NUTRITION – SANT                                                                    E            Coenzyme Q10: multiple be...
energy plant of our cells. At this level it        A minor part is however introduced               widely used anticholes...
penetrate the endothelial cell lining and                                                                                 ...
is a double blind study where a group of                                                                                  ...
be involved in sperm motility. After a       cases quality of life, clinical symptoms      2007 ; Marcoff and Thompson, 20...
results in CoQ10 with the so-called all-        a dossier of Kaneka that provided              cause and effect. Moreover,...
understanding of the newly available             Cooper JM, Schapira AH. Friedreich’s ataxia:      in increased levels of ...
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Littarru Lambrechts Co Q10 Ocl 2011 76 82


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Littarru Lambrechts Co Q10 Ocl 2011 76 82

  1. 1. NUTRITION – SANT E Coenzyme Q10: multiple benefits in one ingredientGian Paolo LITTARRU1 Abstract: Coenzyme Q is a lipid molecule widely diffused in nature; in humans andPeter LAMBRECHTS2 other mammals it is present as coenzyme Q10. (CoQ10). The first recognized role of1 CoQ10 was in mitochondrial bioenergetics, where it plays a central role in the production Department of Biochemistry, Biology of ATP. It is also present in other subcellular organelles, both in its oxidized and in itsGenetics, Polytechnic University of the reduced state (ubiquinol-10). The reduced form of CoQ10 is endowed with powerfulMarche, 60131 Ancona, Italy, phone antioxidant activity: it acts as a chain-breaking antioxidant and is also capable regenerating alpha-tocopherol, the active form of vitamin E. By these mechanisms2 Kaneka Pharma Europe NV, Brussels, CoQ10, together with vitamin E, protects lipoproteins from oxidation a process whichBelgium bears considerable interest in preventing atherosclerosis. CoQ10 has also been found to support cardiovascular function and the latest findings indicate an active role in counteracting endothelial dysfunction, which is closely implicated in cardiovascular disease. CoQ10 also improves sperm motility, an effect which might be related both to its antioxidant and to its bioenergetic properties. Oxidative stress might be involved in neurodegenerative disease, and in migraine, two fields where the positive effects of CoQ10 have been documented. CoQ10 is synthesized by our body but is also present in food and can be taken as a nutritional supplement. The main source of industrially produced CoQ10 is yeast fermentation. The process results in CoQ10 which is identical to the naturally occurring molecule. Ubiquinol, the reduced form of CoQ10, has recently become available. Key words: Coenzyme Q10, bioenergetics, antioxidation, skin metabolism, fermenta- tion, nutritional claimsCoenzyme Q (CoQ) also known as food supplement is natural CoQ10, New progress has been made in eluci-ubiquinone, is a lipid molecule widely extracted from some microorganisms dating CoQ10 in metabolism and nutri-distributed in nature. In mitochondria, which synthesize CoQ10, identical to the tion. This short chapter is mainly focusedlike in other cellular compartments, it one which is found in humans and other on recent findings which will hopefullyis present both in its oxidised state mammals. This issue will be commented contribute to better understand the(ubiquinone) and in its reduced one later on in the text. relationship between basic biochemical(ubiquinol). The first homolog to be mechanisms and certain physiologicaldiscovered about 50 years ago, in beef For a certain number of years CoQ was and clinical effects.mitochondria, was coenzyme Q10 (Crane known for its key role in mitochondrialet al., 1957). In fact, CoQ is made of bioenergetics; later studies demon-benzoquinone moiety and an isoprenoid strated its presence in other subcellular CoQ10 and mitochondrialside chain the length of which is 10 units fractions and in plasma, and extensively bioenergeticsboth in man and many mammals; there- investigated its antioxidant role. Thefore we talk about CoQ10 and reduced rationale supporting the use of CoQ10 The essential role of CoQ10 in bioen-CoQ10 (ubiquinol-10). Other living organ- as a food supplement is mainly based on ergetics was postulated since