Ubiquinone

Ubiquinone also called coenzyme Q10 (CoQ₁₀), ubidecarenone or vitamin Q₁₀ is a benzoquinone compound (a fat-soluble vitamin K-like molecule) that is naturally present in the human body in most body tissues, with the highest levels in your heart, liver, kidneys, and pancreas ¹, ². The lowest amounts are found in your lungs ³. In Coenzyme Q10, the letter Q refers to the quinone ring which is the active catalytic site of the coenzyme (a molecule that binds to an enzyme and is essential for its activity but is not permanently altered by the reaction); the number 10 refers to the 10 isoprene units (a volatile organic compound with the chemical formula C₅H₈) that make up the long tail of the Coenzyme Q10 molecule. The name Ubiquinone refers to the ubiquitous presence of these compounds in living organisms and their chemical structure, which contains a functional group known as a benzoquinone (a compound related to benzene but having two hydrogen atoms replaced by oxygen with the formula C₆H₄O₂). Ubiquinones are fat-soluble molecules with anywhere from 1 to 12 isoprene (5-carbon) units. The ubiquinone found in humans, ubidecaquinone or coenzyme Q10, has a “tail” of 10 isoprene units (a total of 50 carbon atoms) attached to its benzoquinone “head” (Figures 1 and 2) ⁴. All humans, including animals, can synthesize ubiquinones, hence, coenzyme Q10 is not considered a vitamin despite Ubiquinone (Coenzyme Q10) being somewhat similar in structure to vitamin K ⁴.

The largest percentage coenzyme Q10 (CoQ10) is synthetized in the cell (4-hydroxybenzoate is the precursor of a quinone ring, while an isoprenoid tail is derived from the mevalonate pathway), although the pathways involved are not yet completely known ⁵. The biosynthesis of coenzyme Q10 (CoQ10) from the amino acid tyrosine is a complex multistage process (governed by at least 13 genes) requiring at least eight vitamins and several trace elements and a deficiency of any of which can adversely affect the normal coenzyme Q10 (CoQ10) production ⁶, ⁷, ⁸. Furthermore, coenzyme Q10 (CoQ10) can be derived from your diet, about 5 mg/day for a Mediterranean diet ⁵. In particular coenzyme Q10 (CoQ10) is present in fatty fishes, soja, nuts, and spinach ⁹, however, coenzyme Q10 (CoQ10) intake may not be sufficient to counteract physiological or pathological deficiencies ¹⁰. Meat has the highest amount of coenzyme Q10 (CoQ10), followed by dairy, eggs, and plant-based food sources (oils and legumes). Coenzyme Q10 (CoQ10) extracted from living tissues is more expensive than produced in the laboratory by fermentation, yielding consistent quality and cheaper supplements ¹¹. Furthermore, with the widespread consumption of nutrient-deficient fast foods and highly processed foods and the fact that nutritional content of our commercial food supply has been steadily declining since the end of World War II, due to the use of toxic chemicals, artificial fertilizers and other destructive farming practices, it is easy to see why many people have nutritional deficiencies that hinder the body’s ability to synthesize coenzyme Q10. For this reason, nutritional supplementation with coenzyme Q10 (CoQ10) could help to maintain adequate levels within your body.

The first ubiquinone was isolated in 1957 by a biochemist Fred Crane from the University of Wisconsin, who isolated a yellowish substance from beef hearts. He sent samples to a colleague, biochemist Dr. Karl Folkers who worked at the pharmaceutical company Merck, Sharpe and Dohme ⁸. In 1958, Dr. Folkers successfully determined the chemical structure of coenzyme Q10 and conducted some preliminary studies, which led him to believe that coenzyme Q10 had enormous potential as a cardiovascular drug. At the time, Merck executives were not interested in developing a new cardiovascular drug. Consequently, the patent rights to coenzyme Q10 were sold to a company in Japan. Since that time, ubiquinones have been studied extensively in Japan, Russia, and Europe, with research in the United States beginning more recently. In 1978, a British biochemist Peter Mitchell was awarded the Nobel Prize in Chemistry for discovering the key role Coenzyme Q10 plays in the electron transport chain in mitochondrial membranes, which results in the generation of cellular energy in the form of adenosine triphosphate (ATP) ¹². Specifically, coenzyme Q10 facilitates the production of adenosine triphosphate (ATP), carrying the electrons from complexes I and II to complex III of the mitochondrial respiratory chain ¹³, ¹⁴. In addition, coenzyme Q10 is the major lipid-soluble antioxidant and it protects cell membranes and lipoproteins from oxidative damage ¹³. The antioxidant activity of coenzyme Q10 is linked to its reduced form, Ubiquinol, ability to reduce oxidative stress, lipid peroxidation, and regenerate also vitamins C and E back to their active fully reduced forms ¹⁵. Last but not least, some test tube studies have shown the ability of coenzyme Q10 to reduce the inflammatory markers, suggesting that coenzyme Q10 might have anti-inflammatory action through the regulation of gene expression ¹⁶, ¹⁷. However, some factors, such as aging, drugs (e.g., statins), genetic factors, neurodegenerative diseases, and degenerative muscle disorders, are well-known to be associated with reduced plasma concentrations of coenzyme Q10 (CoQ10), resulting in worsening of oxidative stress and inflammatory processes ¹⁵. This takes place through the upregulation of nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) gene expression and chronic activation of immune inflammatory responses ¹⁸.

In the 1970s, Dr. Folkers and his colleague, Dr. Gian-Paolo Littarru of Italy published data they had collected with tissue biopsies from 200 patients, which revealed that patients with heart disease and patients undergoing heart surgery had blood and tissue Coenzyme Q10 levels significantly below normal levels ¹⁹. Due to Dr. Folkers’ early work along with Peter Mitchell’s Nobel prize dramatically increased scientific interest in coenzyme Q10 (CoQ10) around the world. Popular press accounts claim that roughly 12 million Japanese people use ubiquinones as the medication of choice for management of cardiovascular diseases, supplied via more than 250 commercially available preparations. Ubiquinone is touted as an effective treatment for congestive heart failure, heart arrhythmias, high blood pressure, and in reducing hypoxic injury to the myocardium. Other claims include increases in exercise tolerance, stimulation of the immune system, and counteraction of the aging process. Ubiquinone has not been approved by the United States Food and Drug Administration (FDA) for treating any medical condition or therapeutic use; however, it is available as a food supplement ¹, ². While not approved by the FDA for these indications, ubiquinone (coenzyme Q10) has been used for heart attack (acute myocardial infarction), AIDS, Alzheimer’s disease, angina (chest pain or discomfort caused by a lack of blood and oxygen flow to the heart muscle, most commonly due to coronary artery disease), breast cancer, cardiomyopathy (heart muscle disease that weakens the heart’s ability to pump blood throughout the body, leading to potential heart failure), heart protection during surgery, congestive heart failure, exercise performance, high blood pressure, migraine, mitochondrial disease, Kearns-Sayre syndrome, muscular dystrophy, Parkinson’s disease, periodontal disease (an infection of the gums and supporting bone that is caused by plaque), and kidney failure.

Ubiquinone, the oxidized form of coenzyme Q10, is soluble in lipids (fats) and is found in virtually all cell membranes, including mitochondrial membranes. The ability of the benzoquinone head group of coenzyme Q10 to accept and donate electrons is a critical feature to its function. Ubiquinone (oxidized form of coenzyme Q10) plays an essential role in the mitochondrial oxidative phosphorylation as an electron shuttle between complexes I and II of the respiratory chain, and complex III and the production of adenosine triphosphate (ATP). Ubiquinone, the oxidized form of coenzyme Q10, is required for energy production in the mitochondria of all cells except the red blood cells. Specifically, Ubiquinone is required in several steps of the electron transport chain in mitochondrial inner membranes, which is where cellular energy, known as adenosine triphosphate (ATP), is produced. This is the work that earned Peter Mitchell his 1978 Nobel Prize ¹². Ubiquinone also functions as a cofactor of other dehydrogenases, a modulator of the permeability transition pore and an essential antioxidant in cell membranes and lipoproteins. While normally synthesized in the body in adequate amounts, coenzyme Q10 is used as a nutritional supplement for conditions highly dependent upon its actions, some of which are associated with low serum levels of the coenzyme.

A coenzyme Q10 deficiency occurs with age; ubiquinone decreases in the body as people get older due to increased requirements, decreased production or insufficient intake of the chemical precursors needed for coenzyme Q10 synthesis ³, ²⁰. Furthermore, certain drugs can cause depletion of coenzyme Q10 levels, particularly hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins ²¹. Statins are prescribed to reduce cholesterol levels and work by inhibiting HMG-CoA reductase and the mevalonate metabolic pathway ²². Mevalonate is used to synthesize cholesterol as well as coenzyme Q10 ²³, therefore, when statin drugs lower cholesterol levels they simultaneously lower coenzyme Q10 levels. Statins are known to block coenzyme Q10 biosynthesis and reduce serum concentrations of coenzyme Q10 by up to 40% ²⁴. Statin use is often associated with a variety of muscle-related symptoms or myopathies. Research has suggested that coenzyme Q10 supplementation may decrease muscle pain associated with statin treatment ²⁵.

Your body uses coenzyme Q10 to make energy needed for the cells to grow and stay healthy. Your body also uses Coenzyme Q10 as an antioxidant ²⁶, ²⁷, ²⁸, ²⁹, ³⁰. An antioxidant is a substance that protects cells from free radicals, which are highly reactive chemicals, often containing oxygen atoms, capable of damaging important cellular components such as DNA and lipids. In addition, the plasma level of coenzyme Q10 has been used in studies as a measure of oxidative stress ³¹, ³². Conditions such as fibromyalgia, diabetes, cancer, heart failure, and neurodegenerative, mitochondrial, and muscular diseases are associated with decreased circulating levels of Coenzyme Q10 (CoQ10) ³³, ³⁴, ³⁵, ³⁶, ³⁷, ³⁸. Several studies have been conducted to determine whether increasing systemic coenzyme Q10 levels would enhance bodily function ³⁹, ⁴⁰, ⁴¹.

Coenzyme Q10 is sold in the United States as a dietary supplement. Supplementary oral administration of coenzyme Q10 has been shown to increase coenzyme Q10 levels in plasma, platelets, and white blood cells ⁴². Because CoQ10 has important functions in the body and because people with some diseases have reduced levels of this substance, researchers have been interested in finding out whether CoQ10 supplements might have health benefits. Studies suggest that CoQ10 deficiency may be associated with a multitude of diseases as diverse as coronary artery disease and congestive heart failure, Parkinson’s disease, diabetes, and breast cancer, as well as the risk factor, hypertension ⁴². It has been suggested that Coenzyme Q10 has the potential to lower blood pressure without significant adverse events in hypertensive patients ⁴³.

There are also a number of ways that coenzyme Q10 could act favorably to reduce blood pressure. Coenzyme Q10 could act directly on vascular endothelium and decrease total peripheral resistance by acting as an antagonist of vascular superoxide, by either scavenging it, or suppressing its synthesis ⁴⁴. Further to this, a recent meta-analysis has associated CoQ10 supplementation with a significant improvement in arterial endothelial function in patients with and without cardiovascular disease ⁴⁵. Coenzyme Q10’s antioxidant properties may also result in the quenching of free radicals that cause inactivation of endothelium-derived relaxing factor or fibrosis of arteriolar smooth muscle, or both ⁴⁶. In addition, CoQ10 has been found to decrease blood viscosity and improve blood flow to cardiac muscle in patients with ischemic heart disease; therefore it may reduce blood pressure ⁴⁷.

