The functional properties of ubiquinone (CoQ10) in preventing heart disease

Ubiquinone or CoQ is a lipid-soluble micronutrient present in animal cells and in many plants. Ubiquinol is the reduced form of CoQ and it functions as an antioxidant as further detailed below (Frei et al., 1990). CoQ can be synthesized in vivo and is not, therefore, a true vitamin. There are, however, circumstances in which the utilization of CoQ surpasses its rate of synthesis. For example, the use of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA) inhibitors for the treatment of elevated LDL-cholesterol can result in a deficiency of CoQ10. Fortunately, CoQ10 is well absorbed by oral supplementation, resulting in increased levels of serum CoQ. In humans, the primary form of CoQ is CoQ10, in which ten isoprenoid units are present. In contrast, mice and rats have

The most well-characterized function of CoQ10 is in mitochondrial ATP synthesis where it plays a key role in oxidative phosphorylation (Crane, 2001). In particular, CoQ10 is the coenzyme for at least three mitochondrial enzymes essential for the production of ATP. In rats, lifelong supplementation with CoQ10 does not increase lifespan (Lonnrot et al., 1995).

The role of ubiquinol as an antioxidant is much more controversial than its role in ATP synthesis (Beyer, 1992). In liposomes, ubiquinol has antioxidant ability similar to that of alpha-tocopherol but, unlike alpha-tocopherol, is not recycled by vitamin C (ascorbate) (Frei et al., 1990; Shi et al., 1999). There is, however, evidence suggesting that the semiquinone form of CoQ10 may be a pro-oxidant and generate superoxide radicals (Beyer, 1992). In vitro data suggest, however, that CoQ10 can conserve vitamin E in rat liver microsomes and mitochondrial membranes and thereby increase the resistance of these membranes to oxidative damage (Hiramatsu et al., 1991).

Dietary supplementation with CoQ10 is known to increase the level of ubiquinol in LDL and to increase the resistance of LDL to the initiation of lipid peroxidation (Mohr et al., 1992). As detailed above, the ability of dietary antioxidants to prevent the formation of oxLDL may be an important factor in preventing the very early stages of atherosclerosis, i.e. foam cell formation (Giugliano, 2000). In a very well-designed clinical study, Kaikkonen et al. (2000) compared the antioxidant effectiveness of CoQ10 and RRR-alpha­tocopherol (the natural form of vitamin E) in mildly hypercholesterolemic subjects using a randomized placebo-controlled experimental design. In this study, only vitamin E supplementation increased the resistance of LDL to oxidation. In subjects taking both vitamin E and CoQ10 supplements there was no enhanced effect of vitamin E to increase the resistance of LDL to oxidation. This result is somewhat surprising since in vitro experiments suggest that ubiquinol can regenerate alpha-tocopherol from the alpha-tocopheroxyl radical (an oxidized form of vitamin E) and thereby enhance the antioxidative effectiveness of vitamin E (Cabrini et al., 1991).

Compared with vitamin E, there has been only very limited research on the potential cardiovascular benefits of CoQ10. Singh et al. (1998) have reviewed the role of CoQ10 in CVD. CoQ10 deficiency has been observed in a wide variety of cardiovascular disorders, e.g. congestive heart failure, angina pectoris, coronary artery disease, cardiomyopathy, hypertension, mitral value prolapse (Singh et al., 1998). In the apoE gene knockout mice (an excellent model of human atherosclerosis) supplementation with both vitamin E and CoQ10 was found to inhibit atherosclerosis better than with vitamin E or CoQ10 alone (Thomas et al., 2001). It is not known, however, if CoQ10 supplementation in humans can decrease atherosclerosis.

Although ubiquinol may inhibit the formation of oxidized and atherogenic forms of LDL, it is likely that the primary mechanism whereby CoQ10 could prevent heart disease is through its ability to improve ATP synthesis in cells with a high ATP demand such as cardiac myocytes. As an antioxidant, ubiquinol could also inhibit the free radical damage to the myocardium that arises during ischemia-reperfusion injury. Heart failure (due to cardiomyopathy and congestive heart failure), as discussed above, is a major and increasing worldwide health problem. It is logical to suggest that dietary CoQ10 supplementation could increase ATP production and thereby improve myocardial contractility. A meta-analysis of eight randomized controlled studies looking at the effect of dietary CoQ10 supplementation on congestive heart failure indicates an improvement in stoke volume, ejection fraction, cardiac output, cardiac index, and end diastolic volume index (Soja and Mortensen, 1997). These results certainly support a role for dietary CoQ10 supplementation as an adjunctive treatment for congestive heart failure.