the yearsisms possess different species of CoQ, for these two functions. More recent data of its discovery. In fact several yearsinstance Saccharomyces cerevisiae produ- reveal that CoQ10 affects the expression later, the studies of Nobel Prize winnerces CoQ6, other microorganisms CoQ7, of genes involved in human cell signalling, Peter Mitchell highlighted the centraland many mammals CoQ9. Each organ- metabolism and transport (Groneberg role of this quinone in the chemo-ism possesses a dominant homolog of et al., 2005) and some of the effects of osmotic production of ATP. Therefore doi: 10.1684/ocl.2011.0374CoQ, and minor amounts of other exogenously administered CoQ10 may be CoQ10 is a key component of thehomologs. Most of CoQ10 available as a due to this property. mitochondrial machinery, the mainTo cite this article: Littarru GP, Lambrechts P. Coenzyme Q10: multiple benefits in one ingredient. OCL 2011 ; 18(2) : 76-82. doi : 10.1684/ocl.2011.037476 OCL VOL. 18 N8 2 MARS-AVRIL 2011
  2. 2. energy plant of our cells. At this level it A minor part is however introduced widely used anticholesterolemic drugs,operates as a redox couple (ubiquinone/ through the diet; moreover a series of also inhibit CoQ10 biosynthesis and thisubiquinol), responsible for proton and dietary components is essential for the could have important practical implica-electron transport. If mitochondria are proper functioning of CoQ10 biosyn- tions.devoid of CoQ10 they cannot produce thesis (figure 2). Coenzyme Q10 concentration greatlyATP; in some conditions we can have The synthesis of the quinone moiety of varies in different tissues, probablypartial CoQ10 deficiencies. CoQ10 starts from phenylalanine or related to different metabolic demandsEven though the concentration of CoQ10 from tyrosine and the isoprenoid side (figure 3).in mitochondria is rather high compared chain derives from mevalonate. A series Tissue concentrations of CoQ10 alsoto the corresponding concentration of of vitamin cofactors is needed for this vary with age: for different organs another mitochondrial components, it is biosynthesis. According to Karl Folkers increase of CoQ10 has been found in thenot saturating. This practically means that the dominant source of CoQ10 in man initial decades with a subsequentat the actual concentrations of CoQ10 in is biosynthesis. This complex, 17 step decrease (figure 4).these membranes the velocity of the process, requiring at least seven vitaminsrespiratory complexes is not the maximal (vitamin B2 – riboflavin, vitamin B3 –one. In fact, small variations in the niacinamide, vitamin B6, folic acid, CoQ as an antioxidantconcentration of CoQ10 in these mem- vitamin B12, vitamin C, and pantothenicbranes leads to remarkable changes in acid) and several trace elements, is, by its In its reduced form (ubiquinol) coen-the respiratory rates of these cells. This nature, highly vulnerable. Karl Folkers zyme Q acts as a phenolic antioxidant,can explain why, even though a small argues that suboptimal nutrient intake in undergoing hydrogen abstraction bypart of the exogenously administered man is highly possible and that there free radicals, therefore it acts like a chainCoQ10 is uptaken by our cells, the effect is subsequent secondary impairment in breaking antioxidant. This evidence hasis not negligible (figure 1). CoQ10 biosynthesis. It was highlighted been produced by numerous experi- that in a vitamin B6 deficiency plasma mental models, both in vivo and in vitro, CoQ10 levels are also low and they incre- using artificial membranes, isolated sub-Ubiquinone biosynthesis: ase upon improvement of the vitamin B6 cellular organelles, cultured cells, iso-biochemical and clinical deficiency status (Willis et al., 1999). In lated perfused organs and clinical eukaryotes the isoprenoid side chain of models (Dallner and Stocker, 2005).implications coenzyme Q is synthesized through the Ubiquinol may act by slowing down theStrictly speaking CoQ10 is not a vitamin, mevalonate pathway, which also leads to chain propagation reaction, with aas mammals and lower animals are the synthesis of cholesterol. As we will mechanism that is common to the co-capable of synthesizing this molecule. comment below statins, the potent and called ‘‘chain breaking antioxidants’’. Reduced Coenzyme Q is also able to regenerate a-tocopherol, the active form of Vitamin E: in this sense CoQ10 and vitamin E are considered as a lipophilic antioxidant duo of primary