The benefits and pitfalls of coenzyme Q10

Coenzyme Q10 (CoQ10) is a coenzyme found in all animals and most bacteria. Present in all respiring eukaryotic cells, CoQ10 is primarily found in the mitochondria, where it plays a role in the generation of adenosine triphosphate (ATP). Because of the body’s reliance on ATP for most of its energy, CoQ10 is found in higher concentrations in organs that require the most energy—the heart, liver and kidneys.¹

Naturally occurring in the body and found in many foods, including meat, fish, soybean and, to a lesser extent, fruits, nuts and vegetables, CoQ10 is also sold as a dietary supplement and in functional foods targeted toward those who, due to age or underlying condition, do not produce satisfactory levels themselves.

CoQ10 is perhaps best known for two functions: its role in the conversion of glucose and fatty acids to ATP and its role as a powerful antioxidant in cells.²

CoQ10 can exist in three oxidation states: the fully reduced form ubiquinol (CoQ10H2), the radical semiquinone intermediate (CoQ10H·) and the fully oxidized ubiquinone (CoQ10).2 While most CoQ10 products on the market are in the oxidized ubiquinone state, “it is ubiquinol that provides virtually all of benefits associated with CoQ10,” writes Gene Bruno, professor of nutraceutical science and Provost of Huntington College of Health Sciences.2 When the human body is supplemented with ubiquinone, it must first convert it to its fully reduced ubiquinol form. If it is not converted, the ubiquinone will remain inactive, leading Bruno to claim, “in fact, ubiquinol may be thought of as the ‘active antioxidant’ form of CoQ10.”

CoQ10 supplementation is used to help address symptoms of a range of ailments, including diabetes, chronic migraines, statin-induced myopathy and cardiovascular conditions.¹ However, because of its lipophilic nature, the issue of absorption and bioavailability is one that must be cleared for effective supplementation.

Diabetes

Patients with diabetes exhibit significantly lower levels of plasma CoQ10 compared to healthy individuals.³ This deficiency of CoQ10 “may further impair the body’s defensive mechanisms against oxidative stress induced by hyperglycemia in diabetes.” A 2018 pooled analysis on the effects of CoQ10 on overweight and obese patients with type 2 diabetes showed “several studies have demonstrated that the restoration of CoQ10 levels in patients with diabetes by the supplemental use of exogenous CoQ10 could potentially preserve mitochondrial function, alleviate oxidative stress and eventually lead to improvement of glycemic control.”

Additionally, the pooled analysis found CoQ10 to be well-tolerated, with no drug-related adverse reactions, and concluded “our findings provide substantial evidence that daily CoQ10 supplementation has beneficial effects on glucose control and lipid management in overweight and obese patients with [Type 2 diabetes].”³

Migraines

CoQ10 has also been hypothesized to be useful in migraine prevention.⁴ This suggests migraines result in deficiencies in mitochondrial energy in the brain, since CoQ10 plays “an important role in sustaining mitochondrial energy stores,” according to the researchers. Additionally, CoQ10 “counteracts endothelial dysfunction [which may be linked to migraine attacks] by stimulating endothelial release of nitric oxide and has anti-inflammatory effects.”⁵

A 2007 study by Hershey et al. on 1,550 children and adolescents suffering chronic migraines showed that roughly one-third of them had CoQ10 levels below reference range.⁶ The study went on to note that supplementation of this subgroup with 1 to 3 mg/kg/d of CoQ10 “improved coenzyme Q10 level, headache frequency and disability.”

In a 2005 double-blind, randomized, placebo-controlled clinical trial, adult patients with migraines were treated with 100 mg/d of CoQ10 orally for three months.⁷ The trial concluded that supplementation “significantly decreased the frequency of migraine attacks.”

Statin-induced Myopathy

Statins are a class of lipid-reducing drugs often used to treat high cholesterol and reduce the risk of cardiovascular disease (CVD). However, it is estimated that around 10 to 15% of people who take statins experience resultant muscle problems, often in the form of pain and/or weakness and referred to as statin-induced myopathy.

