Coenzyme Q10 (ubiquinone): functions, serum dosage, benefits, deficiency

What is coenzyme Q10?

Coenzyme Q (CoQ) is a naturally occurring compound with properties similar to those of vitamins. Because of its ubiquitous distribution in nature CoQ is also known as ubiquinone. CoQ belongs to a homologous series of compounds that share a common benzoquinone ring structure but differ in the length of the isoprenoid side chain.

CoQ10 is also known by these other names including:

• Q₁₀
• Vitamin Q₁₀
• Ubiquinone and
• Ubidecarenone.

In simple words, this coenzyme helps an enzyme do its job. The body’s cells use CoQ10 to make energy which is essential for the cells to grow and stay healthy. The body also uses CoQ10 as an antioxidant. An antioxidant is a molecule that protects cells from free radicals that can damage DNA and such damage has been linked to some types of cancer. By protecting cells against free radicals, antioxidants help protect the body against cancer.

CoQ10 has a fundamental role in cellular bioenergetics as a cofactor in the mitochondrial electron transport chain (respiratory chain) and is therefore essential for the production of ATP. CoQ10 functions as a mobile redox agent shuttling electrons and also protons in the electron transport chain. The redox functions of CoQ10 extend beyond its role in the mitochondria.

Furthermore, CoQ10 in its reduced form as the hydroquinone (called ubiquinol) is a potent lipophilic antioxidant and is capable of recycling and regenerating other antioxidants such as tocopherol and ascorbate. Other important functions of CoQ10 such as cell signaling and gene expression have also been described.

Coenzyme Q10 chemistry

Coenzyme Q10 is made up of a benzoquinone component which has two carbonyl groups (C=O) which can be reduced to hydroxyl groups (C–OH) by the addition of two hydrogen atoms. Attached to this benzoquinone group are a variable number of so-called isoprene units; the most common mammalian form contains ten of these isoprene units hence coenzyme Q10. Thus ubiquinone can be reduced to ubiquinol by the addition of two hydrogen atoms:

CoQ10 (ubiquinone) + H2 ↔ CoQ10H2 (ubiquinol)

CoQ10 is similar to vitamin K in its chemical structure but it is not considered a vitamin because it is synthesized in the body.

The chemical nomenclature of CoQ10 is 2,3-dimethoxy-5- methyl-6-decaprenyl-1,4-benzoquinone that is in the trans configuration (natural).

Molecular structure:

Molecular weight: 863.3435 g/mol

Molecular formula: C₅₉H₉₀O₄

Coenzyme Q10 synthesis

Coenzyme Q10 is synthesized in most human tissues; the benzoquinone part of the molecule is synthesized from the aromatic amino acids phenylalanine and tyrosine and the isoprene side chain is synthesized from acetyl coenzyme A via a pathway that is partly common to cholesterol biosynthesis.

The isoprene side chain is then coupled to the benzoquinone component to give coenzyme Q10. The enzyme hydroxymethylglutarylCoA reductase (HMG-CoA reductase) is an important regulatory point in both cholesterol biosynthesis and probably also in coenzyme Q10 synthesis.

The most important group of cholesterol-lowering drugs, the statins, work by inhibiting HMG-CoA reductase and this raises the theoretical possibility that taking these drugs may reduce coenzyme Q10 production and thus increase the case for coenzyme Q10 supplements.

There is no evidence that this is the case in practice. There are extremely rare genetic abnormalities of coenzyme Q10 biosynthesis that do respond to supplements but there is no general deficiency syndrome attributable to lack of coenzyme Q10 seen in the general population.

Coenzyme Q10 functions in mitochondrion

The best-known function of coenzyme Q10 is as a component of the electron transport system in the mitochondrion (oxidative phosphorylation). Reduced NADH2 and FADH2 generated by the oxidation of foodstuffs within the cell are reoxidised to NAD and FAD and the hydrogen eventually combined with oxygen to yield water.

Most of the ATP produced by aerobic metabolism of fats and carbohydrates is generated during this electron transfer and reoxidation of these reduced coenzymes. NADH2 transfers its hydrogen atoms to FMN (flavin mononucleotide) to give FMNH2 and this FMNH2 then transfers its hydrogen atoms to the oxidised form of Q10 so converting it to the reduced form.

FADH2 transfers its hydrogen atoms directly to Q10. The electrons of the hydrogen atoms of reduced Q10 are then transferred to a series of cytochromes and the protons (H+) released into the intermembrane space of the mitochondrion creating a proton gradient across the inner mitochondrial membrane.