importance. In order to act as an antioxidant CoQ Vmax must be in the reduced state; several enzymes exert this function of CoQ reductases. There are some conditions where the reducing capacity of the cell might be impaired: in these conditions Exogenous supplementation supplementing CoQ10 already in the reduced state (QH2, ubiquinol-10) might be particularly relevant. Physiological levels Antioxidant function of CoQ10deficit CoQ10 in plasma lipoproteins It is currently believed that high levels of LDL, as well as smoking and hyper- tension, are primary risk factors, among Km [Coenzyme Q10] those contributing to cardiovascular disease. Biochemical mechanisms responsible for the atherogenicity ofFigure 1. The physiological range of CoQ10 in the mitochondrial respiratory chain is close to the LDL have been extensively addressed,Km, the concentration supporting 50% of the maximum velocity (Source: Estornell E, et al. FEBS and experimental evidence bas beenLett 1992; 311 : 107-9). produced indicating that oxidatively OCL VOL. 18 N8 2 MARS-AVRIL 2011 77
  3. 3. penetrate the endothelial cell lining and reach the subendothelial space, where Coenzyme Q10 contents in foodstuffs they undergo oxidative attack. Oxida- 8 tively modified LDL are capable of Average daily intake through diet = 3 to 5 mg (Weber 1997a) triggering further events, including pla- 7 telet activation, and exert a chemotactic attraction on circulating monocytes, 6 which migrate to the subendothelial space, where they become macro- 5 mg/100gr phages. These cells have only low levels 4 of the classical LDL receptor, nonetheless they are able to take up more rapidly 3 oxidatively modified LDL, and this uptake involves a different receptor, 2 called the ‘‘scavenger receptor’’. As dis- cussed above, oxidatively modified LDL 1 are easily recognized by the scavenger receptors. These events lead to an accu- 0 mulation of lipids, mainly cholesterol and Sardine Pork Beef Olive oil Poultry Broccoli Butter Sunflower Cheese cholesterol esters, in the macrophages, oil which will become lipid-laden foam cells. Foam cells may be considered the essence of the atheromatous lesions.Figure 2. Coenzyme Q10 content of different foods (Source: Kamei et al. The Distribution andContent of Ubiquinone in Foods. Internat J Vit Nutr Res 1986; 56: 57-63). LDL are endowed with a number of lipid soluble antioxidants capable of prevent- ing or minimizing lipid peroxidation. Plasma levels of CoQ10 have been extensive investigated (Tomasetti et al.,modified LDL become atherogenic. It a consequence of these changes LDL are 1999). Most plasma CoQ10 is trans-was found that endothelial cells are no longer ‘‘recognized’’ by the normal ported by LDL where, together withinvolved in the oxidative attack against receptors, and are taken up more readily vitamin E, it exerts its antioxidant pro-LDL. Oxidative attack on LDL deeply by the scavenger receptors of macro- tection. Ubiquinol-10 is the most reactiveaffects the apoprotein moiety as well. As phages. LDL leave the blood stream, antioxidant in LDL, and although it is present at lower concentrations com- pared to vitamin E, it is able to regenerate a-tocopherol from the tocopheril radical, Connentration of Coenzyme Q10 making the vitamin E-ubiquinol duo the most important antioxidant system in Heart LDL. CoQ10 enriched LDL, isolated from Kidney plasma of healthy volunteers orally treated with CoQ10 for a few days, were Liver less susceptible to peroxidizability in Q10 Muscle vitro, compared to the same LDL in basal Brain conditions (Mohr et al., 1992). Pancreas Blood CoQ10 is mainly transported by LDL, Lung although it is also present in the other Thyroid gland classes of lipoproteins and in blood cells. Its Testicle concentration is usually reported in micro- Intestine grams/litre of plasma or micromoles/litre. Skin(epithelial) But it is worthwhile to normalize these values according to the blood LDL content Skin(dermal) or at least to plasma cholesterol levels. The Blood plasma CoQ10/total cholesterol level could have a 0 20 40 60 80 100 120 predictive value in cardiovascular disease Connentration (µg/g tissue) (Molyneux et al., 2008). Besides decreas- ing LDL peroxidizability, CoQ10 could have a direct antiatherosclerotic effect,Figure 3. Concentration of coenzymeQ10 in different human tissues (Source: Okamoto T, et in fact animal studies have shown thatal. Internat J Vit Nutr Res 59; 288-92; Aberg et al. Archives of Biochemistry and CoQ10 administration attenuates aorticBiophysics and Biophysics 1992; 295: 230-4; Shindo Y, et al. J Invets Dermatol 1994; atherosclerotic lesions (Witting et al.102 : 122-4. 2000 ; Singh et al. 2000).78 OCL VOL. 18 N8 2 MARS-AVRIL 2011
