Coenzyme Q10 monograph

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Background

Coenzyme Q10 (CoQ10) is a lipid-soluble molecule distributed in all cellular membranes of the human body. It is generally referred to as ubiquinone, due to its ubiquitous, omnipresent nature, and has been used as a therapeutic supplement for more than 30 years.

CoQ10 is an antioxidant nutrient functioning within the mitochondria of all cells as an electron transporter in the respiratory chain producing energy – adenosine triphosphate (ATP).

While small amounts of CoQ10 are available through the diet, the majority is endogenously synthesised via the mevalonate pathway which also produces cholesterol.[1,2]

CoQ10 is present in all tissues in varying amounts. Generally, tissues with high energy requirements or metabolic activity, such as the heart, liver, kidneys, immune system, gingiva and muscle, contain high concentrations of CoQ10 and are more susceptible to deficiency. Being a lipophilic molecule, the distribution of CoQ10 in tissues is also related to their lipid content.[3,4]

Although CoQ10 is found in all tissues and organs of the body, it is not surprising that the highest concentrations are found in the heart.[5]

CoQ10 is not just a single molecule. It is a dynamic compound that can cycle through three redox states in the body, each having an important role to play in various processes:[6]

  • fully oxidised = ubiquinone
  • univalently reduced = ubisemiquinone
  • fully reduced = ubiquinol

Through this cyclical exchange of electrons, ubiquinone can be converted to ubiquinol, and vice versa, as required by the body. These redox pairs are crucial for health, having separate but essential functions.

Although CoQ10 is synthesised in vivo, there are situations in which the body cannot produce sufficient quantities, such as in cases of:

  • nutrient deficiencies
  • genetic or acquired defects in synthesis or utilisation disease states that increase tissue requirements
  • side-effects of certain medications (e.g. statin drugs).

Moreover, endogenous synthesis of CoQ10 declines progressively from the age of 20.[7] For this reason, the elderly in particular may have an increased requirement for the nutrient.

Ubiquinone/ubiquinol

Ubiquinol is the most active form of CoQ10. It is the reduced form of CoQ10, normally created from the addition of two electrons to ubiquinone by a redox (reduction/oxidation) reaction.

Ubiquinol is hence “pre-converted”, and ready for immediate use by the body. When ubiquinone is ingested (either through supplements or food) it is converted to ubiquinol in the enterocytes of the small intestine prior to absorption into the venous blood via the lymphatic system. More than 95% of circulating CoQ10 is in the ubiquinol form.[8]

Ageing and illness can decrease the conversion and absorption of CoQ10.[9] Supplementation of ubiquinol may therefore be beneficial for the middle-aged to elderly to help combat oxidation associated with increasing age.[10]

The chemical structure of ubiquinol also appears to affect its absorption. Ubiquinol is more bioavailable than ubiquinone, exhibiting a 3-fold increase in availability.[5,11,12] Ubiquinol contains two hydroxyl groups, causing an increase in polarity and a potential increase in bioavailability.[13] It may be this increased water-solubility and polarity, along with no requirement for conversion, that explains ubiquinol’s greater bioavailability.[5]

The key functional difference between the two compounds is ubiquinol’s role as a potent lipid-soluble antioxidant.[4] Ubiquinol inhibits the oxidation of proteins, DNA and lipids,[2] and regenerates other lipid-soluble antioxidants.[14] The coenzyme also exhibits anti-inflammatory, redox modulatory and neuroprotective effects.[15]

Both ubiquinone and ubiquinol are present in all cellular membranes in varying ratios in different tissues as well as in blood serum.[16] CoQ10 in the serum is largely found bound to low-density lipoprotein (LDL) cholesterol for transportation.[2]

Dietary supplementation of CoQ10 increases levels of ubiquinol within the circulating lipoproteins.[2]

Stability of ubiquinol

Since ubiquinol is easily oxidised in the air, it has been difficult to develop a stable supply in a supplement form. However, using advanced technology, and backed by more than 10 years of research, development and testing, scientists have been able to perfect a stabilisation process by which ubiquinol remains in its reduced form.