Dietary supplementation with coenzyme Q10 results in increased levels of Ubiquinol (the reduced form of coenzyme Q10) within circulating lipoproteins. In its reduced form the coenzyme Q10 molecule acts as a powerful intracellular antioxidant due to its ability to hold electrons rather loosely, and will quite easily give up one or both electrons. The antioxidant and free radical scavenger effects of coenzyme Q10 can therefore help to prevent lipid peroxidation and thus the progression of atherosclerosis ²⁴. Furthermore, coenzyme Q10 has also been found to modulate the amount of ß-integrin levels on the surface of blood monocytes, strongly suggesting that the anti-atherogenic effects of coenzyme Q10 are mediated by other mechanisms beside its antioxidant properties ⁴⁸.

According to 2022 American College of Cardiology/American Heart Association/The Heart Failure Society of America guidelines for the Management of Heart Failure recommended supplementation with coenzyme Q10 effectively reduced vascular mortality, all-cause mortality, and hospital stays for heart failure at 2 years ⁴⁹. However, long-term supplementation is needed ⁴⁹.

A recently published systematic review showed that supplementation with coenzyme Q10, in addition to standard therapy in patients with moderate-to-severe heart failure, is associated with symptom reduction and reduction of major adverse cardiovascular events ⁴⁰, ⁵⁰. CoQ10 may improve functional capacity, endothelial function, and left ventricle contractility in congestive heart failure patients  ⁴⁰, ⁵¹.

Coenzyme Q10 supplementation shows promising results in improving endothelial function in several subsets of patients. CoQ10 can improve endothelial function in patients with ischemic left ventricular systolic dysfunction and heart failure ⁵², ⁵³. Likewise, compared with placebo, CoQ10 improves endothelial function in the peripheral circulation of patients with type 2 diabetes and hyperlipidemia ⁵⁴. However, routine use of CoQ10 in patients with coronary artery disease apart from congestive heart failure is still inconclusive ⁵², ⁵⁵.

There is also evidence that combined with selenium, CoQ10 supplementation in healthy older patients and older patients with diabetes, hypertension, and ischemic heart disease may decrease cardiovascular mortality risk ⁵⁶. Data are conflicting on whether CoQ10 may play a role in treating high blood pressure ⁵⁷. Coenzyme Q10 shows the potential to decrease pain, fatigue, and morning tiredness compared to a placebo in patients with fibromyalgia ⁵⁸, ⁵⁹. Some data suggest that supplementation with moderate-to-high dose coenzyme Q10 may influence bicycle exercise aerobic capacity in patients with mitochondrial disorders ⁶⁰.

Supplementation with coenzyme Q10 300 mg daily for 24 weeks in men with Peyronie disease may decrease penile plaque size, reduce penile curvature, and improve erectile function ⁶¹. Statin drugs inhibit the production of an intermediate in the mevalonate pathway—a biochemical route leading to CoQ10 synthesis ⁶². Therefore, many researchers theorize that statin drugs may contribute to coenzyme Q10 depletion in the body. Given that muscle pain and cramping are frequent side effects of statins, they attribute these symptoms to the diminished levels of coenzyme Q10 ⁶³.

Although most studies have used patients with preexisting medical conditions, one study of healthy participants did show that oral coenzyme Q10 supplementation improved fatigue and physical performance during bicycle exercise routines ⁶⁴.

Coenzyme Q10 has also shown promise in migraine prevention ³⁵. A cohort study of 1550 children and adolescents with headaches found that this population has low coenzyme Q10 levels ⁶⁵. Coenzyme Q10 supplementation appeared to decrease headache frequency ³⁵ A recent study indicated that CoQ10 is beneficial for the prophylactic treatment of migraine headaches in children without significant adverse effects ⁶⁶. A double-blind, randomized controlled trial showed Coenzyme Q10 300 mg daily to be safe and superior to a placebo for migraine prevention ⁶⁷. Another randomized, double-blind, placebo-controlled trial in adult women showed that Coenzyme Q10 400 mg of supplementation decreased migraine frequency, severity, and duration ³⁵. One study showed that only Coenzyme Q10 100 mg daily reduced the severity of headaches and the number of headaches per month in migraine sufferers ⁶⁸.

Interestingly, CoQ10 levels may be decreased in those with acute influenza infection ⁶⁹. However, studies on coenzyme Q10 supplementation in patients with acute influenza have yet to be done.

Coenzyme Q10 supplemented alongside standard psychiatric medical therapy appears to lessen symptoms of depression in patients with bipolar disorder ⁷⁰. In patients with polycystic ovary syndrome (PCOS), Coenzyme Q10 supplementation may improve fasting blood glucose, insulin levels, and total testosterone levels ⁷¹.

Figure 1. Coenzyme Q10

Footnotes: Coenzyme Q10 exists in 3 oxidation states. The fully oxidized form of coenzyme-Q10 called Ubiquinone. The fully reduced form of coenzyme-Q10 called Ubiquinol. And the intermediate form of oenzyme-Q10 is called Ubisemiquinone. Ubiquinone (oxidized form of coenzyme-Q10) is mainly acknowledged as the key cofactor for mitochondrial enzyme complexes and Ubiquinol (reduced form of coenzyme-Q10) is a potent antioxidant and both functions make coenzyme Q10 especially attractive for healthcare providers ⁸. Ubiquinone and ubiquinol are a redox pair (oxidation-reduction) that can be rapidly converted from one form to the other in cells, lymph or blood depending on the demand for their various functions. When ubiquinone is taken orally, it is converted to ubiquinol during absorption and remains in its reduced form in the lymph and in blood. Ubiquinone is not needed to produce energy when it is circulating in the lymph or blood. This conversion takes place so that reduced ubiquinol form of coenzyme-Q10 can provide antioxidant protection as it is being circulated throughout the body.

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Figure 2. Ubiquinone (oxidized form of Coenzyme Q10)

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Figure 3. Ubiquinol (reduced form of Coenzyme Q10)

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Figure 4. The role of coenzyme Q10 (CoQ10) in mitochondrial electron transport chain (ETC)

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Table 1. Ubiquinone and Ubiquinol distribution in human tissues

Organ	Ubiquinone Concentration (µg/g)	Ubiquinol Concentration (µg/g)
Heart	132	61
Kidneys	77	75
Liver	63.6	95
Muscle	39.7	65
Brain	13.4	23
Pancreas	32.7
Spleen	24.6
Lung	7.9	25
Thyroid	24.7
Testis	10.5
Intestine	11.5	95
Colon	10.7
Ventricle	11.8
Plasma (µmol/mL)	1.1	96

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Coenzyme Q10 (CoQ10) key facts

• Coenzyme Q10 (CoQ10) is made naturally by the human body. Coenzyme Q10 is present in most tissues, but the highest concentrations are found in the following organs ³:
  • Heart
  • Liver
  • Kidneys
  • Pancreas
  • The lowest coenzyme Q10 concentration is found in the lungs ³. Tissue levels of coenzyme Q10 decrease as people age, due to increased requirements, decreased production, or insufficient intake of the chemical precursors needed for synthesis ³, ²⁰. In humans, normal blood levels of coenzyme Q10 have been defined variably, with reported normal values ranging from 0.30 to 3.84 µg/mL ⁷⁴, ⁷⁵, ³², ⁷⁶.
• Coenzyme Q10 helps cells to produce energy (adenosine triphosphate [ATP]), and it acts as an antioxidant ⁷⁴, ⁷⁷, ⁷⁸, ⁷⁹, ⁸⁰, ⁸¹.
• Coenzyme Q10 (CoQ10) is marketed in the United States as a dietary supplement. In human studies, coenzyme Q10 supplementation doses and administration schedules have varied, but usually have been in the range of 90 to 390 mg/day. In humans, coenzyme Q10 is usually taken orally as a pill (gel bead or capsule), but intravenous infusions have been given ⁷⁵. Coenzyme Q10 is absorbed best with fat; therefore, lipid preparations are better absorbed than the purified compound ⁷⁵, ⁷⁴.
• Coenzyme Q10 (CoQ10) has not been shown to be of value in treating cancer ⁸², ⁸³.
• Low blood levels of coenzyme Q10 have been detected in patients with some types of cancer. However, no report of a randomized clinical trial of coenzyme Q10 as a treatment for cancer has been published in a peer-reviewed scientific journal ⁸², ⁸³.
• Coenzyme Q10 has shown an ability to stimulate the immune system and to protect the heart from damage caused by certain chemotherapy drugs (anthracyclines family of chemotherapy drugs) ⁸². Coenzyme Q10 (CoQ10) may reduce the risk of heart damage caused by cancer chemotherapy drug doxorubicin ⁷⁸, ²⁷, ²⁸, ²⁹. It has been postulated that doxorubicin interferes with energy-generating biochemical reactions that involve coenzyme Q10 in heart muscle mitochondria and that this interference can be overcome by coenzyme Q10 supplementation ⁸⁴. Studies with adults and children have confirmed the decrease in heart toxicity observed in animal studies ⁷⁹, ⁷⁴, ⁸⁵, ⁸⁰. A randomized trial of 20 patients tested the ability of coenzyme Q10 to reduce heart toxicity (cardiotoxicity) caused by chemotherapy drug doxorubicin ²⁷, ²⁸, ²⁹.
• Coenzyme Q10 (CoQ10) supplements might be beneficial for treating congestive heart failure ⁴⁰. The 2022 American College of Cardiology/American Heart Association/The Heart Failure Society of America guidelines for the Management of Heart Failure recommended supplementation with coenzyme Q10 effectively reduced vascular mortality, all-cause mortality, and hospital stays for heart failure at 2 years ⁴⁹. However, long-term supplementation is needed ⁴⁹.
• Although findings are mixed, Coenzyme Q10 (CoQ10) might help reduce blood pressure ⁵⁷. Some research also suggests that when combined with other nutrients, CoQ10 might aid recovery in people who’ve had bypass and heart valve surgeries.
• Although more studies are needed, some research suggests that Coenzyme Q10 (CoQ10) may help reduce low-density lipoprotein (LDL) cholesterol and total cholesterol levels in people with diabetes, lowering their risk of heart disease.
• Some research suggests that Coenzyme Q10 (CoQ10) might help ease the muscle weakness and pain sometimes associated with taking statins. Supplementation with 50 mg twice daily has decreased statin-related mild-to-moderate myalgias, resulting in an increased ability to perform daily activities ⁶³. The meta-analysis of randomized controlled trials indicated that CoQ10 supplementation (100 to 600 mg/day) decreased the Statin-Associated Muscle Symptoms (SAMS) ⁸⁶.
• Recent research suggests that even high doses of Coenzyme Q10 (CoQ10) don’t seem to improve symptoms in people with Parkinson’s disease. A major study showed that coenzyme Q10, even in higher-than-usual doses, didn’t improve symptoms in patients with early Parkinson’s disease. A 2017 evaluation of this study and several other, smaller studies concluded that coenzyme Q10 is not helpful for Parkinson’s symptoms.
• Guidelines from the American Academy of Neurology and the American Headache Society say that cCoenzyme Q10 (CoQ10) is “possibly effective” in preventing migraines, but this conclusion is based on limited evidence. Some research suggests that CoQ10 might decrease the frequency of these headaches. A double-blind, randomized controlled trial showed Coenzyme Q10 300 mg daily to be safe and superior to a placebo for migraine prevention ⁶⁷. Another randomized, double-blind, placebo-controlled trial in adult women showed that Coenzyme Q10 400 mg of supplementation decreased migraine frequency, severity, and duration ³⁵. One study showed that only Coenzyme Q10 100 mg daily reduced the severity of headaches and the number of headaches per month in migraine sufferers ⁶⁸.
• Because Coenzyme Q10 (CoQ10) is involved in energy production, it’s believed that this supplement might improve your physical performance. However, research in this area has produced mixed results.
• Coenzyme Q10 (CoQ10) has also been studied for a variety of other conditions, including amyotrophic lateral sclerosis (Lou Gehrig’s disease), Down syndrome, Huntington’s disease, and male infertility, but the research is too limited for any conclusions to be drawn.