  4. 4. is a double blind study where a group of kendo athletes showed lower levels of CK, myoglobin and lipid peroxides 100% compared to the corresponding values 100% 95,3% in the placebo group (Kon et al., 2008). Liver 83,0% In a study where CoQ10 had been taken in combination with vitamin C and E, administration of this antioxidant cocktail 72,6% Lungs further increased the eNOS and uncou- 68,2% pling protein 3 (UCP3) mRNA content 65,3% Kidneys after exercise (Hellsten et al., 2007). For the first time a study examined the 51,7% acute effects of CoQ10 and placebo on Heart 42,9% autonomic nervous activity and energy metabolism at rest and during exercise 20 years 40 years 80 years (Zheng and Moritani, 2008). Fat oxida- tion significantly increased during exer- ciseintheCoQ10 group;resultssuggested that CoQ10 increases autonomic nervous activity during low intensity exercise.Figure 4. The concentration of coenzyme Q10 in the body decreases year by year, indicatingthat it has a close relationship with aging (Kalen A, et al. Lipids1989; 24: 579). In a double blind pilot study patients with post-polio syndrome were treated with 200 mg of CoQ10/day. Muscle strength,CoQ10: analytical aspects (and other CoQs) in vegetable oils and muscle endurance and quality of life generally in fatty samples, due to inter- increased statistically significantly in allCoQ10 is commonly assayed in plasma, ferences mainly with triacylglycerides. A 14 patients but there was no significantboth in basal conditions and after oral clean, efficient separation and quantifi- difference between the CoQ10 and pla-supplementation. Basal CoQ10 levels cation procedure was recently proposed cebo groups (Kough et al., 2008).might reflect CoQ10 deficiency and, as and applied to the determination ofpointed out above, they might have a CoQ9 and CoQ10 contents in differentpredictive value in cardiac failure. Post vegetable oil samples (Rodriguez-Acuna Effects on skinsupplementation levels of CoQ10 are et al., 2008). metabolismalso important, since a clinical responseis much more common if some thresh- The bioenergetic and antioxidant prop-old values are reached. Several studies Physiological effects: erties of CoQ10 have also been studied athave highlighted that a plasma level of CoQ10 and physical skin level. The first report was byat least 2.5 mg/mL should be reached to Hoppe et al. (1999). This paper demon- exercise strated that CoQ10 penetrates into thehave a consistent physiological response(Belardinelli et al., 2006). Of course The key role of coenzyme Q10 in viable layers of the epidermis and reducesquantification of plasma CoQ10 is also mitochondrial bioenergetics has sug- the levels of oxidation measured by weakimportant to assess bioavailability of gested its use in an attempt to improve photon emission. CoQ10 was also effec-different CoQ10 formulations. Methods aerobic capacity and physical perform- tive in human keratinocytes against UVAare usually based on HPLC separation: a ance. Some studies have highlighted an mediated oxidative stress and in sup-simple, yet precise and accurate ergogenic effect while others did not. pressing the expression of collagenase inmethod is the one which appears in These issues have recently been human dermal fibroblasts following UVAthe website of the International CoQ10 addressed in 3 papers published in irradiation. A reduction in wrinkle depthAssociation (Littarru et al., 2004). 2008 (Cooke et al., 2008, following CoQ10 application was also Mizuno et al., 2008, Kon et al., 2008). shown, an effect confirmed by AshidaCoenzyme Q10 can also be quantitatively et al. (2005). The combined effect of One of these articles shows that followingassayed in cells and in biological fluids. creatine and CoQ10 on skin’s energy a single administration of CoQ10 plasmaCoQ10 cellular levels are particularly metabolism was highlighted by Blatt levels significantly correlated withimportant in some ‘‘primary CoQ10 et al. (2005). Recently Inui and collabo- muscle CoQ10 levels, maximal oxygendeficiencies’’. These are conditions where, rators showed that cytokine production consumption and treadmill time todue to genetic reasons one or more of the in keratinocytes is inhibited by