Coenzyme Q10 (CoQ10): Difference between revisions

Latest revision as of 03:32, 21 January 2024

Coenzyme Q₁₀ (CoQ₁₀), a lipophilic substituted benzoquinone, is a naturally occurring nutrient found within every cell of both animal and plant cells. It is endogenously synthesized and plays a critical role in a variety of cellular processes. CoQ₁₀ is an obligatory component of the respiratory chain in the inner mitochondrial membrane and is also the only endogenous lipid antioxidant, highlighting its singular importance in cellular health and function. Its presence is not limited to the mitochondria but extends to all cellular membranes and is detectable in the blood.

Dietary Sources

Vegetable oils are the richest sources of dietary CoQ₁₀; Meat and fish also are quite rich in CoQ₁₀ levels over 50 mg/kg may be found in beef, pork, and chicken heart and liver. Dairy products are much poorer sources of CoQ₁₀ than animal tissues. Among vegetables, parsley and perilla are the richest CoQ₁₀ sources, but significant differences in their CoQ₁₀ levels may be found in the literature. Broccoli, grapes, and cauliflower are modest sources of CoQ₁₀. Most fruit and berries represent a poor to very poor source of CoQ₁₀, with the exception of avocados, which have a relatively high CoQ₁₀

CoQ₁₀ levels in selected foods^[1]
Food		CoQ₁₀ concentration (mg/kg)
Oils	soybean	54–280
	olive	40–160
	grapeseed	64–73
	sunflower	4–15
	canola	64–73
Beef	heart	113
	liver	39–50
	muscle	26–40
Pork	heart	12–128
	liver	23–54
	muscle	14–45
Chicken	breast	8–17
	thigh	24–25
	wing	11
Fish	sardine	5–64
	mackerel (red flesh)	43–67
	mackerel (white flesh)	11–16
	salmon	4–8

Intake

In the developed world, the estimated daily intake of CoQ₁₀ has been determined at 3–6 mg per day, derived primarily from meat.^[1]

South Koreans have an estimated average daily CoQ (Q₉ + Q₁₀) intake of 11.6 mg/d, derived primarily from kimchi.^[2]

Effect of heat and processing

Cooking by frying reduces CoQ₁₀ content by 14–32%.^[3]

Legal

United States (US)

CoQ₁₀ is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of any medical condition.^[4]^[5] However, it is sold as a dietary supplement in the name of UbiQ 300 & UbiQ 100, not subject to the same regulations as medicinal drugs, and is an ingredient in some cosmetics.^[6]^[7] The manufacture of CoQ₁₀ is not regulated, and different batches and brands may vary significantly:^[4] a 2004 laboratory analysis of CoQ₁₀ supplements on sale in the US found that some did not contain the quantity identified on the product label. Amounts ranged from "no detectable CoQ₁₀", through 75% of stated dose, up to a 75% excess.^[8]

Absorption and Metabolism

Absorption

CoQ₁₀ is a crystalline powder insoluble in water. Absorption follows the same process as that of lipids; the uptake mechanism appears to be similar to that of vitamin E, another lipid-soluble nutrient. This process in the human body involves secretion into the small intestine of pancreatic enzymes and bile, which facilitates emulsification and micelle formation required for absorption of lipophilic substances.^[9] Food intake (and the presence of lipids) stimulates bodily biliary excretion of bile acids and greatly enhances absorption of CoQ₁₀. Exogenous CoQ₁₀ is absorbed from the small intestine and is best absorbed if taken with a meal. Serum concentration of CoQ₁₀ in fed condition is higher than in fasting conditions.^[10]

Metabolism

A study with ¹⁴C-labeled CoQ₁₀ in rats showed most of the radioactivity in the liver two hours after oral administration when the peak plasma radioactivity was observed, but CoQ₉ (with only 9 isoprenyl units) is the predominant form of coenzyme Q in rats.^[11] It appears that CoQ₁₀ is metabolised in all tissues, while a major route for its elimination is biliary and fecal excretion. After the withdrawal of CoQ₁₀ supplementation, the levels return to normal within a few days, irrespective of the type of formulation used.^[12]

Pharmacokinetics

Some reports have been published on the pharmacokinetics of CoQ₁₀. The plasma peak can be observed 2–6 hours after oral administration, depending mainly on the design of the study. In some studies, a second plasma peak also was observed at approximately 24 hours after administration, probably due to both enterohepatic recycling and redistribution from the liver to circulation.^[9] Tomono et al. used deuterium-labeled crystalline CoQ10 to investigate pharmacokinetics in humans and determined an elimination half-time of 33 hours.^[13]

Biochemical Function

CoQ₁₀ is integral to the electron transport chain on the inner membrane of mitochondria, facilitating the conversion of electrons from food into ATP. Its roles, however, extend beyond energy production. It is essential for uncoupling proteins and controls the permeability transition pore in mitochondria. Additionally, CoQ₁₀ is involved in extramitochondrial electron transport and affects membrane physicochemical properties. It impacts gene expression, which can alter overall metabolism. The primary alterations in energetic and antioxidant functions are believed to underpin its therapeutic effects ^[14].

Potential Longevity Benefits

Lifespan

Cellular and Molecular Roles

As the only endogenous lipid antioxidant, CoQ₁₀ is critical in neutralizing free radicals, thus protecting against DNA damage and cellular dysfunction that are symptomatic of aging. By preserving cellular integrity, CoQ₁₀'s antioxidant action is proposed to impede aging and potentially extend cellular lifespan.

It also contributes to the regulation of mitochondrial function, such as influencing uncoupling proteins and the mitochondrial permeability transition pore, which are crucial for cell survival and apoptosis, respectively. Such regulation is particularly important as mitochondrial dysfunction is a noted characteristic of aging ^[14].

Potential Therapeutic Role

CoQ10 has been widely researched for its potential in various health applications, including physical fitness, fertility, antiaging, diabetes management, and heart failure treatment. The therapeutic effects of CoQ10 are attributed to its enhancement of oxidative phosphorylation and its ability to mitigate oxidative stress.

Neurological Diseases

Clinical and experimental studies indicate that CoQ₁₀ supplementation may exert beneficial effects on neurological diseases such as migraine, Parkinson's disease, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Friedreich’s ataxia, and multiple sclerosis.^[14]

Hypertension

It is also of interest in the context of central mechanisms controlling blood pressure due to its effects on the brainstem rostral ventrolateral medulla and the hypothalamic paraventricular nucleus, which are related to cardiovascular hypertension.^[14]

Diabetic Retinopathy

A particular area of interest is how CoQ₁₀ might help with a condition called diabetic retinopathy, which is a leading cause of blindness in adults. High blood sugar in diabetes can harm tiny blood vessels in the eye, leading to this condition. The damage causes stress to the eye and can lead to the growth of unhealthy blood vessels, worsening the problem [Citations 55-57]. Since CoQ₁₀ can help the mitochondria work better and has antioxidant properties, it might be useful in treating this eye condition. ^[15]

Phase II clinical trials have been looking at CoQ₁₀ for an early diabetic retinopathy, also called non-proliferative diabetic retinopathy (NPDR). Patients who took 400 mg of CoQ₁₀ every day for 12 weeks to 6 months (different trials) showed improvements in blood flow and energy production in their cells compared to those who didn’t take it. These findings suggest that CoQ₁₀ could help slow down the worsening of this eye disease by improving blood supply and energy use in the eye, which could help prevent the eye damage from getting worse. More studies are needed to see if CoQ₁₀ can help stop diabetic retinopathy from progressing to more severe stages.^[15]

Safety and Dosage

Dosage

While there is no established ideal dosage of CoQ₁₀, a typical daily dose is 100–200 milligrams. Different formulations have varying declared amounts of CoQ₁₀ and other ingredients.

