Scoring a Perfect 10

Coenzyme Q10 (CoQ10) may no longer be a stranger to consumers (ConsumerLab.com noted it was the fifth top-selling supplement in 2010, with 53 percent of supplement users adding it to their daily routine), but understanding it may be a long way off. Not that its the disinterested, unengaged consumers fault; this nutrient is quite tricky.

First off, its described as a vitamin-like substance that is a conditionally essential nutrient, as well as a lipid-soluble enzymatic cofactor. It comes in three main forms: ubiquinone, semiquinone and ubiquinol. Ubiquinone is the fully oxidized form (CoQ10), semiquinone is the partially reduced free radical form (CoQ10H), and ubiquinol is the fully reduced form (CoQ10H2). Ubiquinone is synthesized by the body, stored in the outer membrane of the mitochondria and used in the synthesis of 95 percent of the energy (adenosine triphosphate [ATP]) the body makes. Semiquinone supports the cell by focusing on membrane characteristics. Ubiquinol is an antioxidant that protects against oxidation and helps to produce other antioxidants. Within the cells mitochondria, CoQ10 exists in a 50/50 state between oxidized and reduced form. Semiquinone is only in cell membranes.

All three form a redox (reduction-oxidation) cycle and can be readily converted from one form to the other in cells, lymph or blood when necessary. For example, the lymph system and blood need ubiquinol for antioxidant protection, not for energy; whereas mitochondria need ubiquinone for energy production, not protection from oxidative stress. Depending on where it is in the body, the molecule can change to fit the bodys needs.

While youthful, healthy people produce enough CoQ10 to keep the body moving, those with genetic defects, with nutritional deficiencies, experiencing drug side effects or with advancing ages may need supplementation.

According to William V. Judy, Ph.D., chairman and founder, SIBR Research Inc., most individuals are 50-percent to 60-percent CoQ10 deficient by the time they are 65 years old compared to when then they were 21, and the amount of CoQ10 in foods cannot meet daily needs. And because CoQ10 deficiency is linked to many medical conditions (such as heart failure, obesity, chronic fatigue, Parkinsons, etc.), he said, supplementation is the way to go.

Supplements are also easy for consumers to evaluate due to measureable health effects, according to Robin Koon, senior vice president, Best Formulations, who said, CoQ10 is one of the few nutritional products that have a direct clinical application. CoQ10 is essential for energy, so supplementation is good for: cardiac issues, low-energy syndromes, those taking statin drugs, neurological disease states, etc. The older we get, the less our body makes, so supplementation for energy makes sense.

And science backs CoQ10 as well. CoQ10 is one of the most well-studied dietary supplements out there and has so many great benefits that have been proven by science, said John Jarmul, marketing manager, Kaneka. In fact, there are more than 3,000 published clinicals on CoQ10 on everything from heart health to diabetes, Parkinsons and Downs syndrome.

Consumers awareness and need is energizing CoQ10 sales, as Global Industry Analysts (GIA) projected a global rise that will exceed $133.3 million by the year 2015, primarily due to the growing importance of CoQ10 in the food and beverage processing industries, and the emerging role of the coenzyme in heart health, cognitive health and anti-aging sectors. GRAS status and enhanced availability, as well as the growing market for non-caffeinated energy also boost CoQ10s use in the food and beverage processing industries.

SPINS reported dollar sales in food-drug-mass-natural channels were up 6.6 percent in 2011, from $122.5 million in 2010 to $130.5 million one year later (excluding Whole Foods and Walmart, 52 weeks ending Feb. 19, 2011). And, according to Euromonitor International, CoQ10 earned US$898 million in 2009, with an expected 2009 to 2014 compound annual growth rate (CAGR) of 2.6 percent.

Costs are also down, according to Hamlet Chen, marketing manager, DNP International, making it a popular choice among manufacturers. The raw material price is getting much lower nowadays, and producers can make much more profit. In the nutraceutical industry, the finished products sales price is about $3 to $4/g, which is 10 times higher than the raw material; in the cosmetic industry, its about 10 times higher than the supplement industry.

Omnipresent Health Benefits

CoQ10 is ubiquitous, as the name suggests, as it is found in every cell in the body, but is most concentrated where energy is needed the most, i.e., the heart.¹ It is therefore not surprising that CoQ10 supplementation for cardiovascular disease (CVD) provides the most recognized benefit, said Scott Steinford, president, ZMC-USA LLC. There is substantial scientific evidence supporting CoQ10s role in heart health spanning over 50 years.

