Coenzyme Q10

Last Updated: February 1, 2023

Coenzyme Q10 is a molecule found in mitochondria that has a critical role in producing energy for the body. It also plays an important role in the endogenous antioxidant system.

Coenzyme Q10 is most often used for.



Don't miss out on the latest research

1.

Sources and Structure

1.1

Sources

Coenzyme Q10 (CoQ10) is a pseudovitamin compound (sometimes,[1] but falsely, called Vitamin Q) that is a vital component of cellular energy metabolism; placed within the electron transport chain of the mitochondria to facilitate ATP production (ATP being cellular energy currency, and the ultimate product of fatty acids and glucose being 'used' for energy). CoQ10 is named after its seemingly ubiquitous nature in the body, and differentially named after its reduced form (ubiquinol) and its oxidized form (ubiquinone) which are interchangeable in the body depending on the cell's oxidative state.[2]

CoQ10 is a vitamin-like compounds that is produced in the body for proper functioning of mitochondria, and is also a component of the diet

Food sources of CoQ10 (sometimes both oxidized reduced forms of CoQ10 are measured collectively) include:

Meat (terrestrial):

  • Reindeer meat at 157mg/kg[3]
  • Beef, including heart (113.3mg/kg[3]), liver (39.2–50.5mg/kg[3]) shoulder (40.1mg/kg[4]), sirloin (30.6mg/kg[5]), thigh (30.3mg/kg[4]), tenderloin (26.5mg/kg[5])
  • Pork, including heart (118.1–282mg/kg[3]), liver (22.7–54.0mg/kg[3]) shoulder (45.0mg/kg[4]), sirloin (14.0mg/kg[5]) and thigh (13.8mg/kg[4])
  • Chicken, in the heart (92.3–192mg/kg[6][4][5]), liver (116.2–132.2mg/kg[7]), thigh (24.2–25.0mg/kg[6][4]), breast (7.8–17.1mg/kg[6][4][5]), and wing (11mg/kg[6])

Terrestrial meats are the highest naturally occuring sources of CoQ10 in the diet, with cardiac tissue being the highest source followed by liver meats and then skeletal muscle

Meat (aquatic):

  • Sardines, variable between 5.1–64.3mg/kg[8][9][reference|url=http://www.sciencedirect.com/science/article/pii/S0889157507001755|title=Food content of ubiquinol-10 and ubiquinone-10 in the Japanese diet
  • Yellowtail (12.8–20.7mg/kg[8][4]) and higher (33.4mg/kg[4]) in young fish
  • Herring in heart (120.0–148.4mg/kg[10]) and flesh (14.9–27.0mg/kg[10][11])
  • Baltic herring at 10.6–15.9mg/kg[3][12]
  • Mackerel, 43.3mg/kg in general[8] with higher concentrations in the heart (105.5–109.8mg/kg[10]) and red meat (67.5–67.7mg/kg[10]) with lower content in the white meat (10.6–15.5mg/kg[9][4][10])
  • Horse mackerel, variable as low levels of 3.6-20.7mg/kg[8][9] have been noted yet with one stating 130mg/kg[4]
  • Cuttlefish at 4.7–8.2mg/kg[9][4]
  • Salmon at 4.3–7.6mg/kg[5][11][4]
  • Albacore (Tuna) at 6.2mg/kg[9] and tuna in general at 4.9mg/kg[4] (although canned sources appear to be higher at 14.9-15.9mg/kg[4][3])
  • Pike at 5.4mg/kg[9]
  • Flat fish at 1.8–5.5mg/kg[4]
  • Shrimp at 2.8mg/kg[9]
  • Scallop at 5mg/kg[4]
  • Bogue 3.7mg/kg, Octopus at 3.5mg/kg, Annular sea bream 3.4mg/kg, Common pandora at 3.1mg/kg, European hake at 2.9mg/kg, Bondex murex and Red mullet at 2.6mg/kg, Striped mullet and Red band fish at 2.4mg/kg, Brill at 1.9mg/kg.[9]
  • Common mussel at 9.5mg/kg[9]
  • Grooved carpet shell at 6.6mg/kg[9]

CoQ10 levels are also high in aquatic meats, with the same trend of heart tissue being a high source (with cardiac tissue from fish being comparable to cardiac tissue from terrestrial animals); the amount of CoQ10 in the meat of the fish is comparatively lower than seen with terrestrial meats

Dairy and Eggs:

  • Butter at 7.1mg/kg[8]
  • Cheeses (in general, 1.4-2.1mg/kg[8][6]) including Emmental (1.3mg/kg[3]), Edam (1.2mg/kg[3])
  • Cow milk at 0.5-1.9mg/kg, with a trend for lower levels in UHT milk and lower fat products[3][13]
  • Yogurt, kefir, cream, and curd at 0.3-1.2mg/kg, highly (positively) correlated with fat content[13]
  • Eggs at 0.7-3.7mg/kg[6][8] with the yolk being up to 5.2mg/kg[6]

Dairy and eggs are somewhat decent sources, but relative to meat products they are much less substantial sources of CoQ10

Collectively, nuts and legumes tend to be moderate sources (the highest being peanuts at 26.7mg/kg and sesame at 17.6–23.0mg/kg) while their processed oils may also be decent sources (highest being extra virgin olive oil at 114–160mg/kg, corn oil at 13-139mg/kg, and soybean oil at 53.8-279mg/kg).[6] Vegetables are inhernetly lesser in quantity, with the best sources being parsley (7.5–26.4mg/kg), soybeans (6.8–19.0mg/kg), perilla leaves (2.1–10.2mg/kg), and broccoli (5.9–8.6mg/kg).[6]

Grains seem somewhat comparable to vegetable sources (being much lower than meats) although they appear to mostly only possess a CoQ9 content with nearly undetectable CoQ10 levels.[6]

CoQ10 appears to be somewhat (14–32%) destroyed by frying with boiling not significantly influencing CoQ10 content of foods.[14] It appears to be a bit more heat resistant than some other food-based compounds (such as Vitamin E or Sulforaphane, which are readily destroyed in cooking).

Nuts and oils are the highest plant sources of CoQ10 (although they are only decent sources when consumed in excessive amounts which is not practical) with vegetables being fairly poor sources of CoQ10. Grains are also a seemingly poor source of CoQ10

CoQ10 can be extracted from biological tissues of food sources (despite being expensive to produce en masse)[15] but can also be produced in a laboratory setting using bacteria[2][16] or outright synthesized.[17] Microbial fermentation appears to be desirable due to less solvent usage and being cheaper to produce on a large scale[18][19] and the bacteria Agrobacterium tumefaciens being commonly used due to good synthesis rates.[2][16][20][21][22]

CoQ10 can be extracted from living tissue (expensive) although more commonly the CoQ10 is synthesized by bacteria, making CoQ10 supplements usually vegan (important due to interactions of CoQ10 and veganism, as most food sources are derived from animal tissue)

1.2

Structure and Properties

Coenzyme Q10 belongs to a class of molecules characterized by their benzoquinone ring structure at the end of an isoprenoid side chain, similar to a medieval flail. The length of the sidechain determines the designation of the coenzyme, with CoQ10 possessing ten isoprenoid units in its tail.[23]

image

In its reduced form (ubiquinol) it can sequester some free radicals directly (an antioxidant effect) via conversion to its oxidized form (ubiquinone); a mechanism that is used to donate electrons through the electron transport chain to make ATP. Despite being in an oxidized form, ubiquinone still appears to be an antioxidant.[24]

1.3

Biosynthesis and Regulation

Coenzyme Q10 (henceforth CoQ10) primarily exists and is synthesized in the body for the purpose of being integrated into the Electron Transport Chain (ETC); one of the final stages in cellular energy production.[25][26] The mechanism by which it acts is by a shuttle between segments of the ETC, in which electrons and protons are attracted to the benzoquinone head and the isoprenoid tail 'swings' the head from one segment to the next. Being a component of the cell's membrance (the lipid bilayer), CoQ10 is lipophilic or fat-soluble and should be supplemented with some form of dietary fat or lipophilic transport.[27]

CoQ10 is endogenously produced by 4-hydroxybenzoic acid (produced from L-tyrosine)[1][28] with this intermediate combining with polyprenyl pyrophosphate (produced from farsenyl pyrophosphate (FPP) of the mevalonate pathway[29]) via the enzyme polyprenyl 4-hydroxybenzoic acid transferase into the molecule 4-hydroxypolyprenyl benzoic acid, which is then converted into CoQ10.[30] Synthesis is somewhat impaired by statins as the inhibition of HMG-CoA reduced the free FPP pool, and CoQ10 synthesis rates appear to be somewhat dependent on the FPP pool (increasing this pool via inhibiting alternate pathays has been noted to increase CoQ10 synthesis[31][32]).

The total body stores of CoQ10 are approximately 2g in an otherwise healthy adult and require 500mg of CoQ10 to be replaced daily (combination of endogenous synthesis and dietary intake)[33][34] with an approximately 4 day turnover rate.[35] The suggested daily exogenous intake (from the diet) ranges from 30–100mg in otherwise healthy persons but can be increased to 60–1200mg in some medical conditions such as statin usage.[36][37] When assessing average dietary intake, however, the average intake appears to be around 3-6mg per day (european and asian data) due to the highest sources of cardiac meat and liver not commonly being ingested.[6][14][4][3]

At least one study in rats administering oral CoQ10 assessed whether endogenous production was hindered (via mevalonate injections and subsequent CoQ9 production, as rats produce CoQ9 rather than CoQ10 via a similar pathway) failed to note any suppression after 4 days of supplementation.[38]

1.4

Tissue and Subcellular Distribution

Typically, tissues with higher metabolic activity in the body (heart, brain, kidneys, liver, skeletal muscle) have higher levels of CoQ10 relative to other areas of the body and are typically where most supplemental benefits are seen.[23]

Approximately 14.5% of CoQ10 is located in the cell's cytosol or organelles within the cytosol whereas 41% is located in the mitochondria, with a relativly large portion (37.5%) in the cell nucleus (the final 7% being detected in supernatant)[39] and mostly on the inner mitochondrial membrane.[40] CoQ10 has been found not to correlate well with the lipid disposition of a cell (conversely, VItamin E is known to be highly correlated)[41] and some detectable CoQ10 is found in specific organelles including lysosomes (120pmol/mg), golgi apparati (92pmol/mg), peroxisomes (13pmol/mg) as well as being free in the cytosol (11pmol/mg) or found in the plasma membrane (27pmol/mg); this particular data being derived from rats (known to have more CoQ9 relative to CoQ10, thus may not be the same in humans).[42]

CoQ10, in the cell, appears to be highly localized in the mitochondria although it is not uniquely located in this organelle. Some CoQ10 can be detected in the cytoplasm as well as the nucleus

1.5

Deficiency States

Note: CoQ10 'deficiency' is currently not legitimate terminology. The following states are those which are highly correlated with a lower serum and/or cellular level of CoQ10 when compared to an average an otherwise healthy population

Frequent smokers may be insufficient in CoQ10.[43]

When in circulation, 95% of CoQ10 is in the reduced form (ubiquinol).[23]

2.

Pharmacology

2.1

Gastric and Intestinal

After oral ingestion, supplemental CoQ10 passes the stomach relatively unaffected (whereby CoQ10 from food products experiences enhanced bioavailability due to the denaturation of the protein containing products it exists in).[23]

Similar to other lipophilic nutrients, CoQ10 is taken up into the lymphatic system alongside fat absorption contained in chylomicrons. There is no specific transport identified for CoQ10 in the human or rat intestines.[44] Somewhere before or during packaging into chylomicrons, CoQ10 (ubiquinone) seems to be reduced to its anti-oxidative substrate, ubiquinol as is assessed in in vitro human cells.[45]

2.2

Serum

CoQ10 can appear in serum fairly rapidly following oral ingestion[40][46][38] where single dose administration appears to have a half-life between 5.80-8.10 hours and a (corrected as to exclude basal levels) Cmax of 1.16-1.47μmol/L and an AUC of 44.94-64.01μmol/h/L (180mg liquid based CoQ10 dosing).[47]

Following chronic supplementation, the basal level of approximately 1.1μmol/L in otherwise healthy adults[48] has been noted to be increased with oil based supplements by 0.524μmol/L (100mg),[49] 0.530μmol/L (300mg, but 1 week in length),[50] 1.008μmol/L (120mg),[51] 1.200μmol/L (90mg),[52] 1.214μmol/L (90mg),[53] and 1,900μmol/L (90mg)[54] and with no significant differences observed between time frames (ranging from two weeks to nine months). Powder based supplements increase serum levels to a similar degree by 0.568μmol/L (100mg),[55] 1.124μmol/L (100mg, sustained release),[55] 1.309μmol/L (120mg),[51] and 1.810μmol/L (90mg)[54] while the one study on solubilized CoQ10 (120mg) noted a serum increase of 3.255μmol/L (120mg)[51] while a 1 week trial using an emulsion failed to note any significant improvement over standard oil based supplements (0.500μmol/L with emulsion and 0.530μmol/L with oil with both at 300mg).[50]

This solubilized version of CoQ10 (of which PureSorb-Q40 is a brand name) is a water soluble version of CoQ10 with an average particle size of 0.19µm when dispersed in water,[56] has been confirmed to have a similarly enhanced bioavailability relative to oil based supplements,[57] and appears to exert a similar safety profile to other forms of CoQ10 (no side effects at 2000mg/kg in rats[58] nor at 2250mg daily in humans[56]).

