October 2024 Issue
CoQ10 and Ubiquinol Supplements
By Alexandria Hardy, RDN, LDN
Today’s Dietitian
Vol. 26 No. 8 P. 30
Understanding the Benefits and Risks
Coenzyme Q10 (CoQ10) was discovered in 1957 and named for its chemical structure, which resembles Vitamin K.1 This compound, containing a benzoquinone ring, is ubiquitously found in all cell membranes throughout the body, earning it the name ubiquinone.1 Concentrated in organs with high rates of metabolism such as the heart, CoQ10 helps synthesize adenosine triphosphate and functions as the body’s only lipid-soluble endogenous antioxidant.2
Though it can be found in foods such as oily fish, CoQ10 is also a popular supplement.3 Coenzyme Q10 plays a fundamental role in energy production, contributes to DNA and RNA biosynthesis, supports cell growth and differentiation, and combats oxidative stress both on its own and in combination with vitamin E. Research also suggests that CoQ10 plays an important role in the transport of protons across lysosomal membranes to help preserve the optimal pH inside these specialized cellular debris-clearing organelles.4 Coenzyme Q10 can exist in the following three oxidation states1:
• the fully reduced ubiquinol form, CoQ10H2;
• the radical semiquinone intermediate, CoQ10H; and
• the fully oxidized ubiquinone form, CoQ10.
Ubiquinol is the electron-rich form of CoQ10, which allows it to act as an active antioxidant in the body.5 This differs from the antioxidant activity of CoQ10, as ubiquinol can also regenerate and renew additional antioxidants within the body.1 Ubiquinol helps curb the onset and spread of lipid peroxidation in biological membranes and LDL. It’s most highly concentrated in organs of the body that have increased metabolic demand, like the mitochondria of the kidney, liver, skeletal muscles, and heart.1 This compound is crucial for cellular defense against oxidative harm and supports the effects of vitamin E by assisting with its regeneration from the tocopheroxyl radical.5
Dietary Sources of Coenzyme Q10
Neither CoQ10 nor ubiquinol are classified as vitamins, as both can be synthesized by the body with adequate availability of tyrosine and B vitamins.1 The average dietary intake of CoQ10 is 3 to 6 mg, with half of that estimated to be ubiquinol.3 Foods can be fortified with both forms of the coenzyme, though solubility can impact its ability to be effectively digested and absorbed.3
Protein-rich foods, particularly animal proteins, are the richest sources of CoQ10. Some of the most concentrated sources include meats, organ meats, and oily fish like tuna, salmon, and herring.6,7 Fruit, vegetables, eggs, nuts, seeds, and dairy products are considered moderate sources.5 Supplementation may be recommended in older individuals due to less efficient conversion of dietary CoQ10 to ubiquinol after the age of 60.8
Supplement Considerations
Variables impacting how supplements might be applied include supplement type, timing, cost, and health factors of target populations. Supplements are primarily ingested and are available in liquid, gel soft capsule, and tablet forms. Topical formulations do exist but additional research in more diverse populations is needed to determine effectiveness.6
Supplementation is not recommended during pregnancy or breastfeeding due to a lack of safety data.6 It’s also contraindicated in individuals taking chemotherapeutic agents, those with biliary obstruction or renal impairment, and those who may be prone to hypoglycemia.6 Since vitamin K and CoQ10 share a chemical likeness, individuals who take anticoagulant drugs like warfarin should talk to their doctor to determine any potential adverse reactions before consuming.6 Supplements may be best tolerated when taken early in the day as they have the potential to negatively affect sleep in larger doses.9
Cost is also a consideration when recommending supplementation. CoQ10 tends to be less expensive than ubiquinol, with the latter costing up to five times as much for the same quantity.9 There is also comparatively more abundant data and research on CoQ10.
Absorption Mechanisms and Supplement Selection
Consumer Lab, an independent company, provides product reviews for supplements and other wellness products via rigorous testing. They analyzed 16 CoQ10 and ubiquinol products with a focus on label claims and quality; their top picks for each supplement are listed below.
