Ubiquinol

• Cardiovascular health support
• Mitochondrial energy production enhancement
• Potent antioxidant protection
• Cellular aging defense

• Statin medication side effect reduction
• Neurodegenerative disease protection
• Migraine frequency reduction
• Male fertility enhancement
• Exercise performance improvement
• Periodontal health support
• Blood pressure regulation
• Inflammatory marker reduction
• Skin health and appearance improvement

Ubiquinol, the reduced form of Coenzyme Q10 (CoQ10), exerts its biological effects through multiple mechanisms centered on its dual role as an essential electron carrier in mitochondrial energy production and as a potent lipid-soluble antioxidant. In the mitochondrial electron transport chain, ubiquinol functions as a mobile electron carrier, shuttling electrons from Complex I (NADH dehydrogenase) and Complex II (succinate dehydrogenase) to Complex III (cytochrome bc1 complex). This electron transfer is fundamental to the process of oxidative phosphorylation, which generates adenosine triphosphate (ATP), the primary energy currency of cells. By facilitating this electron flow, ubiquinol directly supports cellular energy production, particularly in high-energy-demanding tissues such as the heart, brain, liver, and skeletal muscles.

As an antioxidant, ubiquinol’s reduced form (containing two additional hydrogen atoms compared to ubiquinone) allows it to donate electrons to neutralize reactive oxygen species (ROS) and free radicals, thereby preventing oxidative damage to cellular components including proteins, lipids, and DNA. This antioxidant activity is particularly significant in cellular and mitochondrial membranes, where ubiquinol integrates into the phospholipid bilayer due to its lipophilic nature. Ubiquinol’s antioxidant capacity is regenerative; after donating electrons and converting to ubiquinone, it can be reduced back to ubiquinol by various cellular enzymes, including NADH-cytochrome b5 reductase and NQO1 (NAD(P)H:quinone oxidoreductase 1), allowing for continuous antioxidant protection. In cardiovascular health, ubiquinol improves endothelial function by enhancing nitric oxide bioavailability and reducing oxidative stress in vascular tissues.

It also supports cardiac contractility by ensuring optimal energy production in cardiomyocytes and protecting the myocardium from oxidative damage. Additionally, ubiquinol modulates inflammatory processes by inhibiting NF-κB activation and reducing the production of pro-inflammatory cytokines, contributing to its cardioprotective effects. For neurodegenerative conditions, ubiquinol’s neuroprotective mechanisms include preserving mitochondrial function in neurons, reducing oxidative stress in brain tissue, and potentially enhancing the clearance of toxic protein aggregates associated with conditions like Alzheimer’s and Parkinson’s diseases. In the context of statin-induced myopathy, ubiquinol supplementation helps counteract the CoQ10 depletion caused by HMG-CoA reductase inhibitors (statins), which block the mevalonate pathway necessary for both cholesterol and CoQ10 biosynthesis.

By restoring CoQ10 levels in muscle tissue, ubiquinol may alleviate muscle pain, weakness, and fatigue associated with statin use. Ubiquinol also influences cellular signaling pathways, including the activation of AMP-activated protein kinase (AMPK), which regulates cellular energy homeostasis and metabolic processes. Furthermore, it modulates gene expression related to mitochondrial biogenesis, antioxidant defense, and inflammatory responses, potentially through interaction with transcription factors such as PGC-1α and Nrf2. Unlike ubiquinone (oxidized CoQ10), which must be converted to ubiquinol in the body before exerting its antioxidant effects, supplemental ubiquinol provides the active form directly, bypassing this conversion step.

This is particularly beneficial for older adults and individuals with certain health conditions who may have diminished capacity to convert ubiquinone to ubiquinol efficiently.

For general health maintenance and antioxidant support, 100-200 mg of ubiquinol daily is typically recommended.

This dosage is sufficient to maintain healthy plasma and tissue levels in most adults. Due to its superior bioavailability compared to ubiquinone (conventional CoQ10), lower doses of ubiquinol may provide equivalent benefits to higher doses of ubiquinone. The dosage can be taken as a single daily dose or divided into two doses for potentially better absorption and sustained blood levels.