Orally ingested CoQ10 levels can increase serum concentrations of CoQ10, with repeated daily dosing able to increase serum CoQ10 concentrations in the range of a 50-150% increase with 90-120mg. There is a degree of unreliability in the spike observed with CoQ10 supplementation in serum, and although there does not appear to be any clear differences in powdered and oil-based supplementation (usually advised to be taken with a meal) there is some evidence a solubilized version may increase serum levels to a higher degree.

In serum CoQ10 exists as part of the chylomicron it was absorbed from (able to exert some antioxidant properties on its carrier[59][60]) and, after deposition in the liver, is carried via lipoproteins such as LDL-C or HDL-C.[23] The vast majority (96%) of CoQ10 at this stage is in the reduced form of ubiquinol[48]

2.3

Distribution and Tissue Concentrations

CoQ10 appears in serum fairly rapidly after oral administration[40][46][38] (although acute doses are somewhat unreliable[54][61]) and can be detected in skeletal muscle, the brain, kidneys, and the heart following prolonged (14wk) supplementation.[62][63][64] Specifics of tissue concentration and transport can be found in the respective subsection, although in general the heart has the greatest concentration of CoQ10 followed by skeletal muscle, the liver and kidneys (similar concentrations at 63.6 and 77nmol/g, respectively) and then with lower concentrations in the intestines (13.3nmol/g), lungs (9.2nmol/g), and brain (15.5nmol/g).[23]

Concentrations in tissues (excluding the liver and spleen) are seen with chronic rather than acute loading, with acute loading not significant raising tissue concentrations of CoQ10.[65][66][67]

2.4

Excretion and Clearance

When measuring red blood cells, CoQ10 levels return to baseline after 12 weeks of supplementation.[68]

2.5

Phase I Enzyme Interactions

An in vitro assay in rat microsomes found that the activity of cytochrome enzymes 1A1 and 1A2 were not affected by CoQ10 at concentrations up to 30µg/mL.[69]

2.6

Known Drug Interactions

CoQ10 has been seen to interact in vitro with P-glycoprotein, a key transporter of xenobiotics which pumps them out of cells, at a concentration of 10µM; this opens up the possibility of drug interactions between CoQ10 and drugs which are transported by P-glycoprotein.[70]

In vitro studies have indicated that CoQ10 activates hydroxylation of both enantiomers of warfarin in human and rat microsomes,[71] an effect that has been seen to reduce the efficacy of warfarin in thinning the blood in rats.[72] as well as in human case reports,[73]|published=1998 May 25|authors=Landbo C1, Almdal TP|journal=Ugeskr Laeger][74] which was explained by one author as possibly being caused by the structural similarities of vitamin K and CoQ10.[74] An observational study of patients being prescribed warfarin found that intake of CoQ10 was significantly associated with an increased risk of self-reported bleeding (odds ratio 3.69, 95% confidence interval 1.88-7.24).[75] However, a double-blind, placebo-controlled crossover study using 100mg CoQ10 on middle-aged outpatients on stabilized warfarin treatment found no statistically significant difference in INR between the CoQ10 group and placebo.[76]

A rat study using a single dose of theophylline (a drug used for asthma and COPD) has indicated that CoQ10 may interact with this drug; after giving the rats varying doses of 300-1200mg/kg of CoQ10 for five consecutive days before administring theophylline, Cmax was raised by 2-3 times that of control, and the AUC of theohylline was approximately doubled, while the tmax increased from 0.5 hours to 2 hours (or 3 hours in the case of the highest dose) and the half-life decreasing by over an hour.[69] The reasons for this change were unclear, as serum protein binding of theophylline and the activity of cytochrome enzymes 1A1 and 1A2 were not affected with concentrations up to 30µg/mL.[69]

Theoretical drug interactions with CoQ10 exist due to its interaction with P-glycoprotein. There is mixed clincial evidence that CoQ10 can also interact with warfarin, and animal studies suggest that it could also interact with theophylline.

3.

Longevity and Mitochondrial Interactions

3.1

Mechanisms

When looking at calorie-restricted mice (one of the only currently reliable manners of life extension), an increase in both CoQ9 and CoQ10 is detected in skeletal muscle and a decrease in Q9 (no effect on Q10) detected in cardiac tissue relative to normal-fed mice,[77] an increase in skeletal muscle has been noted elsewhere[78][79] as well as an increase in kidney CoQ9/Q10[80] although for both cardiac tissue and the liver there is contrasting results.[77][81]

One study noting that statin drugs were able to increase the lifespan of drosophilia noted that this effect was independent of ubiquinone status.[82]

CoQ10 appears to be altered in calorically restricted mice, but it is possible this is merely a biomarker for something else associated with longevity

3.2

Interventions

In nematodes (Caenorhabditis elegans), dietary exclusion of all CoQ10 increases lifespan by around 59%[83] and ablating biosynthesis to reduce levels similarly increases lifespan[84] and clk-1 mutants (who cannot synthesis CoQ9) see a similar increase in lifespan.[85] The dietary exclusion study is somewhat contested, as another study found that life extension properties were due to bacterial metabolism alterations and not dietary CoQ10.[86]

Supplementation of 93mg/kg or 371mg/kg CoQ10 to mice (human estimates for a 150lb person being 507mg and 2,023mg) from 3.5 months of age until their deaths failed to significantly increase lifespan and similarly failed to increase the levels of any antioxidant enzymes (glutathione, catalase, and superoxide dismutase).[87] This lack of effect on lifespan has been noted with lower supplemental dosages in rats[88] and mice.[88][89]

There is currently no convincing evidence that supplemental CoQ10 enhanced the lifespan, with some limited evidence that absolute deprivation enhances lifespan (contested and not yet conducted in mammals)

4.

Neurology

4.1

Distribution

Before supplementation, CoQ10 (as ubiquinol) is located in all tested brain regions with highest concentrations in the cerebral cortex, followed by the hippocampus and striatum (fairly equal) and then progressively less are noted in the midbrain-diencephalon, cerebellum, and brainstem; similar trends are seen with ubiquinone although the striatum and midbrain were lowest while the cortex was equal to the hippocampus and striatum.[90]

Oral CoQ10 at 200mg/kg in rats for 2 months is able to increase brain CoQ10 content in young (12 month) rats (approximately 30% from baseline) and increase CoQ10 levels in aged (24 month) rats to a similar level seen in young rats given CoQ10, and both CoQ9 and Vitamin E also appeared to be increased.[64] An increase in 22% has been noted in another study in the cortex, with no significant influence was found in any other brain region tested (hippocampus, striatum, midbrain-diencephalon, cerebellum, or brainstem) following lifetime ingestion of 0.72mg/g or 2.81mg/g in mice.[90]

An increase in cerebral CoQ10 concentrations are noted in animals given CoQ10 supplementation over a prolonged period of time (no human studies at the moment, due to complications in detecting CoQ10 supplementation in a living person) and the increase is lesser than that of other organs and serum

4.2

Cognition

One study using CoQ10 at a low and high dose (0.72mg/g or 2.81mg/g) in young mice for up to 21 months (lifetime study) noted that high CoQ10 increased physical activity in old age (independent of motor control testing, which was similar between groups) but was associated with reduced spatial memory performance and sensory acuity in older age;[90] the overall dosing was approximately 106mg/kg and 352mg/kg respectively,[90] and estimated human equivalent doses are 8.5mg/kg and 28mg/kg respectively (for a 150lb person, 580mg and 1,909mg daily) based on standard conversion factors.[91] These doses are similar to those seen in another study using lifetime administration of CoQ10 that failed to note any influence on antioxidant enzyme status or lifespan (cognition not measured)[87] and in a study where cognition in older mice was improved, but CoQ10 therapy was 12 weeks in duration and started in older age.[92]

Limited animal evidence to assess lifetime usage of CoQ10, but there does not appear to be any significant influences with standard or slightly elevated doses of CoQ10 although higher doses have been associated with a worsening cognitive profile during aging yet protective when started during advanced age

4.3

Parkinson's Disease

A study feeding rats 1% of the feed as CoQ10 before MPTP injections (toxin that mimics Parkinson's disease[93]) noted that 2 weeks of feeding was able to preserve some dopaminergic function, reducing the loss in dopamine to 26% (control toxin reduced dopamine 56%) which was slightly more protective than creatine although their benefits were additive.[94]

4.4

Huntington's Disease

200mg/kg CoQ10 to rats for 2 months prior to an injection of 3-nitropropionic acid (neurotoxin which creates toxicity similar to that seen in Huntington's Disease) was able to almost absolutely reduce lesion size relative to control (from 19mm3 to 1mm3)[64] although another study noted the protective effect of 1% of the rat feed as CoQ10 reduced lesion size to 62% of control (insignificantly underperforming 2% creatine, which reduced lesion size to 53%[94]). 3-NP is a mitochondrial toxin[95][96] and CoQ10 is thought to exert protective effects at the level of mitochondrial modification; which may extend to L-Carnitine[97] and Creatine supplementation[98] where CoQ10 and creatine appear to be additively neuroprotective.[98][94]

CoQ10 has neuroprotective effects against the 3-nitropropionic acid toxin, an animal model of Huntington's disease. This protective effect is somewhat comparable to creatine supplementation

4.5

Depression

Depression appears to be a state that is highly correlated with increased oxidative and nitrosylative stress[99] and CoQ10 concentrations in serum appear to be reduced in people with treatment resistant depression.[100]

One study using injections of CoQ10 in rats (25-150mg/kg) for 3 weeks in rats with chronic stress induced depression was able to exert anti-depressive effects with a plateau at 100mg/kg, the potency being about 50% normalization (relative to nondepressed control) on immobility and swim time in a forced swim test;[101] this was related to reductions in serum corticosterone and reduced hippocampal oxidative stress.[101]

Other evidence suggest that in geriatric bipolar disorder there is less depressive symptoms associated with CoQ10 supplementation (400mg daily for 2 weeks, then up to 800mg and 1200mg daily).[102]

It is possible that CoQ10 supplementation could alleviate depression, and there are reduced CoQ10 levels in depressed persons and some preliminary evidence suggests therapeutic effects. That being said, the evidence is not robust at this moment in time and uses quite high doses of CoQ10

4.6

Migraine

CoQ10 at 150mg daily has shown some efficacy in an open-label trial in persons with episodic headaches[103] which has been replicated elsewhere against placebo.[104] The open label trial experienced a rather large reduction in symptoms (61.3% of subjects reporting over a halving of symptoms, and the average of 7.34 migraine days being reduced to 2.95 days)[103] with the rate of persons experiencing a halving of symptoms with 300mg under blinded conditions being 47.6% (placebo at 14.4%) with time-dependent reductions over 4 months.[104]

In a study assessing the effects of 100mg CoQ10 in youth (6-17 years of age) for 224 days in children with a high frequency (14.3 per month) and severity (6.3-6.4 on a 1-10 scale) of headaches, the CoQ10 group experienced less overall headaches than did placebo for the first 4 weeks of the trial with the difference no longer existing near the end of the trial.[105] There was no influence on migraine frequency.[105]

May have some migraine and headache reducing effects, which has been noted twice under blinded conditions to be more effective than placebo (one for migraine frequency, the other for headache frequency)

5.

Cardiovascular Health

5.1

Cardiac Tissue (Myocardium)

Human cardiac tissue has a CoQ10 concentration of approximately 132nmol/g (with 61% of CoQ10 being in the reduced form of ubiquinone)[60] which is similar to other animals with cardiac tissue being the highest body store of CoQ10 (hence cardiac tissue being the richest dietary source). Perhaps most interestingly, supplemental CoQ10 has been confirmed to increase cardiac tissue levels and cardiac mitochondrial levels of CoQ10 (surgical biopsy of cardiac tissue in humans)[106] and in pathological changes of cardiac tissue the levels of CoQ10 in the heart appear to be progressively reduced (with class III and IV having lower levels than class I and II[107]) which again is somewhat normalized with CoQ10 supplementation.[107][108]

CoQ10 is present in cardiac tissue, and similar to other animals this is the organ in the human body with the highest CoQ10 concentration. Supplemental CoQ10 has been confirmed to reach cardiac tissue following oral intake

CoQ10 supplementation can reduce damage to the heart from the anti-cancer pharmaceutical class of compounds called anthracyclines (doxorubicin and daunorubicin).[109] CoQ10 does not appear to interfere with the cytotoxicity of doxorubicin in breast cancer cells[110] nor its pharmacokinetic profile.[111] Interesting, this protective effect may extend to other organs such as the kidneys[112] and in general enhance survival times.[113]

It should be noted that this may not be a CoQ10 relative deficiency state (higher circulating[114] and cellular[115] levels of CoQ10 may actually occur).

