Health Benefits, Delivery Forms Expand for CoQ10

Coenzyme Q10 (CoQ10) is found in every living organism, giving rise to its scientific name ubiquinone (from its ubiquitous positioning). It’s also increasingly taking over shelf space in retail stores and finding itself the subject of Web sites and mainstream media articles, and the key compound in products from smoothies to skin cream.

“The market for products containing CoQ10 in the United States is certainly continuing to grow,” noted Eugene Ung, director of marketing, Best Formulations. “Research that has come out about the health benefits associated with CoQ10 supplementation coupled with lower and stabilized pricing of CoQ10 over the past couple of years have helped increase the popularity for CoQ10 products.”

Scott Steinford, president, ZMC-USA, said the U.S. market for CoQ10 has increased more than threefold since 2001, rising from 53 metric tons (MTs) to nearly 190MTs in 2008. Among the factors behind the growth? “First, affordability—raw material prices have dropped dramatically as a result of over capacity by manufacturers,” he said. “Next, science. The evidence associated with CoQ10 is solid and substantial, and it remains one of the most doctor-recommended specialty supplements. Finally, those studies have shown it to be helpful in a wide variety of conditions ranging from heart health and gingivitis to Parkinson’s disease, broadening its applications.”

A report from Mintel noted ongoing research supports the use of CoQ10 beyond its traditional cardiac and energy benefits into eye care, obesity and even fertility. The market research firm added a combination of items, including the aging population and rising health care costs are likely to continue to drive consumers to opt for functional foods and dietary supplements with CoQ10.

That appears to be the case, according to industry members, as the CoQ10 market is growing in spite of the down economy. “With the jobless situation causing fewer people to have health care insurance, people are looking to supplements to prevent them from getting sick,” said Steve Holtby, president/CEO, Soft Gel Technologies Inc. (SGTI). And Tom Schrier, national sales manager, Kaneka, added, “We’ve seen the market for CoQ10 and our new KanekaQH™ ubiquinol grow in spite of the economic downturn.”

That market growth is spanning industry sectors as well, growing beyond its traditional home in the dietary supplement aisle into the food and beverage and personal care areas. “There is certainly growth in the dietary supplement segment; however, we do see many functional food and beverage companies inquiring about CoQ10 and how to stabilize and adapt it for a particular use,” Ung said. “Because CoQ10 is such an expensive nutrient, it will be more challenging for food companies to incorporate. However, we will probably be seeing more CoQ10 in functional foods and beverages in the future. There was a boom in CoQ10 cosmetic products about five years ago, but many of the products contained a miniscule amount just to put CoQ10 on the label for marketing purposes and, therefore, the products didn’t deliver the benefits.”

Rodger Jonas, national business development manager, P.L. Thomas, noted greater availability of CoQ10 has opened up the market. “Two years ago, there wasn’t enough CoQ10 available for the food industry,” he said. “However, Kaneka opened a plant in the United States in 2008, which resolved the issue. So now, beverages are the fastest growing segment for CoQ10, followed by cosmeceuticals.”

Holtby agreed with Jonas’ assessment of the market growth, noting, “The dietary supplement market is saturated with CoQ10 products. The fastest growing category is functional foods and beverages, due to the development of water-dispersible versions of CoQ10. The sports and energy drinks sector has some promising potential, as more consumers learn CoQ10’s role in cellular energy production. And the cosmetic industry is also utilizing CoQ10 in topical skin products.”

Appreciating the Health Effects

To understand the broad appeal of CoQ10 in consumer packaged goods, it’s important to look at some of the research on its health effects. CoQ10 is a lipid-soluble enzymatic cofactor that plays a key role in cellular energy production; its reduced form, ubiquinol, is a potent lipophilic antioxidant that can both protect against oxidative damage and help regenerate other antioxidants.

From the time of its discovery in the late 1950s, scientists looked into its role in cellular energy, longevity and the health of such organs as the heart, kidneys and liver. In fact, CoQ10 is responsible for 95 percent of energy expenditure in some areas of cells. At the metabolic level, CoQ10 plays an important role in the production of adenosine triphosphate (ATP), the form of energy used by the cells, from carbohydrates and fats. Information from the Linus Pauling Institute (LPI) at Oregon State University noted CoQ10 works as part of the mitochondrial electron transport chain, shuttling fatty acids, glucose molecules and protons across the mitochondrial membrane to release energy to produce ATP. In addition, CoQ10 as ubiquinol is an important cellular antioxidant. LPI’s team stated ubiquinol may inhibit lipid peroxidation, neutralize free radicals and regenerate alpha-tocopherol.