Under controlled conditions, the process guarantees ubiquinol does not oxidise to the ubquinone form during manufacture and encapsulation.[17] The ubiquinol is not oxidised into ubiquinone until after digestion of the capsule, and as part of the natural physiological function of conversion and use of ubiquinol and ubiquinone in the body.

Key benefits

  • Required for ATP/energy production
  • Supports healthy cardiovascular function
  • Reduces oxidation of LDL cholesterol
  • Protects cell membranes from free radical damage
  • Supports post-exercise recovery
  • Assists with periodontal health

Clinical applications

  • Fatigue
  • Post-exercise recovery
  • High LDL cholesterol
  • Atherosclerosis
  • Heart disease
  • Periodontal disease
  • Migraines
  • Male fertility
  • Statin use
  • Middle-age to elderly

Mechanisms of action

Cellular energy production

Undoubtedly CoQ10’s most known role is its central part in energy production. Ubiquinone is an essential cofactor in the oxidative phosphorylation process in mitochondria whereby energy is produced in the form of ATP.[18] This process is dependent on ubiquinone, with ubiquinol playing an equally important supporting role. As ubiquinone is in such high demand, ubiquinol is required to rapidly convert into ubiquinone to meet the demand required for energy synthesis.[19]

Physical fatigue 

Researchers have demonstrated that oral administration of CoQ10 (300mg/day for eight days) may improve subjective fatigue sensation and physical performance during fatigue-inducing workload trials.[20]

One double-blind, cross-over trial reported positive effects on aerobic and anaerobic thresholds and physical performance, with 94% of the subjects reporting that supplementation had improved their performance and recovery times.[21] The subjects in this study received 90mg CoQ10/day for six weeks.

A retrospective study has also found muscle CoQ10 levels to be positively correlated to exercise capacity and/or marathon performance, suggesting that runners with the highest levels performed better than those with lower levels.[22]

Antioxidant function

The reduced form of CoQ10, ubiquinol is a potent lipid-soluble antioxidant. It is the only endogenously synthesised lipophilic antioxidant, and can act directly protecting membranes against oxidation as well as inhibiting the peroxidation of plasma lipoprotein lipids.[1] Ubiquinol has also been shown to protect mitochondrial DNA from free-radical induced oxidative damage.[16

Research has shown that ubiquinol is significantly more efficient in inhibiting LDL oxidation than either lycopene, betacarotene, or alpha-tocopherol.[23] The same researchers demonstrated that ubiquinol is always the first lipid-soluble antioxidant to be consumed. When ubiquinol has been exhausted, rates of LDL peroxidation have been shown to increase even when levels of other antioxidants remain high.[23]

Oxidative damage to lipids is directly linked to the development of atherosclerosis.[24] Oxidised low-density lipoproteins (LDLs) and reactive oxygen species (ROS) directly impair endothelial function, which is associated with the development of cardiovascular disease.  

Ubiquinol markedly slows this rate of lipid peroxidation. It does this directly by acting as a chain-breaking antioxidant and indirectly by recycling vitamin E. The ubiquinone formed in preventing oxidative damage is reduced back to ubiquinol by the respiratory chain.[25] CoQ10 is one of the few antioxidants that can readily regenerate to its reduced form after utilisation.[26]

As an electron donor, ubiquinol also recycles and regenerates other antioxidants including vitamins C and E.[8] CoQ10 also has a synergistic action with selenium, another powerful antioxidant.[27]

The antioxidant role of ubiquinol in biological membranes is also of importance for many cellular functions including DNA damage and stability. CoQ10 supplementation seems to be associated with low DNA damage status, with data from in vitro cell culture studies demonstrating reliable effects of CoQ10 treatment on toxin-induced DNA fragmentation, suggesting benefits for genomic stability at 150mg/day for two weeks.[28]

Cardiovascular health

A deficiency of CoQ10 in heart disease was documented in the early 1970s. Since then, a large number of studies have shown that supplementation with the coenzyme goes beyond the correction of a simple deficiency state, with strong evidence for supporting cardiovascular health via the maintenance of optimal cellular and mitochondrial function in cardiomyocytes.[22] Trials also show significant reductions in coronary artery disease risk.[29