CoQ10 may help with doxorubicin-induced cardiomyopathy, which would be of interest to chemotherapy as CoQ10 may not interfere with the efficacy of doxorubicin in destroying cancer cells. Requires some human intervention data though

CoQ10 is known to be an independent risk factor for the disease progression of coronary heart disease,[116] lower in ethnic groups that have higher cardiovascular disease rates,[117] and due to its interactions at the level of the cardiac tissue (and ability to reduce myocardial remodelling following injury in rats[118]) supplementation is thought to be protective.[119][120]

Over the short term, 28 days of CoQ10 supplementation in persons with acute myocardial infarction is associated with better left ventricle function and reduced angina pectoris and arrythmia than placebo[121] and prolonged usage of CoQ10 by persons who suffered myocardial infarction (120mg) was associated with lower amounts of cardiac incidents with CoQ10 (25.3% of persons experiencing a cardiac incident) outperforming placebo (45%; B-vitamin complex).[122]

A study in congestive heart failure was unable to find benefit to left ventricle function[123] which has also been failed to occur in diabetics[124] and 4 months of CoQ10 treatment at 100mg in persons with idiopathic dilated cardiomyopathy failed to show any significant difference relative to placebo on blood or cardiac measurements.[125] One study that noted some cardiac benefit during exercise similarly failed to find a benefit to left ventricle ejection fraction at rest in persons with congestive heart failure.[126]

May have benefit after myocardial infarction, but myocardial infarction may be the only heart condition in which CoQ10 is beneficial. CoQ10 supplementation has failed in other instances of cardiac ailment (congestive heart failure, diabetic cardiomyopathy) to exert any benefit

One study has investigated the role of CoQ10 in isolated diastolic heart failure secondary to cardiohypertrophy,[127] and 200mg CoQ10 daily appeared to reduce left ventricle thickness and improve function as well as quality of life.

May be of use in cardiomegaly, but limited evidence

One of the longest randomized controlled trial to date found that daily supplementation with 200 mg of CoQ10 plus 200 mcg of selenium significantly reduced cardiovascular mortality compared to placebo (5.9% vs 12.6%) in 443 Swedish citizens aged 70-88 years after a 5-year follow-up.[128] The supplement group had a 55% reduced risk of dying from cardiovascular disease compared to placebo.

5.2

Blood Pressure

Mechanistically, it is though that CoQ10 might reduce blood pressure secondary to antioxidative effects. An increase in extracellular superoxide dismutase (SOD) activity has been noted with CoQ10 supplementation for one month at 300mg,[129] and extracellular superoxide dismutase (highly localized to the endothelium[130] and reduced in persons with coronary artery disease[131]) is known to preserve the activity of nitric oxide,[132][133] a vasodilating and blood pressure reducing agent.

The above mechanisms are currently thought to underlie the improvement in endothelial function and blood flow observed in type II diabetics with[134] or without[135] statin therapy, ischemic heart disease patients,[136] and in otherwise healthy obese individuals.[137] This protective effect on blood flow appears to have also been found in a meta-analysis on the topic,[138] where flow-mediated vasodilation just reached statistical significance (no significant effect on nitrate-mediated arterial dilation).

CoQ10 may increase blood flow in persons with otherwise hindered blood flow secondary to acting as an anti-oxidant, which is thought to preserve the actions of nitric oxide on the endothelium

A meta-analysis of trials investigating CoQ10 and blood pressure (assessing double blind trials of more than 3 weeks in length)[139] was able to assess three trials noted a slight decrease in blood pressure in hypertensives (11mmHg and 7mmHg systolic and diastolic) but made note that the observed results were unreliable.[139] Other trials published after this meta-analysis (Oct '09) are one study in persons with high blood pressure and metabolic syndrome given 100mg CoQ10 daily for 12 weeks (failed to influence 24 hour blood pressure, but trended to reduce diastolic overall and reduced daytime diastolic[140])

CoQ10 has been implicated in being in a formulation known as 'Orthospiron' (alongside policosanol, red yeast rice, berberine, and folic acid) which has shown efficacy in reducing 24 hour ambulatory blood pressure in hypertensives.[141]

5.3

Lipoproteins

A 12% increase in HDL-C has been noted in persons who suffered myocardial infarction given 120mg CoQ10 for a year relative to control (B-vitamin complex)[122]

Studies assessing the interaction of CoQ10 and HDL-C note that when pairing statin usage (atorvastatin) against stain plus CoQ10 (100mg) combination therapy, that CoQ10 is associated with an 11.1% improvement in HDL-C relative to statin usage in isolation over 12 weeks.[142]

CoQ10 ingestion does not interfere with the LDL-C and total cholesterol reducing effects of statin drug usage.[142][122]

CoQ10 may have a small effect on increasing HDL cholesterol, but the body of evidence to support this is fairly minimal

CoQ10 is also known to exist on the lipoproteins themselves as a constituent and protects the lipoprotein form oxidation to a greater level than that of Vitamin E at their biological concentrations.[143] Due to this, CoQ10 is thought to be a biomarker of sorts for endothelial oxidative stress[144][145] and possible artherosclerosis.[146]

Can reduce the rate of which low density lipoproteins are oxidized (in which case LDL turns into the artherogenic oLDL) secondary to direct free radical scavenging

CoQ10 has been noted to suppress the inflammatory effects of oxidized LDL cholesterol (oLDL)[147] and reduces subsequent endothelial injuries from oLDL with an ED50 of 4.2μM (130μg/mL for 24 hours).[148] The mechanism appears to be related to inhibiting the increase in NF-kB activation (a proinflammatory effect) secondary to the increase in reactive oxygen species that occurs when oLDL acts upon endothelial cells[147][148] which is thought to be from either preserving nitric oxide function (NO can suppress NF-kB activity when at higher concentrations[149]). Incubation with nitric oxide inhibitors was able to partially block the protective effects of CoQ10.[148]

CoQ10 may have direct inhibitory effects on NF-kB independent of NO (alterations in JAK/STAT signalling),[150] which may explain the portion of protective effects not abolished by nitric oxide inhibitors.[148]

If LDL cholesterol is already oxidized, it is possible that CoQ10 can protect the endothelium from being damaged by oxidized LDL

Supplementation of CoQ10 in persons with coronary artery disease at either 60mg or 150mg daily for 12 weeks was able to significantly increase circulating CoQ10 concentrations in serum and expression of some antioxidant enzymes (catalase and SOD) while decreasing MDA levels (a biomarker of lipid peroxidaiton).[151] An increase in SOD has been noted elsewhere with 300mg CoQ10 in persosn with ischemic heart disease[129] and plasma antioxidant capacity has been noted to be increased in general with 120mg daily.[121][152]

6.

Interactions with Glucose Metabolism

6.1

Insulin

In a small sample of otherwise healthy persons, 12 weeks supplementation of 200mg CoQ10 (as ubiquinol) was noted to increase the insulin:proinsulin ratio and to augment meal-induced insulin release[153] which was hypothesized to be secodnary to aiding pancreatic b-cell function (it has elsewhere[154] been hypothesized CoQ10 can aid in ATP supply of pancreatic b-cells)

6.2

Diabetes

CoQ10 supplementation at 200mg for 12 weeks has been twice noted to reduce circulating HbA1c concentrations,[153][155] while these two studies and two more[156][157] seem to indicate that supplemental CoQ10 has no significant influence on circulating glucose or insulin (two main biomarkers of diabetes). In general, this lack of support for reducing blood glucose with CoQ10 supplementation results in it not being recommended for diabetes prevention.[158]

HbA1c is a biomarker for oxidative stress in diabetics, and is linked to pathological worsening of diabetes related to artherosclerosis (via oxidation of LDL and inflammation) and to AGE production (summary can be read on our benfotiamine page).[159]

At least in animal studies, CoQ10 supplementation has been shown to reduce the pathological progression or occurrence of diabetic kidney disease,[160][161][162] cardiac and blood vessel complications,[134][163] and neuropathy.[164][165]

CoQ10 has shown some protective effects on diabetes via HbA1c (although the reduction is quite small and likely not clinically significant) and has no apparent effect on blood glucose or insulin. Although it is technically protective, the degree or protection is fairly minor and CoQ10 may not be an effective diabetic intervention

7.

Exercise Performance and Skeletal Muscle

7.1

Pharmacology and Tissue deposition

CoQ10 is known to reach skeletal muscle tissue following chronic (but not acute[40]) dietary intake, which applies to all species and underlies why the meat of animals (contractile tissue) is the second best source of dietary CoQ10 and second only to cardiac tissue.[35][23] The average concentration of CoQ10 in skeletal muscle appears to be in the wide range of 140–580pmol/mg (140-580nmol/g) with an average value of 241nmol/g[166] which has been reported elsewhere with similar results[167] although at one time being lower (46nmol/g).[60]

The skeletal muscle levels appear to correlate quite well with levels in immune cells (mononuclear cells) and not with serum,[166] and the state of CoQ10 in skeletal muscle cells is approximately 65% being ubiquinone.[60] Muscle concentrations of CoQ10 are positively correlated with muscle oxidative capacity during a simulated marathon (not correlated with lacate dehydrogenase)[168] and appears to be correalted with aerobic exercise performance.[168]

CoQ10 is present in skeletal muscle tissue of all animals, including humans, where it exerts its standard mechanisms of facilitating mitochondrial function and participating in REDOX reactions (antioxidant and oxidant exchanges)

7.2

Mechanisms

Being being a component of the mitochondrial membrane, incubation of skeletal muscle cells with 100μmol/L of CoQ10 (and 250μmol/L Alpha-Lipoic Acid) is able to induce PGC1α levels by 70% (relative to control) and was subsequently found to induce PPARγ activity (50%) to a lesser degree than the active control of rosiglitazone (1μmol/L) and an increase in antioxidant enzyme levels (γGCS, GSR, GST, Nrf2).[169]

PGC1α is a mitochondrial biogenesis factor that is associated with type I (oxidative) muscle fibers thought to be due to producing more mitochondria, and overexpression of PGC1α in mammals reduces muscular fatigue rates.[170][171] PGC1α is known to decline during aging[172] and be activated by exercise,[173] and as such is a current focus point for attenuating age-related muscular function.

7.3

Muscle Fiber Composition

In a few species, it has been noted that muscle fibers with a higher oxidative capacity (rather than glycolytic) have a relatively higher concentration of CoQ10.[174]

When comparing CoQ10 deficient children against those with normal CoQ10 status, it appears that deficiency is associated with greatly (5.5-fold) increased type 2C muscle fiber content (which may be a useful biomarker for CoQ10 related mitochondrial disorders).[175]

7.4

Power Output

200mg CoQ10 supplementation for 6 weeks in older athletes concurrently taking statin drugs has noted an increase in leg strength as assessed by leg extensions.[176] When youth are given either a single dose of CoQ10 (200mg) prior to exercise or 2 weeks supplementation thereof (50 reps of isokinetic knee extensions), there is no apparent effect on muscular force production of muscular fatigue.[177]

Has been noted to increase power output in older adults on statin therapy, but has failed to produce any effect in youth given CoQ10

7.5

Cardiovascular Exercise

CoQ10 supplementation has failed to increase cardiovascular exercise performance (usually intermittent sprint cycling or VO2 max tests) when ingested at 90mg for 8 weeks in trained men,[178] 300mg for 4 weeks in trained persons,[179] 150mg with or without Vitamin E for 4 weeks in otherwise healthy sedentary men,[180]

Some trials report positive results with 100mg supplementation for 8 weeks in otherwise healthy trained men subject to a Wingate test, where the improvement in performance appeared to be independent of the fatigue reduction (fatigue reduced in both CoQ10 and placebo, although CoQ10 only increased power output).[181] Another trial has used a Wingate test and failed to find benefit with 200mg CoQ10 over placebo.[177]

This failure to increase cardiovascular exercise performance is associated with an increase in antioxidative capacity of the blood and reduced lipid peroxidation, however.[178][182]

Despite evidence in mice suggesting CoQ10 supplementation can reverse statin-induced exercise capacity losses,[183] 200mg CoQ10 supplementation for 6 weeks in older athletes concurrently taking statin drugs has failed to find a significant improvement in anaerobic cardiovascular exercise performance (although this study noted an increase in power output).[176]

In prolonged exercise (210 minutes) where fatigue is noted to be reduced, 300mg CoQ10 was associated with a preservation of power in the last few minutes of the test relative to placebo without influencing overall work conducted.[184]

Despite reducing exercise-induced oxidation, there is no convincing evidence of a benefit of CoQ10 supplementation to cardiovascular exercise performance where fatigue is not a factor. There may be a small benefit when it comes to prolonged exercise where fatigue starts to degrade performance

8.