Ubiquinol demonstrates significantly superior bioavailability compared to ubiquinone (conventional CoQ10), with studies indicating approximately 2-3 times greater plasma concentration achieved with equivalent doses. This enhanced absorption is primarily due to ubiquinol’s reduced form, which eliminates the need for conversion from ubiquinone in the intestinal cells before absorption. The absorption efficiency of standard ubiquinol formulations ranges from approximately 30-50%, compared to 10-20% for ubiquinone. However, this can vary considerably based on formulation technology, individual factors, and administration conditions.

Ubiquinol is absorbed primarily in the small intestine through passive diffusion due to its lipophilic nature, with some evidence suggesting involvement of carrier-mediated transport mechanisms. After absorption, ubiquinol is incorporated into chylomicrons and transported via the lymphatic system, bypassing first-pass hepatic metabolism. Peak plasma concentrations are typically reached within 3-6 hours after oral administration, with steady-state levels achieved after approximately 2-3 weeks of consistent supplementation.

Taking with meals containing moderate fat (10-15g) significantly improves absorption by stimulating bile release and enhancing micelle formation, Liposomal delivery systems can increase bioavailability by up to 3-4 fold compared to standard formulations by facilitating direct cellular uptake, Nano-emulsified formulations with particle sizes below 100nm demonstrate superior absorption due to increased surface area and enhanced mucosal penetration, Oil-based softgel formulations generally provide better absorption than powder-filled capsules or tablets, Medium-chain triglyceride (MCT) oil as a carrier improves absorption due to its rapid digestion and lymphatic transport, Phospholipid complexation enhances cellular uptake and tissue distribution by mimicking natural biological membranes, Cyclodextrin inclusion complexes can improve the water solubility of ubiquinol, enhancing its dissolution in the gastrointestinal tract, Micellized formulations create ultra-small particles that significantly increase the surface area available for absorption, Enteric-coated formulations may protect ubiquinol from degradation in the stomach and deliver it intact to the small intestine, Dividing the daily dose into two administrations (morning and evening) may maintain more consistent blood levels

For optimal absorption, ubiquinol should be taken with meals containing moderate amounts of fat (10-15g), as its lipophilic nature requires fat for efficient absorption. Morning administration with breakfast is generally recommended for once-daily dosing, as this aligns with the body’s natural metabolic rhythms and may enhance uptake. For higher doses (above 200mg daily), dividing into two administrations with breakfast and dinner may improve overall absorption and maintain more consistent blood levels throughout the day. For individuals taking statins, separating ubiquinol administration from statin dosing by at least 6-12 hours may be beneficial, as some evidence suggests potential interactions.

This typically means taking ubiquinol in the morning if statins are taken in the evening, or vice versa. For cardiovascular benefits, consistent daily timing is important to maintain steady-state levels in cardiac tissue. For individuals with sleep disturbances, morning administration is preferable, as some users report increased energy levels that may interfere with sleep if taken in the evening. When using ubiquinol specifically for exercise performance enhancement, taking it approximately 1-2 hours before physical activity may provide optimal benefits, though long-term consistent use is more important than timing relative to exercise.

Absorption may be reduced when taken concurrently with high-fiber meals or fiber supplements, so separating administration by at least 2 hours is advisable.

• Mild gastrointestinal discomfort (occasional nausea, diarrhea, or stomach upset)
• Decreased appetite (rare)
• Headache (uncommon)
• Insomnia if taken late in the day (due to increased energy levels)
• Mild skin rash (very rare)
• Fatigue (paradoxical and rare)
• Dizziness (very rare)
• Irritability (very rare)

• Known hypersensitivity or allergy to ubiquinol or ubiquinone
• Caution advised during pregnancy and lactation due to limited safety data
• Caution in individuals with severe hepatic or renal impairment
• Caution in individuals with bleeding disorders or those taking anticoagulant medications
• Caution in individuals with hypotension (low blood pressure)
• Caution before surgery (consider discontinuing 2 weeks prior to elective procedures due to theoretical anticoagulant effects)

• Anticoagulant/antiplatelet medications (warfarin, aspirin, clopidogrel) – may enhance blood-thinning effects, though clinical significance is unclear
• Antihypertensive medications – potential additive effect in lowering blood pressure
• Insulin and oral hypoglycemic agents – may enhance blood glucose-lowering effects, requiring monitoring of blood sugar levels
• Chemotherapeutic agents – theoretical interference with certain cancer treatments that rely on oxidative mechanisms; consult oncologist before use
• Thyroid medications – may require dose adjustments as ubiquinol may affect thyroid hormone levels
• HMG-CoA reductase inhibitors (statins) – beneficial interaction, as ubiquinol may reduce statin-associated myopathy
• P-glycoprotein substrates – potential for increased absorption of drugs transported by P-glycoprotein

No official upper limit has been established by regulatory agencies. Clinical studies have used doses up to 1200 mg daily for extended periods without significant adverse effects. For general safety, staying below 600 mg daily is recommended for most individuals unless higher doses are specifically indicated and monitored by a healthcare provider. The safety profile of ubiquinol appears to be excellent even at higher doses, with no evidence of toxicity in human studies.