Coenzyme Q10
Absorption of fat-soluble CoQ10 may be best achieved when consuming a higher-fat meal.6 At least one tablespoon of fat should be provided in the meal to enable absorption; this may be an important consideration for individuals with fat malabsorption concerns.9
The Consumer Lab’s top pick for CoQ10 dietary supplementation is Member’s Mark CoQ10 200 mg.9 This product is a medium to large soft gel that is intended to be taken with food once daily. It costs five cents per 100 mg capsule. In a separate product evaluation, the amount of CoQ10 found in the product exceeded the 200 mg label claim, with 227.6 mg found in each capsule.9 Another high-quality, low-cost option is Kirkland Signature [Costco] CoQ10 300 mg. This large soft gel is also intended to be taken once daily with meals and costs eight cents per 100 mg.9
For clients who may not be interested in or able to swallow large capsules, there are several Consumer Lab-approved gummy varieties available at a higher price point. These include Garden of Life Vitamin Code Gummies CoQ10 150 mg (strawberry flavor) at 36 cents per 100 mg and Mary Ruth’s CoQ10 Gummies (raspberry flavor) at 49 cents per 100 mg.9 Both of the gummy products require a two-gummy dose, whereas the soft gel doses are one capsule per day; this may impact the affordability for some clients.
For plant-based clients, Doctor’s Best High Absorption CoQ10 with BioPerine is a Consumer Lab-approved choice.9 This is a large veggie capsule intended to be taken once per day with food. It costs 20 cents per 100 mg and contains slightly less CoQ10 (93.5 mg) than the label claimed in quantitative analysis.9
Ubiquinol
Water-soluble forms may be better absorbed due to their increased bioavailability.6 However, they may be more expensive.
Consumer Lab named Qunol Mega CoQ10 Ubiquinol as their top pick for a bioavailable option. This product is a large soft gel and costs 25 cents per 100 mg capsule. Suggested intake is once per day with or after a meal.9 Another top pick per Consumer Lab is Qunol Ultra CoQ10 100 mg. This is a similar large soft gel capsule that is also taken once daily with a meal and is at a comparable price point.9 Both products exceeded the amount of ubiquinol that was stated on the label (117 mg and 105 mg, respectively).9
For clients interested in a plant-based approach, Consumer Lab approved Healthy Origins Vegan Ubiquinol, a veggie-based medium to large soft gel that can be taken once or twice per day with food.9 In third-party product testing, it was found to exceed label claims for ubiquinol (115 mg) and costs 43 cents per 100 mg.9
Optimal CoQ10 Dosages: Tailoring Quantities to Target Populations
There are many different dosages of CoQ10 available, and the ideal quantity differs based on the disease state one is hoping to address. For example, research suggests 100 to 200 mg/d is an efficacious dose to decrease systolic blood pressure, while 300 to 400mg/d may improve cardiac mitochondrial efficiency.10 The most common dosing range for dietary supplements is 30 to 600 mg per day.6 Efficacy is generally established after four to eight weeks, though it could take longer to reach a therapeutic dose with a measurable clinical impact.11,12 In animal studies, data indicated that ubiquinol could be consumed without adverse effects at a dose of 300 to 600 mg/kg per day.6 CoQ10 is generally studied and considered safe at 100 to 300 mg per day.6
CVD
Supplementation is often utilized by individuals with CVD. This practice may be informed by CoQ10’s ability to restore depleted levels caused by statin use.9 Furthermore, studies suggest that CoQ10 supplementation may improve lipid profiles and alleviate symptoms of congestive heart failure, possibly due to its blood pressure-lowering effects.13 Several reviews suggest that individuals afflicted with cardiometabolic conditions such as stroke, myocardial infarction, hypertension, diabetes, insulin resistance, and nonalcoholic fatty liver disease may derive benefits from CoQ10 supplementation.10,14-16 Emerging evidence also indicates its potential to reduce systolic blood pressure.16
There is currently potential Level One Evidence (indicative of high quality of evidence) that CoQ10 supplementation is beneficial for individuals with congestive heart failure and potential Level Two Evidence that supports CoQ10 supplementation for improved endothelial function and aerobic capacity.6 More research is needed to better understand the mechanisms involved.