At the end of this sequence of cytochromes, protons, electrons and molecular oxygen combine to produce water; this reaction is ‘driven’ by the energy released when protons pass down the proton gradient that coenzyme Q10 has generated across the inner mitochondrial membrane. This means that coenzyme Q10 plays a pivotal role in the generation of the vast bulk of metabolic energy in the form of ATP.

Coenzyme Q10 natural antioxidant functions in the body

Coenzyme Q10 is present in the lipid phase of almost all membranes in its quinol or reduced form where it is believed to be an important antioxidant that in combination with vitamin E protects membranes from oxidative damage by free radicals. There are enzyme systems within membranes that can convert any oxidised CoQ10 (ubiquinone) that is generated back to the reduced CoQ10H2 (ubiquinol) form.

When vitamin E quenches oxygen free radicals (ROS), it becomes oxidised and ubiquinol may then regenerate reduced vitamin E whilst being itself oxidised to the ubiquinone form. Any ubiquinone generated in this way is converted back to the reduced ubiquinol form by enzymes in the membrane.

Coenzyme Q10 function in lysosomes

It has been also suggested that coenzyme Q10 also plays a role in lysosomes where membranes have a relatively high concentration of coenzyme Q10. Lysosomes are responsible for digesting cell debris and they have an acid pH which is important in facilitating the activity of the digestive enzymes within them. Coenzyme Q10 may play a role in generating the protons necessary to maintain their acid pH.

Coenzyme Q10 benefits as a supplement

CoQ10 is available over the counter as a dietary supplement in the US and elsewhere. Potential benefits of CoQ10 supplementation have been recognized with particular reference to cardiovascular and neurodegenerative diseases and as such CoQ10 has become an increasingly popular dietary supplement in recent years.

Because of interest in its use as a therapeutic agent in clinical medicine, this review is intended to provide some basic information on the absorption, tissue distribution, metabolism and pharmacokinetics of CoQ10 along with data on plasma CoQ10 response to oral ingestion of pharmacologic doses.

Top 10 coenzyme Q10 supplements products

Based on personal testing, science backing, and online reviews following best 10 coenzyme Q10 supplements products are:

• Transparent Labs RawSeries Coenzyme Q10
• Life Extension: Super Ubiquinol CoQ10
• NatureWise Ubiquinol
• NutriONN’s Extra Strength CoQ10
• Jarrow Formulas QH-Absorb0
• Now Foods Ubiquinol 100mg
• Nature Made CoQ10
• Vitafusion CoQ10 Gummy Vitamins
• BulkSupplements Pure Coenzyme Q10 Powder
• Heart Savior 6

Coenzyme Q10 mechanism of action

Coenzyme Q10 is an essential cofactor in the mitochondrial electron transport chain. Its works as an acceptor of electrons from the complex I and II and this activity is essential for the production of ATP. It acts as a mobile redox agent shuttling electrons and protons in the electron transport chain.

It also exhibits antioxidant activity in mitochondria and cellular membranes, protecting against peroxidation of lipid membranes as well as inhibiting oxidation of LDL-cholesterol.

Coenzyme Q10 supplements absorption in the body

Being a lipophilic substance the absorption of CoQ10 follows the same process as that of lipids in the gastrointestinal tract. The uptake mechanism for CoQ10 appears to be similar to that of vitamin E, another lipid-soluble nutrient. The absorption of CoQ10 is enhanced in the presence of lipids. Likewise, the absorption of supplemental CoQ10 can be improved if ingested with a fatty meal.

Digestion helps in the release of dietary CoQ10 from the food matrix but for supplemental CoQ10 products that are based on pure CoQ10, gastric digestion does not appear to an important factor. In the small intestine, secretions from the pancreas and bile facilitate emulsification and micelle formation that is required for the absorption fats.

No specific site along the small intestine has been identified for the absorption of CoQ10. Similar to vitamin E and other lipophilic substances, CoQ10 is first incorporated into chylomicrons following absorption and transported via the lymphatics to the circulation. The efficiency of absorption of orally administered CoQ10 is poor because of its insolubility in water, limited solubility in lipids, and relatively large molecular weight.

Coenzyme Q10 supplements distribution in the body

In humans and animals, CoQ is present in all tissues in varying amounts. CoQ9 is the predominant form in relatively short-lived species such as rats and mice whereas in humans and other long-lived mammals the major homolog is CoQ10. As a general rule, tissues with high-energy requirements or metabolic activity such as the heart, kidney, liver and muscle contain relatively high concentrations of CoQ10 [1].