Steve Holtby, president and CEO, Soft Gel Technologies Inc., added, The antioxidant potential of CoQ10 helps our bodies prevent or delay cellular deterioration. It is this deterioration that is one of the predominant causes of heart disease. CoQ10 is essential for healthy heart function, as well as to protect the veins and arteries from free radical damage. Research has shown CoQ10 supplementation exerts a sparing effect on vitamin E in healthy subjects. It also reduces levels of lipid peroxidation, the pivotal step in the cause of atherosclerosis, thereby decreasing the risk of CVDs.

Starting with cholesterol management, those who use statins are often concerned with CoQ10 levels because it shares the biosynthetic pathway with cholesterol. Statin usage is known to deplete CoQ10 levels,² so supplementation is encouraged for those on these drugs. Healthy levels of CoQ10 can reduce the oxidation of low-density lipoprotein (LDL) cholesterolthe first step in the formation of arterial plaque.³ Further, Italian research showed CoQ10 has a direct, antiatherogenic effect, and dietary supplementation with CoQ10 resulted in increased levels of ubiquinol within circulating lipoproteins and increased resistance of human LDL lipid peroxidation.⁴ In March 2011, German researchers found ubiquinol (obtained from Kaneka) reduced the LDL cholesterol of healthy men after two weeks of supplementation.⁵

CoQ10 can also help reduce hypertension. In 2001, researchers from the Department of Veterans Affairs Medical Center, Boise, ID, found 60 mg of oral CoQ10 two times daily reduced the mean systolic blood pressure by 17.8±7.3 mmHg among 46 men and 37 women with isolated systolic hypertension.⁶ A University of Western Australia, Perth, study revealed CoQ10 supplementation significantly decreased systolic (-6.1±2.6 mmHg, P=0.021) and diastolic (-2.9±1.4 mmHg, P=0.048) blood pressure in subjects with type 2 diabetes.⁷

It also has been shown to reduce aortic and coronary artery plaque sizes and coronary atherosclerosis resulting from a high trans-fatty acid diet;⁸ improve functional status, clinical symptoms and quality of life in a 2004 Israel study of heart transplant candidates;⁹ and improve New York Heart Association (NYHA) functional scale results by one class in 58 percent, two classes in 28 percent and three classes in 1.2 percent of 424 patients with various forms of CVD.¹⁰

Combining heart and brain health, a 1999 review by the Danish Nutrition Council, Soborg, Denmark, reported positive clinical and haemodynamic effects (regulation of the blood flow in the brain) of oral CoQ10 supplementation in double blind trials, especially in chronic heart failure.¹¹ And, combining CoQ10 with mild hypothermia immediately after cardiopulmonary resuscitation (CPR) improved survival and neurological outcomes in survivors, according to a U.K. study from 2004.¹²

The brain, like the heart, also requires a lot of energy, and CoQ10 can benefit the head with or without heart benefits. A Cornell University, New York, study found neuroprotection against the MPTP model of Parkinson's disease using both ubiquinone (from Tishcon) and ubiquinol (from Kaneka).¹³ The researchers found ubiquinol produced larger increases in plasma concentrations of CoQ10.

The nutrient also helps the head by reducing migraine frequency and disability,¹⁴ as well as tinnitus (ringing in the ears).¹⁵

When most think energy, they think exercise, but according to Samantha Chmelik, head of global consumer health research, Euromonitor, the multiple uses of CoQ10 make it difficult to market it purely as an energy supplement. She said consumers have traditionally been interested in its anti-aging and immune-boosting properties, but not energy. Still, CoQ10 improved swimming endurance and had an anti-fatigue effect in mice in a 2010 study.¹⁶ And, a 2010 review reported studies have confirmed CoQ10s effect in improving subjective-fatigue sensation and physical performance and in opposing exercise-related damage.¹⁷

CoQ10s antioxidant properties have also made it popular in skin-health formulations. It is thought to limit production of matrix metalloproteinases (MMPs), enzymes that break down matrix proteins such as collagen and elastin. Topically, German researchers reported application of CoQ10 is beneficial for human skin as it rapidly improves skins mitochondrial function in vivo,¹⁸ and a 1-percent CoQ10 cream used for five months reduced wrinkles, as observed by a dermatologist in a Japanese study.¹⁹ In vitro, CoQ10 help reduced skin damage caused by ultraviolet (UV) radiation.²⁰ Further, supplementing with CoQ10 elevated the epidermal level of antioxidants, which Japanese researchers said may be a prerequisite to the reduction of wrinkles and other benefits.²¹

The Right Form for Absorption

Commercial CoQ10 is produced either by partial synthesis of CoQ9 to CoQ10 or through a yeast fermentation extraction process where it is made by a bacterium. The two finished CoQ10 products available are ubiquinone and ubiquinol, and both are available as supplements and creams. Increasingly, interest in foods and beverages has been rising.