Safety

The safety profile of CoQ₁₀ is notably benign, with it being well-tolerated even at high doses.^[14]

Side Effects

It does not induce serious adverse effects in either humans or experimental animals. Minor side effects may include stomach upset, loss of appetite, nausea, and headaches.^[14]

Interactions

CoQ₁₀'s interaction with various medications necessitates a consultation with a healthcare professional before beginning supplementation:

Theophylline: CoQ₁₀ potential to inhibit the effects of theophylline
Blood thinner warfarin: CoQ₁₀ may interfere with warfarin's actions by interacting with cytochrome p450 enzymes thereby reducing the INR, a measure of blood clotting.^[16] The structure of coenzyme Q₁₀ is very similar to that of vitamin K, which competes with and counteracts warfarin's anticoagulation effects. Coenzyme Q₁₀ should be avoided in patients currently taking warfarin due to the increased risk of clotting.^[17]
Chemotherapy drugs^[14]

Todo

2020, Comparative Bioavailability of Different Coenzyme Q10 Formulations in Healthy Elderly Individuals ^[18]
Formulations
2019, Coenzyme Q₁₀ ^[19]
2023, Coenzyme Q10 Metabolism: A Review of Unresolved Issues ^[20]

References

↑ ^{Jump up to: 1.0} ^1.1 Pravst I et al.: Coenzyme Q10 contents in foods and fortification strategies. Crit Rev Food Sci Nutr 2010. (PMID 20301015) [PubMed] [DOI] Abstract
Coenzyme Q10 (CoQ(10)) is an effective natural antioxidant with a fundamental role in cellular bioenergetics and numerous known health benefits. Reports of its natural occurrence in various food items are comprehensively reviewed and critically evaluated. Meat, fish, nuts, and some oils are the richest nutritional sources of CoQ(10), while much lower levels can be found in most dairy products, vegetables, fruits, and cereals. Large variations of CoQ(10) content in some foods and food products of different geographical origin have been found. The average dietary intake of CoQ(10) is only 3-6 mg, with about half of it being in the reduced form. The intake can be significantly increased by the fortification of food products but, due to its lipophilicity, until recently this goal was not easily achievable particularly with low-fat, water-based products. Forms of CoQ(10) with increased water-solubility or dispersibility have been developed for this purpose, allowing the fortification of aqueous products, and exhibiting improved bioavailability; progress in this area is described briefly. Three main fortification strategies are presented and illustrated with examples, namely the addition of CoQ(10) to food during processing, the addition of this compound to the environment in which primary food products are being formed (i.e. animal feed), or with the genetic modification of plants (i.e. cereal crops).
↑ Y.H. Pyo, H.J. Oh: Ubiquinone contents in Korean fermented foods and average daily intakes, 2011 [DOI]
↑ Weber C et al.: The coenzyme Q10 content of the average Danish diet. Int J Vitam Nutr Res 1997. (PMID 9129255) [PubMed] Abstract
The average dietary intake of coenzyme Q10 and coenzyme Q9 of the Danish population was determined, based on food consumption data from a national dietary survey. Selected food items in edible form were analyzed for the coenzyme Q content by HPCL with UV-detection, and their contribution to the total intake calculated. The effect of cooking was a 14-32% destruction of coenzyme Q10 by frying, and no detectable destruction by boiling. The average coenzyme Q10 intake of the Danish population was estimated to 3-5 mg/day, primarily derived from meat and poultry (64% of the daily intake), while cereals, fruit, edible fats, and vegetables only make minor contributions. The intake of coenzyme Q10 is approximately 1 mg/day, primarily derived from vegetable fats and cereals. The alpha-tocopherol content of the selected food samples was analyzed by HPLC with fluorescence detection, and the calculated average intake of alpha-tocopherol was comparable to the estimate from the dietary survey (7-8 vs. 7.4 mg alpha-tocopherol/day, respectively). The commercially available dietary supplements (capsules) provide 10-30 mg CoQ10/day, thus the average diet. The optimal dietary intake of coenzyme Q10 is unknown.
↑ ^{Jump up to: 4.0} ^4.1 PDQ® Coenzyme Q₁₀, http://www.cancer.gov/cancertopics/pdq/cam/coenzymeQ10/HealthProfessional
↑ Mitochondrial disorders in children: Co-enzyme Q10, https://www.nice.org.uk/advice/es11/resources/mitochondrial-disorders-in-children-coenzyme-q10-pdf-1158110303173
↑ Hojerová et al.; "[Coenzyme Q10--its importance, properties and use in nutrition and cosmetics]."
↑ What is coenzyme Q10 (CoQ10) and why is it in skin care products?, https://www.webmd.com/beauty/qa/what-is-coenzyme-q10-coq10-and-why-is-it-in-skin-care-products
↑ ConsumerLab.com finds discrepancies in strength of CoQ₁₀ supplements, https://www.consumerlab.com/news/coq10-coenzyme-q10-tests/01-13-2004/
↑ ^{Jump up to: 9.0} ^9.1 Bhagavan HN & Chopra RK: Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res 2006. (PMID 16551570) [PubMed] [DOI] Abstract
Available data on the absorption, metabolism and pharmacokinetics of coenzyme Q10 (CoQ10) are reviewed in this paper. CoQ10 has a fundamental role in cellular bioenergetics. CoQ10 is also an important antioxidant. Because of its hydrophobicity and large molecular weight, absorption of dietary CoQ10 is slow and limited. In the case of dietary supplements, solubilized CoQ10 formulations show enhanced bioavailability. The T(max) is around 6 h, with an elimination half-life of about 33 h. The reference intervals for plasma CoQ10 range from 0.40 to 1.91 micromol/l in healthy adults. With CoQ10 supplements there is reasonable correlation between increase in plasma CoQ10 and ingested dose up to a certain point. Animal data show that CoQ10 in large doses is taken up by all tissues including heart and brain mitochondria. This has implications for therapeutic applications in human diseases, and there is evidence for its beneficial effect in cardiovascular and neurodegenerative diseases. CoQ10 has an excellent safety record.
↑ Ochiai A et al.: Improvement in intestinal coenzyme q10 absorption by food intake. Yakugaku Zasshi 2007. (PMID 17666877) [PubMed] [DOI] Abstract
Coenzyme Q10 (CoQ10) is widely consumed as a food supplement because of its recognition as an important nutrient in supporting human health. Absorption of compounds from the gastrointestinal tract is one of the important determinants of oral bioavailability. However, the absorption of dietary CoQ10 is slow and limited due to its hydrophobicity and large molecular weight. The absorption of orally applied compounds can be enhanced by interactions with food or food components. Thus, we investigated the effect of food intake on the absorption of CoQ10 after oral supplementation. In this study, we demonstrated that food intake enhanced the intestinal absorption of CoQ10. In order to improve intestinal absorption of CoQ10 after oral supplementation, we developed an emulsion formulation. Intestinal absorption of CoQ10 after administration of the emulsion formulation was also enhanced by food intake. Moreover, the peak concentration and the extent of absorption after administration of the emulsion formulation were greater than those after administration of a suspension formulation. It is possible that administration of CoQ10 in an emulsion formulation enhances the pharmacological effects of CoQ10.
↑ Kishi et al.; "Biomedical and Clinical Aspects of Coenzyme Q"
↑ Ozawa Y et al.: Intestinal absorption enhancement of coenzyme Q10 with a lipid microsphere. Arzneimittelforschung 1986. (PMID 3718593) [PubMed] Abstract
Coenzyme Q10 (ubidecarenone; CoQ10) was administered at a dose of 60 mg/d either using two conventional formulations or in a lipid microsphere to dogs. Plasma concentrations of CoQ10 were determined by HPLC. The bioavailability of CoQ10 from the lipid microsphere formulation was superior to conventional formulations. These results suggest that three daily administrations of the new formulation should be suitable for therapeutic use.
↑ Tomono Y et al.: Pharmacokinetic study of deuterium-labelled coenzyme Q10 in man. Int J Clin Pharmacol Ther Toxicol 1986. (PMID 3781673) [PubMed] Abstract
The pharmacokinetics of coenzyme Q10 (CoQ10) in man was studied by utilizing deuterium-labelled coenzyme Q10 (d5-CoQ10). The absence of an isotope effect in the disposition of d5-CoQ10 in man was confirmed from the plasma concentration time curves after simultaneous oral dosing of d5-CoQ10 and unlabelled CoQ10. After oral administration of 100 mg of d5-CoQ10 to 16 healthy male subjects, the mean plasma CoQ10 level attained a peak of 1.004 +/- 0.370 micrograms/ml at 6.5 +/- 1.5 h after administration, and the terminal elimination half-life was 33.19 +/- 5.32 h. In most of the subjects, plasma d5-CoQ10 showed a second peak at 24 h after dosing. This unusual plasma level curve was well described by a newly proposed compartment model based upon the assumption that absorbed CoQ10 is taken up by the liver and then transferred mainly to VLDL and redistributed from the liver to the systemic blood.
↑ ^{Jump up to: 14.0} ^14.1 ^14.2 ^14.3 ^14.4 ^14.5 ^14.6 Rauchová H: Coenzyme Q10 effects in neurological diseases. Physiol Res 2021. (PMID 35199552) [PubMed] [DOI] [Full text] Abstract