Interactions with Oxidation

8.1

Mechanisms

The reduced form of CoQ10 (Ubiquinone) is called Ubiquinol, this is the form of CoQ10 supplementation that posesses most anti-oxidative properties.[193] Ubiquinone and ubiquinol form a pair of molecules known as a REDOX couplet (reduction-oxidation)[194] which is a property that is crucial for the functioning of CoQ10 within the electron transport chain, where it transports electrons from complex I and II to complex III.[195][196]

CoQ10 also has the ability to prevent lipid peroxidation from either inhibiting lipid peroxyl radicals[197][196][198] and has been noted to restore Vitamin E (α-tocopherol) from its radical state back to its antioxidative state.[198] Protein carbonylation has also been noted to be reduced with CoQ10 (direct inhibition of protein oxidation)[199] but has been noted to not influence the conversion of nitric oxide into peroxynitrate.[200]

Via its anti-oxidant potential, ubiquinone can protect DNA from excess oxidation from H2O2 and potentially act as an anti-carcinogen (as noted in human lymphocytes at least).[201]

CoQ10, via acting as a REDOX couplet, can act as a sacrificial antioxidant molecules and directly sequester free radicals. It shows efficacy against hydrogen peroxide, protein carbonylation, and lipid peroxidation but does not appear effective against peroxynitrate formation

CoQ10 has been once noted to induce activity of Nrf2 (a nuclear protein that regulates the antioxidant response element[202] and induces the activity of antioxidant enzymes[203][204]) at 10-30mg/kg oral intake,[205] where a single oral dose induced expression of Nrf2 in the liver of mice in a dose-dependent manner (40% and 60% increase, respectively) and increased expression of glutamate-cysteine ligase, glutathione S-transferase, and quinone oxidoreductase.[205] This increase in Nrf2 has been noted in skeletal muscle cells in a study using both CoQ10 and Alpha-lipoic acid (somewhat confounded as ALA may activate Nrf2).

It is possible that CoQ10 supplementation may also induce the activity of anti-oxidant enzymes, providing an indirect antioxidative effect; this is not as well researched as the REDOX actions

9.

Longevity and Life Extension

9.1

Rationale

CoQ10 may be altered during the aging process, as the REDOX ratio of ubiquinone (oxidized form) to ubiquinol (reduced form) has been noted to be increased during aging.[206] This conclusion was reached due to an increase in plasma CoQ10 increased from youth (20-39; 17.9+/-6.3nM) towards middle age (40-59; 21.5+/-7.3nM) and again towards an elderly age (60+; 31.8+/-15.5nM) despite no change in ubiquinol concentrations.[206]

10.

Interactions with Aesthetics

10.1

Skin

In aging skin, oxidation may be secondary to impairments in mitochondrial respiration[207][208] (with the other possible source of oxidation beign UV radiation[209]) which is known to influence other factors in a cell such as proteins (transporters and enzymes), DNA and RNA, and possible alterations in the function of the aforementioned.[210][211][212][213] The epidermis appears to have 10-fold the concentration of CoQ10 relative to the dermis (outer layer and inner layer of the skin, respectively)[214] suggesting relevance to protection from external factors as well as internal (as UV radiation influences the epidermis to a larger degree).[215]

CoQ10 is thought to be protective of the skin secondary to being a mitochondrial factor and combination antioxidant, and is thought to be relevant to aging as skin concentrations of CoQ10 decline throughout the aging process (and with excessive exposure to UV radiation)[216] and persons with select disease states (Parkinson's[217] and Huntington's[218]) have lower activity of complex IV of the mitochondria despite similar CoQ10 levels, although those with fibromyalgia may have lower.[219]

Aging skin (biopsy taken from older subjects) also tends to show signs of higher glycolytic levels (trend to increased glucose uptake and significantly more lactate production independent of changes in GLUT1) without a significant alteration in mitochondrial distribution or content and may be more susceptible to UV-induced oxidative damage.[220] This conversion of energy metabolism to glycolytic (away from lipolytic) is correlated with aging, and the normalization associated with CoQ10 is thought to underlie protective effects of CoQ10.[221]

Aged skin is highly correlated with abnormal mitochondrial function and higher oxidant levels, and CoQ10 levels are known to decline with aging (independent of UV radiation) and with excessive UV radiation that induces oxidative stress. This decline of CoQ10 is correlated with less mitochondrial membrane potential and a shift from lipolysis towards glycolysis to sustain energy metabolism

In vitro, CoQ10 has exhibited increased elasticity potential (increased elastin expression[222] and preservation of collagen[221]), anti-wrinkle effects via protection from UV,[223] and depigmentation potential (inhibition of tyrosinase)[222] with more profound effects in cells purposely depleted of CoQ10.[224]

Application of a cream containing 0.01% CoQ10 twice daily for a week in both older and younger subjects is able to increase mitochondrial membrane potential and preserve this potential in lieu of UV radiation to higher levels than unradiated young control skin.[220]

A few studies have used combination therapy, usually with Vitamin E, retinyl palmitate (highly bioactive form of Vitamin A), grape seed extract (as oil) and linseed oil which has noted UV protection and reduced wrinkling in aged subjects.[225]

Appears to have protective effects on skin cells (tested ex vivo) following topical administration in humans

3 weeks of supplementation with CoQ10 in mice (100mg/kg) following a skin lesion noted a suppression of myeloperoxidase and higher levels of Collagen-like polymer (CLP) relative to control which was associated with accelerated wound healing rates.[226]

11.

Other Medical Conditions

11.1

Fibromyalgia

There appear to be lower circulating levels of CoQ10 in immune (blood mononuclear cells)[227][219][228] and skin cells[219] of persons with fibromyalgia although serum levels are more than doubled.[229] The reduced concentration of immune cell CoQ10 correlates with salivary cell CoQ10[230] and is associated with higher oxidation levels in the cells with lower CoQ10 status, thought to play a role in firbomyalgia pathology[231][227] as concentration of CoQ10 correlate very well with levels in skeletal muscle (with serum not being too well correlated with either) in healthy persons.[166]

An altered distribution of CoQ10 is observed in fibromyalgia, with lower cellular levels and higher serum levels (possibly indicative of issues with transportation)

A series of case studies has noted improvement with 300mg CoQ10 in symptoms of fibromyalgia[232][233] and was followed up with a pilot study using 100mg of CoQ10 (ubiquinone) supplementation thrice daily (daily dose of 300mg) for 3 months in persons with fibromyalgia that was found to increase concentrations of CoQ10 in blood mononuclear cells to levels similar to control patients alongside an improvement in headache status in persons with fibromyalgia.[228] This has been followed up with a proper blinded trial, where 40 days of supplementation of 300mg CoQ10 was associated with less fatigue, pain, and joint soreness/stiffness associated with improved mitochondrial biogenesis and AMPK activity[234] and has elsewhere been noted to improve fatigue alongside improvements on cholesterol status.[235]

Supplemental CoQ10 (300mg) appears somewhat effective in reducing symptoms associated with fibromyalgia; all the evidence currently is promising and with feasible doses but it is still fairly preliminary

11.2

Prader-Willis

Those with Prader-Willi Syndrome (a syndrome that begins as hypotonia and failure to thrive as an infant, and manifests itself as increased appetite, obesity, cognitive impairment and multiple endocrinopathies[236]) do not appear to have reduced CoQ10 levels in serum per se (reduced CoQ10 in serum associated with obesity, which affects many people with Prader-Willi Syndrome)[237] and this lack of deficiency state has been noted elsewhere although the correlation between body weight and CoQ10 in serum was not detected.[237]

Despite this, at least one study using CoQ10 at 2.5mg/kg daily in infants with failure to thrice due to Prader-Willi Syndrome noted that supplemental CoQ10 was as effective as the active control of growth hormone (6mg/kg once a week) in helping children develop psychocognitive capacities, although it did not appear to be as effective for promoting growth.[238]

CoQ10 supplementation in children with Prader-Willi Syndrome (PWS) has once been noted to aid in cognitive development over time, which is hindered by the disease state. Despite this, PWS does not appear to be a CoQ10 deficiency state

It is uncertain whether there would be benefit to an adult with PWS

11.3

Chronic Fatigue Syndrome

CoQ10 appears to be a commonly recommended supplement for chronic fatigue syndrome or nonspecific fatigue[239] with one study surveying those with unexplained chronic fatigue noting that 69% of persons who tried CoQ10 reported benefit with it.[240] This may be related to the observations that CoQ10 levels are lower in chronic fatigue originating from depression[100] or myalgic encephalomyelitis[241] relative to nonfatigued controls. Serum CoQ10, in these persons, is correlated with serum NAD(P)H.[242]

It should be noted that some studies in fibromyalgia report less fatigue as an effect of CoQ10 supplementation,[234][235] but these results may not apply to persons without fibromyalgia. Furthermore, one human trial using 200mg of CoQ10 for 12 weeks in obese persons (chronic fatigue syndrome not an inclusion requirement) failed to note any influence on fatigue ratings.[137]

There is insufficient evidence to evaluate the interaction of supplemental CoQ10 and chronic or nonspecific fatigue symptoms

11.4

Conditions of Male Sexuality

CoQ10 is a naturally occurring antioxidant found in seminal fluid[243] and alterations in seminal CoQ10 content are found in asthenozoospermia and varicocele.[244][245] The role of CoQ10 is thought to be in part due to exerting an anti-oxidative effect[246] (and preventing DNA fragmentation from occurring to seminal cells, which is thought to be the link between infertility and oxidative stress[247][248][249]) and in part bioenergetic (to support the large amount of mitochondria in sperm cells and the energy cost of motility[250][245]) and the higher than normal levels of CoQ10 biosynthetic enzymes in rat testes (relative to many other organs) is thought to reflect this.[251] Oxidative damage to sperm cells tends to come from both the sperm itself and invading leukocytes[252] (of which oligospermic have more overall exposure and reactive oxygen species (ROS) damage from relative to healthy controls[253][254][255]). CoQ10 in semen is correlated with sperm count (R=0.504) and motility (R=0.261)[256] and has twice been correlated to total antioxidative capacity of semen.[257][258]

Supplemental CoQ10 to infertile men has been found to increase seminal CoQ10 levels by 202% (42.0+/-5.1 at baseline to 127.1+/-1.9 ng/mL after 6 months of 200mg daily)[259] and has been replicated elsewhere under double-blind conditions.[260]

CoQ10 is highly involved with sperm and likely maintains oxidative stability in the semen. Oral intake of CoQ10 in infertile men can increase seminal CoQ10 concentrations

Seminal CoQ10 actually appears to be elevated in persons with varicocele relative to normal fertile men and infertile controls without varicocele,[261][256] which was proposed to be realted to insufficient utilization of CoQ10.[262] Variococeles appear to occur in 19–41% of infertile men.[263]

In oligoasthenozoospermia, sperm from these men incubated with CoQ10 experience increases in motility[264] and oral intake of 200mg CoQ10 for 6 months has been confirmed to increase sperm motility in infertile men (no influence on morphology or concentration).[259] This increase in motility was eliminated after 6 months of supplement cessation[259] and has been replicated elsewhere[260][265] although only one study has noted increases in sperm density.[265]

Studies that measure fertility rates note an improvement with 60mg CoQ10 daily for approximately 103 days in oligoasthenozoospermic men (in vitro fertilization)[264] and in one pilot study increased fertility (3 out of 22 couples) noted pregnancy.[259]

CoQ10 supplementation in men with poor seminal motility (rather than sperm count or sperm morphology) appears to be somewhat effective at improving seminal motility; preliminary evidence suggests an increase in fertility secondary to this, but larger trials are needed to confirm

One study assessing the interaction of CoQ10 and Peyronie's disease (localized fibrosis of the penis involving the tunica albuginea of the corpus cavernosum resulting in penile curvature and sexual dysfunction[266] which appears to have a 3-9% prevalance rate in men[267]) noted that after 300mg of CoQ10 daily for 24 weeks that the disease progression seen in placebo (56.1%) was greatly attenuated to 13.6%.[268] This study assessed treatment efficacy based on erectile properties and the rating scale of IIEF-5, with a 20% worsening in pain or 5° change in penile curvature as a worsening of disease state.[268]

CoQ10 has preliminary evidence to help with Peyronie's disease and pathological curvature of the penis. This study was an intervention for early stage Peyronie's disease (less calcification) and currently there is no evidence for efficacy in late stage Peyronie's disease

12.

