Coenzyme Q10: History and Development

Coenzyme Q10, a lipid soluble benzoquinone, has been demonstrated to possess excellent antioxidant and membrane stabilizing properties in the cardiac tissues⁵. Coenzyme Q10 was first isolated in pure form by Professor F. L. Crane and his group at the University of Wisconsin in 1957.⁶ The well known medicinal chemist Dr. Karl Folkers reisolated coenzyme Q10 from beef muscle, characterized and elucidated its structure, and synthesized the pure compound by fermentation.^7,8 He further demonstrated that this compound is no way less than an essential vitamin supplement for the maintenance of cardiovascular and immunological health.^7-9 In 1960, Dr. Folkers hypothesized that Coenzyme Q10 was essential to the body’s production of energy in the form of adenosine triphosphate (ATP ).^7,8 Furthermore, Dr. Folkers established his hypothesis that all vitamins as well as Coenzyme Q10 are components of the enzyme or antioxidant complexes involved in respiration and are absolutely essential for human life.⁸

1.Pharmaceutical & Administrative Sciences, Creighton University School of Pharmacy & Allied Health Professions, 2500 California Plaza, Omaha, NE 68178

Coenzyme Q10 has been used as nutritional supplements for humans in Japan since the mid-1960s to treat cardiovascular dysfunctions. Their results were over-whelming positive. It is now distributed in Japan under the name of “ubide-carenone,” and has become one of the top six pharmaceuticals consumed in Japan. Today, a large fraction of Japanese include Coenzyme Q10 in their nutritional regimen. Later, Coenzyme Q10 was introduced in the United States as a nutritional supplement.

antibody levels.⁷Similar findings were demonstrated by the researchers of the Osaka University Medical School, Japan.^7-11 Furthermore, it has been demonstrated by Scientists that people afflicted with cancer and heart disease have an alarmingly low supply of Coenzyme Q10.^5-10 Thus, it is very important to supplement Coenzyme Q10. In an article published by the Linus Pauling Institute of Science and Medicine, it has been stated that supplementation of Coenzyme Q10 strengthens the heart, even without exercise; normalizes blood pressure; elevates energy levels, and contributes to life extension. Other studies have indicated that supplementation of Coenzyme Q10 can replenish depleted Coenzyme Q10 stores, increase stamina and energy, and heighten the effectiveness of the immune system.

Coenzyme Q10: Bioavailability and Health Benefits

The human body is made of trillions of cells. Each individual cell performs various vital biochemical functions of the body. Thus, without the production of energy at the cellular level, life cannot exist. Coenzyme Q10 acts as the catalyst that allows the body to produce energy at the cellular level. This energy enhances the immune system, the body’s primary line of defense against disease. Without adequate enhancement, the immune system can no longer prevent illness. Coenzyme Q10, also known as ubiquinone, is a naturally occurring substance that is essential component of the mitochondrial respiratory chain where aerobic energy is produced.^5-8It is an important regulator of the cardiovascular system. Nutritional researchers describe coenzyme Q10 as a restorative for homeostasis in the heart and blood vessels.^9-11

Coenzyme Q10 is indispensable to biochemical mechanisms of bioenergetics, and it has a specific role as an antioxidant,^5-11 Coenzyme Q10 has demonstrated a hematological activity for the human and has shown an influence on the host defense system. Coenzyme Q10 potentiates transplasma membrane electron transport system which influences healthy tissue regeneration, cell growth and viability.^12,13The human species is not genetically adapted to survive past middle age, and it appears that supplementation of Coenzyme Q10 and other antioxidants is required to ensure a more healthy, elderly population.^8-11 Coenzyme Q10 has been identified to have a profound beneficial effects in the following areas.^8-11

1) Acts as a novel antioxidant 2) Enhances stamina, endurance and energy levels 3) Helps to reduce body weight 4) Normalizes blood pressure 5) Attenuates immune function 6) Protects against cardiovascular dysfunction 7) Reverses periodontal disease 8) Increases effectiveness of various chemotherapeutic agents and antimalarial drugs

Coenzyme Q10: Recent Clinical Observations

The cardioprotective abilities of Coenzyme Q10 have been extensively documented. Furthermore, the following data and knowledge have recently been gathered from biochemical, biomedical and clinical research on Coenzyme Q10:

Coenzyme Q10 Supplementation Protects Lipoprotein Lipids, and Induces Energy Conserving and Free Radical Scavenging Properties in Humans.^14,15

Coenzyme Q10 supplementation to 22 human volunteers resulted in a higher plasma level of reduced Coenzyme Q10, significant decrease in hydroperoxide level and a decreased lipid peroxidation level, but sparing of other plasma antioxidants

(i.e. vitamin C and vitamin E) was not observed. Coenzyme Q10 has been shown to protect lipoprotein lipids against free radicalinduced oxidative damage. Low density lipoproteins (LDL) isolated from Coenzyme Q10 supplemented volunteers