Coenzyme Q10 (CoQ10), a lipophilic substituted benzoquinone, is present in animal and plant cells. It is endogenously synthetized in every cell and involved in a variety of cellular processes. CoQ10 is an obligatory component of the respiratory chain in inner mitochondrial membrane. In addition, the presence of CoQ10 in all cellular membranes and in blood. It is the only endogenous lipid antioxidant. Moreover, it is an essential factor for uncoupling protein and controls the permeability transition pore in mitochondria. It also participates in extramitochondrial electron transport and controls membrane physicochemical properties. CoQ10 effects on gene expression might affect the overall metabolism. Primary changes in the energetic and antioxidant functions can explain its remedial effects. CoQ10 supplementation is safe and well-tolerated, even at high doses. CoQ10 does not cause any serious adverse effects in humans or experimental animals. New preparations of CoQ10 that are less hydrophobic and structural derivatives, like idebenone and MitoQ, are being developed to increase absorption and tissue distribution. The review aims to summarize clinical and experimental effects of CoQ10 supplementations in some neurological diseases such as migraine, Parkinson´s disease, Huntington´s disease, Alzheimer´s disease, amyotrophic lateral sclerosis, Friedreich´s ataxia or multiple sclerosis. Cardiovascular hypertension was included because of its central mechanisms controlling blood pressure in the brainstem rostral ventrolateral medulla and hypothalamic paraventricular nucleus. In conclusion, it seems reasonable to recommend CoQ10 as adjunct to conventional therapy in some cases. However, sometimes CoQ10 supplementations are more efficient in animal models of diseases than in human patients (e.g. Parkinson´s disease) or rather vague (e.g. Friedreich´s ataxia or amyotrophic lateral sclerosis).
↑ ^{Jump up to: 15.0} ^15.1 Hill D et al.: Investigational neuroprotective compounds in clinical trials for retinal disease. Expert Opin Investig Drugs 2021. (PMID 33641585) [PubMed] [DOI] Abstract
INTRODUCTION: Retinal neurodegeneration causes irreversible vision loss, impairing quality of life. By targeting neurotoxic conditions, such as oxidative stress and ischemia, neuroprotectants can slow or stop sight loss resulting from eye disease. Despite limimted clinical use of neuroprotectants, there are several promising compounds in early clinical trials (pre-phase III) which may fulfil new therapeutic roles. Search terms relating to neuroprotection and eye disease were used on ClinicalTrials.gov to identify neuroprotective candidates. AREAS COVERED: Research supporting neuroprotection in eye diseases is focused on, ranging from preclinical to phase II, according to the ClinicalTrials.gov database. The compounds discussed are explored in terms of future clinical applications. EXPERT OPINION: The major challenge in neuroprotection research is translation from basic research to the clinic. A number of potential neuroprotectants have progressed to ophthalmology clinical trials in recent years, with defined mechanisms of action - saffron and CoQ10 - targeting mitochondria, and both CNTF and NGF showing anti-apoptotic effects. Enhancements in trial design and patient cohorts in proof-of-concept trials with enriched patient populations and surrogate endpoints should accelerate drug development. A further important consideration is optimising drug delivery to improve individualised management and patient compliance. Progress in these areas means that neuroprotective strategies have a much improved chance of translational success.
↑ Sharma A et al.: Coenzyme Q10 and Heart Failure: A State-of-the-Art Review. Circ Heart Fail 2016. (PMID 27012265) [PubMed] [DOI] Abstract
Heart failure (HF) with either preserved or reduced ejection fraction is associated with increased morbidity and mortality. Evidence-based therapies are often limited by tolerability, hypotension, electrolyte disturbances, and renal dysfunction. Coenzyme Q10 (CoQ10) may represent a safe therapeutic option for patients with HF. CoQ10 is a highly lipophilic molecule with a chemical structure similar to vitamin K. Although being a common component of cellular membranes, CoQ10's most prominent role is to facilitate the production of adenosine triphosphate in the mitochondria by participating in redox reactions within the electron transport chain. Numerous trials during the past 30 years examining CoQ10 in patients with HF have been limited by small numbers and lack of contemporary HF therapies. The recent publication of the Q-SYMBIO randomized controlled trial demonstrated a reduction in major adverse cardiovascular events with CoQ10 supplementation in a contemporary HF population. Although having limitations, this study has renewed interest in evaluating CoQ10 supplementation in patients with HF. Current literature suggests that CoQ10 is relatively safe with few drug interactions and side effects. Furthermore, it is already widely available as an over-the-counter supplement. These findings warrant future adequately powered randomized controlled trials of CoQ10 supplementation in patients with HF. This state-of-the-art review summarizes the literature about the mechanisms, clinical data, and safety profile of CoQ10 supplementation in patients with HF.
↑ Wyman M et al.: Coenzyme Q10: a therapy for hypertension and statin-induced myalgia?. Cleve Clin J Med 2010. (PMID 20601617) [PubMed] [DOI] Abstract
Some small clinical trials seem to show that coenzyme Q10 supplements can be used to lower blood pressure and to treat or prevent myalgia caused by hydroxymethylglutaryl coenzyme A reductase inhibitors (statins). However, larger trials are needed to determine if they are truly effective for these purposes. The authors examine the evidence and also discuss issues such as bioavailability, elimination, safety, and cost.
↑ Pravst I et al.: Comparative Bioavailability of Different Coenzyme Q10 Formulations in Healthy Elderly Individuals. Nutrients 2020. (PMID 32188111) [PubMed] [DOI] [Full text] Abstract
Coenzyme Q10 (CoQ10) plays a central role in mitochondrial oxidative phosphorylation. Several studies have shown the beneficial effects of dietary CoQ10 supplementation, particularly in relation to cardiovascular health. CoQ10 biosynthesis decreases in the elderly, and consequently, the beneficial effects of dietary supplementation in this population are of greater significance. However, most pharmacokinetic studies have been conducted on younger populations. The aim of this study was to investigate the single-dose bioavailability of different formulations of CoQ10 in a healthy geriatric population. A randomized, three-period, crossover bioavailability study was conducted on 21 healthy older adults (aged 65-74). The treatment was a single dose with a one-week washout period. Three different formulations containing the equivalent of 100 mg of CoQ10 were used: Q10Vital® water-soluble CoQ10 syrup (the investigational product-IP); ubiquinol capsules (the comparative product-CP); and ubiquinone capsules (the standard product-SP). Ubiquinone/ubiquinol was followed in the plasma for 48 h. An analysis of the ratio of the area under the baseline-corrected concentration curve (ΔAUC48) for total CoQ10 and a comparison to SP yielded the following: The bioavailability of CoQ10 in the IP was 2.4-fold higher (95% CI: 1.3-4.5; p = 0.002), while the bioavailability of ubiquinol (CP) was not significantly increased (1.7-fold; 95% CI: 0.9-3.1, p = 0.129). No differences in the redox status of the absorbed coenzyme Q10 were observed between formulations, showing that CoQ10 appeared in the blood mostly as ubiquinol, even if consumed as ubiquinone.
↑ Raizner AE: Coenzyme Q₁₀. Methodist Debakey Cardiovasc J 2019. (PMID 31687097) [PubMed] [DOI] [Full text] Abstract
Coenzyme Q10 (CoQ10) is among the most widely used dietary and nutritional supplements on the market. CoQ10 has several fundamental properties that may be beneficial in several clinical situations. This article reviews the pertinent chemical, metabolic, and physiologic properties of CoQ10 and the scientific data and clinical trials that address its use in two common clinical settings: statin-associated myopathy syndrome (SAMS) and congestive heart failure (CHF). Although clinical trials of CoQ10 in SAMS have conflicting conclusions, the weight of the evidence, as seen in meta-analyses, supports the use of CoQ10 in SAMS overall. In CHF, there is a lack of large-scale randomized clinical trial data regarding the use of statins in patients receiving contemporary treatment. However, one relatively recent randomized clinical trial, Q-SYMBIO, suggests an adjunctive role for CoQ10 in CHF. Recommendations regarding the use of CoQ10 in these clinical situations are presented.
↑ Mantle D et al.: Coenzyme Q10 Metabolism: A Review of Unresolved Issues. Int J Mol Sci 2023. (PMID 36768907) [PubMed] [DOI] [Full text] Abstract
The variable success in the outcome of randomised controlled trials supplementing coenzyme Q10 (CoQ10) may in turn be associated with a number of currently unresolved issues relating to CoQ10 metabolism. In this article, we have reviewed what is currently known about these factors and where gaps in knowledge exist that need to be further elucidated. Issues addressed include (i) whether the bioavailability of CoQ10 could be improved; (ii) whether CoQ10 could be administered intravenously; (iii) whether CoQ10 could be administered via alternative routes; (iv) whether CoQ10 can cross the blood-brain barrier; (v) how CoQ10 is transported into and within target cells; (vi) why some clinical trials supplementing CoQ10 may have been unsuccessful; and (vii) which is the most appropriate tissue for the clinical assessment of CoQ10 status.