A 2018 meta-analysis by Qu et al. on the effects of CoQ10 on statin-induced myopathy found, “[CoQ10] supplementation ameliorated statin‐associated muscle symptoms, such as muscle pain, muscle weakness, muscle cramps and muscle tiredness.”⁸ The meta-analysis went on to explain why this finding is so important, stating, “Coenzyme Q10 supplementation provided a complementary approach to statin‐associated muscle symptoms, which would be significant for the patients with cardiovascular diseases who are intolerant to statin treatment because of statin‐associated muscle symptoms.”

Cardiovascular health

CoQ10 has been shown to treat various cardiovascular disorders, including angina.⁴ One meta-analysis of eight controlled clinical trials concluded that “treatment of [congestive heart failure with CoQ10] revealed a significant improvement in several important cardiac parameters, such as ejection fraction, stroke volume, cardiac output, cardiac index and end diastolic volume index.”⁹

Absorption

Pure CoQ10 is lipophilic, meaning it is insoluble in water, creating challenges for brands attempting to market effective doses.

“This lipophilic nature makes CoQ10’s absorption poor, highly variable and strongly dependent on stomach contents,” said Steve Holtby, president and CEO, Soft Gel Technologies Inc. (SGTI). “CoQ10 is a large molecule, also contributing to its poor absorption.”

Despite the challenges, solutions to the absorption problem exist. SGTI’s CoQsol-CF® is one option. “It is a completely solubilized CoQ10 that does not require heat or synthetic solvents, and this mixture fully resists recrystallization at ambient temperature ranges,” Holtby shared. “By improving dissolution, absorption is enhanced.”

Another such solution comes from AQUANOVA® and its patented NovaSOL technology.

“In order to make CoQ10 water soluble, NovaSOL encapsulates the CoQ10 molecules in an ultrafine structure, using liquid emulsifiers,” said AQUANOVA CEO Frank Benham. “This structure is also called ‘micelle.’ It is derived from nature and is a vital part of human metabolism for lipophilic actives.”

Benham noted the advantages of this approach compared to others, saying, “unlike emulsions, NovaSOL creates a crystal clear and pH- and temperature-stable dissolution.”

A study in the International Journal of Food Services and Nutrition, “Comparison of the relative bioavailability of different coenzyme Q10 formulations with a novel solubilizate (Solu™ Q10),” lended support, concluding “solubilizates were clearly superior to oily dispersions and crystalline CoQ10 in their overall bioavailability, with the best absorption characteristics seen for the novel Solu™ Q10 [identical in makeup to what is now under the NovaSOL trademark] solubilizate.”10

Another company combatting CoQ10’s solubility concerns is Tishcon Corp.

“Ubiquinol is very unstable,” said Marko Rosa, product manager, Tishcon Corp. That’s why Tishcon invented its patented stable liquid ubiquinol.

“It’s a combination of solubilizing the material and combining the ascorbyl palmitate, which kind of turns it into a perpetual ubiquinol factory because as the ubiquinol oxidizes [into ubiquinone] in that environment, it’s automatically being converted back to ubiquinol,” Rosa said.

SGTI has also been working on a formulation that prevents ubiquinol from oxidizing. Holtby explained:

“Soft Gel Technologies Inc. has developed a patent-pending formula to protect ubiquinol from being oxidized. Using Soft Gel’s crystal-free (CF) technology, CoQH-CF® was created. This unique soft gel delivery system with Kaneka QH™ allows individuals who are unable to process CoQ10 effectively on their own … to increase plasma levels of CoQ10 in its reduced form. CoQH-CF® soft gels contain a liquid inner fill of Kaneka QH™, alpha lipoic acid, d-limonene, and capric and caprylic acid. This solution protects the Kaneka QH™ material from oxidation and crystallization.”

Solubility isn’t the only challenge facing manufacturers, however. Differentiation in the market is also important, noted Benham, especially since he notes that raw material pricing for CoQ10 has come down in recent years.