Migraine and Neurodegenerative Disorders
Noncardiac-related benefits of CoQ10 or ubiquinol supplementation may include boosting energy levels and decreasing the frequency and duration of migraine, the most common neurological disorder in the global population.9,17,18
A meta-analysis of five studies published in Biochemistry Research International reviewed the frequency of migraine occurrence and severity in 346 adult and pediatric patients and found that there was no difference in the supplementation and placebo group, though supplementation did decrease the number of migraine days the participants experienced as well as lessened the duration of the migraine attacks.17 A typical therapeutic dose of CoQ10 or ubiquinol for migraine ranges from 30 to 800 mg/day and has been studied in a liquid and capsule format.18
CoQ10 supplementation may also be effective as a therapeutic addition in the treatment of neurodegenerative diseases like Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis.19 This is attributed to its neuroprotective effects due to dysfunction and impairment caused by oxidative stress.19 Supplementation of CoQ10 in individuals with Parkinson’s disease at 1,200 mg/day was linked to a higher level of participation in activities of daily living and was well tolerated with few side effects.20 Several animal studies have shown CoQ10 supplementation may decrease oxidative stress and brain atrophy. More research is needed to see if these positive effects can also be applied to human subjects.20
Adverse Effects of CoQ10 Supplementation: Short- and Long-Term Consequences
Aside from the contraindications discussed earlier, CoQ10 supplements are generally well tolerated by most.1 Occasional side effects may include gastrointestinal symptoms and dizziness; insomnia can occur if daily supplementation exceeds 100 mg.1,6 When daily supplemental intake exceeds 300 mg/day, liver enzyme elevation may occur; this generally does not lead to toxicity.6 The upper limit is 1,200 mg/day.6,10
RDs who are assisting their clients in selecting a supplement may want to work closely with the interdisciplinary team to ensure there are no pharmacological or medical interferences with CoQ10 or ubiquinol supplementation. Supplementation can safely be used long-term, provided the individuals taking these products do not show signs of intolerance and do not fall within the populations referenced in the contraindications.6,10
Study Limitations
Many studies on CoQ10 supplementation have a small sample size and inconsistent trial designs.21,22 Future trials should include a more diverse segment of the population in terms of age, sex, disease state, and socioeconomic background to allow for widespread application of the findings and a limit of risk or bias from the researchers. Finally, much of the available research focuses on supplemental CoQ10 in ubiquinone form and not ubiquinol; additional studies on the effects of the latter, more bioavailable form would be beneficial to determine its effectiveness when compared with CoQ10.12
Future Research
After the COVID-19 pandemic, researchers sought to determine if the positive antioxidant effects of CoQ10 could be extrapolated from chronic disease and applied to infectious diseases.23 There is little existing data, but some researchers believe it could potentially be an effective therapeutic option in addition to more traditional immunotherapy drugs.23 A more thorough understanding of CoQ10 metabolism would also be beneficial, particularly related to the blood-brain barrier, which may help determine the most bioavailable form and method of supplementation.12 Future research could also explore levels of CoQ10 in nonplasma tissue to provide a clearer picture of the necessity of supplementation and where and how CoQ10 is getting absorbed and stored; this could also expand to topical application.12,19
Concerning fertility, CoQ10 supplementation may have a positive impact, but little clinical data currently exists.19 When studied in the context of mental health support, there is often low compliance to protocol as well as limited sample sizes.24 As 30% of the proteins implicated in neurodegenerative diseases overlap with those associated with psychiatric disorders, additional research is needed to determine if CoQ10 could improve outcomes for individuals with psychiatric disorders like schizophrenia, depression, and bipolar disorder.24,25
Bottom Line
Coenzyme Q10, commonly referred to as ubiquinone, is a widely available over-the-counter supplement. This fat-soluble compound plays an important role in mitochondrial function, facilitating electron transport as a coenzyme for various mitochondrial enzymes that drive adenosine triphosphate production. Its reduced form, ubiquinol, acts as a potent antioxidant, safeguarding cells from oxidative stress by neutralizing free radicals and promoting cellular health.
Research indicates that CoQ10 supplementation may reduce the risk of all-cause mortality, although further studies are needed to reveal the underlying mechanisms.26 Given its popularity, affordability, and low risk of adverse effects, CoQ10 and ubiquinol are considered safe and potentially beneficial for short- and long-term use in many people. It may help modulate inflammatory processes, support cardiovascular health, positively impact migraine outcomes, and lower the risk of all-cause mortality in the general population. 27 Dietitians are well equipped to help clients select the appropriate dose and type of CoQ10 or ubiquinol while considering their overall health goals and dietary patterns.
— Alexandria Hardy, RDN, LDN, is a nutrition educator and the owner of Pennsylvania Nutrition Services, an insurance-based private practice located in Lancaster, Pennsylvania.
References
1. Raizner AE. Coenzyme Q10. Methodist Debakey Cardiovasc J. 2019;15(3):185-191.
2. Cerqua C, Casarin A, Pierrel F, et al. Vitamin K2 cannot substitute coenzyme Q10 as electron carrier in the mitochondrial respiratory chain of mammalian cells. Sci Rep. 2019; 25;9(1):6553.
3. Pravst I, Zmitek K, Zmitek J. Coenzyme Q10 contents in foods and fortification strategies. Crit Rev Food Sci Nutr. 2010;50(4):269-280.
4. Hargreaves IP. Coenzyme Q10 in mitochondrial and lysosomal disorders. J Clin Med. 2021;10(9):1970.
5. Ubiquinol. PubChem website. https://pubchem.ncbi.nlm.nih.gov/compound/Ubiquinol. Accessed May 16, 2024.
6. Sood B, Patel P, Keenaghan M. Coenzyme Q10. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2024.
7. Semeniuc CA, Ranga F, Podar AS, et al. Determination of coenzyme Q10 content in food by-products and waste by high-performance liquid chromatography coupled with diode array detection. Foods. 2023;12(12):2296.