CoQ10, exhaustion. A trend for increased timesteps involved in CoQ10 biosynthesis are resulting in a decrease of metalloprotei- to exhaustion was observed followingimpaired. In some cases there is a dra- nases leading to wrinkle reduction. two weeks of CoQ10 supplementationmatic positive response to exogenous (p = 0.06) (Cooke et al., 2008). InCoQ10 administration (Quinzii et al., another trial, oral administration of Reproductive medicine2008). CoQ10 improved subjective fatigue sen-Some analytical problems have been sation and physical performance Impairment of mitochondrial bioener-found in the quantification of CoQ10 (Mizuno et al., 2008). The third article getics and oxidative stress are known to OCL VOL. 18 N8 2 MARS-AVRIL 2011 79
  5. 5. be involved in sperm motility. After a cases quality of life, clinical symptoms 2007 ; Marcoff and Thompson, 2007).series of studies highlighting the impli- and the frequency of hospitalization A small-sized, yet double-blind studycations of CoQ10 in male infertility a were ameliorated upon CoQ10 admin- also points out that CoQ10 exogenousmore recent publication confirmed, in a istration. In some protocols there was administration reduced myopathicplacebo controlled double-blind also an improvement of ejection fraction symptoms in statin treated patientsrandomized trial, the efficacy of and other functional parameters. (Caso et al., 2007). Of course a largeCoQ10 treatment in improving semen Cardiovascular effects of CoQ10 can be double blind clinical trail would bequality in men with idiopathic infertility ascribed to its bioenergetic role, to its necessary in order to assess the capability(Balercia et al., 2009). Oxidized and capability of antagonizing oxidation of of CoQ10 in mitigating statin side effects.reduced CoQ10 concentration signifi- plasma LDL and to its effect in amelio-cantly increased both in seminal plasma rating endothelial function. This effectand sperm cells, together with sperm Neurodegenerative was first seen by Watts et al. in patientsmotility, after 6 months of therapy with affected by Type II diabetes (Watts et al., disease200 mg/day CoQ10. The increased con- 2002) and then further explored bycentration of CoQ10 and QH2 (reduced The positive effect of oral administration Belardinelli et al. in patients affected by of CoQ10 to patients affected by Parkin-CoQ10) in seminal plasma and sperm ischemic heart disease (Belardinellicells, the improvement of semen kinetic son’s disease was investigated in 2002 et al., 2006). Endothelial dysfunction by Shults et al. (2002). Friedreich’s ataxiafeatures and treatment, and the evi- is commonly believed as an early sign ofdence of a direct correlation between is another condition where treatment vascular impairment and the capability with CoQ10 and vitamin E caused aCoQ10 concentrations and sperm motil- of CoQ10 in counteracting it representsity strongly support a cause-effect prolonged improvement in cardiac and a promising field. The mild hypotensive skeletal muscle bioenergetics and clinicalrelationship. Similar results were found effect of CoQ10 is probably related toby Safarinejad (2009). In this study 212 scores (Cooper and Schapira, 2007). this property.infertile men with idiopathic oligoas- In 2005 Sandor et al. studied the effectthenoteratospermia were treated with of CoQ10 (300 mg/day for 3 months) in300 mg/day CoQ10 or placebo for 26 Human CoQ10 42 migraine patients in a double-blind,weeks. Statistically significant improve- deficiencies randomized, placebo-controlled trial.ment was found, in the CoQ10 group, The primary outcome variable in thisregarding sperm count and motility Already in the past CoQ10 had been study was a change of attack frequencyvalues, with a positive correlation shown to be effective in a number of in the third month of treatment com-between treatment duration of CoQ10 cases of mitochondrial myopathies, pared to baseline. The authors showedand sperm count as well as mean sperm which were sometimes associated with that responders were 47.6% in themotility. The CoQ10 group had a low CoQ10 muscle levels. With the CoQ10 treated group vs 14.4% in thesignificant decrease in serum FSH and progress in molecular biology techni- placebo group. A positive effect ofLH at the 26 week treatment phase. The ques primary CoQ10 deficiencies, due to CoQ10 was also demonstrated in a largeauthors highlight that a lower serum mutations in ubiquinone biosynthetic group of pediatric patients