized from acetyl-CoA via the mevalonate pathway (this is the pathway that statins inhibit).

3) A final step is condensing the benzoquinone with the polyisoprenoid side chains to form coenzyme Q. In humans, CoQ10 is the most common form with 10 isoprenoid side chains.[ref]

CoQ10 from food:
In addition to cellular synthesis, most people get about 5 mg/day of CoQ10 from their diet. Organ meats tend to have the highest levels of CoQ10, but many other foods can add CoQ10 in small amounts. However, CoQ10 absorption from food isn’t great, and the body’s biosynthesis pathways are the main source of the molecule.

Genetic mutations in the CoQ10 pathway:

Genetic mutations along the synthesis pathway can affect CoQ10 levels, and rare mutations in the pathway genes are associated with primary CoQ10 deficiency. The genes in the CoQ family include CoQ1 through CoQ11 (named for the date of identification), PDSS1, and PDSS2.[ref]

Primary coenzyme Q10 deficiency is rare and, if detected early enough (usually in infancy), can often be treated with CoQ10 supplementation. Mutations that severely limit CoQ10 production cause symptoms such as ataxia, encephalomyopathy, deafness, lactic acidosis, retinitis pigementosa, and hypertrophic cardiomyopathy.[ref][ref]

Mutations that don’t cause as severe a CoQ10 deficiency can cause problems with muscle control, walking, and balance in adulthood. One example is a case study of siblings who both had problems with writing (i.e. writer’s cramp) in their teens to 20s, which then progressed to problems riding a bike and then walking. They were found to have a single mutation in one of the genes involved in CoQ10 biosynthesis.[ref]

Secondary CoQ10 deficiency results from genetic mutations that aren’t directly related to the synthesis of coenzyme Q. For example, mutations in genes related to tyrosine or phenylalanine, genes related to mitochondrial acyl-CoA synthesis, and certain genes related to heart disease.

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Lifehacks:

This section covers the different types of CoQ10 supplements (there’s a bunch), safety considerations, and clinical trials that involve CoQ10. The clinical trials give solid examples of conditions that may be helped with CoQ10.

Keep in mind the decrease in CoQ10 synthesis with aging. The research studies on young, healthy people show that they may not get as much benefit from CoQ10 supplements — unless they have a chronic disease that affects the mitochondria or a genetic mutation.

As always, talk with your doctor if you have medical questions about a supplement.

The rest of this article is for Genetic Lifehacks members only.  Consider joining today to see the rest of this article.

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