8. Niklowitz P, Onur S, Fischer A, et al. Coenzyme Q10 serum concentration and redox status in European adults: influence of age, sex, and lipoprotein concentration. J Clin Biochem Nutr. 2016;58(3):240-245.
9. CoQ10 and ubiquinol supplements review. Consumer Lab website. https://www.consumerlab.com/reviews/coq10-ubiquinol-supplements-review/coq10/#toppicks. Updated April 15, 2024. Accessed May 16, 2024.
10. Rabanal-Ruiz Y, Llanos-González E, Alcain FJ. The use of coenzyme Q10 in cardiovascular diseases. Antioxidants (Basel). 2021;10(5):755.
11. Saini R. Coenzyme Q10: the essential nutrient. J Pharm Bioallied Sci. 2011;3(3):466-467.
12. Mantle D, Lopez-Lluch G, Hargreaves IP. Coenzyme Q10 metabolism: a review of unresolved issues. Int J Mol Sci. 2023;24(3):2585.
13. Jorat M, Tabrizi R, Mirhosseini N, et al. The effects of coenzyme Q10 supplementation on lipid profiles among patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trials. Lipids Health Dis. 2018;17:230.
14. Liao M, He X, Zhou Y, Peng W, Zhao XM, Jiang M. Coenzyme Q10 in atherosclerosis. Eur J Pharmacol. 2024;970:176481.
15. Sue-Ling CB, Abel WM, Sue-Ling K. Coenzyme Q10 as adjunctive therapy for cardiovascular disease and hypertension: a systematic review. J Nutr. 2022;152(7):1666-1674.
16. Zhao D, Liang Y, Dai S, et al. Dose-response effect of coenzyme Q10 supplementation on blood pressure among patients with cardiometabolic disorders: a grading of recommendations assessment, development, and evaluation (GRADE)-assessed systematic review and meta-analysis of randomized controlled trials. Adv Nutr. 2022;13(6):2180-2194.
17. Zeng Z, Li Y, Lu S, Huang W, Di W. Efficacy of CoQ10 as supplementation for migraine: a meta-analysis. Acta Neurol Scand. 2019;139(3):284-293.
18. Sazali S, Bardic S, Norhayati MN, Idris NS. Coenzyme Q10 supplementation for prophylaxis in adult patients with migraine—a meta-analysis. BMJ Open. 2021;11(1):e039358.
19. Cirilli I, Damiani E, Dludla PV, et al. Role of coenzyme Q10 in health and disease: an update on the last 10 years (2010–2020). Antioxidants (Basel). 2021;10(8):1325.
20. Ebrahimi A, Kamyab A, Hosseini S, et al. Involvement of coenzyme Q10 in various neurodegenerative and psychiatric diseases. Biochem Res Int. 2023;5510874.
21. Di Lorenzo A, Iannuzzo G, Parlato A, et al. Clinical evidence for Q10 coenzyme supplementation in heart failure: from energetics to functional improvement. J Clin Med. 2020;9(5):1266.
22. Claxton L, Simmonds M, Beresford L, et al. Coenzyme Q10 to manage chronic heart failure with a reduced ejection fraction: a systematic review and economic evaluation. Health Technol Assess. 2022;26(4):1-128.
23. Sifuentes-Franco S, Sánchez-Macías DC, Carrillo-Ibarra S, et al. Antioxidant and anti-inflammatory effects of coenzyme Q10 supplementation on infectious diseases. Healthcare (Basel). 2022;10(3):487.
24.Wingo TS, Liu Y, Gerasimov ES, et al. Shared mechanisms across the major psychiatric and neurodegenerative diseases. Nat Commun. 2022;13(1):4314.
25. Maguire A, Mooney C, Flynn G, et al. No effect of coenzyme Q10 on cognitive function, psychological symptoms, and health-related outcomes in schizophrenia and schizoaffective disorder: results of a randomized, placebo-controlled trial. J Clin Psychopharmacol. 2021;41(1):53-57.
26. Saadi TA, Assaf Y, Farwati Y, et al. Coenzyme Q10 for heart failure. Cochrane Database Syst Rev. 2021;2:CD008684.
27. Arnes-Jal M, Suñé-Negre JM, García-Montoya E. Coenzyme Q10 supplementation: efficacy, safety, and formulation challenges. Compr Rev Food Sci Food Safe. 2020;19(2):574-594.