[pmid20301015-1] {Jump up to: 1.0} ^1.1 Pravst I et al.: Coenzyme Q10 contents in foods and fortification strategies. Crit Rev Food Sci Nutr 2010. (PMID 20301015) [PubMed] [DOI] Abstract
Coenzyme Q10 (CoQ(10)) is an effective natural antioxidant with a fundamental role in cellular bioenergetics and numerous known health benefits. Reports of its natural occurrence in various food items are comprehensively reviewed and critically evaluated. Meat, fish, nuts, and some oils are the richest nutritional sources of CoQ(10), while much lower levels can be found in most dairy products, vegetables, fruits, and cereals. Large variations of CoQ(10) content in some foods and food products of different geographical origin have been found. The average dietary intake of CoQ(10) is only 3-6 mg, with about half of it being in the reduced form. The intake can be significantly increased by the fortification of food products but, due to its lipophilicity, until recently this goal was not easily achievable particularly with low-fat, water-based products. Forms of CoQ(10) with increased water-solubility or dispersibility have been developed for this purpose, allowing the fortification of aqueous products, and exhibiting improved bioavailability; progress in this area is described briefly. Three main fortification strategies are presented and illustrated with examples, namely the addition of CoQ(10) to food during processing, the addition of this compound to the environment in which primary food products are being formed (i.e. animal feed), or with the genetic modification of plants (i.e. cereal crops).

[10.1016/j.jfca.2011.03.018-2] Y.H. Pyo, H.J. Oh: Ubiquinone contents in Korean fermented foods and average daily intakes, 2011 [DOI]

[pmid9129255-3] Weber C et al.: The coenzyme Q10 content of the average Danish diet. Int J Vitam Nutr Res 1997. (PMID 9129255) [PubMed] Abstract
The average dietary intake of coenzyme Q10 and coenzyme Q9 of the Danish population was determined, based on food consumption data from a national dietary survey. Selected food items in edible form were analyzed for the coenzyme Q content by HPCL with UV-detection, and their contribution to the total intake calculated. The effect of cooking was a 14-32% destruction of coenzyme Q10 by frying, and no detectable destruction by boiling. The average coenzyme Q10 intake of the Danish population was estimated to 3-5 mg/day, primarily derived from meat and poultry (64% of the daily intake), while cereals, fruit, edible fats, and vegetables only make minor contributions. The intake of coenzyme Q10 is approximately 1 mg/day, primarily derived from vegetable fats and cereals. The alpha-tocopherol content of the selected food samples was analyzed by HPLC with fluorescence detection, and the calculated average intake of alpha-tocopherol was comparable to the estimate from the dietary survey (7-8 vs. 7.4 mg alpha-tocopherol/day, respectively). The commercially available dietary supplements (capsules) provide 10-30 mg CoQ10/day, thus the average diet. The optimal dietary intake of coenzyme Q10 is unknown.

[NCI-4] {Jump up to: 4.0} ^4.1 PDQ® Coenzyme Q₁₀, http://www.cancer.gov/cancertopics/pdq/cam/coenzymeQ10/HealthProfessional

[5] Mitochondrial disorders in children: Co-enzyme Q10, https://www.nice.org.uk/advice/es11/resources/mitochondrial-disorders-in-children-coenzyme-q10-pdf-1158110303173

[6] Hojerová et al.; "[Coenzyme Q10--its importance, properties and use in nutrition and cosmetics]."

[7] What is coenzyme Q10 (CoQ10) and why is it in skin care products?, https://www.webmd.com/beauty/qa/what-is-coenzyme-q10-coq10-and-why-is-it-in-skin-care-products

[8] ConsumerLab.com finds discrepancies in strength of CoQ₁₀ supplements, https://www.consumerlab.com/news/coq10-coenzyme-q10-tests/01-13-2004/

[pmid16551570-9] {Jump up to: 9.0} ^9.1 Bhagavan HN & Chopra RK: Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res 2006. (PMID 16551570) [PubMed] [DOI] Abstract
Available data on the absorption, metabolism and pharmacokinetics of coenzyme Q10 (CoQ10) are reviewed in this paper. CoQ10 has a fundamental role in cellular bioenergetics. CoQ10 is also an important antioxidant. Because of its hydrophobicity and large molecular weight, absorption of dietary CoQ10 is slow and limited. In the case of dietary supplements, solubilized CoQ10 formulations show enhanced bioavailability. The T(max) is around 6 h, with an elimination half-life of about 33 h. The reference intervals for plasma CoQ10 range from 0.40 to 1.91 micromol/l in healthy adults. With CoQ10 supplements there is reasonable correlation between increase in plasma CoQ10 and ingested dose up to a certain point. Animal data show that CoQ10 in large doses is taken up by all tissues including heart and brain mitochondria. This has implications for therapeutic applications in human diseases, and there is evidence for its beneficial effect in cardiovascular and neurodegenerative diseases. CoQ10 has an excellent safety record.