Unlike ubiquinone, which shows decreased absorption efficiency at higher doses, ubiquinol maintains good absorption even at doses above 300 mg, reducing concerns about ineffective dosing at higher levels. Long-term safety studies (up to 2 years) at doses of 300-600 mg daily have not identified any significant safety concerns or cumulative toxicity.

In the United States, ubiquinol is regulated as a dietary supplement under the Dietary Supplement Health and Education Act (DSHEA) of 1994. It is not approved as a drug for any specific health conditions. As a dietary supplement, ubiquinol products must comply with FDA regulations regarding manufacturing practices (cGMPs), labeling, and safety, but do not require pre-market approval. The FDA allows qualified structure/function claims for ubiquinol related to antioxidant protection, energy production, and cardiovascular health, but prohibits specific disease treatment or prevention claims without approved drug status.

Ubiquinol is generally recognized as safe (GRAS) when used within typical supplemental doses. The FDA does not distinguish between ubiquinol and ubiquinone in its regulatory framework, treating both as forms of Coenzyme Q10.

Eu: In the European Union, ubiquinol is regulated under the Food Supplements Directive (2002/46/EC) and must comply with all relevant EU food safety regulations. The European Food Safety Authority (EFSA) has evaluated health claims for CoQ10 (including ubiquinol) but has not approved specific health claims under Regulation (EC) No 1924/2006, citing insufficient evidence for the proposed claims. Ubiquinol is permitted in food supplements throughout the EU, with no specific upper limit established at the EU level, though some member states may have national guidelines.

Japan: In Japan, ubiquinol has achieved FOSHU (Foods for Specified Health Uses) status for certain applications, allowing specific health claims related to cardiovascular function. Japan has a long history of CoQ10 use, with ubiquinone having been approved as a drug for congestive heart failure since the 1970s. Ubiquinol is widely available both as a supplement and in functional foods in the Japanese market.

Canada: Health Canada regulates ubiquinol as a Natural Health Product (NHP) under the Natural Health Products Regulations. Products containing ubiquinol must have a Natural Product Number (NPN) to be legally sold in Canada. Health Canada allows certain claims related to antioxidant activity, energy production, and cardiovascular health for ubiquinol products with appropriate supporting evidence.

Australia: The Therapeutic Goods Administration (TGA) in Australia regulates ubiquinol as a complementary medicine. It is listed in the Australian Register of Therapeutic Goods (ARTG) and must comply with quality and safety standards. The TGA permits limited claims related to antioxidant activity and energy production for ubiquinol products.

China: In China, ubiquinol is regulated as a health food ingredient by the National Medical Products Administration (NMPA). Health foods containing ubiquinol must be registered or filed with the NMPA before marketing. Specific health claims are tightly regulated and require substantial scientific evidence and approval.

South Korea: The Korean Ministry of Food and Drug Safety (MFDS) regulates ubiquinol as a functional ingredient in health functional foods. It allows specific health claims related to antioxidant activity and cardiovascular health based on scientific evidence.

Medium to high

For standard ubiquinol supplements (100 mg softgels), the cost typically ranges from $0.80 to $2.50 per day for maintenance doses (100-200 mg daily) and $1.60 to $5.00 per day for therapeutic doses (200-400 mg daily). Premium formulations with enhanced delivery systems (liposomal, micellized, or nano-emulsified) generally cost 30-50% more than standard softgels but may provide better value due to significantly improved bioavailability. Ubiquinol is consistently more expensive than ubiquinone (conventional CoQ10), with prices typically 40-100% higher for equivalent dosages. However, considering that ubiquinol demonstrates approximately 2-3 times greater bioavailability than ubiquinone, the cost per absorbed milligram may be comparable or even favorable for ubiquinol.

Bulk purchasing can significantly reduce costs, with savings of 20-40% commonly available when purchasing 3-6 month supplies compared to monthly quantities.