Coenzyme Q10: New Findings

The major target of free radicals include lipids, proteins and biological macromolecules, antioxidant enzymes and DNA. Since various cardiac disorders are associated with oxidative stress, we have recently evaluated²³ ethanolinduced oxidative stress and DNA damage in cultured cardiac cells in vitro, and determined the protective ability of Coenzyme Q10. In a recent study, we have isolated and cultured cardiac cells from fertile chicken eggs, and assessed the concentration-dependent cardioprotective ability of Coenzyme Q10 in ethanol-induced enhanced lipid peroxidation and DNA damage in cultured cardiac cells. Lipid peroxidation was determined based on the formation of thiobarbituric acid reactive substances (TBARS), while DNA damage was determined by quantitating DNA fragmentation. Ethanol-induced enhanced production of free radicals including superoxide anion and hydroxyl radicals, were determined by cytochrome c reduction and HPLC assay, and the protective ability of Coenzyme Q10 was assessed. Furthermore, ethanol-induced changes in cell morphology and modulation of intra-cellular oxidized states in cultured cardiac cells were measured by laser scanning confocal microscopy. DNA fragmentation and laser scanning confocal microscopic techniques have recently been considered as markers of apoptopic cell death. Our results indicate that Coenzyme Q10 can significantly ameliorate ethanol-induced oxidative stress and pathophysiology in cultured cardiac cells.

In a separate series of experiment, we have assessed the in vivo cardioprotective ability of Coenzyme Q10.²⁴ Since ischemia and reperfusion are associated with the development of oxidative stress and lipid peroxidation, and free radical scavengers/ antioxidants have been shown to be beneficial for ischemic myocardium, we hypothesized that stimulation of Coenzyme Q10 may protect hearts from ischemiareperfusion injury. To test this hypothesis, a group of adult pigs were fed Coenzyme Q10-supplemented diet for four weeks, while another group of pigs were fed regular diets for the same period of time. Normothermic regional ischemia was induced for 60 minutes by LAD occlusion followed by 60 minutes of reperfusion. The effects of Coenzyme Q10 were evaluated by measuring left ventricular functions and creatine kinase (CK) and malondialdehyde (MDA) releases as well as by assessing the infarct size. Coenzyme Q10 improved the systolic and diastolic function in the postischemic hearts and reduced CK and MDA release suggesting lowering of tissue injury and oxidative stress. Infarct size of the LAD region was also reduced by Coenzyme Q10 supplementation. Measurement of Coenzyme Q10 in hearts revealed an increased amount of Coenzyme Q10 in mitochondria in the Coenzyme Q10-supplemented animals compared to that of control. The results of this study demonstrated an increased amount of Coenzyme Q10 in mitochondria in the Coenzyme Q10-supplemented animal in concert with reduced formation of malondialdehyde, a presumptive bio-marker for lipid peroxidation, and improved postischemic ventricular recovery. Thus, Coenzyme Q10 salvaged the pig hearts from ischemia reperfusion injury by reducing the oxidative stress. Furthermore, Coenzyme Q10 supplementation has been demonstrated to upregulate ubiquitin gene expression in the cardiac tissues of Coenzyme Q10-supplemented animals. The size of the three different transcripts are UbA 1.3 kb, UbB 2.5 kb and UbC 3.5 kb. Upregulation of ubiquitin gene expression in the hearts of Coenzyme Q10-supplemented animals definitely predicts a superior cardioprotection through Coenzyme Q10 supplementation.

ADP-Fe³⁺, and that this effect is independent of the presence of vitamin E.³¹ Supplementation of Coenzyme Q10 has been shown to be a potent blocker of lipid peroxidation in biological systems.^24,31 Coenzyme Q10 is thus a potent antioxidant and in its reduced form, ubiquinol, acts as a free radical scavenger^8-11.

In mitochondria, Coenzyme Q10 acts as a mobile distributor of reducing equivalents between the NADH dehydrogenase, succinate dehydrogenase, and cytochrome b-c1 segment of the electron transport chain and as participants of the proton motive Q cycle responsible for the transfer of protons across the coupling membrane.^8-12

Conclusion

These findings indicate a close relationship between oxidative tissue injury, lipid peroxidation and modulation of integral membrane proteins in the mitochondrial inner membrane, and an important role of endogenous ubiquinol in attenuating these effects. The physiological implications of these results may not necessarily be restricted to the inner mitochondrial membrane, because it is well established that protein modification accompanying lipid peroxidation and DNA damage can also occur in other biological membranes and cellular sites, as well as in serum low density lipoprotein (LDL), and that ubiquinol is present in all of these locations and serve as a potent antioxidant.

Thus, Coenzyme Q10 has been identified as a novel antioxidant and a “miracle” nutrient. Because of its ability to boost the human immune system, extensive research continues apace in the fields of myocardial ischemia-reperfusion injury, congestive heart failure, diabetes, transplant surgeries, coronary angioplasty, muscular dystrophies and neurogenic atrophies, retinal degeneration, treatment of dyspermic patients, breast cancer and regression of metastases, AIDS and immune system.