[King Kabuki]

So I've told you guys that one of my former co-workers in Florida is a Biologist. She recently had to do a quick paper on CoQ10. If any of you or any of your Family Members have problems with cholesterol and take statin drugs (even Red Yeast Rice, it acts like the statin drugs do in-terms of liver taxation), this should be pretty informative.

Ubiquinone (Coenzyme Q10)

Statin family values: a matter of the heart

Coronary heart disease is a major health concern and the leading cause of death in the United States. In 2002, approximately 17% of the adult population in the United States had high blood cholesterol, a significant but modifiable risk factor for poor coronary health.15 The Center for Disease Control and Prevention has instituted several programs aimed at reducing the prevalence of heart disease by focusing on the treatment of high cholesterol. The attempt to reduce the incidence of heart disease and high cholesterol has led to an increased use of lipid lowering medications.12 Among the most widely used drug for this purpose is atorvastatin, known popularly as Lipitor, which belongs to a family of drugs known collectively as the statins.

Statin drug use constituted 87 percent of all cholesterol-lowering drugs used in 2002.12 Statins limit cholesterol production early in its biosynthetic pathway by inhibition of a key enzyme, HMG-CoA reductase.3 As with any pharmaceutical drug, clinical trials of the efficacy and safety of the statins have been documented and are ongoing. Controversies over potential side-effects have arisen including their promotion of liver dysfunction and myopathy, a condition characterized by pain and weakness in the muscles. Manufacturers of statin products provide information about all possible side effects to consumers in addition to the prescribing information made available to practitioners. The prescribing information for drugs details chemical and clinical aspects of the compound including mechanisms of action, other biochemical effects and outcomes of use especially where potential risk is involved.

In the case of statin drugs, including, but not limited to, atorvastatin (Lipitor®),11 lovastatin (Mevacol®), pravastatin (Pravachol®), and simvastatin (Zocor®), both the prescribing and consumer information lacks mention of possible depletion of ubiquinone.11 More commonly known as Coenzyme Q10, ubiquinone is a non-essential, vitamin-like substance that has a vital role in cellular ****bolism, energy production, and immunity 4,6,9,10. The term non-essential, meaning normally synthesized in healthy individuals as opposed to being required strictly through dietary consumption, should not be mistaken for unnecessary, as ubiquinone is linked to processes that make daily function possible. Ubiquinone shares a common biosynthetic pathway with cholesterol: both require the activity of HMG-CoA reductase.10 Scientists have been investigating the role of ubiquinone in cardiovascular health and the treatment of coronary heart disease since its discovery.10 Given the substantial body of research documented and continuously being conducted on the mechanisms of statin-induced ubiquinone depletion, why is it not addressed in the literature prepared by the pharmaceutical companies? Should these companies be required to disclose reduction of ubiquinone levels as a possible side-effect?

Chemical Structure of Ubiquinone 13, 17

IUPAC nomenclature: 2,3-dimethoxy-5-methyl-6-decaprenyl benzoquinone

Empirical Formula: C59H90O4

Molecular Weight: 863.36

Involved in synthesis reactions, free radical chemistry, the transport of protons and electrons along the pathway of adenosine triphosphate synthesis.


History of ubiquinone

Coenzyme Q10 was first discovered in 1957 at the University of Wisconsin by Dr. Frederick Crane, et al, who was able to isolate the compound from the mitochondria of bovine cardiac tissue.7 Crane writes "Coenzyme Q is a lipid-soluble quinone which has been shown to be an integral part of the electron transport system of beef heart mitochondria... previously referred to as Q275."7 It was noted to be a brightly colored, crystalline substance with a melting point range of 48-49oC.10 Morton, who found it later in rat liver, called it ubiquinone, for ubiquitous (seeming to be everywhere) quinone.10 Ubiquinone was subsequently found in cardiac muscle and organ tissue of several other mammals7, microbial species7, and higher plants, 9 underscoring the essential role that is plays in the ****bolic function of living organisms. In 1958, Karl Folkers and a team of researchers at Merck determined the structure as 2,3-dimethoxy-5-methyl-6-decaprenyl benzoquinone, synthesized and fermented it.10 Based on the work of Yamamura, a Japanese medical researcher, on treating congestive heart failure with Q6, Folkers and other research scientists began investigational trials on Q10, the isomer of ubiquinone found in humans. The eighties marked a new turn in the amount of research that was being done. The Japanese were able to mass produce ubiquinone and new technology for the testing of serum levels of the substance had become available.