[pmid17666877-10] Ochiai A et al.: Improvement in intestinal coenzyme q10 absorption by food intake. Yakugaku Zasshi 2007. (PMID 17666877) [PubMed] [DOI] Abstract
Coenzyme Q10 (CoQ10) is widely consumed as a food supplement because of its recognition as an important nutrient in supporting human health. Absorption of compounds from the gastrointestinal tract is one of the important determinants of oral bioavailability. However, the absorption of dietary CoQ10 is slow and limited due to its hydrophobicity and large molecular weight. The absorption of orally applied compounds can be enhanced by interactions with food or food components. Thus, we investigated the effect of food intake on the absorption of CoQ10 after oral supplementation. In this study, we demonstrated that food intake enhanced the intestinal absorption of CoQ10. In order to improve intestinal absorption of CoQ10 after oral supplementation, we developed an emulsion formulation. Intestinal absorption of CoQ10 after administration of the emulsion formulation was also enhanced by food intake. Moreover, the peak concentration and the extent of absorption after administration of the emulsion formulation were greater than those after administration of a suspension formulation. It is possible that administration of CoQ10 in an emulsion formulation enhances the pharmacological effects of CoQ10.

[11] Kishi et al.; "Biomedical and Clinical Aspects of Coenzyme Q"

[pmid3718593-12] Ozawa Y et al.: Intestinal absorption enhancement of coenzyme Q10 with a lipid microsphere. Arzneimittelforschung 1986. (PMID 3718593) [PubMed] Abstract
Coenzyme Q10 (ubidecarenone; CoQ10) was administered at a dose of 60 mg/d either using two conventional formulations or in a lipid microsphere to dogs. Plasma concentrations of CoQ10 were determined by HPLC. The bioavailability of CoQ10 from the lipid microsphere formulation was superior to conventional formulations. These results suggest that three daily administrations of the new formulation should be suitable for therapeutic use.

[pmid3781673-13] Tomono Y et al.: Pharmacokinetic study of deuterium-labelled coenzyme Q10 in man. Int J Clin Pharmacol Ther Toxicol 1986. (PMID 3781673) [PubMed] Abstract
The pharmacokinetics of coenzyme Q10 (CoQ10) in man was studied by utilizing deuterium-labelled coenzyme Q10 (d5-CoQ10). The absence of an isotope effect in the disposition of d5-CoQ10 in man was confirmed from the plasma concentration time curves after simultaneous oral dosing of d5-CoQ10 and unlabelled CoQ10. After oral administration of 100 mg of d5-CoQ10 to 16 healthy male subjects, the mean plasma CoQ10 level attained a peak of 1.004 +/- 0.370 micrograms/ml at 6.5 +/- 1.5 h after administration, and the terminal elimination half-life was 33.19 +/- 5.32 h. In most of the subjects, plasma d5-CoQ10 showed a second peak at 24 h after dosing. This unusual plasma level curve was well described by a newly proposed compartment model based upon the assumption that absorbed CoQ10 is taken up by the liver and then transferred mainly to VLDL and redistributed from the liver to the systemic blood.

[pmid35199552-14] {Jump up to: 14.0} ^14.1 ^14.2 ^14.3 ^14.4 ^14.5 ^14.6 Rauchová H: Coenzyme Q10 effects in neurological diseases. Physiol Res 2021. (PMID 35199552) [PubMed] [DOI] [Full text] Abstract
Coenzyme Q10 (CoQ10), a lipophilic substituted benzoquinone, is present in animal and plant cells. It is endogenously synthetized in every cell and involved in a variety of cellular processes. CoQ10 is an obligatory component of the respiratory chain in inner mitochondrial membrane. In addition, the presence of CoQ10 in all cellular membranes and in blood. It is the only endogenous lipid antioxidant. Moreover, it is an essential factor for uncoupling protein and controls the permeability transition pore in mitochondria. It also participates in extramitochondrial electron transport and controls membrane physicochemical properties. CoQ10 effects on gene expression might affect the overall metabolism. Primary changes in the energetic and antioxidant functions can explain its remedial effects. CoQ10 supplementation is safe and well-tolerated, even at high doses. CoQ10 does not cause any serious adverse effects in humans or experimental animals. New preparations of CoQ10 that are less hydrophobic and structural derivatives, like idebenone and MitoQ, are being developed to increase absorption and tissue distribution. The review aims to summarize clinical and experimental effects of CoQ10 supplementations in some neurological diseases such as migraine, Parkinson´s disease, Huntington´s disease, Alzheimer´s disease, amyotrophic lateral sclerosis, Friedreich´s ataxia or multiple sclerosis. Cardiovascular hypertension was included because of its central mechanisms controlling blood pressure in the brainstem rostral ventrolateral medulla and hypothalamic paraventricular nucleus. In conclusion, it seems reasonable to recommend CoQ10 as adjunct to conventional therapy in some cases. However, sometimes CoQ10 supplementations are more efficient in animal models of diseases than in human patients (e.g. Parkinson´s disease) or rather vague (e.g. Friedreich´s ataxia or amyotrophic lateral sclerosis).

[pmid33641585-15] {Jump up to: 15.0} ^15.1 Hill D et al.: Investigational neuroprotective compounds in clinical trials for retinal disease. Expert Opin Investig Drugs 2021. (PMID 33641585) [PubMed] [DOI] Abstract
INTRODUCTION: Retinal neurodegeneration causes irreversible vision loss, impairing quality of life. By targeting neurotoxic conditions, such as oxidative stress and ischemia, neuroprotectants can slow or stop sight loss resulting from eye disease. Despite limimted clinical use of neuroprotectants, there are several promising compounds in early clinical trials (pre-phase III) which may fulfil new therapeutic roles. Search terms relating to neuroprotection and eye disease were used on ClinicalTrials.gov to identify neuroprotective candidates. AREAS COVERED: Research supporting neuroprotection in eye diseases is focused on, ranging from preclinical to phase II, according to the ClinicalTrials.gov database. The compounds discussed are explored in terms of future clinical applications. EXPERT OPINION: The major challenge in neuroprotection research is translation from basic research to the clinic. A number of potential neuroprotectants have progressed to ophthalmology clinical trials in recent years, with defined mechanisms of action - saffron and CoQ10 - targeting mitochondria, and both CNTF and NGF showing anti-apoptotic effects. Enhancements in trial design and patient cohorts in proof-of-concept trials with enriched patient populations and surrogate endpoints should accelerate drug development. A further important consideration is optimising drug delivery to improve individualised management and patient compliance. Progress in these areas means that neuroprotective strategies have a much improved chance of translational success.

