Coenzyme Q10: Difference between revisions
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CoEnzyme Q levels are decreased in the setting of [[heart failure]], and progressive heart failure leads to lower and lower levels of CoEnzyme Q. There have been modest sized [[double blind]] [[randomized controlled trials]] that have demonstrated CoEnzyme Q is associated with improved symptoms, functional capacity and quality of life in patients with heart failure. The drug is generally well tolerated, with few side effects. | CoEnzyme Q levels are decreased in the setting of [[heart failure]], and progressive heart failure leads to lower and lower levels of CoEnzyme Q. There have been modest sized [[double blind]] [[randomized controlled trials]] that have demonstrated CoEnzyme Q is associated with improved symptoms, functional capacity and quality of life in patients with heart failure. The drug is generally well tolerated, with few side effects. | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Coenzyme Q10 (also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ10, CoQ, Q10, or Q) is a benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the isoprenyl chemical subunits.
This vitamin-like substance is, by nature, present in most human cells except red blood cells and eye lens cells (no mitochondria) and are responsible for the production of the body’s own energy. In each human cell, food energy is converted into energy in the mitochondria with the aid of CoQ10. Ninety-five percent of all the human body’s energy requirements (ATP) is converted with the aid of CoQ10.[1][2] Therefore, those organs with the highest energy requirements – such as the heart and the liver – have the highest CoQ10 concentrations.[3][4][5]
History
Coenzyme Q was first discovered by professor Fred L. Crane and colleagues at the University of Wisconsin-Madison Enzyme Institute in 1957.[6][7] In 1958, its chemical structure was reported by Professor Karl Folkers and coworkers at Merck.[8][7]
Occurrence in nature
CoQ10 occurs in mackerel and herring fresh heart tissue in concentrations of 105-148 μg/g. In fresh mackerel "red and white tissue," CoQ10 concentrations of 67 and 15 μg/g, respectively, have been reported. In fresh herring tissue, an amount of 15–24 μg/g of CoQ10 has been reported.[9]
CoQ10 Content of various foods:[10]
| Food | CoQ10 [μg/g] |
Portion of Food [g] |
CoQ10 Amount in Portion [mg] |
|---|---|---|---|
| Pork heart | 203 | 120 | 24 |
| Chicken leg | 17 | 120 | 2.0 |
| Beef heart | 41 | 120 | 4.8 |
Chemical properties
The oxidized structure of CoQ, or Q, is given here. The various kinds of Coenzyme Q can be distinguished by the number of isoprenoid side-chains they have. The most common CoQ in human mitochondria is Q10. The image to the right has three isoprenoid units and would be called Q3.
If Coenzyme Q is reduced by one equivalent, the following structure results, a ubisemiquinone, and is denoted QH. Note the free-radical on one of the ring oxygens (either oxygen may become a free-radical, in this case the top oxygen is shown as such).
If Coenzyme Q is reduced by two equivalents, the compound becomes a ubiquinol, denoted QH2:
Biochemical role
CoQ is found in the membranes of endoplasmic reticulum, peroxisomes, lysosomes, vesicles, and the inner membrane of the mitochondrion, where it is an important part of the electron transport chain; there it passes reducing equivalents to acceptors such as Coenzyme Q: cytochrome c - oxidoreductase:
- CoQH2+ 2 FeIII-cytochrome c → CoQ + 2 FeII-cytochrome c
CoQ is also essential in the formation of the apoptosome, along with other adapter proteins. The loss of trophic factors activates pro-apoptotic enzymes, causing the breakdown of mitochondria.
Biosynthesis
The benzoquinone portion of Coenzyme Q10 is synthesized from tyrosine, whereas the isoprene sidechain is synthesized from acetyl-CoA through the mevalonate pathway. The mevalonate pathway is used for the first steps of cholesterol biosynthesis.
Supplementation
Because of its ability to transfer electrons and therefore act as an antioxidant, Coenzyme Q is also used as a dietary supplement. When you are younger the body can synthesize Q10 from the lower-numbered ubiquinones such as Q6 or Q8. The sick and elderly may not be able to make enough, thus Q10 becomes a vitamin later in life and in illness.
Mitochondrial disorders
Supplementation of Coenzyme Q10 is a treatment for some of the very rare and serious mitochondrial disorders and other metabolic disorders, where patients are not capable of producing enough coenzyme Q10 because of their disorder. Coenzyme Q10 is then prescribed by a physician.[11]
Cardiac and Vascular Disease
Congestive Heart Failure
CoEnzyme Q levels are decreased in the setting of heart failure, and progressive heart failure leads to lower and lower levels of CoEnzyme Q. There have been modest sized double blind randomized controlled trials that have demonstrated CoEnzyme Q is associated with improved symptoms, functional capacity and quality of life in patients with heart failure. The drug is generally well tolerated, with few side effects.