Ubiquinone Food sources

It has been estimated that dietary consumption contributes to about 25% of plasma coenzyme Q10, but there are currently no specific dietary intake recommendations for coenzyme Q10 from the US National Academy of Medicine or other agencies ⁸⁷. The extent to which dietary coenzyme Q10 consumption contributes to tissue coenzyme Q10 concentrations is not clear.

Based on studies employing food frequency questionnaires, the average dietary intake of coenzyme Q10 is about 3 to 6 mg/day ⁸⁸. Rich sources of dietary coenzyme Q10 include mainly meat, poultry, and fish. Other good sources include soybean, corn, olive, and canola oils; nuts; and seeds. Fruit, vegetables, eggs, and dairy products are moderate sources of coenzyme Q10 ⁸⁸. Some dietary sources are listed in Table 2.

Table 2. Ubiquinone Food sources

Food	Serving	Coenzyme Q10 (mg)
Beef, fried	3 ounces*	2.6
Herring, marinated	3 ounces	2.3
Chicken, fried	3 ounces	1.4
Soybean oil	1 tablespoon	1.3
Canola oil	1 tablespoon	1.0
Rainbow trout, steamed	3 ounces	0.9
Peanuts, roasted	1 ounce	0.8
Sesame seeds, roasted	1 ounce	0.7
Pistachio nuts, roasted	1 ounce	0.6
Broccoli, boiled	½ cup, chopped	0.5
Cauliflower, boiled	½ cup, chopped	0.4
Orange	1 medium	0.3
Strawberries	½ cup	0.1
Egg, boiled	1 medium	0.1

Footnotes: * A three-ounce serving of meat or fish is about the size of a deck of cards.

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Ubiquinone mechanism of action

Ubiquinone also called coenzyme Q10 (CoQ10) is a lipid-soluble benzoquinone that has 10 isoprenyl units in its side chain and is a key component of the mitochondrial respiratory chain for adenosine triphosphate (ATP) synthesis by acting as an electron carrier in mitochondria and as a co-enzyme for mitochondrial enzymes ⁸⁹, ⁹⁰. In cell membranes, coenzyme Q10 acts as an antioxidant, protecting cells from damage caused by unstable oxygen-containing molecules (free radicals), which are byproducts of energy production. Studies have indicated that coenzyme Q10 (CoQ10) is also an intracellular antioxidant that can protects membrane phospholipids, mitochondrial membrane protein, and low density lipoprotein-cholesterol (LDL-C) from free radical-induced oxidative damage ⁹¹. Coenzyme Q10 can potentially increase the production of vital antioxidants, such as superoxide dismutase, an enzyme that effectively reduces vascular oxidative stress in individuals with high blood pressure ⁹². In addition, coenzyme Q10 (CoQ10) lowers lipid peroxidation levels by diminishing pro-oxidative compounds ⁹³. Furthermore, coenzyme Q10 can improve blood flow and safeguard blood vessels by preserving nitric oxide.

Coenzyme Q10 is used by cells of your body in a process known variously as ⁸⁴:

• Aerobic respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also called aerobic metabolism, cell respiration, and oxidative metabolism.
• Aerobic metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also called aerobic respiration, cell respiration, and oxidative metabolism.
• Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also called aerobic metabolism, aerobic respiration, and cell respiration
• Cell respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also called aerobic metabolism, aerobic respiration, and oxidative metabolism.

The “Q” and the “10” in Coenzyme Q10 refer to the quinone chemical group and the 10 isoprenyl subunits that are part of this compound’s structure ⁸⁴. The term “coenzyme” denotes it as an organic (meaning it contains carbon atoms) nonprotein molecule necessary for the proper functioning of its protein partner (an enzyme or an enzyme complex) ⁸⁴.

Ubiquinones participate in oxidation-reduction reactions in the mitochondrial respiratory chain. Ubiquinones also have properties of hydrogen carriers, providing a coupling of proton translocation to respiration by means of a chemiosmotic mechanism. Ubiquinol (the reduced form of ubiquinone), present in all cellular membranes, is a recognized antioxidant that can reduce oxidized tocopherol and ascorbate after free radicals have been removed. Other membrane-related functions have been identified for coenzyme Q10, including the activation of the sodium/hydrogen ion antiporter, apoptosis control, and nicotinamide adenine dinucleotide/nicotinamide/adenine dinucleotide hydrogen ratio control. Reviews of the actions of coenzymes have been published ², ⁹⁴.

Test tube and animal studies have demonstrated that coenzyme Q10 (CoQ10) not only plays an antioxidant, but also has anti-inflammation effects by modulating the expression of cyclooxygenase-2 and nuclear factor-κB (NF-κB) in the liver tissue of rats with hepatocellular carcinoma  ⁹⁵, ⁹⁶.

Mitochondrial ATP synthesis

Coenzyme Q10 (CoQ10) is crucial for efficiently transferring electrons within the mitochondrial oxidative respiratory chain and producing adenosine triphosphate (ATP), which is a packet of energy for cell growth and maintenance ⁹⁷, ²⁶, ²⁷, ⁹⁸, ⁹⁹. The conversion of energy from carbohydrates and fats to adenosine triphosphate (ATP), the form of energy used by cells, requires the presence of coenzyme Q10 (CoQ10) in the inner mitochondrial membrane ⁷². As part of the mitochondrial electron transport chain (ETC), coenzyme Q10 accepts electrons from reducing equivalents generated during fatty acid and glucose metabolism and then transfers them to electron acceptors ⁷². At the same time, coenzyme Q10 contributes to transfer protons (H⁺) from the mitochondrial matrix to the intermembrane space, creating a proton gradient across the inner mitochondrial membrane ⁷². The energy released when the protons flow back into the mitochondrial interior is used to form ATP (Figure 4) ¹⁰⁰. In addition to coenzyme Q10 (CoQ10) role in ATP synthesis, mitochondrial coenzyme Q10 mediates the oxidation of dihydroorotate to orotate in the pyrimidine synthesis, which are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell ⁷².

Lysosomal function

Lysosomes are organelles within cells that are specialized for the digestion of cellular debris. The digestive enzymes within lysosomes function optimally at an acidic pH, meaning they require a permanent supply of protons. The lysosomal membranes that separate those digestive enzymes from the rest of the cell contain relatively high concentrations of coenzyme Q10. Research suggests that coenzyme Q10 plays an important role in the transport of protons across lysosomal membranes to maintain the optimal pH ¹⁰¹, ¹⁰².

Antioxidant functions

Antioxidants protect cells from the damaging effects of free radicals, which are molecules that contain an unshared electron. Free radicals damage cells and might contribute to the development of cardiovascular disease and cancer ¹⁰³. Unshared electrons are highly energetic and react rapidly with oxygen to form reactive oxygen species (ROS). Your body forms reactive oxygen species (ROS) endogenously when it converts food to energy, and antioxidants might protect cells from the damaging effects of reactive oxygen species (ROS). Your body is also exposed to free radicals from environmental exposures, such as cigarette smoke, air pollution, and ultraviolet radiation from the sun. Reactive oxygen species (ROS) are part of signaling mechanisms among cells.

Ubiquinol, a fully reduced form of coenzyme Q10, is an effective fat-soluble antioxidant that protects cell membranes and lipoproteins from oxidation ⁷². The presence of a significant amount of ubiquinol in cell membranes, along with enzymes capable of reducing oxidized coenzyme Q10 (ubiquinone) back to ubiquinol (i.e., NAD(P)H oxidoreductases), supports the idea that ubiquinol is an important cellular antioxidant ¹⁰⁴. Ubiquinol (reduced form of coenzyme Q10) has been found to inhibit lipid peroxidation when cell membranes and low-density lipoproteins (LDL) are exposed to oxidizing conditions. When LDL is oxidized, Ubiquinol is the first antioxidant consumed. In isolated mitochondria, coenzyme Q10 can protect membrane proteins and mitochondrial DNA from the oxidative damage that accompanies lipid peroxidation ⁸¹. Furthermore, when present, Ubiquinol was found to limit the formation of oxidized lipids and the consumption of alpha-tocopherol (a form of vitamin E with antioxidant properties) ¹⁰⁵. In addition to neutralizing free radicals directly, Ubiquinol is capable of regenerating antioxidants like alpha-tocopherol and ascorbate (vitamin C) ¹⁰⁴. Finally, the role of coenzyme Q10 as an antioxidant is also exemplified by recent evidence showing that mitochondrial coenzyme Q10 deficiency causes an increased production of mitochondrial superoxide radical anion (O2^–) which might be driving insulin resistance in fatty (adipose) and muscle tissues ¹⁰⁶.

Pharmacokinetics

Absorption: Coenzyme Q10 (CoQ10) is a lipophilic molecule (“fat-loving” meaning it can dissolve in or be attracted to lipids [fats]) with a high molecular weight; absorption of dietary coenzyme Q10 is slow but is improved in the presence of fatty meals. Solubilized coenzyme Q10 formulations provide improved bioavailability, with peak plasma concentrations typically ranging from 5.80 to 8.10 hours, depending on the specific formulation. Various formulations such as liposome, nanocapsule, and nanoemulsion are being explored to improve bioavailability. A second plasma peak may also be observed due to the enterohepatic recycling and redistribution from the liver to the circulation.

Distribution: Coenzyme Q10 (CoQ10) is primarily absorbed from the small intestine, and coenzyme Q10 is incorporated into chylomicrons and is redistributed via the bloodstream, primarily within VLDL, LDL, and HDL. Preclinical studies indicate that coenzyme Q10 in large doses is taken up by all tissues, including heart and brain mitochondria; consequently, a beneficial effect is observed in cardiovascular and neurodegenerative diseases. The highest levels of coenzyme Q10 in human tissues exist in the heart, liver, kidneys, and muscles (high energy requirements) ¹⁰⁷.

Metabolism: Coenzyme Q10 (CoQ10) is metabolized (broken down) in all tissues, and the resulting metabolites are phosphorylated in the cells and transported through the plasma. Coenzyme Q10 is reduced to Ubiquinol during or after absorption in the small intestine, and the reduced form (Ubiquinol) represents approximately 95% of the circulating coenzyme Q10 in humans.

Elimination: The primary route of coenzyme Q10 elimination is biliary and fecal. A small fraction of coenzyme Q10 is eliminated in the urine ⁷³.

Ubiquinone vs Ubiquinol

Coenzyme Q10 (CoQ10) is poorly absorbed because of its lipophilic nature (“fat-loving” or “fat-soluble” meaning it can dissolve in or be attracted to lipids [fats]) and its high molecular weight. In 2006, Kaneka Corporation in Japan began marketing the Ubiquinol (reduced form of coenzyme Q10) with claims that it was better absorbed than Ubiquinone (oxidized form of coenzyme-Q10) and hence, more effective. This has been a very successful marketing strategy for Kaneka, but actually, the claims are not scientifically accurate.