sufferingFSH implies a better spermatogenesis. genes, have been identified and some of from migraine (Hershey et al., 2007).Moreover, Inhibin B, which reflects these syndromes have shown excellentSertoli’s cell function, increased in the responses to oral CoQ10 treatmentCoQ10 group. (Quinzii et al., 2008). Sourcing: main natural origins, Kaneka’s processThese studies did not address the keyissue of pregnancy rate; they were simply Statins and CoQ10 (yeast fermentation)aimed at determining an effect of CoQ10 There are 3 methods used for theon sperm motility and quality. Other Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase manufacturing of CoQ10: yeast fermen-variables should of course be taken into tation, bacteria fermentation and chem-account in order to determine whether inhibitors which decrease synthesis of mevalonate, a key metabolic step in the ical synthesis. The latter was the firstCoQ10 has an influence on pregnancy industrial method, introduced by Nis-rate. cholesterol synthesis pathway. These efficient drugs can produce a variety shin in the early 70s. Greater amounts of of muscle-related complaints or myo- CoQ10 became available when Japan-CoQ10 supports pathies. Since the mevalonate pathway based Kaneka Corporation began pro- also leads to the biosynthesis of the ducing natural CoQ10 (also calledcardiovascular function KANEKA Q10TM) via patented yeast isoprenoid side chain of coenzyme Q10,CoQ10 deficiency at myocardial level different studies have addressed the fermentation in 1977. Kaneka is nowhas been documented in different possibility of CoQ10 being an etiologic the world’s largest manufacturer ofstudies. Although in most cases the factor in statin myopathy. There is no CoQ10 and is the only producer todeficiency was not the cause of the doubt that statins decrease plasma and manufacture CoQ10 in US market.cardiopathy this might have contrib- leukocyte CoQ10 levels; a few studies The yeast-fermentation method, alonguted to the severity of the disorder. also report a decrease of muscle CoQ10 with Kaneka’s rigorous manufacturingNumerous trials have been conducted level upon statin treatment. This con- standards, makes KanekaQ10TM theon the effect of CoQ10 as coadjuvant in troversial issue has been extensively purest commercial-grade CoQ10 avail-the treatment of cardiac failure. In many investigated (Littarru and Langsjoen, able on the market today. The process80 OCL VOL. 18 N8 2 MARS-AVRIL 2011
  6. 6. results in CoQ10 with the so-called all- a dossier of Kaneka that provided cause and effect. Moreover, for Vitaminstrans configuration, which means that it scientific arguments to substantiate and Minerals EFSA accepts ‘‘textbook’’is identical to naturally occurring CoQ10 the safety of CoQ10 up to 200 mg/day knowledge as evidence.found in meat, fish and other products and higher. The 200 mg level is being As a general rule, EFSA does not acceptand also bio-identical to CoQ10 pro- followed by other European Union human studies conducted on patients,duced in the human body (figure 5). countries, and potentially all of them, yet medicinal paradigms are expected.The Kaneka yeast fermentation process by the legal principle of new Mutual Unfortunately, up to now, many CoQ10is in accordance with pharmaceutical Recognition Regulation. This Regulation health benefits (as for other nutraceut-GMP standards and does not contain requires products lawfully marketed in icals) have been studied in patients.impurities found in synthetic material. one EU member state to be permitted Because of this evolution, most generic entry into another member state’s claims for Other Substances have notKaneka Q10TM is the only CoQ10 backed market. The mutual recognition regu-by published human safety studies and is been accepted by EFSA. This is also true lation plays a key role in the future EU for the generic CoQ10 claims: energy,the primary CoQ10 used in most scientific market for CoQ10.studies. As purest, most rigorously tested antioxidant, and blood pressure nor-CoQ10 available, KanekaQ10 has been According the new European Health malizing. We are facing a situationused in all major CoQ10 clinical trials Claim regulation (EC 1924/2006) the where study designs, which are accept-approved by the FDA and funded by the generic health claims were planned to able in the scientific community, are notNIH (e.g. Phase III Clinical Trial on be disclosed in a positive list that EU usable for marketing purposes.Coenzyme Q10’s Effects on Huntington’s would give access to by end of January Only in 2011 and 2012, which is moreand Parkinson Disease in US). 