[pmid27012265-16] Sharma A et al.: Coenzyme Q10 and Heart Failure: A State-of-the-Art Review. Circ Heart Fail 2016. (PMID 27012265) [PubMed] [DOI] Abstract
Heart failure (HF) with either preserved or reduced ejection fraction is associated with increased morbidity and mortality. Evidence-based therapies are often limited by tolerability, hypotension, electrolyte disturbances, and renal dysfunction. Coenzyme Q10 (CoQ10) may represent a safe therapeutic option for patients with HF. CoQ10 is a highly lipophilic molecule with a chemical structure similar to vitamin K. Although being a common component of cellular membranes, CoQ10's most prominent role is to facilitate the production of adenosine triphosphate in the mitochondria by participating in redox reactions within the electron transport chain. Numerous trials during the past 30 years examining CoQ10 in patients with HF have been limited by small numbers and lack of contemporary HF therapies. The recent publication of the Q-SYMBIO randomized controlled trial demonstrated a reduction in major adverse cardiovascular events with CoQ10 supplementation in a contemporary HF population. Although having limitations, this study has renewed interest in evaluating CoQ10 supplementation in patients with HF. Current literature suggests that CoQ10 is relatively safe with few drug interactions and side effects. Furthermore, it is already widely available as an over-the-counter supplement. These findings warrant future adequately powered randomized controlled trials of CoQ10 supplementation in patients with HF. This state-of-the-art review summarizes the literature about the mechanisms, clinical data, and safety profile of CoQ10 supplementation in patients with HF.

[pmid20601617-17] Wyman M et al.: Coenzyme Q10: a therapy for hypertension and statin-induced myalgia?. Cleve Clin J Med 2010. (PMID 20601617) [PubMed] [DOI] Abstract
Some small clinical trials seem to show that coenzyme Q10 supplements can be used to lower blood pressure and to treat or prevent myalgia caused by hydroxymethylglutaryl coenzyme A reductase inhibitors (statins). However, larger trials are needed to determine if they are truly effective for these purposes. The authors examine the evidence and also discuss issues such as bioavailability, elimination, safety, and cost.

[pmid32188111-18] Pravst I et al.: Comparative Bioavailability of Different Coenzyme Q10 Formulations in Healthy Elderly Individuals. Nutrients 2020. (PMID 32188111) [PubMed] [DOI] [Full text] Abstract
Coenzyme Q10 (CoQ10) plays a central role in mitochondrial oxidative phosphorylation. Several studies have shown the beneficial effects of dietary CoQ10 supplementation, particularly in relation to cardiovascular health. CoQ10 biosynthesis decreases in the elderly, and consequently, the beneficial effects of dietary supplementation in this population are of greater significance. However, most pharmacokinetic studies have been conducted on younger populations. The aim of this study was to investigate the single-dose bioavailability of different formulations of CoQ10 in a healthy geriatric population. A randomized, three-period, crossover bioavailability study was conducted on 21 healthy older adults (aged 65-74). The treatment was a single dose with a one-week washout period. Three different formulations containing the equivalent of 100 mg of CoQ10 were used: Q10Vital® water-soluble CoQ10 syrup (the investigational product-IP); ubiquinol capsules (the comparative product-CP); and ubiquinone capsules (the standard product-SP). Ubiquinone/ubiquinol was followed in the plasma for 48 h. An analysis of the ratio of the area under the baseline-corrected concentration curve (ΔAUC48) for total CoQ10 and a comparison to SP yielded the following: The bioavailability of CoQ10 in the IP was 2.4-fold higher (95% CI: 1.3-4.5; p = 0.002), while the bioavailability of ubiquinol (CP) was not significantly increased (1.7-fold; 95% CI: 0.9-3.1, p = 0.129). No differences in the redox status of the absorbed coenzyme Q10 were observed between formulations, showing that CoQ10 appeared in the blood mostly as ubiquinol, even if consumed as ubiquinone.

[pmid31687097-19] Raizner AE: Coenzyme Q₁₀. Methodist Debakey Cardiovasc J 2019. (PMID 31687097) [PubMed] [DOI] [Full text] Abstract
Coenzyme Q10 (CoQ10) is among the most widely used dietary and nutritional supplements on the market. CoQ10 has several fundamental properties that may be beneficial in several clinical situations. This article reviews the pertinent chemical, metabolic, and physiologic properties of CoQ10 and the scientific data and clinical trials that address its use in two common clinical settings: statin-associated myopathy syndrome (SAMS) and congestive heart failure (CHF). Although clinical trials of CoQ10 in SAMS have conflicting conclusions, the weight of the evidence, as seen in meta-analyses, supports the use of CoQ10 in SAMS overall. In CHF, there is a lack of large-scale randomized clinical trial data regarding the use of statins in patients receiving contemporary treatment. However, one relatively recent randomized clinical trial, Q-SYMBIO, suggests an adjunctive role for CoQ10 in CHF. Recommendations regarding the use of CoQ10 in these clinical situations are presented.

[pmid36768907-20] Mantle D et al.: Coenzyme Q10 Metabolism: A Review of Unresolved Issues. Int J Mol Sci 2023. (PMID 36768907) [PubMed] [DOI] [Full text] Abstract
The variable success in the outcome of randomised controlled trials supplementing coenzyme Q10 (CoQ10) may in turn be associated with a number of currently unresolved issues relating to CoQ10 metabolism. In this article, we have reviewed what is currently known about these factors and where gaps in knowledge exist that need to be further elucidated. Issues addressed include (i) whether the bioavailability of CoQ10 could be improved; (ii) whether CoQ10 could be administered intravenously; (iii) whether CoQ10 could be administered via alternative routes; (iv) whether CoQ10 can cross the blood-brain barrier; (v) how CoQ10 is transported into and within target cells; (vi) why some clinical trials supplementing CoQ10 may have been unsuccessful; and (vii) which is the most appropriate tissue for the clinical assessment of CoQ10 status.