Ubiquinol offers moderate to good value for its cost, particularly for specific populations who benefit most from its enhanced bioavailability. For adults over 40, especially those over 60, ubiquinol provides superior value compared to ubiquinone due to the age-related decline in the body’s ability to convert ubiquinone to ubiquinol efficiently. For individuals with cardiovascular conditions, particularly heart failure, the clinical benefits of ubiquinol may justify its higher cost compared to conventional treatments alone, potentially reducing hospitalizations and improving quality of life. For statin users experiencing muscle symptoms, ubiquinol supplementation may provide excellent value by allowing continued use of these medications while reducing side effects, potentially preventing the need for more expensive alternative cholesterol-lowering therapies.

The value proposition is enhanced for formulations with improved bioavailability, as the cost per absorbed milligram is reduced. Liposomal and nano-emulsified formulations, while more expensive, may provide 2-3 times better absorption, effectively reducing the cost per active dose. For general antioxidant support in healthy young adults, ubiquinol may offer less value compared to other antioxidants with lower costs, though its specific role in mitochondrial function remains unique. When comparing cost-effectiveness across different health applications, ubiquinol appears to offer the best value for cardiovascular support, statin-associated myopathy, and age-related energy decline.

For athletic performance enhancement, the cost-benefit ratio is less favorable unless used by elite athletes where marginal improvements may justify the expense. The multifunctional nature of ubiquinol (addressing energy production, oxidative stress, and cardiovascular health simultaneously) increases its overall value proposition for individuals with multiple health concerns. When factoring in potential healthcare cost savings from improved health outcomes, particularly in cardiovascular conditions, the long-term economic value of ubiquinol supplementation may be significantly higher than the direct supplement cost suggests.

Properly formulated and packaged ubiquinol supplements typically have a shelf life of 18-36 months from the date of manufacture, depending on the specific stabilization technology employed. Kaneka QH™, the primary commercial form of stabilized ubiquinol, generally maintains at least 95% of its potency for 24 months when stored according to recommendations. After opening, softgel products maintain stability for approximately 60-90 days, while liquid formulations may have reduced stability of 30-60 days once opened. The actual shelf life can vary significantly based on formulation technology, with advanced delivery systems like liposomal or microencapsulated forms potentially offering extended stability.

Manufacturers’ stability testing typically ensures that products retain at least 90% of labeled potency through the expiration date when stored properly.

Store ubiquinol supplements in their original container at room temperature (59-77°F or 15-25°C), away from direct sunlight, heat sources, and moisture. Refrigeration (36-46°F or 2-8°C) is not necessary for most formulations but may extend shelf life by slowing oxidation processes, particularly in hot or humid climates. Avoid freezing ubiquinol supplements, as temperature extremes and freeze-thaw cycles can disrupt the stabilization matrix and accelerate degradation. Keep containers tightly closed when not in use to minimize exposure to oxygen, which can convert ubiquinol back to ubiquinone.

For products packaged in blister packs, keep unused units in the original packaging until needed to maintain maximum protection. If transferring to pill organizers or other containers, do so just before use and minimize air exposure. For liquid formulations, refrigeration after opening is generally recommended, and the dropper or cap should not touch other surfaces to prevent contamination. Avoid storing near strong-smelling substances, as some ubiquinol formulations may absorb odors over time.

Oxidation – the primary degradation pathway, as ubiquinol naturally converts back to ubiquinone when exposed to oxygen, Light exposure – particularly UV light, which catalyzes photo-oxidation reactions, Heat – temperatures above 77°F (25°C) significantly accelerate oxidation reactions, Moisture – can compromise the integrity of capsules and create an environment conducive to oxidation, Metal ions – particularly iron and copper, which catalyze oxidation reactions, pH extremes – ubiquinol is most stable at slightly acidic to neutral pH (5-7), Mechanical stress – excessive handling or crushing of capsules can expose ubiquinol to air, Incompatible excipients – certain formulation ingredients may accelerate degradation, Microbial contamination – particularly in liquid formulations after opening, Freeze-thaw cycles – can disrupt stabilization matrices and protective encapsulation

Synthesis Methods

Natural Sources

Quality Considerations

Ubiquinol, as the reduced form of Coenzyme Q10 (CoQ10), has a relatively recent history in terms of supplementation, though CoQ10 itself has been studied for several decades. The history of ubiquinol is intrinsically linked to the discovery and research of CoQ10. Coenzyme Q10 was first isolated from beef heart mitochondria by Dr. Frederick Crane at the University of Wisconsin-Madison in 1957.