2010. Yet, early 2011 there is still no list than 4 years after publication of the available. In the meanwhile, national health claim regulation, EFSA will organ- regulation still applies and all health ise guidance meetings and publishRegulatory status claims that are well supported by documents to provide more clarity on science can continue to be used. their idea of how health claims shouldCoQ10 is a well-established ingredientthat is present in many food supple- EFSA has started to deliver scientific be substantiated for different fields suchments, fortified foods and cosmetic opinions on art. 13 regarding generic as weight management, cardiovascularbrands all over Europe. There is an health claims. EFSA is taking the stance to health, joint health, physical perform-increasing acceptance of the role of treat Vitamins and Minerals very differ- ance, etc. Guidelines specifying the typenon-vitamin and mineral ingredients, ently from Other Substances - examples of of studies, the proper biomarkers to besuch as CoQ10 and its levels move the latter are CoQ10, glucosamine, lutein, used and other pertinent issues shouldtowards higher levels than were consid- lycopene, carnitine, etc. For Vitamins and also be established. The scientific com-ered a decade ago based on risk Minerals a ‘‘scientific consensus’’ is usu- munity is just beginning to come toassessment approach and supportive ally sufficient to substantiate a health terms with health claim regulations anddata. A Belgian ministerial order deter- claim, whereas for Other Substances, this process is ongoing. The full impactmined CoQ10 was safe for use in food golden standard human trials are of the regulations is still evolving andsupplements at 200 mg after reviewing required with conclusive evidence of many grey areas are apparent. An independent economic impact assess- ment of existing and potential effects of the health claims regulation concluded O that all initial objectives of the health O Trans-isomer = Natural occurring CoQ10 claims regulation, notably relating to objectives such as consumer protection, O O fair competition, and promotion of RD, were only poorly or weakly O O addressed (Brookes, 2010). Cis-isomer O O Ubiquinol Ubiquinol, the reduced form of CoQ10 has recently become available in stable form, and is manufactured exclusively by Kaneka. Ubiquinol represents 93- 95% of CoQ10 pool in plasma of healthy human and is the predominant Coen- zyme Q10 form in a healthy cell. Several studies suggest that ubiquinol-ratio in human plasma may represent a sensitive index of oxidative stress in vivo espe- cially indicative of early oxidative dam- age. CoQ10 researchers from around theFigure 5. The trans and cis isomers of coenzyme Q10. world are working to advance the OCL VOL. 18 N8 2 MARS-AVRIL 2011 81
  7. 7. understanding of the newly available Cooper JM, Schapira AH. Friedreich’s ataxia: in increased levels of ubiquinol-10 withinubiquinol. Recently, Japanese research- coenzyme Q10 and vitamin E therapy. circulating lipoproteins and increased resist-ers showed protective effects of ubiq- Mitochondrion 2007; 7: S127-35. ance of human low-density lipoprotein to theuinol on influenza virus infection Crane FL, Hatefi Y, Lester RL, Widmer C. initiation of lipid peroxidation. Biochim Bio-in mice. Isolation of a quinone from beef heart phys Acta 1992; 1126: 247-54. mitochondria. Biochim Biophys Acta 1957; Molyneux SL, Florkowski CM, George PM, 25: 220-1. et al. Coenzyme Q10: an independentConclusion Dallner G, and Stocker R. Coenzyme Q. In: predictor of mortality in chronic heart failure. Encyclopedia of dietary supplements. New J Am Coll Cardiol 2008; 52: 1435-41.CoQ10 is a highly studied nutrientwhose biochemical and physiological York: Marcel Dekker, 2005: 121-31. Quinzii CM, Lopez LC, Naini A, Dimauro S,role has been established. What is Groneberg DA, Kindermann B, Althammer Hirano M. Human CoQ10 deficiencies. Bio- M, et al. Coenzyme Q10 affects expression of factors 2008; 32: 113-8.special about this molecule is its involve-ment both in the bioenergetic and in genes involved in cell signalling, metabolism Rodriguez-Acuna R, Brenne E, Lacoste F.the antioxidant processes. While wait- and transport in human CaCo-2 cells. Int J Determination of coenzyme Q10 and Q9 ining for a definite pronunciation by