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-'''Coenzyme Q10 (CoQ10)''', a lipophilic substituted benzoquinone, is a naturally occurring nutrient found within every cell of both animal and plant cells. It is endogenously synthesized and plays a critical role in a variety of cellular processes. CoQ10 is an obligatory component of the respiratory chain in the inner mitochondrial membrane and is also the only endogenous lipid antioxidant, highlighting its singular importance in cellular health and function. Its presence is not limited to the mitochondria but extends to all cellular membranes and is detectable in the blood.
+{{DISPLAYTITLE:Coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>)}}
+[[File:CoenzymeQ10.svg|right|frameless]]
+'''Coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>)''', a lipophilic substituted benzoquinone, is a naturally occurring nutrient found within every cell of both animal and plant cells. It is endogenously synthesized and plays a critical role in a variety of cellular processes. CoQ<sub>10</sub> is an obligatory component of the respiratory chain in the inner mitochondrial membrane and is also the only endogenous lipid [[Antioxidant|antioxidant]], highlighting its singular importance in cellular health and function. Its presence is not limited to the mitochondria but extends to all cellular membranes and is detectable in the blood.
+==Dietary Sources ==
+Vegetable oils are the richest sources of dietary CoQ<sub>10</sub>; Meat and fish also are quite rich in CoQ<sub>10</sub> levels over 50&nbsp;mg/kg may be found in beef, pork, and chicken heart and liver. Dairy products are much poorer sources of CoQ<sub>10</sub> than animal tissues. Among vegetables, parsley and perilla are the richest CoQ<sub>10</sub> sources, but significant differences in their CoQ<sub>10</sub> levels may be found in the literature. Broccoli, grapes, and cauliflower are modest sources of CoQ<sub>10</sub>. Most fruit and berries represent a poor to very poor source of CoQ<sub>10</sub>, with the exception of avocados, which have a relatively high CoQ<sub>10</sub>
+{| class="wikitable"
+|+CoQ<sub>10</sub> levels in selected foods{{pmid|20301015}}
+! colspan="2" |Food !!CoQ<sub>10</sub> concentration (mg/kg)
+|-
+| rowspan="5" |Oils
+|soybean||54–280
+|-
+|olive||40–160
+|-
+|grapeseed|| 64–73
+|-
+|sunflower||4–15
+|-
+| canola||64–73
+|-
+| rowspan="3" |Beef
+|heart|| 113
+|-
+|liver||39–50
+|-
+|muscle|| 26–40
+|-
+| rowspan="3" |Pork
+|heart||12–128
+|-
+|liver||23–54
+|-
+|muscle||14–45
+|-
+| rowspan="3" |Chicken
+|breast||8–17
+|-
+| thigh
+|24–25
+|-
+|wing
+|11
+|-
+| rowspan="5" |Fish
+|sardine||5–64
+|-
+| mackerel (red flesh) ||43–67
+|-
+|mackerel (white flesh)||11–16
+|-
+|salmon||4–8
+|}
+===Intake===
+In the developed world, the estimated daily intake of CoQ<sub>10</sub> has been determined at 3–6&nbsp;mg per day, derived primarily from meat.{{pmid|20301015}}
+South Koreans have an estimated average daily CoQ (Q<sub>9</sub> + Q<sub>10</sub>) intake of 11.6&nbsp;mg/d, derived primarily from kimchi.{{doi|10.1016/j.jfca.2011.03.018|Y.H. Pyo, H.J. Oh: Ubiquinone contents in Korean fermented foods and average daily intakes, 2011}}
+===Effect of heat and processing===
+Cooking by frying reduces CoQ<sub>10</sub> content by 14–32%.{{pmid|9129255}}
+== Legal ==
+=== United States (US) ===
+CoQ<sub>10</sub> is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of any medical condition.<ref name="NCI">{{cite web |last1= White |first1=J. |date= 14 May 2014 |title= PDQ® Coenzyme Q<sub>10</sub> |url= http://www.cancer.gov/cancertopics/pdq/cam/coenzymeQ10/HealthProfessional |publisher= [[National Cancer Institute]], [[National Institutes of Health]], [[United States Department of Health and Human Services|U.S. Dept. of Health and Human Services]] |access-date= 29 June 2014}}</ref><ref>{{Cite web |url=https://www.nice.org.uk/advice/es11/resources/mitochondrial-disorders-in-children-coenzyme-q10-pdf-1158110303173 |title=Mitochondrial disorders in children: Co-enzyme Q10 |date=28 March 2017 |publisher=National Institute for Health and Care Excellence |location=UK}}</ref> However, it is sold as a dietary supplement in the name of UbiQ 300 & UbiQ 100, not subject to the same regulations as medicinal drugs, and is an ingredient in some cosmetics.<ref>{{cite journal |last1=Hojerová |first1=J |title=[Coenzyme Q10--its importance, properties and use in nutrition and cosmetics]. |journal=Ceska a Slovenska Farmacie: Casopis Ceske Farmaceuticke Spolecnosti a Slovenske Farmaceuticke Spolecnosti |date=May 2000 |volume=49 |issue=3 |pages=119–23 |pmid=10953455}}</ref><ref>{{cite web |title=What is coenzyme Q10 (CoQ10) and why is it in skin care products? |url=https://www.webmd.com/beauty/qa/what-is-coenzyme-q10-coq10-and-why-is-it-in-skin-care-products |website=WebMD |language=en}}</ref> The manufacture of CoQ<sub>10</sub> is not regulated, and different batches and brands may vary significantly:<ref name="NCI" /> a 2004 laboratory analysis of CoQ<sub>10</sub> supplements on sale in the US found that some did not contain the quantity identified on the product label. Amounts ranged from "no detectable CoQ<sub>10</sub>", through 75% of stated dose, up to a 75% excess.<ref>{{cite web |url=https://www.consumerlab.com/news/coq10-coenzyme-q10-tests/01-13-2004/ |date= Jan 2004 |title= ConsumerLab.com finds discrepancies in strength of CoQ<sub>10</sub> supplements |website=ConsumerLab.com}}</ref>
+==Absorption and Metabolism==
+===Absorption===
+CoQ<sub>10</sub> is a crystalline powder insoluble in water. Absorption follows the same process as that of lipids; the uptake mechanism appears to be similar to that of vitamin E, another lipid-soluble nutrient. This process in the human body involves secretion into the small intestine of pancreatic enzymes and bile, which facilitates emulsification and micelle formation required for absorption of lipophilic substances.{{pmid|16551570}} Food intake (and the presence of lipids) stimulates bodily biliary excretion of bile acids and greatly enhances absorption of CoQ<sub>10</sub>. Exogenous CoQ<sub>10</sub> is absorbed from the small intestine and is best absorbed if taken with a meal. Serum concentration of CoQ<sub>10</sub> in fed condition is higher than in fasting conditions.{{pmid|17666877}}
+=== Metabolism===
+A study with <sup>14</sup>C-labeled CoQ<sub>10</sub> in rats showed most of the radioactivity in the liver two hours after oral administration when the peak plasma radioactivity was observed, but CoQ<sub>9</sub> (with only 9 isoprenyl units) is the predominant form of coenzyme Q in rats.<ref>{{cite book |first1=H. |last1=Kishi |first2=N. |last2=Kanamori |first3=S. |last3=Nisii |first4=E. |last4=Hiraoka |first5=T. |last5=Okamoto |first6=T. |last6=Kishi |chapter=Metabolism and Exogenous Coenzyme Q<sub>10</sub> in vivo and Bioavailability of Coenzyme Q<sub>10</sub> Preparations in Japan |title=Biomedical and Clinical Aspects of Coenzyme Q |pages=131–142 |publisher=Elsevier |location=Amsterdam |year=1964}}</ref> It appears that CoQ<sub>10</sub> is metabolised in all tissues, while a major route for its elimination is biliary and fecal excretion. After the withdrawal of CoQ<sub>10</sub> supplementation, the levels return to normal within a few days, irrespective of the type of formulation used.{{pmid|3718593}}
+===Pharmacokinetics===
+Some reports have been published on the [[Pharmacokinetics|pharmacokinetics]] of CoQ<sub>10</sub>. The [[Maximum Serum Concentration (Cmax)|plasma peak]] can be observed 2–6 hours after oral administration, depending mainly on the design of the study. In some studies, a second plasma peak also was observed at approximately 24 hours after administration, probably due to both enterohepatic recycling and redistribution from the liver to circulation.{{pmid|16551570}} Tomono ''et al''. used deuterium-labeled crystalline CoQ10 to investigate pharmacokinetics in humans and determined an [[Elimination Half-Life|elimination half-time]] of 33 hours.{{pmid|3781673}}
 == Biochemical Function ==
-CoQ10 is integral to the electron transport chain on the inner membrane of mitochondria, facilitating the conversion of electrons from food into ATP. Its roles, however, extend beyond energy production. It is essential for uncoupling proteins and controls the permeability transition pore in mitochondria. Additionally, CoQ10 is involved in extramitochondrial electron transport and affects membrane physicochemical properties. It impacts gene expression, which can alter overall metabolism. The primary alterations in energetic and antioxidant functions are believed to underpin its therapeutic effects {{pmid|35199552}}.