Nutrient-Nutrient Interactions

12.1

Carnitine

There is some rationale behind treating mitochondrial pathology with combination therapy rather than isolated molecules[269] targeting mitochondrial structure (CoQ10), enzymatic function (carnitine) antioxidative properties (CoQ10, alpha lipoic acid, vitamin e), and alternate energy pathways (creatine).

Carnitine is an amino acid compound present in the mitochondria at a rate-limiting step of fatty acid oxidation, and mechanistically (in regards to the function in the mitochondria, not oral supplementation) they are synergistic intermediates in mitochondrial function in general.[270]

One study in people on dialysis and statin therapy given either CoQ10 (100mg daily), carnitine (1000mg IV thrice a week), or their combination failed to find a beneficial effect of combination therapy over either monotherapy in regards to a standard lipid panel.[271]

12.2

Creatine

Creatine is a performance enhancing supplement that works via increasing an intracellular pool of creatine and phosphocreatine, exchanging phosphate groups with ADP to replenish the cellular concentration of ATP (main energy currency within a cell); creatine itself appears to positively influence mitochondrial function (similar to CoQ10[97]) and exert neuroprotective effects (being tested in models of Parkinson's and Huntington's disease[98])

Combination therapy with CoQ10 (1% of feed) and creatine (2% of feed) exert additive protective effects in an animal model of Parkinson's (MPTP toxicity) and Huntington's disease (3-nitropropionic acid toxicity) with combination therapy reducing the lesion sizes to 17% (3-NP) and attenuating the dopamine loss from MPTP from 56% to 13%.[94]

12.3

Alpha-Lipoic Acid

Alpha-Lipoic Acid (ALA) is a mitochondrial factor and fatty acid that appears to be synergistic with CoQ10 in vitro in inducing the mitochondrial transcription factor A (TFAM)[169] secondary to activating both PGC1 and NRF1, two factors that coactive TFAM to then induce mitochondrial biogenesis.[272][273]

The combination was also found synergistic in inducing ornithine decarboxylase 1,[169] which is a rate-limiting enzyme of polyamine synthesis induced by exercise[274] and are genoprotective.[275]

12.4

Statins

'Statin' is a term used to refer to the mechanisms of inhibiting the HMG-CoA enzyme, a rate limiting enzyme in the mevalonate pathway that converts 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) into mevalonic acid. Inhibiting this enzyme produced less mevalonic acid, and eventually produces less cholesterol (which is eventually produced in the chain of events following mevalonic acid production).[276] Statins tend to refer to pharmaceutical drugs, but are present in some supplements such as Pu-Erh tea[277] and Red Yeast Rice (which contains the pharmaceutical known as lovastatin).

Statin usage (long-term, not short-term[278]) is known to cause lower serum CoQ10 levels (as CoQ10 synthesis also occurs after the HMG-CoA enzyme),[279] and this lower CoQ10 level is an independent predictor of statin-related cardiovascular disease risk[116] while being associated with depression[100] and possible causative of statin-related myopathy (via an intermediate known as GGPP).[280][281]

Prolonged statin usage is causative of reduced circulating CoQ10 levels, and this reduction of CoQ10 below normal levels is thought to mediate a large amount of adverse effects associated with statin treatment

Supplementation of CoQ10 during statin usage may reverse some cardiovascular complications[282] and is able to reverse the deficiency, with one study noting a 42% reduction was reversed to a 127% increase (relative to baseline) following supplementation of 100mg CoQ10.[142] CoQ10 usage alongside statin usage is commonly seen as a way to prevent statin-related myopathy.[283][284][285]

Ingestion of at least 90-100mg CoQ10 daily alongside statin usage is associated with greatly reduced risk from statin-related pathologies

The combination of CoQ10 and statins seem to work additively in increasing HDL-C.[286]

May have other beneficial effects with combination therapy

12.5

Grapefruit

As CoQ10 efflux (in intestinal cells) is mediated by P-glycoprotein[70] and grapefruit juice is known to inhibit this transporter,[287][288] the combination has been tested in vitro and grapefruit juice has been found to enhance the absorption of CoQ10 to about 150% of control secondary to preventing less efflux (1% of the medium as grapefruit juice and 10μM CoQ10) to a greater degree than the reference drug (rhodamine 123).[289]

Grapefruit juice, or other potent P-glycoprotein inhibitors, may increase CoQ10 bioavailability

12.6

Pycnogenol

Pycnogenol is a supplement brand name derived from Pine Bark extract, with the main bioactive of procyanidins (same structures also found in Grape seed extract). Combination therapy with pycnogenol and CoQ10 has been noted to increase left ventricular ejection fraction (22.4%) and reduce blood pressure in persons with heart failure.[290]

Both agents are cardioprotective in persons with poor cardiovascular health, no apparent or known synergy yet demonstrated between the two molecules

13.

Safety and Toxicity

13.1

General

CoQ10 is generally very well tolerated at doses not exceeding 500mg (the standard upper limit for treatment of ailments that tends to be recommended).[291][292][293][294] Despite this limit, no acute side effects aside from gastrointestinal (digestive) distress are reported with doses up to 3,000mg daily[295][296][297] and usage of 900mg daily for prolonged periods (4 weeks) was not associated with any clinically relevant adverse effects.[298]

Animal models have suggested that superloading dosages of CoQ10 (estimated to be around 350mg/kg bodyweight) results in an exacerbation of the effects of aging but not overall mortality, whereas doses around 100mg/kg bodyweight do not have this threat.[90] Using the human:mouse body surface area ratio of 12.3, these dosages would be 1700mg and 500mg (total) per day.[90][299] The mechanism seen here is not fully elucidated, but believed to be related to mitochondrial bioenergetics, and are in contrast to an earlier study by the same group.[87]

There are no established toxic effects of CoQ10 supplementation in humans and CoQ10 has a remarkable safety profile. There may be some non-lethal and long term adverse effects with very high doses of CoQ10, but these are not yet demonstrated to be relevant in humans