One of the most active areas of research for CoQ10 is in the area of heart health. Because CoQ10 works to prevent oxidation of cholesterol, particularly LDL cholesterol, it may help prevent the onset of atherosclerosis. Indian researchers noted administration of 3 mg/d of CoQ10 (Q-Gel®, from Tishcon) in rabbits with high trans fat levels helped limit oxidative damage and atherosclerosis development.¹ Supplementing with a combination of CoQ10 and alpha-tocopherol has been shown to increase plasma levels of vitamin E and beneficial high-density lipoprotein (HDL) cholesterol,² and reduce atherosclerosis at the aortic root and descending thoracic aorta.³ Research also supports its therapeutic use as an adjunct to treatment for congestive heart failure.⁴ In addition, CoQ10 may help lower systolic and diastolic blood pressure in hypertension.⁵ The Natural Standard Patient Monograph on CoQ10 noted there is good scientific evidence for the use of CoQ10 for lowering blood pressure, and that low blood levels of CoQ10 are found in people with hypertension.

Interestingly, with all CoQ10’s heart health benefits, patients being treated with pharmaceuticals for high cholesterol may find themselves in a worse position. The enzyme hydroxymethylglutaryl (HMG)-CoA reductase plays an important role in regulating cholesterol synthesis; inhibiting this activity is the goal of the statin class of cholesterol-reducing pharmaceuticals. Unfortunately, the same HMG-CoA reductase pathway also regulates CoQ10 synthesis. Italian researchers noted statin treatment generally results in lower plasma levels of CoQ10, possibly related to the fact that the drugs lower levels of LDL, the primary transport molecule for CoQ10; however, there is also a decrease of CoQ10 seen in the platelets and lymphocytes, suggesting CoQ10 synthesis itself may be inhibited.⁶ Interestingly, new studies suggest statin treatment may also lead to type 2 diabetes as it reduces the body’s stores of CoQ10.⁷

Intervention studies with statins have examined the impact of the drugs on CoQ10 levels. Japanese researchers found treatment with pitavastatin reduced CoQ10 levels in patients with hypercholesterolemia by 7.7 percent; atorvastatin reduced those levels by 26.1 percent.⁸ Similarly, Italian researchers reported three months of statin therapy dose dependently reduced total cholesterol, as well as levels of ubiquinol and ubiquinone in plasma.⁹ The researchers concluded: “The concomitant administration of ubiquinone with statins, leading to its increase in plasma, lymphocytes and liver may cooperate in counteracting the adverse effects of statins.”

CoQ10 may also be an important neuroprotective agent. Because CoQ10 levels decline with age,¹⁰ accelerating precursors of beta-amyloid deposition, CoQ10 supplementation may be preventive against Alzheimer’s disease (AD), Parkinson’s disease (PD) and other neurodegenerative disorders.¹¹ In one study, CoQ10 therapy attenuated amyloid beta-peptide toxicity in brain mitochondria isolated from elderly rats.¹² Hong Kong researchers similarly found in a group of 48 mice (four genotypes), those treated with CoQ10 (1,200 mg/d) after ischemic injury for 28 days had amyloid precursor protein (APP) mutations and smaller infarct volumes, while the volumes of hemisphere and hippocampus on the infarcted side were larger than those treated with placebo, suggesting CoQ10 could protect the brain from ischemic-related atrophy in aged and susceptible transgenic mice.¹³ A follow-up study by the team using 112 aged mice found 2,400 mg/d of CoQ10 exerted a neuroprotective effect against age related neurodegeneration, suggesting application for the nutrient in preventing mild cognitive impairment and AD.¹⁴

A study out of Weill Medical College of Cornell University, New York, found administration of CoQ10 via the diet could protect against the loss of dopamine, exerting neuroprotective effects in a model of PD.¹⁵ Japanese researchers also found a link between oxidized CoQ10 levels in cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS), suggesting mitochondrial oxidative damage may play a role in pathogenesis of ALS.¹⁶

Researchers are also examining CoQ10’s effects on energy production and athletic performance. “CoQ10 is being increasingly recognized to provide benefits for sustained endurance athletic activities such as running or cycling, as opposed to the more usually recognized benefits associated with weight lifting and muscle mass,” Steinford noted. Japanese researchers have reported oral supplementation with CoQ10 (300 mg/d) can improve physical performance in a workload trial¹⁷ and reduce exercise-induced muscle injury.¹⁸ Similarly, Chinese researchers report CoQ10 supplementation could not only attenuate strain-induced muscle damage, but enhance regeneration.¹⁹ And a trial in 22 aerobically trained and 19 untrained male and female adults who received a placebo or fast-melt CoQ10 supplement for 14 days reported supplementation increased muscle CoQ10 concentration and lowered serum superoxide dismutase (SOD) oxidative stress, while also increasing plasma CoQ10 concentrations and time to exercise exhaustion.²⁰ Finally, CoQ10 also appears to assist in fat oxidation, as supplementation with CoQ10 augments autonomic nervous activity during exercise.²¹