Q-SYMBIO Trial
In a modest sized, multicenter, double blind,randomized controlled trial, 420 patients with New York Heart Association (NYHA) Class III or IV heart failure who were receiving standard therapy, were randomized to either CoEnzyme Q or placebo. The patients were followed for two years. [12]. The primary endpoint (MACE=unplanned hospitalization due to worsening of heart failure, cardiovascular death, urgent cardiac transplantation and mechanical circulatory support) was reduced from 29 events (14%) in patients randomized to CoEnzyme Q10 compared to 55 (25%) in patients randomized to placebo (hazard ratio=2; p=0.003 by time to event analysis). Randomization to Coenzyme Q10 was associated with a halving of all cause mortality: there were 18 (9%) deaths among patients in the CoQ10 group versus 36 (17%) deaths among patients in the placebo group (hazard ratio=2.1; p=0.01). Cardiovascular mortality was also reduced (p-0.02) as was the risk of rehospitalisations for heart failure (p=0.05). There tended to be fewer adverse events among patients randomized to CoEnzyme Q10 compared to the placebo (p=0.073). It is unclear if there were greater benefits among patients treated with statins, drugs that lower CoEnzyme Q.
Treatment of Statin Intolerance
Coenzyme Q10 shares a common biosynthetic pathway with cholesterol. The synthesis of an intermediary precursor of Coenzyme Q10, mevalonate, is inhibited by some beta blockers, blood pressure-lowering medication,[13] and statins, a class of cholesterol-lowering drugs.[14] Statins can reduce serum levels of coenzyme Q10 by up to 40%.[15] Some research suggests the logical option of supplementation with coenzyme Q10 as a routine adjunct to any treatment that may reduce endogenous production of coenzyme Q10, based on a balance of likely benefit against very small risk.[16][17]
Cardiac arrest
Another recent study shows a survival benefit after cardiac arrest if coenzyme Q10 is administered in addition to commencing active cooling (to 32–34 degrees Celsius).[18]
Hypertension
There are several reports concerning the effect of CoQ10 on blood pressure in human studies.[19] In a recent meta-analysis of the clinical trials of CoQ10 for hypertension, a research group led by Professor FL Rosenfeldt (from the Cardiac Surgical Research Unit, Alfred Hospital, Melbourne, Australia) reviewed all published trials of Coenzyme Q10 for hypertension, and assessed overall efficacy, consistency of therapeutic action, and side-effect incidence. Meta-analysis was performed in 12 clinical trials (362 patients) comprising three randomized controlled trials, one crossover study, and eight open-label studies. The research group concluded that coenzyme Q10 has the potential in hypertensive patients to lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by up to 10 mm Hg without significant side-effects.[20]
Migraine headaches
Supplementation of Coenzyme Q10 has been found to have a beneficial effect on the condition of some sufferers of migraine headaches. So far, three studies have been done, of which two were small, did not have a placebo group, were not randomized, and were open-label,[21] and one was a double-blind, randomized, placebo-controlled trial, which found statistically significant results despite its small sample size of 42 patients.[22] Dosages were 150 to 300 mg/day.
Cancer
It is also being investigated as a treatment for cancer, and as relief from cancer treatment side-effects.[23]
Brain health and neurodegenerative diseases
Recent studies have shown that the antioxidant properties of Coenzyme Q10 benefit the body and the brain in animal models.[24] Some of these studies indicate that Coenzyme Q10 protects the brain from neurodegenerative disease such as Parkinson's,[25] although it does not relieve the symptoms.[26] Dosage was 300 mg per day.
Lifespan
Studies have shown that low dosages of Coenzyme Q10 reduce oxidation and DNA double-strand breaks, and a combination of a diet rich in polyunsaturated fatty acids and Coenzyme Q10 supplementation leads to a longer lifespan in rats[27]
See Also
- Idebenone - synthetic analog with reduced oxidant generating properties
External links
- A User-Friendly Summary of CoQ10
- An Introduction to Coenzyme Q10 at University of Washington
- Possible Health Benefits of Coenzyme Q10 at Oregon State University
- Study Suggests Coenzyme Q10 Slows Functional Decline in Parkinson's Disease at National Institute of Neurological Disorders and Stroke
References
- ↑ Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271: 195-204, 1995
- ↑ Dutton PL, Ohnishi T, Darrouzet E, Leonard, MA, Sharp RE, Cibney BR, Daldal F and Moser CC. 4 Coenzyme Q oxidation reduction reactions in mitochondrial electron transport (pp 65-82) in Coenzyme Q: Molecular mechanisms in health and disease edited by Kagan VE and Quinn PJ, CRC Press (2000), Boca Raton
- ↑ Okamoto, T.et al (1989) Interna.J.Vit.Nutr.Res.,59,288-292
- ↑ Aberg,F.et al (1992)Archives of Biochemistry and Biophysics, 295, 230-234
- ↑ Shindo, Y., Witt, E., Han, D., Epstein, W., and Packer, L., Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin, Invest. Dermatol., 102 (1994) 122-124.