References
6.^Pravst I, Zmitek K, Zmitek JCoenzyme Q10 contents in foods and fortification strategiesCrit Rev Food Sci Nutr.(2010 Apr)
8.^Kamei M, Fujita T, Kanbe T, Sasaki K, Oshiba K, Otani S, Matsui-Yuasa I, Morisawa SThe distribution and content of ubiquinone in foodsInt J Vitam Nutr Res.(1986)
9.^Passi S, Cataudella S, Di Marco P, De Simone F, Rastrelli LFatty acid composition and antioxidant levels in muscle tissue of different Mediterranean marine species of fish and shellfishJ Agric Food Chem.(2002 Dec 4)
11.^Weber C, Bysted A, Hølmer GCoenzyme Q10 in the diet--daily intake and relative bioavailabilityMol Aspects Med.(1997)
13.^Strazisar M, Fir M, Golc-Wondra A, Milivojevic L, Prosek M, Abram VQuantitative determination of coenyzme Q10 by liquid chromatography and liquid chromatography/mass spectrometry in dairy productsJ AOAC Int.(2005 Jul-Aug)
14.^Weber C, Bysted A, Hłlmer GThe coenzyme Q10 content of the average Danish dietInt J Vitam Nutr Res.(1997)
16.^Yoshida H, Kotani Y, Ochiai K, Araki KProduction of ubiquinone-10 using bacteriaJ Gen Appl Microbiol.(1998 Feb)
18.^Cluis CP, Burja AM, Martin VJCurrent prospects for the production of coenzyme Q10 in microbesTrends Biotechnol.(2007 Nov)
19.^Choi JH, Ryu YW, Seo JHBiotechnological production and applications of coenzyme Q10Appl Microbiol Biotechnol.(2005 Jul)
23.^Bhagavan HN, Chopra RKCoenzyme Q10: absorption, tissue uptake, metabolism and pharmacokineticsFree Radic Res.(2006 May)
25.^Nohl H, Gille L, Staniek KThe biochemical, pathophysiological, and medical aspects of ubiquinone functionAnn N Y Acad Sci.(1998 Nov 20)
26.^Mancuso M, Orsucci D, Volpi L, Calsolaro V, Siciliano GCoenzyme Q10 in neuromuscular and neurodegenerative disordersCurr Drug Targets.(2010 Jan)
27.^Beg S, Javed S, Kohli KBioavailability enhancement of coenzyme Q10: an extensive review of patentsRecent Pat Drug Deliv Formul.(2010 Nov)
29.^Goldstein JL, Brown MSRegulation of the mevalonate pathwayNature.(1990 Feb 1)
30.^Bentinger M, Tekle M, Dallner GCoenzyme Q--biosynthesis and functionsBiochem Biophys Res Commun.(2010 May 21)
31.^Thelin A, Peterson E, Hutson JL, McCarthy AD, Ericsson J, Dallner GEffect of squalestatin 1 on the biosynthesis of the mevalonate pathway lipidsBiochim Biophys Acta.(1994 Dec 8)
34.^Kalén A, Appelkvist EL, Dallner GAge-related changes in the lipid compositions of rat and human tissuesLipids.(1989 Jul)
35.^Ernster L, Dallner GBiochemical, physiological and medical aspects of ubiquinone functionBiochim Biophys Acta.(1995 May 24)
36.^Bonakdar RA, Guarneri ECoenzyme Q10Am Fam Physician.(2005 Sep 15)
38.^Zhang Y, Aberg F, Appelkvist EL, Dallner G, Ernster LUptake of dietary coenzyme Q supplement is limited in ratsJ Nutr.(1995 Mar)
41.^Saito Y, Fukuhara A, Nishio K, Hayakawa M, Ogawa Y, Sakamoto H, Fujii K, Yoshida Y, Niki ECharacterization of cellular uptake and distribution of coenzyme Q10 and vitamin E in PC12 cellsJ Nutr Biochem.(2009 May)
46.^Bentinger M, Dallner G, Chojnacki T, Swiezewska EDistribution and breakdown of labeled coenzyme Q10 in ratFree Radic Biol Med.(2003 Mar 1)
48.^Miles MV, Horn PS, Morrison JA, Tang PH, DeGrauw T, Pesce AJPlasma coenzyme Q10 reference intervals, but not redox status, are affected by gender and race in self-reported healthy adultsClin Chim Acta.(2003 Jun)
49.^Lönnrot K, Metsä-Ketelä T, Molnár G, Ahonen JP, Latvala M, Peltola J, Pietilä T, Alho HThe effect of ascorbate and ubiquinone supplementation on plasma and CSF total antioxidant capacityFree Radic Biol Med.(1996)
50.^Lyon W, Van den Brink O, Pepe S, Wowk M, Marasco S, Rosenfeldt FLSimilar therapeutic serum levels attained with emulsified and oil-based preparations of coenzyme Q10Asia Pac J Clin Nutr.(2001)
51.^Chopra RK, Goldman R, Sinatra ST, Bhagavan HNRelative bioavailability of coenzyme Q10 formulations in human subjectsInt J Vitam Nutr Res.(1998)
52.^Weber C, Sejersgård Jakobsen T, Mortensen SA, Paulsen G, Hølmer GAntioxidative effect of dietary coenzyme Q10 in human blood plasmaInt J Vitam Nutr Res.(1994)
53.^Folkers K, Moesgaard S, Morita MA one year bioavailability study of coenzyme Q10 with 3 months withdrawal periodMol Aspects Med.(1994)
54.^Kaikkonen J, Nyyssönen K, Porkkala-Sarataho E, Poulsen HE, Metsä-Ketelä T, Hayn M, Salonen R, Salonen JTEffect of oral coenzyme Q10 supplementation on the oxidation resistance of human VLDL+LDL fraction: absorption and antioxidative properties of oil and granule-based preparationsFree Radic Biol Med.(1997)
56.^Nuku K, Matsuoka Y, Yamagishi T, Miyawaki H, Sato KSafety assessment of PureSorb-Q40 in healthy subjects and serum coenzyme Q10 level in excessive dosingJ Nutr Sci Vitaminol (Tokyo).(2007 Jun)
57.^Nukui K, Yamagishi T, Miyawaki H, Kettawan A, Okamoto T, Sato KComparison of uptake between PureSorb-Q40 and regular hydrophobic coenzyme Q10 in rats and humans after single oral intakeJ Nutr Sci Vitaminol (Tokyo).(2007 Apr)
58.^Nukui K, Koike T, Yamagishi T, Ihota H, Nagase T, Kimura H, Sato KA 91-d repeated dose oral toxicity study of PureSorb-Q(TM)40 in ratsJ Nutr Sci Vitaminol (Tokyo).(2007 Aug)
59.^Laaksonen R, Riihimäki A, Laitila J, Mårtensson K, Tikkanen MJ, Himberg JJSerum and muscle tissue ubiquinone levels in healthy subjectsJ Lab Clin Med.(1995 Apr)
60.^Aberg F, Appelkvist EL, Dallner G, Ernster LDistribution and redox state of ubiquinones in rat and human tissuesArch Biochem Biophys.(1992 Jun)
62.^Sohal RS, Forster MJCoenzyme Q, oxidative stress and agingMitochondrion.(2007 Jun)
64.^Matthews RT, Yang L, Browne S, Baik M, Beal MFCoenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effectsProc Natl Acad Sci U S A.(1998 Jul 21)
66.^Kwong LK, Kamzalov S, Rebrin I, Bayne AC, Jana CK, Morris P, Forster MJ, Sohal RSEffects of coenzyme Q(10) administration on its tissue concentrations, mitochondrial oxidant generation, and oxidative stress in the ratFree Radic Biol Med.(2002 Sep 1)
68.^Niklowitz P, Sonnenschein A, Janetzky B, Andler W, Menke TEnrichment of coenzyme Q10 in plasma and blood cells: defense against oxidative damageInt J Biol Sci.(2007 Apr 5)
69.^Baskaran R1, Shanmugam S, Nagayya-Sriraman S, Kim JH, Jeong TC, Yong CS, Choi HG, Yoo BKThe effect of coenzyme Q10 on the pharmacokinetic parameters of theophyllineArch Pharm Res.(2008 Jul)
70.^Itagaki S1, Ochiai A, Kobayashi M, Sugawara M, Hirano T, Iseki KInteraction of coenzyme Q10 with the intestinal drug transporter P-glycoproteinJ Agric Food Chem.(2008 Aug 27)
77.^Parrado-Fernández C, López-Lluch G, Rodríguez-Bies E, Santa-Cruz S, Navas P, Ramsey JJ, Villalba JMCalorie restriction modifies ubiquinone and COQ transcript levels in mouse tissuesFree Radic Biol Med.(2011 Jun 15)
78.^Lass A, Kwong L, Sohal RSMitochondrial coenzyme Q content and agingBiofactors.(1999)
79.^Ramsey JJ, Hagopian K, Kenny TM, Koomson EK, Bevilacqua L, Weindruch R, Harper MEProton leak and hydrogen peroxide production in liver mitochondria from energy-restricted ratsAm J Physiol Endocrinol Metab.(2004 Jan)
81.^Armeni T, Principato G, Quiles JL, Pieri C, Bompadre S, Battino MMitochondrial dysfunctions during aging: vitamin E deficiency or caloric restriction--two different ways of modulating stressJ Bioenerg Biomembr.(2003 Apr)
82.^Spindler SR, Li R, Dhahbi JM, Yamakawa A, Mote P, Bodmer R, Ocorr K, Williams RT, Wang Y, Ablao KPStatin treatment increases lifespan and improves cardiac health in Drosophila by decreasing specific protein prenylationPLoS One.(2012)
84.^Asencio C, Rodríguez-Aguilera JC, Ruiz-Ferrer M, Vela J, Navas PSilencing of ubiquinone biosynthesis genes extends life span in Caenorhabditis elegansFASEB J.(2003 Jun)
85.^Branicky R, Bénard C, Hekimi Sclk-1, mitochondria, and physiological ratesBioessays.(2000 Jan)
87.^Sohal RS, Kamzalov S, Sumien N, Ferguson M, Rebrin I, Heinrich KR, Forster MJEffect of coenzyme Q10 intake on endogenous coenzyme Q content, mitochondrial electron transport chain, antioxidative defenses, and life span of miceFree Radic Biol Med.(2006 Feb 1)
89.^Lee CK, Pugh TD, Klopp RG, Edwards J, Allison DB, Weindruch R, Prolla TAThe impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in miceFree Radic Biol Med.(2004 Apr 15)
90.^Sumien N, Heinrich KR, Shetty RA, Sohal RS, Forster MJProlonged intake of coenzyme Q10 impairs cognitive functions in miceJ Nutr.(2009 Oct)
93.^Fornai F, Schlüter OM, Lenzi P, Gesi M, Ruffoli R, Ferrucci M, Lazzeri G, Busceti CL, Pontarelli F, Battaglia G, Pellegrini A, Nicoletti F, Ruggieri S, Paparelli A, Südhof TCParkinson-like syndrome induced by continuous MPTP infusion: convergent roles of the ubiquitin-proteasome system and alpha-synucleinProc Natl Acad Sci U S A.(2005 Mar 1)
94.^Yang L, Calingasan NY, Wille EJ, Cormier K, Smith K, Ferrante RJ, Beal MFCombination therapy with coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson's and Huntington's diseasesJ Neurochem.(2009 Jun)
98.^Beal MFNeuroprotective effects of creatineAmino Acids.(2011 May)
102.^Forester BP, Zuo CS, Ravichandran C, Harper DG, Du F, Kim S, Cohen BM, Renshaw PFCoenzyme Q10 effects on creatine kinase activity and mood in geriatric bipolar depressionJ Geriatr Psychiatry Neurol.(2012 Mar)
103.^Rozen TD, Oshinsky ML, Gebeline CA, Bradley KC, Young WB, Shechter AL, Silberstein SDOpen label trial of coenzyme Q10 as a migraine preventiveCephalalgia.(2002 Mar)
104.^Sándor PS, Di Clemente L, Coppola G, Saenger U, Fumal A, Magis D, Seidel L, Agosti RM, Schoenen JEfficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trialNeurology.(2005 Feb 22)
105.^Slater SK, Nelson TD, Kabbouche MA, LeCates SL, Horn P, Segers A, Manning P, Powers SW, Hershey ADA randomized, double-blinded, placebo-controlled, crossover, add-on study of CoEnzyme Q10 in the prevention of pediatric and adolescent migraineCephalalgia.(2011 Jun)
106.^Rosenfeldt F, Marasco S, Lyon W, Wowk M, Sheeran F, Bailey M, Esmore D, Davis B, Pick A, Rabinov M, Smith J, Nagley P, Pepe SCoenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissueJ Thorac Cardiovasc Surg.(2005 Jan)
107.^Folkers K, Vadhanavikit S, Mortensen SABiochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10Proc Natl Acad Sci U S A.(1985 Feb)
110.^Greenlee H, Shaw J, Lau YK, Naini A, Maurer MLack of effect of coenzyme q10 on doxorubicin cytotoxicity in breast cancer cell culturesIntegr Cancer Ther.(2012 Sep)
111.^Zhou Q, Chowbay BEffect of coenzyme Q10 on the disposition of doxorubicin in ratsEur J Drug Metab Pharmacokinet.(2002 Jul-Sep)
112.^El-Sheikh AA, Morsy MA, Mahmoud MM, Rifaai RA, Abdelrahman AMEffect of coenzyme-q10 on Doxorubicin-induced nephrotoxicity in ratsAdv Pharmacol Sci.(2012)
114.^Eaton S, Skinner R, Hale JP, Pourfarzam M, Roberts A, Price L, Bartlett KPlasma coenzyme Q(10) in children and adolescents undergoing doxorubicin therapyClin Chim Acta.(2000 Dec)
115.^Brea-Calvo G, Rodríguez-Hernández A, Fernández-Ayala DJ, Navas P, Sánchez-Alcázar JAChemotherapy induces an increase in coenzyme Q10 levels in cancer cell linesFree Radic Biol Med.(2006 Apr 15)
116.^Molyneux SL, Florkowski CM, George PM, Pilbrow AP, Frampton CM, Lever M, Richards AMCoenzyme Q10: an independent predictor of mortality in chronic heart failureJ Am Coll Cardiol.(2008 Oct 28)
117.^Hughes K, Lee BL, Feng X, Lee J, Ong CNCoenzyme Q10 and differences in coronary heart disease risk in Asian Indians and ChineseFree Radic Biol Med.(2002 Jan 15)
118.^Kalenikova EI, Gorodetskaya EA, Kolokolchikova EG, Shashurin DA, Medvedev OSChronic administration of coenzyme Q10 limits postinfarct myocardial remodeling in ratsBiochemistry (Mosc).(2007 Mar)
119.^Littarru GP, Tiano LClinical aspects of coenzyme Q10: an updateCurr Opin Clin Nutr Metab Care.(2005 Nov)
120.^Sarter BCoenzyme Q10 and cardiovascular disease: a reviewJ Cardiovasc Nurs.(2002 Jul)
121.^Singh RB, Wander GS, Rastogi A, Shukla PK, Mittal A, Sharma JP, Mehrotra SK, Kapoor R, Chopra RKRandomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarctionCardiovasc Drugs Ther.(1998 Sep)