+CoQ<sub>10</sub> is integral to the electron transport chain on the inner membrane of mitochondria, facilitating the conversion of electrons from food into ATP. Its roles, however, extend beyond energy production. It is essential for uncoupling proteins and controls the permeability transition pore in mitochondria. Additionally, CoQ<sub>10</sub> is involved in extramitochondrial electron transport and affects membrane physicochemical properties. It impacts gene expression, which can alter overall metabolism. The primary alterations in energetic and [[Antioxidant|antioxidant]] functions are believed to underpin its therapeutic effects {{pmid|35199552}}.
+== Potential Longevity Benefits ==
+=== Lifespan ===
-== CoQ10 and Longevity ==
 === Cellular and Molecular Roles ===
-As the only endogenous lipid antioxidant, CoQ10 is critical in neutralizing free radicals, thus protecting against DNA damage and cellular dysfunction that are symptomatic of aging. By preserving cellular integrity, CoQ10's antioxidant action is proposed to impede aging and potentially extend cellular lifespan.
+As the only endogenous lipid [[Antioxidant|antioxidant]], CoQ<sub>10</sub> is critical in neutralizing free radicals, thus protecting against DNA damage and cellular dysfunction that are symptomatic of aging. By preserving cellular integrity, CoQ<sub>10</sub>'s antioxidant action is proposed to impede aging and potentially extend cellular lifespan.
+It also contributes to the regulation of mitochondrial function, such as influencing uncoupling proteins and the mitochondrial permeability transition pore, which are crucial for cell survival and [[Apoptosis|apoptosis]], respectively. Such regulation is particularly important as mitochondrial dysfunction is a noted characteristic of aging {{pmid|35199552}}.
+== Potential Therapeutic Role ==
+CoQ10 has been widely researched for its potential in various health applications, including physical fitness, fertility, antiaging, diabetes management, and heart failure treatment. The therapeutic effects of CoQ10 are attributed to its enhancement of oxidative phosphorylation and its ability to mitigate oxidative stress.
+=== [[Neurological Disorders|Neurological Diseases]] ===
+Clinical and experimental studies indicate that CoQ<sub>10</sub> supplementation may exert beneficial effects on [[Neurological Disorders|neurological diseases]] such as migraine, Parkinson's disease, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Friedreich’s ataxia, and multiple sclerosis.{{pmid|35199552}}
+=== Hypertension ===
+It is also of interest in the context of central mechanisms controlling blood pressure due to its effects on the brainstem rostral ventrolateral medulla and the hypothalamic paraventricular nucleus, which are related to cardiovascular hypertension.{{pmid|35199552}}
+=== Diabetic Retinopathy ===
+A particular area of interest is how CoQ<sub>10</sub> might help with a condition called diabetic retinopathy, which is a leading cause of blindness in adults. High blood sugar in diabetes can harm tiny blood vessels in the eye, leading to this condition. The damage causes stress to the eye and can lead to the growth of unhealthy blood vessels, worsening the problem [Citations 55-57]. Since CoQ<sub>10</sub> can help the mitochondria work better and has [[Antioxidant|antioxidant]] properties, it might be useful in treating this eye condition. {{pmid|33641585}}
+Phase II clinical trials have been looking at CoQ<sub>10</sub> for an early diabetic retinopathy, also called non-proliferative diabetic retinopathy (NPDR). Patients who took 400 mg of CoQ<sub>10</sub> every day for 12 weeks to 6 months (different trials) showed improvements in blood flow and energy production in their cells compared to those who didn’t take it. These findings suggest that CoQ<sub>10</sub> could help slow down the worsening of this eye disease by improving blood supply and energy use in the eye, which could help prevent the eye damage from getting worse. More studies are needed to see if CoQ<sub>10</sub> can help stop diabetic retinopathy from progressing to more severe stages.{{pmid|33641585}}
+== Safety and Dosage ==
+=== Dosage ===
+While there is no established ideal dosage of CoQ<sub>10</sub>, a typical daily dose is 100–200 milligrams. Different formulations have varying declared amounts of CoQ<sub>10</sub> and other ingredients.
+=== Safety ===
+The safety profile of CoQ<sub>10</sub> is notably benign, with it being well-tolerated even at high doses.{{pmid|35199552}}
+=== Side Effects ===
+It does not induce serious adverse effects in either humans or experimental animals. Minor side effects may include stomach upset, loss of appetite, nausea, and headaches.{{pmid|35199552}}
-It also contributes to the regulation of mitochondrial function, such as influencing uncoupling proteins and the mitochondrial permeability transition pore, which are crucial for cell survival and apoptosis, respectively. Such regulation is particularly important as mitochondrial dysfunction is a noted characteristic of aging {{pmid|35199552}}.
+=== Interactions ===
+CoQ<sub>10</sub>'s interaction with various medications necessitates a consultation with a healthcare professional before beginning supplementation:
-=== Therapeutic Potential ===
+*'''Theophylline''': CoQ<sub>10</sub> potential to inhibit the effects of theophylline
-Clinical and experimental studies indicate that CoQ10 supplementation may exert beneficial effects on neurological diseases such as [[migraine]], [[Parkinson's disease]], [[Huntington's disease]], [[Alzheimer's disease]], [[amyotrophic lateral sclerosis]], [[Friedreich’s ataxia]], and [[multiple sclerosis]]. It is also of interest in the context of central mechanisms controlling blood pressure due to its effects on the brainstem rostral ventrolateral medulla and the hypothalamic paraventricular nucleus, which are related to [[cardiovascular hypertension]] {{pmid|35199552}}.
+*'''Blood thinner warfarin''': CoQ<sub>10</sub> may interfere with warfarin's actions by interacting with cytochrome p450 enzymes thereby reducing the INR, a measure of blood clotting.{{pmid|27012265}} The structure of coenzyme Q<sub>10</sub> is very similar to that of vitamin K, which competes with and counteracts warfarin's anticoagulation effects. Coenzyme Q<sub>10</sub> should be avoided in patients currently taking warfarin due to the increased risk of clotting.{{pmid|20601617}}
+*'''Chemotherapy drugs'''{{pmid|35199552}}
+==See Also==
-== Dietary Sources and Supplementation ==
+*Wikipedia - [[Wikipedia:Coenzyme Q10|Coenzyme Q10]]
-CoQ10 is found naturally in meats, including organ meats such as liver and kidney, fatty fish, and whole grains. Supplementation of CoQ10 has been shown to be safe and well-tolerated, even at high doses, and does not cause serious adverse effects in humans or experimental animals. Newer formulations of CoQ10 and structural derivatives like idebenone and MitoQ are in development to improve absorption and tissue distribution {{pmid|35199552}}.
-== Safety and Side Effects ==
+== Todo ==
-The safety profile of CoQ10 is notably benign, with it being well-tolerated even at high doses. It does not induce serious adverse effects in either humans or experimental animals. Minor side effects may include stomach upset, loss of appetite, nausea, and headaches. CoQ10's interaction with various medications, such as blood thinners and chemotherapy drugs, necessitates a consultation with a healthcare professional before beginning supplementation {{pmid|35199552}}.
-== Current Research and Perspectives ==
+* {{pmid text|32188111}}
-The latest research aims to summarize the clinical and experimental effects of CoQ10 supplementation, particularly in neurological diseases. Although CoQ10 supplementation has shown promise in animal models, its efficacy in human diseases such as Parkinson’s disease can be inconsistent, and its effectiveness in conditions like Friedreich’s ataxia or amyotrophic lateral sclerosis remains unclear. Nevertheless, recommending CoQ10 as an adjunct to conventional therapy may be reasonable in certain cases {{pmid|35199552}}.
+* Formulations
+* {{pmid text|31687097}}
+* {{pmid text|36768907}}
-== References ==
+==References==
-<references/>
+<references />
-[[Category:Orally Consumable Longevity Molecules]]
+[[Category:Orally Consumable Longevity Compounds]]
+[[Category:Antioxidant Compounds]]