Being a lipophilic molecule, the distribution of CoQ10 in tissues is related not only to its metabolic activity but also to its lipid content. Data on the subcellular distribution of CoQ10 show a large portion (40–50%) of CoQ10 localized in the mitochondrial inner membrane, with smaller amounts in the other organelles and also in the cytosol.

The high concentration of CoQ10 in the mitochondria reflects its important role in mitochondrial function. A major portion of CoQ10 in tissues is in the reduced form as the hydroquinone or ubiquinol, with the exception of brain and lungs. This appears to be a reflection of increased oxidative stress in these two tissues. In blood, about 95% of CoQ10 is in the reduced form.

Among blood cells, lymphocytes and platelets contain significant amounts of CoQ10 whereas red blood cells which lack mitochondria contain only a tiny amount that is likely to be associated with membranes. Lymphocyte CoQ10 content can be increased by CoQ10 supplementation with concomitant functional improvement as evidenced by enhanced reversal of oxidative DNA damage.

Coenzyme Q10 supplements metabolism in the body

Data on the metabolism of CoQ10 in animals and humans are very limited. In the few animal studies available, both rats and guinea pigs have been used to examine the in vivo metabolism of CoQ10. While CoQ9 is the major CoQ homolog in rats, CoQ10 is the primary form in guinea pigs and it would therefore appear that this species might be a more appropriate animal model for studying CoQ10 metabolism.

Coenzyme Q10 supplements excretion

The main elimination route of coenzyme Q10 is through the bile. After its oral administration, over 60% of the dose is excreted in the feces in the form of unchanged coenzyme Q10 and a small fraction of the metabolites. In the urine, coenzyme Q10 is bound to saposin B protein and represents only 8.3% of the total administered dose

Coenzyme Q10 dosage

CoQ10 is available as a dietary supplement in strengths generally ranging from 15 to 100 mg. In cardiovascular disease patients CoQ10 dosages generally range from 100 to 200 mg a day. Dosages of up to 15 mg/kg/day are being employed in the case of mitochondrial cytopathy patients. A dosage of 600 mg a day was used in the Huntington’s disease trial whereas a dosage of up to 1200 mg a day was employed in the Parkinson’s disease trial.

Efficacy of coenzyme Q10 supplements

Oral supplementation with coenzyme Q10 does increase blood levels but there is no evidence that it increases tissue levels in young healthy people or animals. Levels of coenzyme Q10 in some tissues decline in old age and there is some evidence that supplements can increase some tissue levels in elderly animals or people.

It is not clear whether this age-related decline in tissue levels should be regarded as an indication of deficiency and thus whether there is any merit in trying to increase them by the use of supplements.

Over the counter supplements of coenzyme Q10 usually provide between 15 and 60 mg/day although considerably higher doses have been used in some therapeutic trials. No serious adverse symptoms have been reported for coenzyme Q10 supplements except that it interferes with anticoagulant therapy (warfarin and other coumarin-type drugs).

Dietary supplements usually provide up to 60 mg of coenzyme Q10 in tablet form but clinical trials done under medical supervision have used substantially higher doses than this. In general, there seems to be little evidence that supplements of coenzyme Q10 offer any advantage to healthy young people nor does it seem to significantly improve athletic performance.

Indeed, supplements may not even raise tissue levels under these circumstances. Suggestions that it may play some role in reducing the effects of ageing are at present largely speculative. Supplements of coenzyme Q10 may have a role to play as adjuncts to the management of some cardiovascular diseases but this research is still in its preliminary stages.

Coenzyme Q10 side effects

No serious side effects have been reported from the use of CoQ10 supplements. The most common side effects include the following:

• Insomnia (being unable to fall sleep or stay asleep).
• Higher than normal levels of liver enzymes.
• Rashes.
• Nausea.
• Pain in the upper part of the abdomen.
• Dizziness.
• Feeling sensitive to light.
• Feeling irritable.
• Headache.
• Heartburn.
• Feeling very tired.

But it is important to check with health care providers to find out if CoQ10 can be safely used along with other drugs. Certain drugs, such as those that are used to lower cholesterol, blood pressure, or blood sugar levels, may decrease the effects of CoQ10. CoQ10 may change the way the body uses warfarin (a drug that prevents the blood from clotting) and insulin.