Ubiquinol products are substantially more expensive than Ubiquinone products. However, when ubiquinol is ingested, it is oxidized by gastric acid to ubiquinone before it is absorbed ⁸. Hence, people pay more for ubiquinol, but really do not get added benefit(s) ⁸. Research has shown that it is not necessary to take ubiquinol in order to significantly increase ubiquinol levels in plasma and in plasma lipoproteins. Taking a ubiquinone supplement will do the same ⁸.

Coenzyme Q10 deficiency

Coenzyme Q10 deficiency has not been described in the general population, so it is generally assumed that normal coenzyme Q10 biosynthesis, with or without a varied diet, provides sufficient coenzyme Q10 to sustain energy production in healthy individuals ⁷⁵. Coenzyme Q10 concentrations have been found to decline gradually with age in a number of different tissues, but it is unclear whether this age-associated decline constitutes a coenzyme Q10 deficiency ⁸¹, ¹⁰⁸, ¹⁰⁹. Decreased plasma coenzyme Q10 concentrations have been observed in individuals with diabetes mellitus, cancer, and congestive heart failure. Lipid-lowering medications that inhibit the activity of 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase (statins), a critical enzyme in both cholesterol and coenzyme Q10 biosynthesis, decrease plasma coenzyme Q10 concentrations, although it remains unproven that this has any clinical implications ⁷².

Coenzyme Q10 deficiency can be Primary coenzyme Q10 deficiency, a rare autosomal recessive disorder caused by COQ genes mutations involved in coenzyme Q10 biosynthesis. Or Secondary coenzyme Q10 deficiency that results from mutations or deletions in genes that are not directly related to coenzyme Q10 biosynthetic pathway ¹¹⁰, ⁷². Secondary coenzyme Q10 deficiency has been described in patients with mitochondrial DNA (mtDNA) mutations or deletions, with mitochondrial DNA depletion syndrome, Kearns-Sayre syndrome, or multiple acyl-CoA dehydrogenase deficiency (MADD) and in patients with mutations in APTX, ETFDH, BRAF, ACADVL or NPC genes ¹¹¹, ¹¹², ¹¹³, ¹¹⁴, ¹¹⁵, ¹¹⁶, ¹¹⁷, ¹¹⁸, ¹¹⁹.

Primary Coenzyme Q10 deficiency

Primary Coenzyme Q10 deficiency is a rare autosomal recessive disorder caused by COQ genes mutations that provide instructions for making proteins involved in the production (synthesis) of coenzyme Q10 with clinical features of steroid-resistant nephrotic syndrome (SRNS), optic atrophy, retinopathy, and encephalopathy ¹²⁰, ¹²¹. To date, mutations in at least nine COQ genes have been identified ¹²⁰. Most of the identified mutations have occurred in the COQ2, COQ4, COQ6, COQ8A, and COQ8B genes ¹²². Smaller numbers of mutations in other COQ genes have also been found to cause primary coenzyme Q10 deficiency ¹²². Coenzyme Q10 deficiency can also be caused by mutations in genes that are not directly related to the synthesis of coenzyme Q10. In these cases, the condition is referred to as secondary coenzyme Q10 deficiency. Secondary coenzyme Q10 deficiency is a common feature of certain other genetic conditions.

As noted above, coenzyme Q10 has several critical functions in cells throughout the body. In cell structures called mitochondria, coenzyme Q10 plays an essential role in a process called oxidative phosphorylation, which converts the energy from food into a form cells can use. Coenzyme Q10 is also involved in producing pyrimidines, which are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell. In cell membranes, coenzyme Q10 acts as an antioxidant, protecting cells from damage caused by unstable oxygen-containing molecules (free radicals), which are byproducts of energy production.

Some mutations in the COQ genes greatly reduce or eliminate the production of the corresponding proteins; others change the structure of a protein, impairing its function. A lack of functional protein produced from any one of the COQ genes decreases the normal production of coenzyme Q10. Studies suggest that a deficiency of coenzyme Q10 impairs oxidative phosphorylation and increases the vulnerability of cells to damage from free radicals. A deficiency of coenzyme Q10 may also disrupt the production of pyrimidines. These changes can cause cells throughout the body to malfunction, which may help explain the variety of organs and tissues that can be affected by primary coenzyme Q10 deficiency.

As a result, primary coenzyme Q10 deficiency is a clinically heterogeneous disorder that includes five major clinical features ⁷²:

1. Severe infantile multi-systemic disease
2. Encephalomyopathy
3. Cerebellar ataxia
4. Isolated myopathy
5. Nephrotic syndrome (steroid-resistant nephrotic syndrome). Steroid-resistant nephrotic syndrome (SRNS), an unusual feature of mitochondrial disorders, is a hallmark of primary coenzyme Q10 deficiency. If not treated with supplementation of high-dose oral coenzyme Q10 (20 mg/kg), steroid-resistant nephrotic syndrome (SRNS) usually progresses to irreversible kidney failure (end-stage renal disease).

Primary coenzyme Q10 deficiency can affect many parts of the body, especially the brain, muscles, and kidneys. The severity, combination of signs and symptoms, and age of onset of primary coenzyme Q10 deficiency vary widely. In the most severe cases, the condition becomes apparent in infancy and causes severe brain dysfunction combined with muscle weakness (encephalomyopathy) and the failure of other body systems. These problems can be life-threatening. The mildest cases of primary coenzyme Q10 deficiency can begin as late as a person’s sixties and often cause cerebellar ataxia, which refers to problems with coordination and balance due to defects in the part of the brain that is involved in coordinating movement (cerebellum) ¹²². Other neurological abnormalities that can occur in primary coenzyme Q10 deficiency include seizures, intellectual disability, poor muscle tone (hypotonia), involuntary muscle contractions (dystonia), progressive muscle stiffness (spasticity), abnormal eye movements (nystagmus), vision loss caused by degeneration (atrophy) of the optic nerves or breakdown of the light-sensing tissue at the back of the eyes (retinopathy), and sensorineural hearing loss, which is caused by abnormalities in the inner ear ¹²². The neurological problems gradually get worse unless treated with coenzyme Q10 supplementation. Unlike other most mitochondrial diseases, oral coenzyme Q10 supplementation has been shown to improve muscular symptoms in some (yet not all) patients with primary coenzyme Q10 deficiency ¹¹¹. Neurological symptoms in patients with cerebellar ataxia are only partially relieved by Ubiquinol supplementation ¹¹¹.

A type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy) can also occur in primary coenzyme Q10 deficiency.

A type of kidney dysfunction called nephrotic syndrome is another common feature of primary coenzyme Q10 deficiency ¹²². It can occur with or without neurological abnormalities. Nephrotic syndrome occurs when damage to the kidneys impairs their function, which allows protein from the blood to pass into the urine (proteinuria). Other signs and symptoms of nephrotic syndrome include increased cholesterol in the blood (hypercholesterolemia), an abnormal buildup of fluid in the abdominal cavity (ascites), and swelling (edema). Affected individuals may also have blood in the urine (hematuria), which can lead to a reduced number of red blood cells in the body (anemia), abnormal blood clotting, or reduced amounts of certain white blood cells. Low white blood cell counts can lead to a weakened immune system and frequent infections in people with nephrotic syndrome. If not treated with coenzyme Q10 supplementation, affected individuals eventually develop irreversible kidney failure (end-stage renal disease). Affected individuals often present initially with steroid-resistant nephrotic syndrome (SRNS) that leads to end-stage renal disease, followed by an encephalomyopathy with seizures and stroke-like episodes resulting in severe neurologic impairment and ultimately death ¹²³, ¹²⁴, ¹²⁵. Some affected individuals manifest only steroid-resistant nephrotic syndrome (SRNS) with onset in the first or second decade of life and slow progression to end-stage renal disease without extrarenal manifestations ¹²⁶. One of the two individuals in a family with COQ9 gene related primary coenzyme Q10 deficiency manifested tubulopathy within a few hours after birth ¹²⁰.

No clinical practice guidelines for management of primary coenzyme Q10 (CoQ10) deficiency have been published. There is no cure for primary coenzyme Q10 deficiency, but coenzyme Q10 replacement therapy is indicated for primary coenzyme Q10 deficiency ¹²⁷, ¹²¹. In patients with primary coenzyme Q10 deficiency, early treatment with high-dose coenzyme Q10 supplementation (ranging from 5 to 50 mg/kg/day) can limit disease progression ¹¹⁰, ¹²⁷. High-dose coenzyme Q10 supplementation (ranging from 5 to 50 mg/kg/day) should be instituted as early as possible because it can limit disease progression and reverse some manifestations ¹²⁸; however, established severe neurologic and/or kidney damage cannot be reversed ¹²⁰.

A recent study of coenzyme Q10 supplementation (20 mg/kg) demonstrated promising results in patients with primary coenzyme Q10 deficiency with nephrotic syndrome and steroid-resistant nephrotic syndrome (SRNS) ¹²⁷. Children with severe multisystem coenzyme Q10 deficiency respond poorly to treatment and generally die within the neonatal period or in the first year of life ¹²⁷.

Data on the prognosis of primary coenzyme Q10 deficiency are limited due to the small number of affected individuals reported to date ¹²⁷. It is a progressive disorder, with variable rates of progression and tissue involvement depending on the gene involved and the severity of the coenzyme Q10 deficiency ¹²⁷.

Individuals with later-onset disease show better response to supplementation with high-dose oral coenzyme Q10 ¹²⁷. In many instances treatment can change the natural history of the disease by blocking progression of the kidney disease and preventing the onset of neurologic manifestations in persons with homozygous mutations in the COQ2, COQ6, COQ8B, or PDSS2 genes ¹²⁹, ¹²⁵, ¹²⁸, ¹²⁷.

Secondary Coenzyme Q10 deficiency

Secondary coenzyme Q10 deficiency results from mutations or deletions in genes that are not directly related to coenzyme Q10 biosynthetic pathway ¹¹⁰, ⁷². Secondary coenzyme Q10 deficiency has been described in patients with mitochondrial DNA (mtDNA) mutations or deletions, with mitochondrial DNA depletion syndrome, Kearns-Sayre syndrome, or multiple acyl-CoA dehydrogenase deficiency (MADD) and in patients with mutations in APTX, ETFDH, BRAF, ACADVL or NPC genes ¹¹¹, ¹¹², ¹¹³, ¹¹⁴, ¹¹⁵, ¹¹⁶, ¹¹⁷, ¹¹⁸, ¹¹⁹. Interestingly, coenzyme Q10 levels may be decreased in those with acute influenza infection ⁶⁹.

Secondary coenzyme Q10 deficiency has also been identified in non-mitochondrial disorders, such as cardiofaciocutaneous syndrome and Niemann-Pick-type C disease ¹³⁰. Secondary coenzyme Q10 deficiency can also be secondary to the inhibition of HMG-CoA reductase by statin drugs. A 2015 meta-analysis of six small, randomized controlled trials found no reduction in statin-induced muscle pain with 100 to 400 mg/day of supplemental coenzyme Q10 for one to three months ¹³¹. The trials failed to establish a diagnosis of relative coenzyme Q10 deficiency before the intervention started, hence limiting the conclusion of the meta-analysis. While statin therapy may not necessary lead to a reduction in circulating coenzyme Q10 concentrations, further research needs to examine whether secondary coenzyme Q10 deficiency might be predisposing patients to statin-induced myalgia ¹³².