Holtby noted, Launches of foods and beverages containing water-dispersible versions of CoQ10 as a functional ingredient are on the upturn, as its use expands beyond the supplement market. Products launched this year span a variety of food and beverage categories, from energy drinks to yogurts, particularly in the European and Japanese markets. The sports and energy drinks sector has some promising potential, as more consumers learn CoQ10s role in cellular energy production. The cosmetic industry is also utilizing CoQ10 in topical skin products.

While both ubiquinone and ubiquinol are commercially available and are a redox pair, not all products are absorbed equally, according to Koon. Plain powder forms (tablets, capsules, etc.) only absorb about 1 percent or less of the CoQ10, pretty low, he said. Typically, soft gels are much better absorbed.

Because CoQ10 is fat soluble, its better absorbed when taken with a lipid mediumsoybean oil is commonly usedor when taken with food.²²

But many product manufacturers like ubiqunone powders because they are stable. Both the reduced and semioxidized forms of CoQ10 are highly unstable because they oxidize easily, according to Koon. The manufacturers primarily sell CoQ10 crystalline powder in the oxidized form, which is highly stable, he said. However, Koon noted, crystalline powder, while quite stable, poses absorption problems in the body due to a melting point for the crystals that is as much as 20-degrees higher than the bodys temperature. Because of the large size, the body cannot absorb the CoQ10 crystal.

To combat this issue, Best Formulations supplies Q-Best, a crystal-free CoQ10 combined with a lipid carrier molecule to facilitate absorption that was shown in an unpublished study to be better absorbed than a CoQ10 powder. A trial from SIBR Research that included 20 healthy volunteers, found Q-Best was absorbed more than standard dry-powder CoQ10 by 759 percent (P<0.001). Q-Best also boasted bioavailability, according to the study. Bioavailability is a measure of accumulated CoQ10 in blood that is available to the body cells; whereas absorption is a rapid event (six to eight hours) and must occur before CoQ10 can be made bioavailable to cells. In the study, Q-Best was 363-percent more bioavailable than the powdered form.

As noted by Mark Anderson, Ph.D., director of Triarco research and development, Ubiquinone is the form of CoQ10 that has been studied most extensively. It is the fully oxidized form of CoQ10, making it more stable to work with and store, as opposed to the nonoxidized ubiquinol. Inside the body, ubiquinone is converted into ubiquinol for absorption. Because it is difficult to keep ubiquinol stable outside of the body, manufacturers may prefer the fully oxidized ubiquinone.

Triarco also has studies showing the superior absorption of its CoQ10 water-dispersible powder. Anderson noted pre-clinical studies of Triarcos Aqua 10® have shown it to be absorbed 52-percent more than a standard CoQ10 powder.

CoQsol®-CF (crystal-free), an all-natural soft gel formulation from Soft Gel Technologies of CoQ10, beta-carotene and mixed tocopherols in a crystal-free formula, has also competed with dry CoQ10 powder. A double blind, randomized, two-armed parallel group study conducted by KGK Synergize included 15 subjects who took 100 mg/d of CoQsol-CF and 15 subjects who took 100 mg/d powdered CoQ10 two-piece, hard-shell capsules for 28 days. Supplementation with CoQsol-CF led to a 124-percent increase in plasma CoQ10 levels, from 0.79 g/mL at baseline to 1.77 g/mL on day 28. The rate of absorption after five hours following the final dose of CoQ10 was 5.5 times higher for CoQsol-CF than for the powdered CoQ10. The CoQsol-CF-supplemented group also showed increased antioxidant status and anti-atherosclerotic potential based on treatment-induced changes in the levels of selected markers, including serum levels of glutathione, 8-isoprostanes, C-reactive protein (CRP) and total antioxidants.

An additional study on CoQsol-CF from SIBR Research involved three men and two women who rested and fasted prior to consuming 60 mg CoQsol-CF. Within four hours after ingesting CoQ10-CF, the plasma levels for the group increased significantly from 0.88 g/ml to 1.36 g/ml; peak plasma levels occurred six hours later at 2.28 g/ml. The subjects continued taking 60 mg/d CoQsol-CF for 28 days. In seven days, the mean plasma CoQ10 level increased significantly to 2.39 g/ml. At the 28th day, the mean plasma CoQ10 was 2.75 g/ml, resulting in a 200-percent increase in 28 days.

While ubiquinone has been used and studied for about four decades, some studies have shown the recently (in comparison) marketed ubiquinol has better absorption. And with CoQ10, no matter the form, absorption is key to realizing health benefits. Because the oxidized ubiquinone must be converted to uniquinol in the body, some argue it is not absorbed as well by those who have a deficiency in their ability to convert the molecule.