Lipid peroxidation and atherosclerosis: Ubiquinol protects low density lipoproteins (LDLs) against lipid peroxidation.[4,29] Oxidation of LDLs is believed to be an initiating factor in the development of atherosclerosis, a major contributing factor of CVD. CoQ10 supplementation is proven to significantly inhibit the formation of atherosclerotic lesions.[30,31]

Hypertension: CoQ10 has been shown to have a hypotensive effect. Nitric oxide (NO) works within the endothelium as a vasodilator to assist in the maintenance of healthy blood pressure. ROS generated in the vasculature can reduce the available concentration of NO. CoQ10 scavenges ROS thus protecting NO from attack, with a consequent NO-induced vasodilation. In one study, more than 50% of subjects treated with CoQ10 were able to cease at least one of their hypertensive medications.[5]

Migraine and fibromyalgia

Dysfunction in mitochondrial energy metabolism is thought to play a role in at least a subset of migraine sufferers. Since CoQ10 has been shown to improve mitochondrial oxidative phosphorylation, it has been studied as a potential prophylactic treatment for migraine headaches.

Research indicates that supplemental CoQ10 (150-300mg/day) may reduce the attack frequency, number of days with migraine headache and nausea.[32,33] The effect of supplementation on migraine symptoms may begin within four weeks of initiating therapy, but it usually takes 12 weeks to achieve a greater than 50% reduction in days with migraine.[32]

Headaches are a common symptom experienced by fibromyalgia (FM) sufferers. Mitochondrial dysfunction and high ROS are thought to be an important factor in the pain of fibromyalgia and complications associated with it (e.g. depression, fatigue, headaches).[34]

A 2012 study on FM patients confirmed significant correlations between lipid peroxidation levels and headache symptoms. Antioxidant (CoQ10) and ATP levels also showed a significant negative correlation with headache symptoms. CoQ10 supplementation saw a marked improvement in headache symptoms and a significant recovery in oxidative stress markers.[34]

CoQ10 administration has also shown benefits for improving fatigue, hyperalgesia and quality of life in patients with FM.[15]

Neuroprotection

Due to its biological functions, CoQ10 depletion has potential repercussions in neurological health and has been implicated in the pathogenesis and progression of neurological illnesses such as Parkinson’s disease, depression, myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia.[15

CoQ10 treatment has been demonstrated to improve quality of life in patients with Parkinson’s disease and may play a role in delaying the progression of the disorder. Administration of CoQ10 has antidepressive effects,[15] and preliminary studies suggest it may represent a promising therapeutic strategy for type 2 diabetes neuropathy.[35]

Sperm health

Low seminal plasma concentrations of CoQ10 have been correlated with impaired sperm parameters[36] (e.g. count/density, morphology, motility). It has been shown that CoQ10 supplementation in men with idiopathic oligoasthenoteratozoospermia (OAT) results in improved semen parameters.[37,38]

Results of a randomised trial administering ubiquinol (200mg/day) or placebo to 228 men with unexplained infertility revealed treatment to be significantly effective. Improvements in sperm density, sperm motility and sperm morphology were achieved.[37] Another 12 month study on 287 infertile men with idiopathic OAT supplemented subjects with 300mg CoQ10 twice daily. Not only were sperm count, motility and morphology improved but 34.1% achieved pregnancy within a mean period of 8.4 months.[38]

Periodontal disease

Deficiency of CoQ10 has been found to be responsible for periodontal destruction.[39] Gingival biopsies have revealed subnormal tissue levels of the nutrient in patients with periodontal disease.[4]

Periodontal disease is an inflammatory disease process resulting from the interaction of a bacterial attack and host inflammatory response. ROS are important mediators and consequences of the the inflammatory response. Periodontal pathogens can induce ROS overproduction and thus may cause collagen and periodontal cell breakdown. Since ubiquinol scavenges these ROS, it may reduce collagen degradation, suppress periodontal inflammation[40] and have an anti-gingivitis effect.[39]

Furthermore, healing and repair of periodontal tissues requires efficient energy production, which depends in part on an adequate supply of CoQ10.[41] CoQ10 may be taken orally or applied topically to support periodontal health.