It is not clear to what extent coenzyme Q10 supplementation might have therapeutic benefit in patients with inherited secondary Q10 deficiencies, because the therapeutic potential of supplemental coenzyme Q10 is limited to its capacity to restore electron transfer in a defective mitochondrial respiratory chain and/or to increase antioxidant defense ⁷². For example, multiple acyl-CoA dehydrogenase deficiency (MADD), caused by mutations in genes that impair the activity of enzymes involved in the transfer of electrons from acyl-CoA to coenzyme Q10, is usually responsive to riboflavin (vitamin B2) monotherapy yet patients with low coenzyme Q10 concentrations might also benefit from co-supplementation with coenzyme Q10 and riboflavin ¹³³. Another study suggested clinical improvements in secondary coenzyme Q10 deficiency with supplemental coenzyme Q10 in patients presenting with ataxia ¹³⁴. Because the cause of secondary coenzyme Q10 in inherited conditions is generally unknown, it is difficult to predict whether improving coenzyme Q10 status with supplemental coenzyme Q10 would lead to clinical benefits for the patients ⁷².

Ubiquinone supplement benefits

The U.S. Food and Drug Administration (FDA) does not approve dietary supplements as safe or effective. The company that makes the dietary supplements is responsible for making sure that they are safe and that the claims on the label are true and do not mislead the patient. The way that supplements are made is not regulated, so all batches and brands of coenzyme q10 supplements may not be the same.

Ubiquinone for cancer

There have been few clinical trials on the use of coenzyme Q10 to prevent side effects of cancer treatment, treat side effects of cancer treatment, and/or as a treatment for cancer ¹³⁵, ⁸⁴. A trial of 236 breast cancer patients were randomized to receive either Coenzyme q10 or placebo, each combined with vitamin E, for 24 weeks. The study found that levels of fatigue and quality of life were not improved in patients who received Coenzyme q10 compared to patients who received the placebo ¹³⁵.

A randomized trial of 20 children treated for acute lymphoblastic leukemia or non-Hodgkin lymphoma looked at whether Coenzyme q10 would protect the heart from the damage caused by doxorubicin. The results reported that CoQ10 decreased the harmful effects of doxorubicin on the heart ¹³⁵. It has been postulated that doxorubicin interferes with energy-generating biochemical reactions that involve coenzyme Q10 in heart muscle mitochondria and that this interference can be overcome by coenzyme Q10 supplementation ²⁷, ⁹⁸, ⁹⁹. Studies with adults and children, including the aforementioned randomized trial, have confirmed the decrease in heart toxicity observed in animal studies ²⁷, ²⁹, ⁷⁸, ²⁸. A randomized trial ²⁹ of 20 patients tested the ability of coenzyme Q10 to reduce cardiotoxicity caused by anthracycline drugs.

Anecdotal reports of coenzyme Q10 lengthening the survival of patients with pancreatic, lung, rectal, laryngeal, colon, and prostate cancers also exist in the peer-reviewed scientific literature ²⁸. The patients described in these reports also received therapies other than coenzyme Q10, including chemotherapy, radiation therapy, and surgery.

A recent observational study conducted with 1,134 patients with breast cancer enrolled in an National Cancer Institute multi-institution clinical trial (SWOG S0221) suggested that the use of antioxidant supplements, including coenzyme Q10, prior to and during cancer treatment may be associated with increased recurrence rates and decreased survival ¹³⁶.

Reversal of statin-induced myopathy

Statins (HMG-CoA reductase inhibitors) deplete circulating coenzyme Q10 levels by interfering with its biosynthesis ¹³⁷. 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) ¹³⁸. The use of ezetimibe alone or in combination with a statin does not offer protection against depletion of coenzyme Q10 ¹³⁸. No correlation has been established for decreased serum coenzyme Q10 and cardiovascular events ¹³⁸. 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 ¹³⁹, ¹³⁸.

Neurological disorders

The case for coenzyme Q10 as a treatment option in neurological (mitochondrial-related) disease is not as strong ¹⁴⁰. The role of coenzyme Q10 in Parkinson, Alzheimer, and Huntington diseases; amyotrophic lateral sclerosis; and Friedreich ataxia is postulated but not established ¹⁴¹.

Studies in Friedreich and non-Friedreich ataxia have largely shown a continued worsening of disease, as measured by the International Cooperative Ataxia Group rating scale, irrespective of coenzyme q10 use (5 mg/kg/day) ¹⁴².

A link between mitochondrial dysfunction and Parkinson disease has been established, but the relationship with coenzyme Q10 has not ¹⁴³. A multicenter clinical trial found a decrease in worsening of symptoms in patients with early Parkinson disease receiving coenzyme Q10 1,200 mg/day, but not at lower dosages ¹⁴⁴. Effects were not apparent at 1 month, but were evident at 8 months. Changes in daily living factors were more pronounced than clinical disease progression changes ¹⁴⁵. Increases in plasma coenzyme Q10 were recorded. A larger trial using higher dosages (coenzyme Q10 600 mg chewable wafers 4 times a day) found a mean change in total rating score high enough to warrant a phase 3 trial ¹⁴⁶; however, the trial was not designed to evaluate efficacy ¹⁴⁶. A multicenter trial of patients receiving anti-Parkinson medication found no difference in symptoms over placebo ¹⁴⁷.

The role of mitochondrial stress in Alzheimer disease led to more studies of coenzyme Q10 ¹⁴². Multicenter clinical trials 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 ¹⁴⁸. Similarly, no slowing of decline was noted in Huntington disease ¹⁴⁹.

Parkinson’s disease

Parkinson’s disease is a degenerative neurological disorder characterized by tremors, muscular rigidity, and slow movements. Parkinson’s disease is estimated to affect approximately 1% of Americans over the age of 65. Mitochondrial dysfunction and oxidative damage in a part of the brain called the substantia nigra may play a role in the development of the disease ¹⁵⁰. Decreased ratios of reduced-to-oxidized coenzyme Q10 have been found in platelets of individuals with Parkinson’s disease ¹⁵¹, ¹⁵². One study also found higher concentrations of oxidized coenzyme Q10 in the cerebrospinal fluid of patients with untreated Parkinson’s disease compared to healthy controls ¹⁵³. Additionally, a study in postmortem Parkinson’s disease patients found lower concentrations of total coenzyme Q10 in the cortex region of the brain compared to age-matched controls, but no differences were seen in other brain areas, including the striatum, substantia nigra, and cerebellum ¹⁵⁴.

A 16-month randomized, placebo-controlled phase II clinical trial evaluated the safety and efficacy of 300, 600, or 1,200 mg/day of coenzyme Q10 in 80 people with early Parkinson’s disease ¹⁵⁵. Coenzyme Q10 supplementation was well tolerated at all doses and resulted in a slower deterioration of function in Parkinson’s disease patients in the group taking 1,200 mg/day. A phase III clinical trial was then designed to further examine the effect of high-dose coenzyme Q10 (1,200-2,400 mg/day) and vitamin E (1,200 IU/day) supplementation on both motor and non-motor symptoms associated with Parkinson’s disease. This trial was prematurely terminated because it was unlikely that such a treatment was effective in treating Parkinson’s disease ¹⁵⁶. A smaller placebo-controlled trial showed that oral administration of 300 mg/day of coenzyme Q10 for 48 to 96 months moderately improved motor symptoms in treated patients with Levodopa with re-emerging symptoms but not in patients at an early stage of Parkinson’s disease ¹⁵⁷. Two recent meta-analyses of randomized, placebo-controlled trials found no evidence that coenzyme Q10 improved motor-related symptoms or delayed the progression of Parkinson’s disease when compared to placebo ¹⁵⁸, ¹⁵⁹.

Huntington’s disease

Huntington’s disease is an inherited neurodegenerative disorder characterized by selective degeneration of nerve cells known as striatal spiny neurons. Huntington’s disease symptoms, such as movement disorders and impaired cognitive function, typically develop in the fourth decade of life and progressively deteriorate over time. Animal models indicate that impaired mitochondrial function and glutamate-mediated neurotoxicity may be involved in the pathology of Huntington’s disease. Some, but not all, studies in mouse models of Huntington’s disease have suggested that coenzyme Q10 supplementation could improve motor performance, overall survival, and various hallmarks of Huntington’s disease, i.e., brain atrophy, ventricular enlargement, and striatal neuronal atrophy ¹⁶⁰, ¹⁶¹. Interestingly, co-administration of coenzyme Q10 with remacemide (an NMDA receptor antagonist), the antibiotic minocycline, or creatine led to greater improvements in most biochemical and behavioral parameters ¹⁶⁰, ¹⁶¹, ¹⁶².

To date, only two clinical trials have examined whether coenzyme Q10 might be efficacious in human patients with Huntington’s disease. A 30-month, randomized, placebo-controlled trial of coenzyme Q10 (600 mg/day), remacemide, or both in 347 patients with early Huntington’s disease found that neither coenzyme Q10 nor remacemide significantly altered the decline in total functional capacity, although coenzyme Q10 supplementation (with or without remacemide) resulted in a nonsignificant trend toward a slower decline ¹⁶³. A 20-week pilot trial examined the safety and tolerability of increasing dosages of coenzyme Q10 (1,200 mg/day, 2,400 mg/day, and 3,600 mg/day) in eight healthy subjects and in 20 patients with Huntington’s disease; 22 of the subjects completed the study ¹⁶⁴. All dosages were generally well tolerated, with gastrointestinal symptoms being the most frequently reported adverse effect. Blood concentrations of coenzyme Q10 at the end of the study were maximized with the daily dose of 2,400 mg ¹⁶⁴. Coenzyme Q10 2,400 mg dose was tested in a multicenter phase III clinical trial in 609 participants with early-stage Huntington’s disease ¹⁶⁵. Participants were randomized to receive either 2,400 mg/day of coenzyme Q10 or placebo for five years ¹⁶⁵. The trial was prematurely halted because it appeared unlikely to demonstrate any health benefit in supplemented patients — about one-third of participants completed the trial at the time of study termination ¹⁶⁵. Although coenzyme Q10 is generally well tolerated, there is no evidence that supplementation can improve functional and cognitive symptoms in Huntington’s disease patients.

Friedreich’s ataxia

Friedreich’s ataxia is an autosomal recessive neurodegenerative disease caused by mutations in the FXN gene that encodes for the mitochondrial protein, frataxin. Frataxin is needed for the making of iron-sulfur clusters (ISC). Iron-sulfur clusters-containing subunits are especially important for the mitochondrial respiratory chain and for the synthesis of heme-containing proteins ¹⁶⁶. Frataxin deficiency is associated with imbalances in iron-sulfur containing proteins, mitochondrial respiratory chain dysfunction and lower ATP production, and accumulation of iron in the mitochondria, which increases oxidative stress and oxidative damage to macromolecules of the respiratory chain ¹⁶⁷. Clinically, Friedreich’s ataxia is a progressive disease characterized by ataxia, areflexia, speech disturbance (dysarthria), sensory loss, motor dysfunction, cardiomyopathy, diabetes, and scoliosis ¹⁶⁷. A pilot study administering coenzyme Q10 (200 mg/day) and vitamin E (2,100 IU/day) to 10 Friedreich’s ataxia patients found that energy metabolism of cardiac and skeletal muscle was improved after only three months of therapy ¹⁶⁸. Follow-up assessments at 47 months indicated that cardiac and skeletal muscle improvements were maintained and that Friedreich’s ataxia patients showed significant increases in fractional shortening, a measure of cardiac function. Moreover, the therapy was effective at preventing the progressive decline of neurological function ¹⁶⁹. Another study reported both coenzyme Q10 and vitamin E deficiencies among Friedreich’s ataxia patients and suggested that co-supplementation with both compounds, at doses as low as 30 mg/day of coenzyme Q10 and vitamin E 4 IU/day, might improve disease symptoms ¹⁷⁰. Large-scale, randomized controlled trials are necessary to determine whether coenzyme Q10, in conjunction with vitamin E, has therapeutic benefit in Friedreich’s ataxia. At present, about one-half of patients use coenzyme Q10 and vitamin E supplements despite the lack of proven therapeutic benefit (77).