Coenzyme Q10 supplements antioxidant activity in treating/preventing cancer and cardiovascular diseases

Given its role as an antioxidant, according to the oxidant theory of disease inadequate amounts of coenzyme Q10 would be expected to increase susceptibility to those diseases, such as cancer and cardiovascular disease, that are believed to be promoted by oxidative damage to free radicals. For example, one might speculate that coenzyme Q10 might reduced the oxidation of LDL that is thought to be a key initiating step in atherosclerosis.

At the moment, coenzyme Q10 is just one of many antioxidants that are postulated to help prevent these diseases and there is no convincing and specific evidence that supplements of coenzyme Q10 have any protective effect. But, studies found that there was no convincing evidence either to refute or support the value of coenzyme Q10 in cardiovascular disease.

Coenzyme Q10 supplements anti-ageing effects

The age-related decline in tissue levels of coenzyme Q10 has prompted speculation that supplements might be beneficial in reducing the effects of ageing and perhaps in extending life expectancy.

There is no evidence from animal studies that prolonged use of coenzyme Q10 supplements produces any measurable benefit on the rate of ageing (e.g. increased life expectancy) apart from the reported rise in tissue levels in elderly subjects referred to earlier.

Coenzyme Q10 supplements for preventing/treating angina pectoris, hypertension, myocardial infarction and congestive heart failure

Large doses of coenzyme Q10 have been tested as possible adjuncts to other clinical treatments in the management of several types of cardiovascular disease including angina pectoris, hypertension and congestive heart failure. It is also proposed that it might reduce myocardial damage if given immediately after a myocardial infarction (heart attack).

Re-perfusion and re-oxygenation of heart muscle after an ischaemic attack may generate extra oxygen free radicals and this may increase the amount of damage to the myocardium after the heart attack. Coenzyme Q10 might reduce this re-perfusion injury because of its antioxidant activity.

Most of the trials in this area have been small and preliminary studies and the results are as yet inconclusive. One meta-analysis found that there were significant improvements in several measures of cardiac function in the Q10 supplemented groups as compared to the placebo groups.

Coenzyme Q10 supplements for enhancing sport performances

The pivotal role of coenzyme Q10 in cellular energy production has prompted speculation that supplements might improve athletic performance. There is no substantial evidence to support this proposal and no evidence that even prolonged use of large supplements causes any rise in muscle levels of coenzyme Q10 in healthy young animals or people.

Coenzyme Q10 supplements for Parkinson disease treatment and prevention

Because of its role as an antioxidant and its role in energy production in the substantia nigra (the affected area in Parkinson’s disease) of the brain that coenzyme Q10 might slow down the progression of Parkinson’s disease. However, these are only suggestions.

Coenzyme Q10 reversal of statin-induced myopathy

Statins or HMG-CoA reductase inhibitors deplete circulating coenzyme Q10 levels by interfering with its biosynthesis. Most studies indicate a correlation between the decrease in serum coenzyme Q10 and decreases of total and low-density lipoprotein cholesterol levels.

This effect may be particularly important in elderly patients, in whom coenzyme Q10 levels are already compromised, and is also associated with higher dosages (lower dosages do not seem to affect intramuscular levels of coenzyme Q10). The use of ezetimibe alone or in combination with a statin does not offer protection against depletion of coenzyme Q10.

No correlation has been established for decreased serum coenzyme Q10 and cardiovascular events.  Supplemental coenzyme Q10 increased circulating levels of the compound. However, results from randomized clinical trials are inconsistent in showing an effect on statin-associated myopathy.

Coenzyme Q10 use for Friedreich ataxia

Idebenone, an analog of coenzyme Q10, was commonly employed in these trials at dosages of 5 mg/kg/day to a maximum of 300 mg/day and used for periods of 6 months to 5 years.  Increases in heart and skeletal muscle bioenergetics are reported for all the studies, as well as decreases in ventricular hypertrophy (left ventricular mass index).

Results for fractional shortening and ejection fraction are mixed, with 1 study reporting a deterioration and another citing improvement in cardiac function.

Coenzyme Q10 use for Alzheimer disease

The role of mitochondrial stress in Alzheimer disease led to more studies of coenzyme Q10. Studies using idebenone dosages of up to 360 mg 3 times a day found no effect on the rate of decline over placebo. Analyses using various rating scales showed some differences that were not considered clinically important, mirroring other older trials. Similarly, no slowing of decline was noted in Huntington disease.

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