“It is vital to differentiate finished products beyond mere price competition,” he said. “One way to achieve such differentiation is to focus on scientifically proven value-add formulas, such as NovaSOL. Another way is to consider alternative finished product formats other than capsules, such as liquid sticks or shots.”

Additionally, the production process can be a tricky one.

“CoQ10 is known to be light-sensitive,” said Holtby. “Ubiquinol, especially, is easily oxidized and requires strong protection throughout the production process to ensure its stability.”

With so many products on the market, and price no longer a major limiting factor, ensuring a CoQ10 product is both effective and convenient is key to standing out.

So, what’s next for the competitive CoQ10 market?

“For sure, more innovative finished product formats are required to revitalize CoQ10 business,” Benham said. “Beyond its traditional positioning in cardiovascular health, it is worth it to explore the available science on benefits in other segments.”

For Rosa, the next step is increased education of the potential consumer base about the benefits of CoQ10 supplementation. "Many of the challenges have been overcome—at least by us—so at this stage I think it’s more the awareness and education.”

References:

1 Ernster L, Dallner G. "Biochemical, physiological and medical aspects of ubiquinone function." Biochimica et Biophysica Acta. 1995;1271(1):195-204. doi:10.1016/0925-4439(95)00028-3.

2 “CoQ10 As Ubiquinone & Ubiquinol - For Cardiovascular Health & More.” Vitamin Retailer Magazine, Vitamin Retailer Magazine, 26 June 2014, vitaminretailer.com/supplement-sciencecoq10-as-ubiquinone-ubiquinol-for-cardiovascular-health-more/.

3 Huang, Haohai et al. “Effects of coenzyme Q10 on cardiovascular and metabolic biomarkers in overweight and obese patients with type 2 diabetes mellitus: a pooled analysis” Diabetes, metabolic syndrome and obesity : targets and therapy vol. 11 875-886. 29 Nov. 2018, doi:10.2147/DMSO.S184301

4 Guilbot, Angèle et al. “A combination of coenzyme Q10, feverfew and magnesium for migraine prophylaxis: a prospective observational study” BMC complementary and alternative medicine vol. 17,1 433. 30 Aug. 2017, doi:10.1186/s12906-017-1933-7

5 Rajapakse, T. and Pringsheim, T. (2016), Nutraceuticals in Migraine: A Summary of Existing Guidelines for Use. Headache, 56: 808-816. doi:10.1111/head.12789

6 Hershey, A. D., Powers, S. W., Vockell, A. B., LeCates, S. L., Ellinor, P. L., Segers, A. , Burdine, D. , Manning, P. and Kabbouche, M. A. (2007), Coenzyme Q10 Deficiency and Response to Supplementation in Pediatric and Adolescent Migraine. Headache: The Journal of Head and Face Pain, 47: 73-80. doi:10.1111/j.1526-4610.2007.00652.x

7 P. S. Sándor, L. Di Clemente, G. Coppola, U. Saenger, A. Fumal, D. Magis, L. Seidel, R. M. Agosti, J. Schoenen Neurology Feb 2005, 64 (4) 713-715; DOI: 10.1212/01.WNL.0000151975.03598.ED

8 Qu, Hua, et al. “Effects of Coenzyme Q10 on Statin‐Induced Myopathy: An Updated Meta‐Analysis of Randomized Controlled Trials.” Journal of the American Heart Association, vol. 7, no. 19, 2018, doi:10.1161/jaha.118.009835

9 Soja AM, Mortensen SA. Treatment of chronic cardiac insufficiency with coenzyme Q10, results of meta-analysis in controlled clinical trials. Ugeskr Laeger. 1997;159(49):7302-8.

10 Schulz, Christiane, et al. “Comparison of the Relative Bioavailability of Different Coenzyme Q10formulations with a Novel Solubilizate (Solu™ Q10).” International Journal of Food Sciences and Nutrition, vol. 57, no. 7-8, 2006, pp. 546–555., doi:10.1080/09637480601058320.