Spinocerebellar ataxias

Spinocerebellar ataxias are a group of rare autosomal dominant neurodegenerative diseases characterized by gait difficulty, loss of hand dexterity, dysarthria, and cognitive decline ¹⁷¹. To date, more than 40 distinct genetic spinocerebellar ataxias have been identified which are classified according to the genetic loci in order of identification. SCA1, 2, 3, and 6 are the most common spinocerebellar ataxias ¹⁷². In vitro coenzyme Q10 treatment of forearm skin fibroblasts isolated from patients with SCA2 was found to reduce oxidative stress and normalize complex I and II-III activity of the mitochondrial respiratory chain ¹⁷³. A multicenter prospective cohort study that followed 319 patients with spinocerebellar ataxias (≥15 years) found no difference in the rate of disease progression over two years between those taking supplemental coenzyme Q10 (median dose, 600 mg/day) and nonusers ¹⁷².

Aging

According to the free radical and mitochondrial theories of aging, oxidative damage of cell structures by reactive oxygen species (ROS) plays an important role in the functional declines that accompany aging ¹⁷⁴. Reactive oxygen species (ROS) are generated by mitochondria as a byproduct of ATP production. If not neutralized by antioxidants, reactive oxygen species (ROS) may damage mitochondria over time, causing them to function less efficiently and to generate more damaging reactive oxygen species (ROS) in a self-perpetuating cycle ⁷². Coenzyme Q10 plays an important role in mitochondrial ATP synthesis and functions as an antioxidant in mitochondrial membranes. One of the hallmarks of aging is a decline in energy metabolism in many tissues, especially liver, heart, and skeletal muscle. Tissue concentrations of coenzyme Q10 have been found to decline with age, thereby accompanying age-related declines in energy metabolism ¹⁰⁸. Early animal studies have not been able to demonstrate an effect of lifelong dietary supplementation with coenzyme Q10 on the lifespan of rats or mice ¹⁷⁵, ¹⁷⁶, ¹⁷⁷. Nonetheless, more recent studies have suggested that supplemental coenzyme Q10 could promote mitochondrial biogenesis and respiration and delay senescence in transgenic mice ¹⁷⁸, ¹⁷⁹. At the present time, there is limited scientific evidence to suggest that coenzyme Q10 supplementation prolongs life or prevents age-related functional declines in humans. In a small randomized controlled trial, elderly individuals (>70 years) who received a combination of selenium (100 µg/day) and coenzyme Q10 (200 mg/day) for four years reported an improvement in vitality, physical performance, and quality of life ¹⁸⁰. Furthermore, a 12-year follow-up of these participants showed a reduction in cardiovascular mortality with supplemental selenium and coenzyme Q10 compared to placebo ⁵⁶.

Blood lipids

Elevated plasma lipoprotein-A concentration is an independent risk factor for cardiovascular disease. A meta-analysis of six controlled trials of which five were randomized in 409 participants found a reduction in plasma lipoprotein-A concentration with coenzyme Q10 supplementation 100-300 mg/day for 4 to 12 weeks ¹⁸¹. Other effects of coenzyme Q10 on blood lipids have not been reported ¹⁸¹, ¹⁸², ¹⁸³.

A therapeutic approach combining coenzyme Q10 with other antioxidants might prove to be more effective to target co-existing metabolic disorders in individuals at risk for cardiovascular disease ¹⁸⁴.

Atherosclerosis

Oxidative modification of low-density lipoproteins (LDL), also known as “bad” cholesterol, in arterial walls is thought to represent an early event leading to the development of atherosclerosis. Ubiquinol or reduced coenzyme Q10 inhibits the oxidation of LDL in the test tube (in vitro) and works together with alpha-tocopherol (active form of vitamin E) to inhibit LDL oxidation by regenerating tocopheroxyl radical (oxidized form of vitamin E) back to alpha-tocopherol (reduced form of vitamin E) ¹⁸⁵. In the absence of a co-antioxidant, such as ubiquinol or vitamin C, tocopheroxyl radical (oxidized form of vitamin E) can, under certain conditions, promote the oxidation of LDL in test tube study ¹⁰⁵. Supplementation with coenzyme Q10 increases the concentration of ubiquinol (reduced coenzyme Q10) in human LDL ¹⁸⁶. Studies in apolipoprotein E-deficient mice, an animal model of atherosclerosis, found that coenzyme Q10 supplementation with supra-pharmacological amounts of coenzyme Q10 inhibited lipoprotein oxidation in the blood vessel wall and the formation of atherosclerotic lesions ¹⁸⁷. Interestingly, co-supplementation of these mice with alpha-tocopherol (vitamin E) and coenzyme Q10 was more effective in inhibiting atherosclerosis than supplementation with either alpha-tocopherol (vitamin E) or coenzyme Q10 alone ¹⁸⁸.

Another important step in the development of atherosclerosis is the recruitment of immune cells known as monocytes into the blood vessel walls. This recruitment is dependent in part on monocyte expression of cell adhesion molecules (integrins). Supplementation of 10 healthy men and women with 200 mg/day of coenzyme Q10 for 10 weeks resulted in significant decreases in monocyte expression of integrins, suggesting another potential mechanism for the inhibition of atherosclerosis by coenzyme Q10 ¹⁸⁹. Although coenzyme Q10 supplementation shows promise as an inhibitor of LDL oxidation and atherosclerosis, more research is needed to determine whether coenzyme Q10 supplementation can inhibit the development or progression of atherosclerosis in humans.

Cardiovascular risk factors

Normally functioning vascular endothelium promotes blood vessel relaxation (vasodilation) when needed (for example, during exercise) and inhibits the formation of blood clots. Atherosclerosis is associated with impairment of vascular endothelial function, thereby compromising vasodilation and normal blood flow. Endothelium-dependent vasodilation is impaired in individuals with elevated serum cholesterol concentrations, as well as in patients with coronary heart disease or diabetes mellitus. A 2012 meta-analysis examining the results of five small randomized controlled trials in 194 subjects in total found that supplemental coenzyme Q10 with 150-300 mg/day for 4 to 12 weeks resulted in a clinically significant, 1.7% increase in flow-dependent endothelial-mediated dilation ¹⁹⁰. Evidence from larger studies is needed to further establish the effect of coenzyme Q10 on endothelium-dependent vasodilation.

Several small randomized controlled trials in patients at increased cardiovascular disease risk or with established cardiovascular disease have examined the effect of supplemental coenzyme Q10 for ≤3 months on circulating inflammation markers i.e., C-reactive protein (CRP), interleukin-6 (IL-6) and/or tumor necrosis factor alpha (TNF-α). Recently published pooled analyses of these trials have given mixed results ¹⁹¹, ¹⁸², ¹⁹². Larger studies are needed to examine the effect of coenzyme Q10 supplementation on low-grade inflammation.

Congestive heart failure

Impairment of the heart’s ability to pump enough blood for all of the body’s needs is known as congestive heart failure. In coronary heart disease (coronary artery disease), accumulation of atherosclerotic plaque in the coronary arteries may prevent parts of the heart muscle from getting adequate blood supply, ultimately resulting in heart damage and impaired pumping ability. Heart failure can also be caused by heart attack (myocardial infarction), high blood pressure (hypertension), diseases of the heart valves, cardiomyopathy (diseases of the heart muscle), and congenital heart diseases. Because physical exercise increases the demand on the weakened heart, measures of exercise tolerance are frequently used to monitor the severity of heart failure. Echocardiography is also used to determine the left ventricular ejection fraction, an objective measure of the heart’s pumping ability ¹⁹³.

A study of 1,191 heart failure patients found that low plasma coenzyme Q10 concentration was a good biomarker of advanced heart disease ¹⁹⁴. A number of small intervention trials that administered supplemental coenzyme Q10 to congestive heart failure patients have been conducted. A recently published systematic review showed that supplementation with coenzyme Q10, in addition to standard therapy in patients with moderate-to-severe heart failure, is associated with symptom reduction and reduction of major adverse cardiovascular events ⁴⁰, ⁵⁰. Another meta-analysis of 14 randomized, placebo-controlled trials in 2,149 participants with heart failure found that coenzyme Q10 supplementation (30-300 mg/day) resulted in a 39% reduction in mortality (seven studies), improved exercise capacity (four studies), but had no effect on left ventricular ejection fraction (nine studies) compared to placebo ¹⁹⁵. Coenzyme Q10 may improve functional capacity, endothelial function, and left ventricle contractility in congestive heart failure patients ⁴⁰, ⁵¹.

Coenzyme Q10 cupplementation shows promising results in improving endothelial function in several subsets of patients. Coenzyme Q10 can improve endothelial function in patients with ischemic left ventricular systolic dysfunction and heart failure ⁵², ⁵³. Likewise, compared with placebo, coenzyme Q10 improves endothelial function in the peripheral circulation of patients with type 2 diabetes mellitus and hyperlipidemia ⁵⁴. Routine use of coenzyme Q10 in patients with coronary artery disease apart from congestive heart failure is still inconclusive ⁵⁵, ⁵².

There is also evidence that combined with selenium, coenzyme Q10 supplementation in healthy older patients and older patients with diabetes, hypertension, and ischemic heart disease may decrease cardiovascular mortality risk ⁵⁶.

A trial is presently being conducted to assess the value of supplemental coenzyme Q10 and/or D-ribose in the treatment of congestive heart failure in patients with normal left ventricular ejection fraction ¹⁹⁶.

A 2021 literature review identified 11 small randomized controlled trials involving 1573 participants examining the effect of coenzyme Q10 supplementation (60-200 mg/day for ≤3 months in most trials) in heart failure patients ¹⁹⁷. The analyses show that based on currently available evidence it is not sufficient to draw robust conclusions about the safety and efficacy of coenzyme Q10 in heart failure ¹⁹⁷.

According to the 2022 American College of Cardiology, American Heart Association and the Heart Failure Society of America guidelines, coenzyme Q10 supplementation effectively reduced vascular mortality, all-cause mortality, and hospital stays for heart failure at 2 years ¹⁹⁸. However, long-term supplementation is needed ⁴⁹.

Ischemia-reperfusion injury

The heart muscle may become oxygen-deprived (ischemic) as the result of a heart attack (myocardial infarction) or during heart surgery. Increased generation of reactive oxygen species (ROS) when the heart muscle’s oxygen supply is restored (reperfusion) might be an important contributor to heart muscle damage occurring during ischemia-reperfusion ¹⁹⁹. Pretreatment of animals with coenzyme Q10 has been found to preserve heart function following ischemia-reperfusion injury by increasing ATP concentration, enhancing antioxidant capacity and limiting oxidative damage, regulating autophagy, and reducing cardiomyocyte apoptosis ²⁰⁰. Another potential source of ischemia-reperfusion injury is aortic clamping during some types of cardiac surgery, such as coronary artery bypass graft (CABG) surgery. Early placebo-controlled trials found that coenzyme Q10 pretreatment with coenzyme Q10 60-300 mg/day for 7-14 days prior to surgery provided some benefit in short-term outcome measures after coronary artery bypass graft (CABG) surgery ²⁰¹, ²⁰². In a small randomized controlled trial in 30 patients, oral administration of coenzyme Q10 for 7 to 10 days before coronary artery bypass graft (CABG) surgery reduced the need for mediastinal drainage, platelet transfusion, and positive inotropic drugs (e.g. dopamine) and the risk of arrhythmia within 24 hours post-surgery ²⁰³. In one trial that did not find preoperative coenzyme Q10 supplementation to be of benefit, patients were treated with 600 mg of coenzyme Q10 12 hours prior to surgery, suggesting that preoperative coenzyme Q10 treatment may need to commence at least one week prior to CABG surgery to improve surgical outcomes ²⁰⁴. The combined administration of coenzyme Q10, lipoic acid, omega-3 fatty acids, magnesium orotate, and selenium at least two weeks before CABG surgery and four weeks after was examined in a randomized, placebo-controlled trial in 117 patients with heart failure ²⁰⁵. The treatment resulted in lower concentration of troponin-I (a marker of heart muscle injury), shorter length of hospital stay, and reduced risk of postoperative transient cardiac dysfunction compared to placebo ²⁰⁵.