122.^Singh RB, Neki NS, Kartikey K, Pella D, Kumar A, Niaz MA, Thakur ASEffect of coenzyme Q10 on risk of atherosclerosis in patients with recent myocardial infarctionMol Cell Biochem.(2003 Apr)
123.^Khatta M, Alexander BS, Krichten CM, Fisher ML, Freudenberger R, Robinson SW, Gottlieb SSThe effect of coenzyme Q10 in patients with congestive heart failureAnn Intern Med.(2000 Apr 18)
124.^Chew GT, Watts GF, Davis TM, Stuckey BG, Beilin LJ, Thompson PL, Burke V, Currie PJHemodynamic effects of fenofibrate and coenzyme Q10 in type 2 diabetic subjects with left ventricular diastolic dysfunctionDiabetes Care.(2008 Aug)
125.^Permanetter B, Rössy W, Klein G, Weingartner F, Seidl KF, Blömer HUbiquinone (coenzyme Q10) in the long-term treatment of idiopathic dilated cardiomyopathyEur Heart J.(1992 Nov)
126.^Hofman-Bang C, Rehnqvist N, Swedberg K, Wiklund I, Aström HCoenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure. The Q10 Study GroupJ Card Fail.(1995 Mar)
131.^Landmesser U, Merten R, Spiekermann S, Büttner K, Drexler H, Hornig BVascular extracellular superoxide dismutase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilationCirculation.(2000 May 16)
133.^Fukai T, Folz RJ, Landmesser U, Harrison DGExtracellular superoxide dismutase and cardiovascular diseaseCardiovasc Res.(2002 Aug 1)
135.^Watts GF, Playford DA, Croft KD, Ward NC, Mori TA, Burke VCoenzyme Q(10) improves endothelial dysfunction of the brachial artery in Type II diabetes mellitusDiabetologia.(2002 Mar)
136.^Belardinelli R, Muçaj A, Lacalaprice F, Solenghi M, Seddaiu G, Principi F, Tiano L, Littarru GPCoenzyme Q10 and exercise training in chronic heart failureEur Heart J.(2006 Nov)
139.^Ho MJ, Bellusci A, Wright JMBlood pressure lowering efficacy of coenzyme Q10 for primary hypertensionCochrane Database Syst Rev.(2009 Oct 7)
140.^Young JM, Florkowski CM, Molyneux SL, McEwan RG, Frampton CM, Nicholls MG, Scott RS, George PMA randomized, double-blind, placebo-controlled crossover study of coenzyme Q10 therapy in hypertensive patients with the metabolic syndromeAm J Hypertens.(2012 Feb)
141.^Trimarco V, Cimmino CS, Santoro M, Pagnano G, Manzi MV, Piglia A, Giudice CA, De Luca N, Izzo RNutraceuticals for blood pressure control in patients with high-normal or grade 1 hypertensionHigh Blood Press Cardiovasc Prev.(2012 Sep 1)
142.^Mabuchi H, Nohara A, Kobayashi J, Kawashiri MA, Katsuda S, Inazu A, Koizumi J; Hokuriku Lipid Research GroupEffects of CoQ10 supplementation on plasma lipoprotein lipid, CoQ10 and liver and muscle enzyme levels in hypercholesterolemic patients treated with atorvastatin: a randomized double-blind studyAtherosclerosis.(2007 Dec)
145.^Yamamoto Y, Yamashita SPlasma ratio of ubiquinol and ubiquinone as a marker of oxidative stressMol Aspects Med.(1997)
147.^Tsai KL, Huang YH, Kao CL, Yang DM, Lee HC, Chou HY, Chen YC, Chiou GY, Chen LH, Yang YP, Chiu TH, Tsai CS, Ou HC, Chiou SHA novel mechanism of coenzyme Q10 protects against human endothelial cells from oxidative stress-induced injury by modulating NO-related pathwaysJ Nutr Biochem.(2012 May)
148.^Tsai KL, Chen LH, Chiou SH, Chiou GY, Chen YC, Chou HY, Chen LK, Chen HY, Chiu TH, Tsai CS, Ou HC, Kao CLCoenzyme Q10 suppresses oxLDL-induced endothelial oxidative injuries by the modulation of LOX-1-mediated ROS generation via the AMPK/PKC/NADPH oxidase signaling pathwayMol Nutr Food Res.(2011 Sep)
149.^Marshall HE, Merchant K, Stamler JSNitrosation and oxidation in the regulation of gene expressionFASEB J.(2000 Oct)
150.^Schmelzer C, Lindner I, Rimbach G, Niklowitz P, Menke T, Döring FFunctions of coenzyme Q10 in inflammation and gene expressionBiofactors.(2008)
152.^Singh RB, Niaz MA, Sharma JP, Kumar R, Bishnoi I, Begom RPlasma levels of antioxidant vitamins and oxidative stress in patients with acute myocardial infarctionActa Cardiol.(1994)
153.^Mezawa M, Takemoto M, Onishi S, Ishibashi R, Ishikawa T, Yamaga M, Fujimoto M, Okabe E, He P, Kobayashi K, Yokote KThe reduced form of coenzyme Q10 improves glycemic control in patients with type 2 diabetes: an open label pilot studyBiofactors.(2012 Nov-Dec)
155.^Hodgson JM, Watts GF, Playford DA, Burke V, Croft KDCoenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetesEur J Clin Nutr.(2002 Nov)
158.^Golbidi S, Ebadi SA, Laher IAntioxidants in the treatment of diabetesCurr Diabetes Rev.(2011 Mar)
161.^Sourris KC, Harcourt BE, Tang PH, Morley AL, Huynh K, Penfold SA, Coughlan MT, Cooper ME, Nguyen TV, Ritchie RH, Forbes JMUbiquinone (coenzyme Q10) prevents renal mitochondrial dysfunction in an experimental model of type 2 diabetesFree Radic Biol Med.(2012 Feb 1)
163.^Huynh K, Kiriazis H, Du XJ, Love JE, Jandeleit-Dahm KA, Forbes JM, McMullen JR, Ritchie RHCoenzyme Q10 attenuates diastolic dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis in the db/db mouse model of type 2 diabetesDiabetologia.(2012 May)
164.^Shi TJ, Zhang MD, Zeberg H, Nilsson J, Grünler J, Liu SX, Xiang Q, Persson J, Fried KJ, Catrina SB, Watanabe M, Arhem P, Brismar K, Hökfelt TGCoenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db-/db- mouse, a type 2 diabetes modelProc Natl Acad Sci U S A.(2013 Jan 8)
165.^Zhang YP, Eber A, Yuan Y, Yang Z, Rodriguez Y, Levitt RC, Takacs P, Candiotti KAProphylactic and Antinociceptive Effects of Coenzyme Q10 on Diabetic Neuropathic Pain in a Mouse Model of Type 1 DiabetesAnesthesiology.(2013 Apr)
167.^Miles MV, Horn PS, Tang PH, Morrison JA, Miles L, DeGrauw T, Pesce AJAge-related changes in plasma coenzyme Q10 concentrations and redox state in apparently healthy children and adultsClin Chim Acta.(2004 Sep)
168.^Karlsson J, Lin L, Sylvén C, Jansson EMuscle ubiquinone in healthy physically active malesMol Cell Biochem.(1996 Mar 23)
170.^Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E, Olson EN, Lowell BB, Bassel-Duby R, Spiegelman BMTranscriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibresNature.(2002 Aug 15)
171.^Liang H, Ward WFPGC-1alpha: a key regulator of energy metabolismAdv Physiol Educ.(2006 Dec)
172.^Anderson R, Prolla TPGC-1alpha in aging and anti-aging interventionsBiochim Biophys Acta.(2009 Oct)
174.^Nierobisz LS, Hentz NG, Felts JV, Mozdziak PEFiber phenotype and coenzyme Q₁₀ content in Turkey skeletal musclesCells Tissues Organs.(2010)
175.^Sommerville RB, Zaidman CM, Pestronk ACoenzyme Q10 deficiency in children: Frequent type 2C muscle fibers with normal morphologyMuscle Nerve.(2013 Mar 14)
177.^Cooke M, Iosia M, Buford T, Shelmadine B, Hudson G, Kerksick C, Rasmussen C, Greenwood M, Leutholtz B, Willoughby D, Kreider REffects of acute and 14-day coenzyme Q10 supplementation on exercise performance in both trained and untrained individualsJ Int Soc Sports Nutr.(2008 Mar 4)
178.^Ostman B, Sjödin A, Michaëlsson K, Byberg LCoenzyme Q10 supplementation and exercise-induced oxidative stress in humansNutrition.(2012 Apr)
179.^Bloomer RJ, Canale RE, McCarthy CG, Farney TMImpact of oral ubiquinol on blood oxidative stress and exercise performanceOxid Med Cell Longev.(2012)
180.^Zhou S, Zhang Y, Davie A, Marshall-Gradisnik S, Hu H, Wang J, Brushett DMuscle and plasma coenzyme Q10 concentration, aerobic power and exercise economy of healthy men in response to four weeks of supplementationJ Sports Med Phys Fitness.(2005 Sep)
182.^Gül I, Gökbel H, Belviranli M, Okudan N, Büyükbaş S, Başarali KOxidative stress and antioxidant defense in plasma after repeated bouts of supramaximal exercise: the effect of coenzyme Q10J Sports Med Phys Fitness.(2011 Jun)
183.^Muraki A, Miyashita K, Mitsuishi M, Tamaki M, Tanaka K, Itoh HCoenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise enduranceJ Appl Physiol.(2012 Aug)
184.^Mizuno K, Tanaka M, Nozaki S, Mizuma H, Ataka S, Tahara T, Sugino T, Shirai T, Kajimoto Y, Kuratsune H, Kajimoto O, Watanabe YAntifatigue effects of coenzyme Q10 during physical fatigueNutrition.(2008 Apr)
185.^Kon M, Kimura F, Akimoto T, Tanabe K, Murase Y, Ikemune S, Kono IEffect of Coenzyme Q10 supplementation on exercise-induced muscular injury of ratsExerc Immunol Rev.(2007)
186.^Nagai S, Miyazaki Y, Ogawa K, Satake T, Sugiyama S, Ozawa TThe effect of Coenzyme Q10 on reperfusion injury in canine myocardiumJ Mol Cell Cardiol.(1985 Sep)
187.^Kambara N, Takagi K, Satake T, Sugiyama S, Ozawa TMechanism responsible for endotoxin-induced lung microsomal dysfunction in ratsLung.(1983)
188.^Kon M, Tanabe K, Akimoto T, Kimura F, Tanimura Y, Shimizu K, Okamoto T, Kono IReducing exercise-induced muscular injury in kendo athletes with supplementation of coenzyme Q10Br J Nutr.(2008 Oct)
190.^Fu X, Ji R, Dam JAntifatigue effect of coenzyme Q10 in miceJ Med Food.(2010 Feb)
191.^Sun M, Qian F, Shen W, Tian C, Hao J, Sun L, Liu JMitochondrial nutrients stimulate performance and mitochondrial biogenesis in exhaustively exercised ratsScand J Med Sci Sports.(2012 Dec)
192.^Glover EI, Martin J, Maher A, Thornhill RE, Moran GR, Tarnopolsky MAA randomized trial of coenzyme Q10 in mitochondrial disordersMuscle Nerve.(2010 Nov)
193.^Crane FLBiochemical functions of coenzyme Q10J Am Coll Nutr.(2001 Dec)
194.^Linnane AW, Kopsidas G, Zhang C, Yarovaya N, Kovalenko S, Papakostopoulos P, Eastwood H, Graves S, Richardson MCellular redox activity of coenzyme Q10: effect of CoQ10 supplementation on human skeletal muscleFree Radic Res.(2002 Apr)
195.^Turunen M, Olsson J, Dallner GMetabolism and function of coenzyme QBiochim Biophys Acta.(2004 Jan 28)
196.^Bentinger M, Brismar K, Dallner GThe antioxidant role of coenzyme QMitochondrion.(2007 Jun)
200.^Forsmark-Andrée P, Persson B, Radi R, Dallner G, Ernster LOxidative modification of nicotinamide nucleotide transhydrogenase in submitochondrial particles: effect of endogenous ubiquinolArch Biochem Biophys.(1996 Dec 1)
202.^Lewis KN, Mele J, Hayes JD, Buffenstein RNrf2, a guardian of healthspan and gatekeeper of species longevityIntegr Comp Biol.(2010 Nov)
203.^Reuland DJ, Khademi S, Castle CJ, Irwin DC, McCord JM, Miller BF, Hamilton KLUpregulation of phase II enzymes through phytochemical activation of Nrf2 protects cardiomyocytes against oxidant stressFree Radic Biol Med.(2013 Mar)
204.^Hybertson BM, Gao B, Bose SK, McCord JMOxidative stress in health and disease: the therapeutic potential of Nrf2 activationMol Aspects Med.(2011 Aug)
205.^Choi HK, Pokharel YR, Lim SC, Han HK, Ryu CS, Kim SK, Kwak MK, Kang KWInhibition of liver fibrosis by solubilized coenzyme Q10: Role of Nrf2 activation in inhibiting transforming growth factor-beta1 expressionToxicol Appl Pharmacol.(2009 Nov 1)
206.^Wada H, Goto H, Hagiwara S, Yamamoto YRedox status of coenzyme Q10 is associated with chronological ageJ Am Geriatr Soc.(2007 Jul)
209.^Fuchs J, Groth N, Herrling T, Milbradt R, Zimmer G, Packer LElectron paramagnetic resonance (EPR) imaging in skin: biophysical and biochemical microscopyJ Invest Dermatol.(1992 May)
211.^Sun Y, Oberley LWRedox regulation of transcriptional activatorsFree Radic Biol Med.(1996)
212.^Cerutti PA, Trump BFInflammation and oxidative stress in carcinogenesisCancer Cells.(1991 Jan)
213.^Suzuki YJ, Forman HJ, Sevanian AOxidants as stimulators of signal transductionFree Radic Biol Med.(1997)
214.^Shindo Y, Witt E, Han D, Epstein W, Packer LEnzymic and non-enzymic antioxidants in epidermis and dermis of human skinJ Invest Dermatol.(1994 Jan)
215.^Podda M, Traber MG, Weber C, Yan LJ, Packer LUV-irradiation depletes antioxidants and causes oxidative damage in a model of human skinFree Radic Biol Med.(1998 Jan 1)
216.^Hoppe U, Bergemann J, Diembeck W, Ennen J, Gohla S, Harris I, Jacob J, Kielholz J, Mei W, Pollet D, Schachtschabel D, Sauermann G, Schreiner V, Stäb F, Steckel FCoenzyme Q10, a cutaneous antioxidant and energizerBiofactors.(1999)
217.^del Hoyo P, García-Redondo A, de Bustos F, Molina JA, Sayed Y, Alonso-Navarro H, Caballero L, Arenas J, Agúndez JA, Jiménez-Jiménez FJOxidative stress in skin fibroblasts cultures from patients with Parkinson's diseaseBMC Neurol.(2010 Oct 19)