Ubiquinone is involved in the chain of ****bolic reactions occurring in the mitochondria of the cells. Mitochondria are the energy manufacturing plants of cellular structures and their main product is adenosine triphosphate (ATP), the primary currency for energy exchange in the cell. All other ****bolic processes occur with the expenditure of ATP. In the human body, mitochondria, and therefore ubiquinone, are found in virtually in the cells every type of tissue. Tissues that require more energy for function (i.e. muscle cell contraction) have greater amounts of mitochondria. The heart, skeletal muscle, liver, kidneys, and pancreas all have elevated amounts of ubiquinone, due to their greater need for ATP for proper function. The radical structure of ubiquinone allows it to transport electrons and protons to and from other compounds in a process called phosphorylation. Because it is involved in free radical chemistry, it has been studied for its antioxidant value and its protective effects on cellular integrity.10

Ubiquinone is formed through a complex biosynthetic pathway, requiring at least 15 reactions and the involvement of several other vitamins and enzymes.9 Its structure has two main groups: benzoquinone and the isoprene sidechain. Benzoquinone is synthesized from amino acids, while the isoprene portion is synthesized down the mevalonate pathway from acetyl CoA.10 It is this portion of its synthesis that is common to that of cholesterol. Statin drugs that inhibit HMG-CoA reductase prevent the formation of a common precursor, mevalonate. Apart from biosynthesis, ubiquinone can also be obtained through exogenous dietary consumption. It is found in small amounts in certain types of foods, including meat, fish, vegetable oils, some legumes and cruciferous vegetables. The average daily intake of ubiquinone, however, is about five milligrams, an amount far below that required for sustaining ****bolic function. In studies of people who were placed on ubiquinone-free diets, endogenous production decreased by 50% over one week9. Endogenous production of ubiquinone is known to be substantially lower in the elderly population, making the case for its consideration as an essential nutrient.9

In Japan, ubiquinone has been approved as a treatment for congestive heart failure, circa 1974, after publication of a critique reviewing a decade worth of documented clinical successes. Although supplemental sources of ubiquinone have not been approved in the United States, much independent research on the deleterious effects of ubiquinone deficiency and its use for treatment of cardiovascular disease has been conducted . Pharmaceutical corporations in the United States have not shown interest in developing products containing ubiquinone as it is non-patentable and naturally occurring.1,9,10 Studies have linked ubiquinone deficiency to cardiomyopathy, congestive heart failure, high blood pressure, gingivitis, and impaired immune function.1,3,4,5,9,10 Contemporary research suggests it may have a beneficial role in the treatment of high cholesterol, ****bolic disorders, diabetes mellitus, auto-immune diseases, Alzheimer's disease and others.2,4,8,9,10,14

The reduction of serum ubiquinone induced by the use of statin drugs has been documented, although the complete mechanism and other variables are subject to ongoing investigation. Drug companies that produce statins, as well as the Federal Drug Administration, are aware of ubiquinone depletion as a potential side effect. The question is then raised, do drug companies have the ethical obligation of informing practitioners and consumers about ubiquinone depletion? The topic has stirred controversy in the circles of advocacy for complementary and alternative medicine. Some of the more radical perspectives that predominate the discussion implicate conspiracy between the multi-billion dollar drug companies and the FDA. Their claims that pharmaceutical companies want to suppress information about a effective alternative or complementary treatment for high cholesterol and cardiovascular disease, because they cannot patent it or make it a profitable venture. While the correlation between ubiquinone levels and the etiology of other diseases is still questionable, there is a generally accepted understanding that it plays a crucial role in the treatment of cardiovascular disorders.16

[King Kabuki]

The rest:

As the new generations of doctors and researchers become more well-versed with complementary and alternative medicine, and the field of clinical nutrition becomes more advanced, there are more investigations on the subject of therapeutic and prophylactic supplementation with Coenzyme Q10. There is a great need, however for the both the side effects and possible benefits to be communicated effectively to the prescribing authorities within the medical community. Without being fully informed, practitioners are working without the ability to elucidate the "bigger picture." Many symptoms of ubiquinone depletion such as muscular weakness, sciatic and femoral pain, and lack of energy can be written off by patients themselves and never reported as an adverse event. Patient education is equally as important as physician education, and it is the right of the consumer of these medications to be appropriately informed.