Although trials have included relatively few people and examined mostly short-term, post-surgical outcomes, the results are promising ¹⁹⁶.

Periprocedural myocardial injury

Coronary angioplasty also called percutaneous coronary intervention (PCI) is a minimally invasive medical procedure for treating narrowed or blocked coronary arteries, including unstable angina pectoris, acute myocardial infarction, and multivessel coronary heart disease. Coronary angioplasty involves temporarily inserting a catheter with a balloon and inflating a tiny balloon into the blocked artery to help restore the blood flow to the heart and a stent is often inserted to keep the artery open. Periprocedural myocardial injury that occurs in up to one-third of patients undergoing otherwise uncomplicated angioplasty increases the risk of morbidity and mortality at follow-up.

A prospective cohort study followed 55 patients with acute ST segment elevation myocardial infarction (a type of heart attack characterized by the death of some myocardial tissue) who underwent coronary angioplasty ²⁰⁶. Plasma coenzyme Q10 concentration one month after angioplasty was positively correlated with less inflammation and oxidative stress and predicted favorable left ventricular end-systolic volume remodeling at six months ²⁰⁶. One randomized controlled trial has examined the effect of coenzyme Q10 supplementation on periprocedural myocardial injury in patients undergoing coronary angioplasty ²⁰⁷. The administration of 300 mg of coenzyme Q10 12 hours before the angioplasty to 50 patients reduced the concentration of C-reactive protein (CRP; a marker of inflammation) within 24 hours following the procedure compared to placebo. However, there was no difference in concentrations of two markers of myocardial injury (creatine kinase and troponin-I) or in the incidence of major adverse cardiac events one month after angioplasty between active treatment and placebo ²⁰⁷. Additional trials are needed to examine whether coenzyme Q10 therapy can improve clinical outcomes in patients undergoing coronary angioplasty.

Angina pectoris

Myocardial ischemia a condition where the heart muscle doesn’t get enough oxygen-rich blood, usually because a coronary artery is partially or completely blocked by plaque may also lead to chest pain known as angina pectoris. People with angina pectoris often experience symptoms when the demand for oxygen exceeds the capacity of the coronary circulation to deliver it to the heart muscle, e.g., during exercise. Five small placebo-controlled studies have examined the effects of oral coenzyme Q10 supplementation (60-600 mg/day) in addition to conventional medical therapy in patients with chronic stable angina ²⁰⁸. In most of the studies, coenzyme Q10 supplementation improved exercise tolerance and reduced or delayed electrocardiographic changes associated with myocardial ischemia compared to placebo. However, only two of the studies found significant decreases in symptom frequency and use of nitroglycerin with coenzyme Q10 supplementation. Presently, there is only limited evidence suggesting that coenzyme Q10 supplementation would be a useful adjunct to conventional angina therapy.

High blood pressure

Data are conflicting on whether coenzyme Q10 may play a role in treating high blood pressure ⁵⁷. Very few high-quality trials have examined the potential therapeutic benefit of coenzyme Q10 supplementation in the treatment of primary hypertension or essential hypertension where high blood pressure without a single identifiable cause ²⁰⁹. A systematic review identified two small randomized, double-blind, placebo-controlled trials that found little evidence of a reduction in systolic or diastolic blood pressure following the administration of coenzyme Q10 (100-200 mg/day) for three months ²⁰⁹. In contrast, a meta-analysis that used less stringent selection criteria included 17 small trials and found evidence of a blood pressure-lowering effect of coenzyme Q10 in patients with cardiovascular disease or metabolic disorders ²¹⁰. The effect of coenzyme Q10 on blood pressure needs to be examined in large, well-designed clinical trials.

Diabetes mellitus

Diabetes mellitus or diabetes, is a chronic condition characterized by high blood glucose (sugar) levels, resulting from the pancreas not producing enough insulin or the body being unable to use its insulin effectively. Symptoms include increased thirst and urination, fatigue, and blurred vision. It can be managed through a combination of lifestyle changes and medication, and common types include Type 1 diabetes, Type 2 diabetes, and gestational diabetes. Plasma concentrations of reduced coenzyme Q10 (Ubiquinol) have been found to be lower in diabetic patients than healthy controls after normalization to plasma cholesterol concentrations ²¹¹, ²¹². Tthe pathogenesis of type 2 diabetes mellitus involves the early onset of glucose intolerance and hyperinsulinemia associated with the progressive loss of tissue responsiveness to insulin. Recent experimental studies tied insulin resistance to a decrease in coenzyme Q10 expression and showed that supplementation with coenzyme Q10 could restore insulin sensitivity ¹⁰⁶. Coenzyme Q10 supplementation might thus be a more useful tool for the primary prevention of type 2 diabetes rather than for its management.

Randomized controlled trials that examined the effect of coenzyme Q10 supplementation found little evidence of benefits on glycemic control in patients with diabetes mellitus. A meta-analysis of six trials in participants with type 2 diabetes and one trial in participants with type 1 diabetes found that 100 to 200 mg/day of coenzyme Q10 for three to six months lowered neither fasting plasma glucose nor levels of glycated hemoglobin ([HbA1c]; a measure of glycemic control). Maternally inherited diabetes mellitus-deafness syndrome is caused by a mutation in mitochondrial DNA, which is inherited exclusively from one’s mother. Maternally inherited diabetes mellitus-deafness syndrome accounts for less than 1% of all cases of diabetes. Some early evidence suggested that long-term coenzyme Q10 supplementation (150 mg/day) may improve insulin secretion and prevent progressive hearing loss in these patients ²¹³, ²¹⁴.

Athletic performance

There is little evidence that supplementation with coenzyme Q10 improves athletic performance in healthy individuals ²¹⁵, ²¹⁶, ²¹⁷, ²¹⁸, ²¹⁹. A few placebo-controlled trials have examined the effects of 100 to 150 mg/day of supplemental coenzyme Q10 for three to eight weeks on physical performance in trained and untrained men. Most did not find significant differences between the group taking coenzyme Q10 and the group taking placebo with respect to measures of aerobic exercise performance, such as maximal oxygen consumption (VO2 max) and exercise time to exhaustion ²¹⁵, ²¹⁶, ²¹⁷, ²¹⁸, ²¹⁹. One study found the maximal cycling workload to be slightly (4%) increased after eight weeks of coenzyme Q10 supplementation compared to placebo, although measures of aerobic power were not increased ²²⁰. Two studies actually found significantly greater improvement in measures of anaerobic and aerobic exercise performance with a placebo than with supplemental coenzyme Q10 ²¹⁵, ²¹⁶. More recent studies have suggested that coenzyme Q10 could help reduce both muscle damage-associated oxidative stress and low-grade inflammation induced by strenuous exercise ²²¹, ²²², ²²³, ²²⁴. Studies on the effect of coenzyme Q10 supplementation on physical performance in women are lacking, but there is little reason to suspect a gender difference in the response to coenzyme Q10 supplementation.

Other uses

Coenzyme Q10 has also shown promise in migraine prophylaxis (prevention). Coenzyme Q10 has been evaluated in migraine versus placebo in small trials. A cohort study of 1550 children and adolescents with headaches found that this population has low coenzyme Q10 levels ⁶⁵. Decreases in migraine attack frequency, days with headache, and days with nausea were found for a daily dose of 300 mg coenzyme Q10 (1 to 3 mg/kg per day) ⁶⁷, ⁶⁵. A recent study indicated that coenzyme Q10 (coenzyme Q10 30 mg for children <30 kg and coenzyme Q10 60 mg for children over 30 kg) is beneficial for the prophylactic (preventive) treatment of migraine headaches in children without significant adverse effects ⁶⁶.

Coenzyme Q10 supplemented alongside standard psychiatric medical therapy appears to lessen symptoms of depression in patients with bipolar disorder ⁷⁰. In patients with polycystic ovary syndrome (PCOS), coenzyme Q10 supplementation may improve fasting blood glucose, insulin levels, and total testosterone levels ⁷¹.

The coadministration of ubiquinone with tamoxifen mitigated the hyperlipidemia associated with tamoxifen, and tumor marker levels indicated an antiangiogenesis effect ²²⁵. An Agency for Healthcare Research and Quality review of clinical trials reported no evidence to support the use of ubiquinone in the prevention or treatment of cancer ²²⁶.

Deficiencies of coenzyme Q10 have been described, predominantly affecting children, in a spectrum of diseases including infantile-onset, multisystem diseases, as well as adult-onset cerebellar ataxia and pure myopathies ¹⁴¹. Lymphocyte and platelet coenzyme Q10 levels were lower in Down syndrome ²²⁷, while lowered serum levels are associated with phenylketonuria and mevalonic aciduria ²²⁸.

In infants with Prader-Willi syndrome, coenzyme Q10 had no effect on lean mass versus growth hormone ²²⁹.

Coenzyme Q10 cupplementation shows the potential to decrease pain, fatigue, and morning tiredness compared to a placebo in patients with fibromyalgia ⁵⁸, ⁵⁹. Some data suggest that supplementation with moderate-to-high dose coenzyme Q10 may influence bicycle exercise aerobic capacity in patients with mitochondrial disorders ⁶⁰.

Although most coenzyme Q10 studies have used patients with preexisting medical conditions, one study of healthy participants did show that oral coenzyme Q10 supplementation improved fatigue and physical performance during bicycle exercise routines ⁶⁴.

Supplementation with coenzyme Q10 in men with Peyronie disease may decrease penile plaque size, reduce penile curvature, and improve erectile function ⁶¹.

Statin drugs inhibit the production of an intermediate in the mevalonate pathway—a biochemical route leading to coenzyme Q10 synthesis ⁶². Therefore, many researchers theorize that statin drugs may contribute to coenzyme Q10 depletion in the body. Given that muscle pain and cramping are frequent adverse effects of statins, they attribute these symptoms to the diminished levels of coenzyme Q10 ⁶³.

Ubiquinone dosage

Several dosage forms exist, including compressed and chewable tablets, powder-filled and gel-filled capsules, liquid syrups, and newer solubilized formulations. The reduced form of coenzyme Q10, ubiquinol, is also commercially available. It may also be given by injection into a vein (IV).

Most human studies on coenzyme Q10 (CoQ10) have focused on its oral supplementation. Available in various forms, such as tablets, capsules, soft gels, and liquid formulations, these oral supplements range from 30 to 600 mg per unit and are easily accessible over the counter. While topical over-the-counter preparations applied to the skin are also available, research on this mode of administration is limited. For instance, one study explored the effectiveness of a topical coenzyme Q10 treatment for age-related skin oxidative damage ²³⁰.