CoQ10 also supports skin health, both topically and internally. German researchers recently noted as CoQ10 positively influences age-related cellular metabolism, it fights the signs of aging at a cellular level, and can improve mitochondrial function via topical application.²² In vitro studies have shown the ability of CoQ10 to reduce the production of inflammatory cytokines in skin fibroblasts, created by ultraviolet (UV) B exposure, thereby protecting dermal fiber and preventing wrinkles and related degeneration.^23,24 Italian researchers conducted animal studies and reported CoQ10 could enhance the antioxidant defenses of the skin, aiding skin healing and synergistically enhancing the duration of other cosmetic procedures.²⁵ Additionally, supplementation with CoQ10 was found by Japanese researchers to increase CoQ10 levels in the serum and epidermis of mice, suggesting it may exert anti-aging, anti-wrinkle and energizing effects on the skin when taken internally.²⁶

Delivering the Goods

With so many beneficial properties, it’s no wonder formulators are looking for ways to add CoQ10 into consumer health products. Unfortunately, there are inherent challenges in working with the fat-soluble nutrient. Raj Chopra, CEO, Tishcon, noted CoQ10’s lipophilic form presents absorption challenges, because it is almost insoluble in aqueous media. “The lack of adequate oral bioavailability of CoQ10 has led to the search for delivery technologies that would render it more water-friendly,” he said. Tishcon, for example, developed the patented BioSolv® process, which involves the use of a nonionic surfactant and a polyhydric alcohol to facilitate the hydrosolubility of CoQ10 (U.S. Patent No. 6,056,971). Other patented systems include the complexation of CoQ10 with cyclodextrins (U.S. Patent No. 6,861,447); the formulation of liposomal dispersions of CoQ10 (U.S. Patent No. 6,445,072); the formulation of self-emulsifying CoQ10 complexes; and numerous other processes.

SGTI developed its CoQsol® and CoQsol-CF™ formulations, using a lipid-based soft gel delivery system, to increase absorption. “A soft gel delivery system plays a key role in enhancing the effectiveness of CoQ10 getting into the bloodstream,” Holtby noted. Additionally, SGTI developed the CoQH-CF™ product, soft gels with a liquid inner fill of solubilized Kaneka QH ubiquinol plus alpha-lipoic acid, d-limonene and capric and caprylic acid to protect the CoQ10 from oxidation. “This unique soft gel delivery system allows individuals who are unable to process CoQ10 effectively on their own to increase plasma levels of CoQ10 in its reduced form.”

In a randomized, placebo-controlled study, researchers determined the differences in steady state absorption during a 30-day period (60 mg/d) and five-hour peak absorption characteristics (30 mg) between CoQsol and dry CoQ10 powder in a two-piece hard shell capsule. After 30 days supplementation, the average basal blood CoQ10 levels for the CoQsol group increased by 165 percent, compared to an 80-percent increase in the dry powder group. Further, in the five-hour trial portion, 30 mg of CoQsol increased peak absolute CoQ10 levels by 0.48 µg/ml blood compared to an increase of 0.19 µg/ml for the subjects taking 30 mg dry CoQ10 powder. CoQsol-CF was the subject of a pilot clinical trial, in which supplementation with 60 mg/d increased mean CoQ10 plasma levels by 200 percent over 28 days.

Best Formulations created a proprietary, patent-pending, lipid tri-blend formulation to produce Q-BEST®, a 100-percent crystal-free form of CoQ10; the proprietary treatment of the lipid tri-blend keeps the CoQ10 solubilized and enhances absorption. “Since CoQ10 is an expensive nutrient, absorption is even more critical to get an efficacious dose at a reasonable cost,” Ung said. “Our patent-pending concept is relatively simple, but it took many years to develop the formulation combination and manufacturing processes to achieve a successful product.”

To reinforce its bioavailability claims, Best supported an IRB-registered human clinical trial on the Q-BEST formula. Results of the 36-hour peak absorption study showed Q-BEST had a total absorption of 11.65 percent, compared to dry powder with an absorption of 1.32 percent. In addition, results of a 28-day steady state study showed at the end of the intervention, 8,989 mcg of Q-BEST were available for use by the cells, compared to 1,623 mcg of dry powder.

Kaneka has also supported research on the safety and bioavailability of its CoQ10 ingredients. “The major concerns about delivering an efficacious dose of Q10 or ubiquinol are dealing with the oil-soluble nature of the products and getting it absorbed in the body,” said Robert Barry, Ph.D., scientific affairs director, Kankea. “Absorption can be increased by delivering it with some fats or oils. And, in identical formulas, ubiquinol has proven to be much more absorbable than Q10.”