218.^del Hoyo P, García-Redondo A, de Bustos F, Molina JA, Sayed Y, Alonso-Navarro H, Caballero L, Arenas J, Jiménez-Jiménez FJOxidative stress in skin fibroblasts cultures of patients with Huntington's diseaseNeurochem Res.(2006 Sep)
219.^Cordero MD, Moreno-Fernández AM, Carmona-López MI, Sánchez-Alcázar JA, Rodríguez AF, Navas P, de Miguel MMitochondrial dysfunction in skin biopsies and blood mononuclear cells from two cases of fibromyalgia patientsClin Biochem.(2010 Sep)
220.^Prahl S, Kueper T, Biernoth T, Wöhrmann Y, Münster A, Fürstenau M, Schmidt M, Schulze C, Wittern KP, Wenck H, Muhr GM, Blatt TAging skin is functionally anaerobic: importance of coenzyme Q10 for anti aging skin careBiofactors.(2008)
222.^Zhang M, Dang L, Guo F, Wang X, Zhao W, Zhao RCoenzyme Q(10) enhances dermal elastin expression, inhibits IL-1α production and melanin synthesis in vitroInt J Cosmet Sci.(2012 Jun)
223.^Inui M, Ooe M, Fujii K, Matsunaka H, Yoshida M, Ichihashi MMechanisms of inhibitory effects of CoQ10 on UVB-induced wrinkle formation in vitro and in vivoBiofactors.(2008)
224.^López LC, Quinzii CM, Area E, Naini A, Rahman S, Schuelke M, Salviati L, Dimauro S, Hirano MTreatment of CoQ(10) deficient fibroblasts with ubiquinone, CoQ analogs, and vitamin C: time- and compound-dependent effectsPLoS One.(2010 Jul 30)
225.^Felippi CC, Oliveira D, Ströher A, Carvalho AR, Van Etten EA, Bruschi M, Raffin RPSafety and efficacy of antioxidants-loaded nanoparticles for an anti-aging applicationJ Biomed Nanotechnol.(2012 Apr)
226.^Choi BS, Song HS, Kim HR, Park TW, Kim TD, Cho BJ, Kim CJ, Sim SSEffect of coenzyme Q10 on cutaneous healing in skin-incised miceArch Pharm Res.(2009 Jun)
227.^Cordero MD, De Miguel M, Moreno Fernández AM, Carmona López IM, Garrido Maraver J, Cotán D, Gómez Izquierdo L, Bonal P, Campa F, Bullon P, Navas P, Sánchez Alcázar JAMitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the diseaseArthritis Res Ther.(2010)
228.^Cordero MD, Cano-García FJ, Alcocer-Gómez E, De Miguel M, Sánchez-Alcázar JAOxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q₁₀ effect on clinical improvementPLoS One.(2012)
229.^Cordero MD, Moreno-Fernández AM, deMiguel M, Bonal P, Campa F, Jiménez-Jiménez LM, Ruiz-Losada A, Sánchez-Domínguez B, Sánchez Alcázar JA, Salviati L, Navas PCoenzyme Q10 distribution in blood is altered in patients with fibromyalgiaClin Biochem.(2009 May)
230.^Cordero MD, Santos-García R, Bermejo-Jover D, Sánchez-Domínguez B, Jaramillo-Santos MR, Bullón PCoenzyme Q10 in salivary cells correlate with blood cells in Fibromyalgia: improvement in clinical and biochemical parameter after oral treatmentClin Biochem.(2012 Apr)
231.^Cordero MD, de Miguel M, Carmona-López I, Bonal P, Campa F, Moreno-Fernández AMOxidative stress and mitochondrial dysfunction in fibromyalgiaNeuro Endocrinol Lett.(2010)
232.^Cordero MD, Cotán D, del-Pozo-Martín Y, Carrión AM, de Miguel M, Bullón P, Sánchez-Alcazar JAOral coenzyme Q10 supplementation improves clinical symptoms and recovers pathologic alterations in blood mononuclear cells in a fibromyalgia patientNutrition.(2012 Nov-Dec)
233.^Cordero MD, Alcocer-Gómez E, de Miguel M, Cano-García FJ, Luque CM, Fernández-Riejo P, Fernández AM, Sánchez-Alcazar JACoenzyme Q(10): a novel therapeutic approach for Fibromyalgia? case series with 5 patientsMitochondrion.(2011 Jul)
234.^Cordero MD, Alcocer-Gómez E, de Miguel M, Culic O, Carrión AM, Alvarez-Suarez JM, Bullon P, Battino M, Fernández-Rodríguez A, Sánchez-Alcázar JACan Coenzyme Q10 improve clinical and molecular parameter in FibromyalgiaAntioxid Redox Signal.(2013 Mar 4)
235.^Miyamae T, Seki M, Naga T, Uchino S, Asazuma H, Yoshida T, Iizuka Y, Kikuchi M, Imagawa T, Natsumeda Y, Yokota S, Yamamoto YIncreased oxidative stress and coenzyme Q10 deficiency in juvenile fibromyalgia: amelioration of hypercholesterolemia and fatigue by ubiquinol-10 supplementationRedox Rep.(2013)
236.^Goldstone APPrader-Willi syndrome: advances in genetics, pathophysiology and treatmentTrends Endocrinol Metab.(2004 Jan-Feb)
237.^Miller JL, Lynn CH, Shuster J, Driscoll DJCarnitine and coenzyme Q10 levels in individuals with Prader-Willi syndromeAm J Med Genet A.(2011 Mar)
238.^Eiholzer U, Meinhardt U, Rousson V, Petrovic N, Schlumpf M, l'Allemand DDevelopmental profiles in young children with Prader-Labhart-Willi syndrome: effects of weight and therapy with growth hormone or coenzyme Q10Am J Med Genet A.(2008 Apr 1)
240.^Bentler SE, Hartz AJ, Kuhn EMProspective observational study of treatments for unexplained chronic fatigueJ Clin Psychiatry.(2005 May)
242.^Mikirova N, Casciari J, Hunninghake RThe assessment of the energy metabolism in patients with chronic fatigue syndrome by serum fluorescence emissionAltern Ther Health Med.(2012 Jan-Feb)
243.^Mancini A, Milardi D, Conte G, Festa R, De Marinis L, Littarru GPSeminal antioxidants in humans: preoperative and postoperative evaluation of coenzyme Q10 in varicocele patientsHorm Metab Res.(2005 Jul)
244.^Balercia G, Mancini A, Paggi F, Tiano L, Pontecorvi A, Boscaro M, Lenzi A, Littarru GPCoenzyme Q10 and male infertilityJ Endocrinol Invest.(2009 Jul)
245.^Mancini A, Balercia GCoenzyme Q(10) in male infertility: physiopathology and therapyBiofactors.(2011 Sep-Oct)
246.^Balercia G, Armeni T, Mantero F, Principato G, Regoli FTotal oxyradical scavenging capacity toward different reactive oxygen species in seminal plasma and sperm cellsClin Chem Lab Med.(2003 Jan)
247.^Aitken RJ, Clarkson JS, Fishel SGeneration of reactive oxygen species, lipid peroxidation, and human sperm functionBiol Reprod.(1989 Jul)
248.^Aitken RJ, Baker MA, De Iuliis GN, Nixon BNew insights into sperm physiology and pathologyHandb Exp Pharmacol.(2010)
249.^Desai N, Sabanegh E Jr, Kim T, Agarwal AFree radical theory of aging: implications in male infertilityUrology.(2010 Jan)
250.^Fawcett DWThe mammalian spermatozoonDev Biol.(1975 Jun)
252.^Aitken RJ, Buckingham DW, Brindle J, Gomez E, Baker HW, Irvine DSAnalysis of sperm movement in relation to the oxidative stress created by leukocytes in washed sperm preparations and seminal plasmaHum Reprod.(1995 Aug)
255.^Wolff H, Politch JA, Martinez A, Haimovici F, Hill JA, Anderson DJLeukocytospermia is associated with poor semen qualityFertil Steril.(1990 Mar)
256.^Mancini A, Milardi D, Conte G, Bianchi A, Balercia G, De Marinis L, Littarru GPCoenzyme Q10: another biochemical alteration linked to infertility in varicocele patientsMetabolism.(2003 Apr)
257.^Mancini A, Leone E, Festa R, Grande G, Silvestrini A, de Marinis L, Pontecorvi A, Maira G, Littarru GP, Meucci EEffects of testosterone on antioxidant systems in male secondary hypogonadismJ Androl.(2008 Nov-Dec)
258.^Mancini A, Leone E, Silvestrini A, Festa R, Di Donna V, De Marinis L, Pontecorvi A, Littarru GP, Meucci EEvaluation of antioxidant systems in pituitary-adrenal axis diseasesPituitary.(2010 Jun)
259.^Balercia G, Mosca F, Mantero F, Boscaro M, Mancini A, Ricciardo-Lamonica G, Littarru GCoenzyme Q(10) supplementation in infertile men with idiopathic asthenozoospermia: an open, uncontrolled pilot studyFertil Steril.(2004 Jan)
260.^Balercia G, Buldreghini E, Vignini A, Tiano L, Paggi F, Amoroso S, Ricciardo-Lamonica G, Boscaro M, Lenzi A, Littarru GCoenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trialFertil Steril.(2009 May)
261.^Angelitti AG, Colacicco L, Callà C, Arizzi M, Lippa SCoenzyme Q: potentially useful index of bioenergetic and oxidative status of spermatozoaClin Chem.(1995 Feb)
262.^Mancini A, Conte G, Milardi D, De Marinis L, Littarru GPRelationship between sperm cell ubiquinone and seminal parameters in subjects with and without varicoceleAndrologia.(1998 Feb-Mar)
263.^Naughton CK, Nangia AK, Agarwal APathophysiology of varicoceles in male infertilityHum Reprod Update.(2001 Sep-Oct)
264.^Lewin A, Lavon HThe effect of coenzyme Q10 on sperm motility and functionMol Aspects Med.(1997)
266.^Pryor J, Akkus E, Alter G, Jordan G, Lebret T, Levine L, Mulhall J, Perovic S, Ralph D, Stackl WPeyronie's diseaseJ Sex Med.(2004 Jul)
267.^Lindsay MB, Schain DM, Grambsch P, Benson RC, Beard CM, Kurland LTThe incidence of Peyronie's disease in Rochester, Minnesota, 1950 through 1984J Urol.(1991 Oct)
272.^Duguez S, Féasson L, Denis C, Freyssenet DMitochondrial biogenesis during skeletal muscle regenerationAm J Physiol Endocrinol Metab.(2002 Apr)
273.^Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BMMechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1Cell.(1999 Jul 9)
274.^Turchanowa L, Rogozkin VA, Milovic V, Feldkoren BI, Caspary WF, Stein JInfluence of physical exercise on polyamine synthesis in the rat skeletal muscleEur J Clin Invest.(2000 Jan)
275.^Lee NK, MacLean HEPolyamines, androgens, and skeletal muscle hypertrophyJ Cell Physiol.(2011 Jun)
276.^Buhaescu I, Izzedine HMevalonate pathway: a review of clinical and therapeutical implicationsClin Biochem.(2007 Jun)
277.^Jeng KC, Chen CS, Fang YP, Hou RC, Chen YSEffect of microbial fermentation on content of statin, GABA, and polyphenols in Pu-Erh teaJ Agric Food Chem.(2007 Oct 17)
278.^Keith M, Mazer CD, Mikhail P, Jeejeebhoy F, Briet F, Errett LCoenzyme Q10 in patients undergoing CABG: Effect of statins and nutritional supplementationNutr Metab Cardiovasc Dis.(2008 Feb)
279.^Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, Greco AV, Littarru GPEvidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled studyJ Clin Pharmacol.(1993 Mar)
281.^Nielsen ML, Pareek M, Henriksen JEReduced synthesis of coenzyme Q10 may cause statin related myopathyUgeskr Laeger.(2011 Nov 14)
282.^Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger AEffect of atorvastatin on left ventricular diastolic function and ability of coenzyme Q10 to reverse that dysfunctionAm J Cardiol.(2004 Nov 15)
283.^Sikka P, Kapoor S, Bindra VK, Sharma M, Vishwakarma P, Saxena KKStatin intolerance: now a solved problemJ Postgrad Med.(2011 Oct-Dec)
284.^Harper CR, Jacobson TAEvidence-based management of statin myopathyCurr Atheroscler Rep.(2010 Sep)
285.^Wyman M, Leonard M, Morledge TCoenzyme Q10: a therapy for hypertension and statin-induced myalgiaCleve Clin J Med.(2010 Jul)
286.^Toyama K, Sugiyama S, Oka H, Iwasaki Y, Sumida H, Tanaka T, Tayama S, Jinnouchi H, Matsui K, Ogawa HRosuvastatin combined with regular exercise preserves coenzyme Q10 levels associated with a significant increase in high-density lipoprotein cholesterol in patients with coronary artery diseaseAtherosclerosis.(2011 Jul)
288.^Honda Y, Ushigome F, Koyabu N, Morimoto S, Shoyama Y, Uchiumi T, Kuwano M, Ohtani H, Sawada YEffects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug effluxBr J Pharmacol.(2004 Dec)
290.^Belcaro G, Cesarone MR, Dugall M, Hosoi M, Ippolito E, Bavera P, Grossi MGInvestigation of Pycnogenol® in combination with coenzymeQ10 in heart failure patients (NYHA II/III)Panminerva Med.(2010 Jun)
291.^Hidaka T, Fujii K, Funahashi I, Fukutomi N, Hosoe KSafety assessment of coenzyme Q10 (CoQ10)Biofactors.(2008)
292.^Marcoff L, Thompson PDThe role of coenzyme Q10 in statin-associated myopathy: a systematic reviewJ Am Coll Cardiol.(2007 Jun 12)
293.^Rosenfeldt FL, Haas SJ, Krum H, Hadj A, Ng K, Leong JY, Watts GFCoenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trialsJ Hum Hypertens.(2007 Apr)
295.^Ferrante KL, Shefner J, Zhang H, Betensky R, O'Brien M, Yu H, Fantasia M, Taft J, Beal MF, Traynor B, Newhall K, Donofrio P, Caress J, Ashburn C, Freiberg B, O'Neill C, Paladenech C, Walker T, Pestronk A, Abrams B, Florence J, Renna R, Schierbecker J, Malkus B, Cudkowicz MTolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALSNeurology.(2005 Dec 13)
296.^Shults CW, Flint Beal M, Song D, Fontaine DPilot trial of high dosages of coenzyme Q10 in patients with Parkinson's diseaseExp Neurol.(2004 Aug)
298.^Ikematsu H, Nakamura K, Harashima S, Fujii K, Fukutomi NSafety assessment of coenzyme Q10 (Kaneka Q10) in healthy subjects: a double-blind, randomized, placebo-controlled trialRegul Toxicol Pharmacol.(2006 Apr)