the Biochem Cell Biol 2005; 37: 1208-18. vegetable oils. J Agric Food Chem 2008; 56:European authorities, national regula- Hellsten Y, Nielsen JJ, Lykkesfeldt J, et al. 6241-5.tions still apply and the number of Antioxidant supplementation enhances the Safarinejad MR. Efficacy of coenzyme Q10 onhealth claims that are well supported by exercise-induced increase in mitochondrial semen parameters, sperm function andscience can continue to be used. uncoupling protein 3 and endothelial nitric reproductive hormones in infertile men. J oxide synthase mRNA content in human Urol 2009; 182: 237-48. skeletal muscle. Free Radic Biol Med 2007; 43: Shults CW, Oakes D, Kieburtz K, et al.REFERENCES 353-61. (Parkinson Study Group). Effects of coen-Ashida Y, Yamanishi H, Terada T, Oota N, Hershey AD, Powers SW, Vockell AL, et al. zyme Q10 in early Parkinson disease: evidenceSekine K, Watabe K. CoQ10 supplementa- Coenzyme Q10 deficiency and response to of slowing of the functional decline. Archtion elevates the epidermal CoQ10 level in supplementation in pediatric and adolescent Neurol 2002; 59: hairless mice. Biofactors 2005; 25: 175- migraine. Headache 2007; 47: 73-80. Singh RB, Shinde SN, Chopra RK, Niaz MA,8. Hoppe U, Bergemann J, Diembeck W, et al. Thakur AS, Onouchi Z. Effect of coenzymeBalercia G, Buldreghini E, Vignini A, et al. Coenzyme Q10, a cutaneous antioxidant and Q10 on experimental atherosclerosis andCoenzyme Q10 treatment in infertile men energizer. Biofactors 1999; 9: 371-8. chemical composition and quality of athe-with idiopathic asthenozoospermia: a pla- Kon M, Tanabe K, Akimoto T, et al. Reducing roma in rabbits. Atherosclerosis 2000; 148:cebo-controlled, double-blind randomized exercise-induced muscular injury in kendo 275-82.trial. Fertil Steril 2009; 91: 1785-92. athletes with supplementation of coenzyme Tomasetti M, Alleva R, Solenghi MD, Littarru Q10. Br J Nutr 2008; 100: 903-9. ¸ajBelardinelli R, Muc A, Lacalaprice F, et al. GP. Distribution of antioxidants amongCoenzyme Q10 and exercise training in Kough K, Krossen C, Heiwe S, Theorell H, blood components and lipoproteins: signifi-chronic heart failure. Eur Heart J 2006; 27: Borg K. Effects of resistance training in cance of lipids/CoQ10 ratio as a possible2675-81. combination with coenzyme Q10 supple- marker of increased risk for atherosclerosis. mentation in patients with post-polio: a pilot Biofactors 1999; 9: 231-40.Blatt T, Lenz H, Koop U, et al. Stimulation of study. J Rehabil Med 2008; 40: 773-5. Watts Gf, Playford Da, Croft Kd, Ward Nc,skin’s energy metabolism provides multiplebenefits for mature human skin. Biofactors Littarru GP, Mosca F, Fattorini D, Bompadre Mori Ta, Burke V. Coenzyme Q(10) improves2005; 25: 179-85. S, Battino M. Assay of coenzyme Q10 in endothelial dysfunction of the brachial artery plasma by a single dilution step. Methods in Type II diabetes mellitus. DiabetologiaBrookes G. Economic Impact Assessment of Enzymol 2004; 378: 170-6. 2002; 45: 420-6.the European Union (EU)’s Nutrition Health Claims Regulation on the EU food Littarru GP, Langsjoen P. Coenzyme Q10 and Willis R, Anthony M, Sun L, Honse Y, Qiao G.supplement sector and market for the statins: biochemical and clinical implications. Clinical implications of the correlationEuropean Health Claims Alliance (EHCA), Mitochondrion 2007; 7: S168-74. between coenzyme Q10 and vitamin B62010. Marcoff L, Thompson PD. The role of status. Biofactors 1999; 9: 359-63.Caso G, Kelly P, Mcnurlan Ma, Lawson WE. coenzyme Q10 in statin-associated myopa- Witting PK, Pettersson K, Letters J, Stocker R.Effect of coenzyme Q10 on myopathic thy: a systematic review. J Am Coll Cardiol Anti-atherogenic effect of coenzyme Q10 insymptoms in patients treated with statins. 2007; 49: 2231-7. apolipoptrotetin E gene knockout mice. FreeAm J Cardiol 2007; 99: 1409-12. Mizuno K, Tanaka M, Nozaki S, et al. Radic Biol Med 2000; 29: 295-30.Cooke M, Iosia M, Buford T, et al. Effects of Antifatigue effects of coenzyme Q10 Zheng A, Moritani T. Influence of CoQ10acute and 14-day coenzyme Q10 supplemen- during physical fatigue. Nutrition 2008; 24: on autonomic nervous activity and energytation on exercise performance in both 293-9. metabolism during exercise in healthytrained and untrained individuals. J Int Soc Mohr D, Bowry VW, Stocker R. Dietary subjects. J Nutr Sci Vitaminol 2008; 54:Sports Nutr 2008; 4: 5: 8. supplementation with coenzyme Q10 results 286-90.82 OCL VOL. 18 N8 2 MARS-AVRIL 2011