The following year, Professor Karl Folkers at Merck determined its chemical structure and named it ubiquinone, reflecting its ubiquitous presence in living organisms and its quinone chemical structure. In 1961, Peter Mitchell proposed the chemiosmotic theory of oxidative phosphorylation, which explained CoQ10’s crucial role in mitochondrial energy production. This work later earned Mitchell the Nobel Prize in Chemistry in 1978 and established the fundamental importance of CoQ10 in cellular bioenergetics. Throughout the 1960s and 1970s, research on CoQ10 expanded, primarily focusing on its role in mitochondrial function and energy production.

The first clinical applications began in Japan in the late 1960s, where CoQ10 (in the form of ubiquinone) was approved as a treatment for congestive heart failure. By the 1980s, CoQ10 supplementation had gained popularity in Japan and parts of Europe, particularly for cardiovascular conditions. During this period, all CoQ10 supplements contained the oxidized form (ubiquinone), as stable supplemental ubiquinol had not yet been developed. The distinction between ubiquinone and ubiquinol was well understood in biochemical research, with scientists recognizing that ubiquinol is the active antioxidant form in the body.

However, technological limitations prevented the commercial production of stable ubiquinol supplements. A significant breakthrough came in 2006 when Kaneka Corporation of Japan developed a method to stabilize ubiquinol in a supplemental form. This innovation, marketed as Kaneka QH™, made it possible for consumers to directly supplement with the reduced, active form of CoQ10 for the first time. Prior to this, all CoQ10 supplements contained ubiquinone, which the body needed to convert to ubiquinol to utilize its antioxidant properties.

Following the introduction of stabilized ubiquinol supplements, research began to demonstrate its superior bioavailability compared to ubiquinone, particularly in older adults and individuals with certain health conditions who may have diminished capacity to convert ubiquinone to ubiquinol efficiently. From 2007 onward, ubiquinol supplements gained increasing popularity, especially among older adults, individuals with cardiovascular concerns, and those taking statin medications, which can deplete endogenous CoQ10 levels. Clinical research on ubiquinol expanded significantly in the 2010s, with studies investigating its effects on cardiovascular health, neurodegenerative conditions, exercise performance, fertility, and various other health parameters. Today, ubiquinol represents a significant segment of the CoQ10 supplement market, with continued research exploring its potential benefits for various aspects of health and longevity.

While it has a shorter history as a supplement compared to many traditional nutrients, the fundamental importance of CoQ10 in human physiology has been recognized for over 60 years, with ubiquinol now understood as the more bioavailable and biologically active form for supplementation.

Fotino AD, Thompson-Paul AM, Bazzano LA. Effect of coenzyme Q₁₀ supplementation on heart failure: a meta-analysis. American Journal of Clinical Nutrition. 2013;97(2):268-275. doi:10.3945/ajcn.112.040741, Zhai J, Bo Y, Lu Y, Liu C, Zhang L. Effects of Coenzyme Q10 on Markers of Inflammation: A Systematic Review and Meta-Analysis. PLoS One. 2017;12(1):e0170172. doi:10.1371/journal.pone.0170172, Jorat MV, Tabrizi R, Mirhosseini N, Lankarani KB, Akbari M, Heydari ST, Mottaghi R, Asemi Z. 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 in Health and Disease. 2018;17(1):230. doi:10.1186/s12944-018-0876-4

Ubiquinol for Cognitive Function in Older Adults (UBIQ-COG) – Investigating the effects of 6 months of ubiquinol supplementation on cognitive function, oxidative stress markers, and mitochondrial function in adults over 65 years., Ubiquinol in Heart Failure with Preserved Ejection Fraction (UBIQ-HFpEF) – Examining the effects of ubiquinol on exercise capacity, quality of life, and cardiac function in patients with HFpEF., Ubiquinol for Statin-Associated Muscle Symptoms (UBIQ-SAMS) – Large-scale trial investigating whether ubiquinol can prevent or reduce muscle symptoms in patients initiating statin therapy., Ubiquinol in Parkinson’s Disease Progression (UBIQ-PD) – Studying the potential neuroprotective effects of high-dose ubiquinol on disease progression in early-stage Parkinson’s disease.