In one study, conducted out of Haradoi Hospital, researchers assessed the safety of Kaneka Q10 in a double blind, placebo-controlled, randomized study in 88 healthy adults.²⁷ Kaneka Q10 in capsule form was taken for four weeks at doses of 300, 600 and 900 mg/d; no serious adverse events were reported, and adverse events were even across the placebo and intervention groups and judged to have no relationship to Kaneka Q10. Plasma CoQ10 concentration after eight-month withdrawal was almost the same as before administration.

In a second study, Kaneka researchers evaluated the safety and bioavailability of ubiquinol (as Kaneka QH) in a single blind, placebo-controlled study; healthy volunteers received a single oral dose of 150 or 300 mg, and then oral administration of 90, 150 or 300 mg/d for four weeks.²⁸ There were no clinically relevant changes in standard lab tests, while mean plasma ubiquinol concentration-time curves increased non-linearly after single administration. There was also significant absorption seen, in non-linear dose fashion, during the four week study.

The issue of bioavailability was also a key consideration for Jesse Lopez, president/CEO, SourceOne Global Partners, which partnered with Vesifact to develop CoQsource®, a CoQ10 formulation using the patented VESIsorb® lipid-based formulation that mimics the mixed micellar absorption pathway. “It is known that poorly water-soluble drugs, such as fat-soluble vitamins, are better absorbed when administered after a meal containing fat,” he explained. “One of the reasons for the improved absorption is the enhanced drug solubilization by bile salt mixed micelles, formed from the digestion products of dietary triglycerides and bile. The task of naturally formed bile salt-mixed micelles is to transport the lipophilic molecules through the aqueous environment of the gastrointestinal tract and across the unstirred water layer to the absorptive epithelium.”

A recent study compared the bioavailability of CoQsource to three other CoQ10 formulations; comparing the relative bioavailability of a single oral dose of 120 mg of CoQ10 resulted in CoQsource having a 622-percent higher bioavailability than the oil-based formula and a 499-percent higher bioavailability than a solubilized formula.²⁹

Marc Weder, co-founder and CEO of Vesifact, commented: “These results highlight the many advantages that this delivery system represents. We have been able to broaden the applications for certain bio-active ingredients like CoQ10 into functional foods, drink mixes, beverages and cosmetic products. We have succeeded in this area by addressing issues such as water solubility, oxidative stability, shelf life and uniformity of dispersion in the delivery medium.”

Expanding the Market

After ingredient bioavailability, formulators next must overcome challenges in product development. Mintel’s report noted technical service and formulation assistance are key items for a supplier to offer. “Users indicate there have been problems with incorporating CoQ10 into beverages due to its fat-soluble nature,” the report stated. “Water-soluble CoQ10 is becoming more widely available as manufacturers try to develop a product that can be used in functional beverages. Manufacturers are also offering CoQ10 in matrix or beadlet form, which is easier to incorporate into beverages.”

Across the board, suppliers agreed marketers are tapping into formulation expertise. “We are increasingly being requested to assist with cold water-soluble application for the food and beverage market,” Steinford said. “While this market remains small in terms of total volume, its potential for both growth and volume remains an important element in the future of CoQ10 consumer introductions.”

Jonas agreed, noting initial beverage formulations were more along the smoothie-type options. “However, now there is water-soluble CoQ10 available for clear beverages, and improved solubility leads to improved bioavailability,” he said. “We help our customers formulate, work through process issues and provide clinical studies to support our claims. We continue to work on is improved forms for efficacious use, determining the dose needed per serving in different process conditions. While we have developed a strong data bank, we are always learning new applications.”

As suppliers and formulators team up to develop new applications, marketers face a different challenge—helping to educate the public, media and health care providers about the myriad benefits CoQ10 offers. Most suppliers offer scientific dossiers on their ingredients, which marketers can use to support structure/function claims in product packaging and labeling. Ung noted Best has also supplied information to physician groups and other researchers to help them understand the clinical uses. “However,” he said, “consumers do have a good understanding that CoQ10 is important for their heart and overall health. And many physicians are now recommending taking this supplement, especially if the patient is also taking statin drugs.”

Kaneka is hoping to expand the media messaging on the benefits of CoQ10 and the bioavailability of ubiquinol through a consumer branding campaign featuring figure skater Peggy Fleming as the spokesperson. “We want to raise the education and awareness of ubiquinol, the new ‘body-ready’ form of CoQ10,” Schrier said. “We hope to garner strong media attention to help us spread the word about this incredibly important supplement, which can really help a lot of people, if they just knew about it.”

The benefits truly are wide-ranging, making supplementation almost a ubiquitous need. Concluded Ung, “It is truly an incredible compound with many health benefits, and few nutritional compounds are this powerful.”

References on the next page...

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