- ↑ Crane F, Hatefi Y, Lester R, Widmer C (1957). "Isolation of a quinone from beef heart mitochondria". Biochim Biophys Acta. 25 (1): 220–1. PMID 13445756.
- ↑ 7.0 7.1 Peter H. Langsjoen, "Introduction of Coezyme Q10"
- ↑ Wolf DE, Hoffman CH, Trenner NR, Arison BH, Shunk CH, Linn BD, McPherson JF, and Folkers K. Structure studies on the coenzyme Q group. J Am Chem Soc 1958: 80:4752.
- ↑ Nathalie Soucheta and Serge Laplante, Seasonal variation of Co-enzyme Q10 content in pelagic fish tissues from Eastern Quebec
- ↑ www.thefactsaboutfitness.com
- ↑ Berbel-Garcia, A. (2004). "Coenzyme Q 10 improves lactic acidosis, strokelike episodes, and epilepsy in a patient with MELAS". Clinical Neuropharmacology. 27: 187–191. PMID 15319706. Unknown parameter
|coauthors=ignored (help); Unknown parameter|month=ignored (help);|access-date=requires|url=(help) - ↑ http://www.escardio.org/about/press/press-releases/pr-13/Pages/first-drug-in-decade-improves-heart-failure-mortality.aspx
- ↑ Kishi T, Watanabe T, Folkers K (1977). "Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors". Res Commun Chem Pathol Pharmacol. 17 (1): 157–64. PMID 17892.
- ↑ The Synthesis of Cholesterol
- ↑ Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, Greco A, Littarru G (1993). "Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study". J Clin Pharmacol. 33 (3): 226–9. PMID 8463436.
- ↑ Sarter B (2002). "Coenzyme Q10 and cardiovascular disease: a review". J Cardiovasc Nurs. 16 (4): 9–20. PMID 12597259.
- ↑ Thibault A, Samid D, Tompkins A, Figg W, Cooper M, Hohl R, Trepel J, Liang B, Patronas N, Venzon D, Reed E, Myers C (1996). "Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer". Clin Cancer Res. 2 (3): 483–91. PMID 9816194.
- ↑
Damian, M. S. (2004). "Coenzyme Q10 Combined With Mild Hypothermia After Cardiac Arrest". Circulation, American Heart Foundation. 110: 3011–3016. Retrieved 2006-12-01. Unknown parameter
|month=ignored (help); Unknown parameter|coauthors=ignored (help) - ↑ Cupp MJ and Tracy TS. Chapter 4: Coenzyme Q10 (Ubiquinone, Ubidecarenone), pp 53-85 in Dietary Supplements edited by Cupp MJ and Tracy TS Humana press, Totowa, New Jersey (2003)
- ↑ Rosenfeldt FL, Haas SJ, Krum H, Hadj A, Ng K, Leong J-Y, Watts GF. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Human Hypertension 21: 297-306, 2007
- ↑ Rozen T, Oshinsky M, Gebeline C, Bradley K, Young W, Shechter A, Silberstein S (2002). "Open label trial of coenzyme Q10 as a migraine preventive". Cephalalgia. 22 (2): 137–41. PMID 11972582.
- ↑ Sándor PS; et al. (2005). "Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial". Neurology. 64: 713–715.
- ↑ Katsuhisa Sakano, Mami Takahashi, Mitsuaki Kitano, Takashi Sugimura, Keiji Wakabayashi: Suppression of Azoxymethane-induced Colonic Premalignant Lesion Formation by Coenzyme Q10 in Rats. Asian Pacific J Cancer Prev, 7, 599-603, 2006
- ↑ Matthews, R. T. (1998). "Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects". PNAS. 95: 8892–8897. Retrieved 2006-12-01. Unknown parameter
|month=ignored (help); Unknown parameter|coauthors=ignored (help) - ↑ Biol Signals Recept. 2001 May-Aug;10(3-4):224-53
- ↑ Alexander Storch, MD; Wolfgang H. Jost, MD; Peter Vieregge, MD; Jörg Spiegel, MD; Wolfgang Greulich, MD; Joachim Durner, MD; Thomas Müller, MD; Andreas Kupsch, MD; Henning Henningsen, MD; Wolfgang H. Oertel, MD; Gerd Fuchs, MD; Wilfried Kuhn, MD; Petra Niklowitz, MD; Rainer Koch, PhD; Birgit Herting, MD; Heinz Reichmann, MD; for the German Coenzyme Q10 Study Group (May 14, 2007). "Randomized, Double-blind, Placebo-Controlled Trial on Symptomatic Effects of Coenzyme Q10 in Parkinson Disease". Archives of Neurologu.
- ↑ Quiles JL, Ochoa JJ, Huertas JR, Mataix J (2004). "Coenzyme Q supplementation protects from age-related DNA double-strand breaks and increases lifespan in rats fed on a PUFA-rich diet". Exp Gerontol. 39 (2): 189–94. PMID 15036411.
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