The most innovative product launch involving CoQ10 in the past few years was from Kaneka Corp., which introduced the reduced form of CoQ10, ubiquinol, Holtby said. This form shows great promise for specific groups of people that are older and/or have oxidative stress from specific diseases or situations. Holtby added Soft Gel uses its crystal-free (CF) technology in CoQH-CF®, a soft gel capsule that contains Kaneka QH, to protect the CoQ10 from being oxidized and crystallized.

A Kaneka-supported mouse study found its reduced form of CoQ10 was better absorbed and had better effects on cholesterol metabolism than the oxidized form.²³ And, a double blind, randomized, two-arm crossover study sponsored by Soft Gel Technologies Inc. found a 100-mg dose of CoQH-CF induced significantly higher (P<0.001) plasma concentrations at five, six, eight, 12, 24, 48 and 72 hours post-dose compared to a CoQ10 hard-shell capsule in 10 subjects older than 60.²⁴ CoQH-CF supplementation resulted in a 430-percent higher plasma CoQ10 level after 72 hours compared to the oxidized CoQ10 (P<0.001).

An additional study using Tishcon Corp. products found ubiquinol, the reduced from, was better absorbed than the oxidized ubiquinone.²⁵

Market and Formulation Opportunities

Perhaps these studies are persuading consumers. According to Jamul, Right now there is a huge upswing in ubiquinol sales over the last year. The education is finally getting out there, and we are really seeing a turning point in consumers choosing ubiquinol over CoQ10.

Or, perhaps sales are up because most products on the market are true to their label claims and are thus truly benefiting consumers. In March 2011, ConsumerLab.com reported all 31 products it tested that contained CoQ10 or ubiquinol met label claims for active ingredients. However, the organization stated labels on a few products did contain health claims that appeared to be in violation of federal regulations. ConsumerLab also reported a wide range in suggested daily serving size (from 22 mg to 400 mg) and in pricing; to obtain 100 mg of CoQ10, prices ranged from $0.11 to more than $3.

Marketing needs to deal with claims that might violate federal rules, especially as most in the industry say CoQ10 development hasnt yet been hindered by regulation, but the ConsumerLab report shows companies deserve a pat on the back for the due diligence it takes to create CoQ10 ingredients.

CoQ10 is notoriously difficult to work with because of its lipophilic nature and large molecular weight, Anderson said. Traditionally, manufacturers have struggled with solubility issues and dread CoQ10 that falls out of solution. Manufacturers can choose oil carriers and soft gel delivery to get around this problem, but this limits their options in terms of delivery formats. With a strong benefits profile and a presence in several of the topselling natural product markets, it would be a shame to limit CoQ10 because of underperformance in formulation or bioavailability. He added this is why Triarco uses the Exel Delivery system, which he said enhances absorption.

Kaneka uses ubiquinol, which, as noted earlier, can pose stability issues. Because CoQ10 is an oxidized molecule, it by nature remains very stable in most applications, Jamul said. Ubiquinol, on the other hand, is a powerful antioxidant and readily converts to CoQ10 if not handled properly. Kaneka ensures every contract manufacturer is certified in handling ubiquinol appropriately. For example, we require the blend tanks to maintain a nitrogen blanket as to avoid oxidation of the ubiquinol during manufacturing.

Testing quality and increasing absorption rates bodes well for the CoQ10 market, especially as consumers are becoming more familiar with the nutrient. The continuing investment in research by natural product companies, and educational and medical institutions indicates a promising trend for the use of CoQ10 in the future, Anderson predicted. In fact, a good portion of recent research focuses on how to incorporate a more bioavailable form of CoQ10 into products. This parallels a shift in natural products from, Why should we use CoQ10 in our product? to How can we use CoQ10 in our product? The why seems clear. Even companies outside of the natural channels are looking for ways to incorporate the benefits of CoQ10 into everyday foods like pasta.

And, Steinford said science has only started to realize the benefits of CoQ10. We are more clearly understanding the important role CoQ10 plays not only in the recognized cardiovascular role, but in every cell and function of the human body. Eventually, the benefits of CoQ10 involving everything from skin care to sustained energy will be more scientifically understood and proven. As consumers become more educated to realize the impact CoQ10 has on ATP production and the importance the benefits of to the human body, the acceptance and significance of CoQ10 supplementation will increase.

While the science on CoQ10 and its various forms may still be murky to many consumers, they seem to have gotten the message that CoQ10 supplementation works and is beneficial, especially for those 35 million Americans on statins and those older than 60. As long as the industry keeps up the high level of lab quality and stays away from illegal marketing claims, ubiquinone and ubiquinol should keep energizing supplement, beverage and food sales.

References are on the next page...

References for "CoQ10: Scoring a Perfect 10"

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