While the law does not provide for an opportunity to confront drug companies on this issue, ultimately, there is a line being drawn between financial prosperity of major pharmaceutical institutions and the best interests of the state of health of our people. As the face of healthcare in this country changes, there will be new opportunities for advocacy for patient rights and ethical disclosure of information. It is only under these circumstances can people chose freely to be responsible for and participatory in the management of their health.

Works Cited

1. Cardiologists Overlook Lifesaving Discovery. n.d. Life Extension Magazine. 17 Apr. 2007 http://www.stopfda.org/feb2004_awsi_02.htm

2. Beal, M F. "Coenzyme Q10 as a possible treatment for neurodegenerative diseases.." Free Radic Res 36.4 2002: 455-460

3. Berthold, H K, A Naini, S Di Mauro, et al. "Effect of ezetimibe and/or simvastatin on coenzyme Q10 levels in plasma: a randomized trial.." Drug Safety 29.8 2006: 703-712. Drug Commission of the German Medical Association. 17 Apr. 2007 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=16872244"

4. Bonakdar, M.D., Robert A and Erminia Guarneri, M.D.. American Family Physician. 15 Sept. 2005. Scripps Center for Integrative Medicine. 17 Apr. 2007 http://www.aafp.org/afp/20050915/1065.html"

5. Cholesterol-Lowering Medications, HMG-CoA Reductase Inhibitors. 2004. University of Maryland Medical Center. 17 Apr. 2007 http://www.umm.edu/altmed/ConsDeplet...ibitorscl.html

6. Coenzyme Q10 - Mayo Clinic.com. 1 May 2006. Natural Standards Research Collaboration. 17 Apr. 2007 http://www.mayoclinic.com/health/coenzyme-q10/NS_patient-coenzymeq10"

7. Crane, F L, Y Hatefi, and R I. Lester. "Isolation of quinone from beef heart mitochondria.." Biochimica et Biophys. Acta 25. 1957: 220-221.

8. Folkers, K, P Langsjoen, and Y Nara. "Biochemical Deficiencies of CoQ10 in HIV infection and exploratory treatment." Biochem Biophys Res Commun. 153. 1988: 888-896.

9. Gissen, A S. Bio-Coenzyme-Q10. n.d. 17 Apr. 2007 http://www.campo-research.com/campo/products/bio/part1.html" ..l "struct

10. Langsjoen, M.D., F.A.C.C., Peter H. Introduction to Coenzyme Q10. 1994. 17 Apr. 2007 http://http://faculty.washington.edu/ely/coenzq10.html

11. Lipitor Prescribing Information. n.d. Pfizer. n.d. http://www.lipitor.com/content/LipitorPI.pdf

12. Ma, Jun, Niraj L. Sehgal, John Z. Ayanian, et al. "National Trends in Statin Use by Coronoary Heart Disease Risk Category." PLoS Medicine 2.5 2005: 123.

13. ****Cyc compound: Ubiquinone-10. Nucleic Acids Res 34. 2006: D511-516. 07 Apr. 2007 http://biocyc.org/****/NEW-IMAGE?object=UBIQUINONE-10

14. Mortenson, S A, S Vadhanavikit, K Folkers, et al. "Deficiency of coenzyme Q10 in myocardial failure.." Drugs Exptl Clin Res 10.7 1984: 497-502. n.d.

15. National Center for Health Statistics. Chartbook on Health of Americans. Hyattsville, Maryland: n.p., 2005.
Available at "http://www.cdc.gov/nchs/hus.htm"

16. PDR Health - Coenzyme Q10 http://www.pdrhealth.com/drug_info/n...coe_0084.shtml

17. Ubiquinone-10. n.d. n.d. <"http://www.cyberlipid.org/images/pict61.gif">.