Pharmacokinetic studies suggest split dosing is superior to single daily dosing; for tissue uptake and crossing the blood-brain barrier, plasma coenzyme Q10 levels should be higher than normal ²³¹.

Coenzyme Q10 (CoQ10) is a fat-soluble nutrient and coenzyme Q10 dissolved in an oil matrix is more effective than the same amount of crystalline coenzyme Q10 in raising coenzyme Q10 serum levels ¹⁷⁵. Coenzyme Q10 (CoQ10) supplements should be taken at a meal that contains some fat. This enhances the absorption of the coenzyme Q10 (CoQ10). Coenzyme Q10 (CoQ10) 200 mg in oil/soft gel formulation caused a larger increase in coenzyme Q10 serum levels than 100 mg ¹⁷⁵. Because coenzyme Q10 is a large molecular weight, fat-soluble compound, its absorption is slow and limited. This explains why better blood levels are achieved with divided doses rather than taking a large single dose of coenzyme Q10. The following data was gathered from multiple human clinical trials. On average, participants’ pre-test coenzyme Q10 blood levels were 1.09 ug/ml. After ingestion of a single 100 mg dose of coenzyme Q10, blood levels increased to 2.33 ug/ml. However, when people ingested 200 mg of coenzyme Q10 in a single dose, the blood level only increased to 2.35 ug/ml, almost no different than the blood level following a 100 mg dose. However, when individuals took 100 mg of coenzyme Q10 in divided doses, twice daily, blood levels rose to 3.47 ug/ml. Divided dosages (2 x 100 mg) of coenzyme Q10 caused a larger increase in serum levels of coenzyme Q10 than a single dose of 200 mg ¹⁷⁵.

Usual adult dose of coenzyme-Q10 is 30 to 200 mg/day oral.

Supplementation with coenzyme Q10 (CoQ10) 50 mg twice daily has decreased statin-related mild-to-moderate myalgias, resulting in an increased ability to perform daily activities ⁶³. The meta-analysis of randomized controlled trials indicated that coenzyme Q10 supplementation (100 to 600 mg/day) decreased the Statin-Associated Muscle Symptoms ⁸⁶.

Supplementation with coenzyme Q10 (CoQ10) 300 mg daily for 24 weeks in men with Peyronie disease may decrease penile plaque size, reduce penile curvature, and improve erectile function ⁶¹.

A double-blind, randomized controlled trial showed coenzyme Q10 300 mg daily to be safe and superior to a placebo for migraine prevention ⁶⁷. Another randomized, double-blind, placebo-controlled trial in adult women showed that 400 mg of supplementation decreased migraine frequency, severity, and duration ³⁵. One study showed that only 100 mg daily reduced the severity of headaches and the number of headaches per month in migraine sufferers ⁶⁸.

In patients with primary coenzyme Q10 deficiency (a rare genetic disorder caused by mutations in COQ genes essential for coenzyme Q10 biosynthesis, leading to low coenzyme Q10 levels in the body), early treatment with high-dose coenzyme Q10 supplementation (ranging from 5 to 50 mg/kg/day) can limit disease progression ¹²⁰. A recent study of coenzyme Q10 supplementation (20 mg/kg) demonstrated promising results in patients with primary coenzyme Q10 deficiency with steroid-resistant nephrotic syndrome and sensorineural hearing loss ¹²¹, ²³².

In observational studies and clinical trials (12 studies, total of 362 patients) has shown that coenzyme Q10 supplementation reduces blood pressure ²³³. Dose of coenzyme Q10 ranged between 34 and 225 mg/day and duration of individual studies from one to 56 weeks.

Cardiovascular and neurologic trials predominately use coenzyme Q10 dosages of 300 mg/day or coenzyme Q10 dosages of 5 mg/kg/day.

Coenzyme Q10 supplementation is well tolerated up to 1200 mg/day ⁴¹. High-dose coenzyme Q10 (1,200 mg/day) was used in patients with early Parkinson disease ¹⁴⁴, while dosages of 2,700 to 3,000 mg/day were used in amyotrophic lateral sclerosis trials ²³⁴. An open-label study that included children evaluated tolerability of high-dose coenzyme Q10. Daily dosages of 60 mg/kg given in 3 divided doses were used for 1 month ²³⁵.

Liver impairment

Coenzyme Q10 supplementation reduces systemic inflammation and biochemical parameters in nonalcoholic fatty liver disease (NAFLD). However, as mentioned in pharmacokinetics, CoQ10 is excreted in bile. Hence, the use is not advised in patients with biliary obstruction.[34]

Kidney impairment

According to a recent article on Kidney Disease Improving Global Outcomes (KDIGO 2022), coenzyme Q10 supplementation may benefit patients with nephrotic syndrome due to primary coenzyme Q10 deficiency ²³⁶. However, studies of coenzyme Q10 in patients with kidney impairment are lacking. Coenzyme Q10 supplements should be avoided in patients with kidney impairment and used only for the indications mentioned in Kidney Disease Improving Global Outcomes guidelines ²³⁶.

Pregnancy

According to the manufacturer, coenzyme Q10 is not advised during pregnancy. However, a recent meta-analysis demonstrated that supplementation with coenzyme Q10 may benefit clinical pregnancy rates in women using assisted reproductive technologies (ART) to get pregnant ²³⁷.

Breastfeeding

Coenzyme Q10 (ubiquinone) is a normal part of the diet, and is also endogenously synthesized. Coenzyme Q10 (ubiquinone) is a normal component of human milk, but milk levels are slightly low in the breastmilk of mothers with preterm infants ²³⁸. Coenzyme Q10 has no specific lactation-related uses and no data exist on the safety and efficacy of supplementation in nursing mothers or infants ²³⁸. Coenzyme Q10 supplements are usually well tolerated with only infrequent, minor side effects.

Milk levels of coenzyme Q10 have not been measured after exogenous administration in humans. Coenzyme Q10 is a normal component of human milk; however, values appear to vary depending on the country in which they are measured, possibly because of dietary, genetic or other population differences as well as assay differences ²³⁹.

Older patients

No specific dosing recommendations for older or pediatric patients are available.

Ubiquinone Contraindications

Patients receiving chemotherapeutic drugs should also avoid coenzyme Q10, as there is insufficient data on its interaction with these drugs. As coenzyme Q10 lowers fasting blood glucose in some patients, it should be used cautiously in those with diabetes and patients prone to hypoglycemic episodes ²⁴⁰. Researchers in one study sounded a cautionary note when they found that coadministration of coenzyme Q10 and radiation therapy decreased the effectiveness of the radiation therapy ²⁴¹. In this study, mice inoculated with human small cell lung cancer cells (a xenograft study), and then given coenzyme Q10 and single-dose radiation therapy, showed substantially less inhibition of tumor growth than mice in the control group that were treated with radiation therapy alone ²⁴¹. Since radiation leads to the production of free radicals, and since antioxidants protect against free radical damage, the effect in this study might be explained by coenzyme Q10 acting as an antioxidant.

Coenzyme Q10 is contraindicated in patients with known hypersensitivity reactions to coenzyme Q10 or excipients. Some supplements contain silicon dioxide, which may be responsible for hypersensitivity reactions ²⁴².

Ubiquinone side effects

No serious toxicity associated with the use of coenzyme Q10 has been reported ⁷⁴, ⁷⁵, ²⁴³, ²⁴⁴. Doses of 100 mg/day or higher have caused mild insomnia or digestive upsets in some individuals ⁸². Liver enzyme elevation has been detected in patients taking doses of coenzyme Q10 300 mg/day for extended periods of time, but no liver toxicity has been reported ²⁴⁵. Researchers in one cardiovascular study reported that coenzyme Q10 caused rashes, nausea, and epigastric (upper abdominal) pain that required withdrawal of a small number of patients from the study ²⁴⁶. Other reported side effects have included dizziness, photophobia (abnormal visual sensitivity to light), irritability,[5] headache, heartburn, and fatigue ²⁴⁷.

Reported side effects from the use of Coenzyme-Q10 include the following:

• High levels of liver enzymes.
• Nausea.
• Heartburn.
• Headache.
• Pain in the upper part of the abdomen.
• Dizziness.
• Rashes.
• Unable to fall sleep or stay asleep.
• Feeling very tired.
• Feeling irritable.
• Sensitive to light.

In a prospective study that explored the association between supplement use and breast cancer outcomes (SWOG S0221), the use of any antioxidant supplement before and during treatment–including coenzyme Q10, vitamin A, vitamin C, vitamin E, and carotenoids was associated with a trend showing an increased hazard of recurrence ²⁶.

Certain lipid-lowering drugs, such as the statins (lovastatin, pravastatin, and simvastatin) and gemfibrozil, as well as oral agents that lower blood sugar, such as glyburide and tolazamide, cause a decrease in serum levels of coenzyme Q10 and reduce the effects of coenzyme Q10 supplementation ²⁴⁸, ⁷⁴, ²⁴⁹, ²⁵⁰. Beta-blockers (drugs that slow the heart rate and lower blood pressure) can inhibit coenzyme Q10-dependent enzyme reactions. The contractile force of the heart in patients with high blood pressure can be increased by coenzyme Q10 administration ⁷⁴. Coenzyme Q10 can reduce the body’s response to the anticoagulant drug warfarin ²⁴⁸. Finally, coenzyme Q10 can decrease insulin requirements in individuals with diabetes.

It is important to check with your doctor to find out if coenzyme Q10 can be safely used 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 Coenzyme-Q10. CoQ10 may change the way the body uses warfarin (a drug that prevents the blood from clotting) and insulin.

Coenzyme-Q10 may interact with the anticoagulant (blood thinner) warfarin and the diabetes drug insulin, and it may not be compatible with some types of cancer treatment.

Coenzyme Q10 Overdose

Coenzyme-Q10 toxicity is unlikely up to a daily intake of 1200 mg/day, although typical dosages have been 100 to 200 mg/day ²⁵¹. In preclinical studies, ubiquinol’s No-Observed-Adverse-Effect Level (NOAEL) is 300 to 600 mg/kg (Sprague Dawley rats).

The human supplementation dose of CoQ10 is generally 100 to 300 mg/day. Assuming the human dose is 300 mg/day (5 mg/kg body weight), the safety factor is 60 to -120 times. The study indicated that chronic use of ubiquinol as a dietary supplement in humans is safe ²⁵².

What other drugs will affect Coenzyme Q10?

Do not take Coenzyme Q10 without medical advice if you are using any of the following medications:

• omega-3 fatty acids;
• vitamins (especially A, C, E, or K);
• blood pressure medicine;
• cancer medicine; or
• warfarin (Coumadin, Jantoven). Coenzyme Q10 is chemically similar to vitamin K, and some reports are available in the literature for potential warfarin and coenzyme Q10 interaction. There are chances of warfarin treatment failure when patients are taking coenzyme Q10 supplements with warfarin therapy. This interaction is reversible ²⁵³, ²⁵⁴, ²⁵⁵.

This list is not complete. Other drugs may affect Coenzyme Q10, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Toxicology

A review of animal experiments and clinical trials has estimated an acceptable daily intake for coenzyme Q10 to be 12 mg/kg (ie, 720 mg/day for a 60 kg person) based on a no-observed-adverse-effect level in rats of 1,200 mg/kg/day. An observed safety level based on clinical data is given as 1,200 mg/day. No accumulation in plasma or tissue following cessation of coenzyme Q10 consumption was noted and endogenous biosynthesis was not affected ²⁵⁶.

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