Clinical studies

CoQ10 as antioxidant in coronary artery disease

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. The known traditional risk factors for coronary artery disease (CAD) are smoking, obesity, hypertension, a family history of CAD, diabetes mellitus and hyperlipidemia. Increased oxidative stress is associated with the pathogenesis of CAD. This study investigates the relationship between CoQ10 concentration and lipid peroxidation, antioxidant enzymes activities and the risk of CAD.

Subjects/Method: Subjects (51) identified by cardiac catheterisation as having at least 50% stenosis of one major coronary artery or receiving percutaneous transluminal coronary angioplasty (PTCA).

Intervention: Subjects were measured for correlations between plasma coenzyme Q10 and the ratios of CoQ10 to lipid profiles, lipid peroxidation, and antioxidant enzyme activities.

Results: Plasma CoQ10 concentration had statistically significant reductions in the risk CAD. Patients with lower CoQ10 concentration might have compromised mitochondrial function, correlating to the severity of disease. Patients with CAD were exposed to a higher level of oxidative stress and a lower CoQ10 concentration. Results indicate a strong correlation between the plasma CoQ10 and reductions in the risk of CAD.

Lee BJ, Lin YC, Huang YC, et al. The relationship between coenzyme Q10, oxidative stress, and antioxidant enzymes activities and coronary artery disease. ScientificWorldJournal 2012;2012:792756.

Some medications deplete CoQ10 in the body

Background: Hydroxyl-methylglutaryl coenzyme A reductase inhibitors or statins interfere with the production of mevalonic acid, which is a precursor in the synthesis of CoQ10. The statin medications routinely result in lower CoQ10 levels in the serum.

Subjects/Method: Discussion of trials on effects of medications, such as atorvastatin, Simvastatin, pravastatin, on CoQ10 and impact of supplementation of CoQ10 on the elderly and those taking statins.

Results: Given the low risk of toxicity and the potential benefit in treating statin-induced myopathy, a trial of 200 mg of CoQ10 daily should be considered for patients taking statins.

Deichmann R, Lavie C, Andrews S. Coenzyme Q10 and statin-induced mitochondrial dysfunction. Ochsner J 2010;10:16-21

Preventing migraines with CoQ10

Background: The objective was to assess the efficacy of coenzyme Q10 as a preventive treatment for migraine headaches.

Subjects/Method: Thirty-two patients (26 women, 6 men) with a history of episodic migraine with or without aura.

Intervention: Treated with 150mg/day CoQ10.

Results:  61.3% of patients had a greater than 50% reduction in number of days with migraine headache. After three months, the average number of days with migraine decreased from 7.34 to 2.95; migraine frequency increased from 13.1% to 55.3%; migraine attack frequency decreased from 4.85 to 2.81 attacks by the end of the study period.

Rozen TD, Oshinsky ML, Gebeline CA, et al. Open label trial of coenzyme Q10 as a migraine preventive. Cephalalgia 2002;22(2):137-141.

Dosage range for conditions according to clinical studies

Cautions and contraindications

  • Although the safety of CoQ10 has been shown in numerous studies, its use in pregnancy and lactation has not been scientifically validated.[22]
  • By inhibiting HMG-CoA reductase, widely prescribed cholesterol-lowering medication (statins) compromise endogenous CoQ10 synthesis.[2] 
  • Beta-adrenergic antagonists induce CoQ10 depletion.[22]
  • There are three case reports suggesting that CoQ10 may decrease the international normalised ratio (INR) in patients previously stabilised on anticoagulants. Observe patients using high CoQ10 doses and taking warfarin.[22]

References

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melissalee's picture
Melissa Lee
Melissa is a designer turned nutritionist, who for the past 6 years has been combining the two modalities to create purposeful designs for various health publications and websites. Having initially studied Multimedia Systems Design, she then went on to complete a BHSc in Nutritional Medicine which led to her involvement in the integrative medicine industry and eventually to FX Medicine.