Volume 2, Issue 9
Published by AEGIS Communications
Coenzyme Q10 and the Treatment of Periodontitis
Dennis Flanagan, DDS
Connecticut Dental Groups
There has recently been great interest in antioxidants for the treatment and prevention of disease. Because it is an antioxidant, coenzyme Q10 (also known as ubiquinone) has received much research attention in the medical literature in the last several years. However, there is a dearth of new information for Q10 in the treatment of periodontal conditions. A search on PubMed for “coenzyme Q10 and periodontitis” returns only three citations,1-3 while “ubiquinone and periodontitis” gives 11 citations, most dated before 1984.4-11 Q10 has been studied for the treatment of many diseases, and the results of these studies may point to Q10 as an adjunctive therapy for periodontal diseases.
CHEMOPHYSIOLOGY OF COENZYME Q10
Q10 was isolated from beef hearts at the University of Wisconsin in 1957 and characterized in 1958.12,13 This technology was taken over by a Japanese entity. Subsequently, for a time, most of the attention directed at Q10 had been in Japan.
Basic coenzyme Q is found in plants, animals, and microorganisms. The number after the Q stands for the amount of isoprenoid units attached to the six position on the benzoquinoid ring of the coenzyme Q unit. Q10 is found primarily in humans while Q9 is predominant in rodents. Q10 acts with enzymes involved in cellular respiration and adenosine triphosphate production.14
Coenzyme Q10 is a quinine derivative. Chemically, it is 2-methyl-5,6-dimethoxyl-1,4-benzoquinone. It is fat soluble and important in the chain of biological function. Q10 is amphipathic (biphasic), meaning that it has hydrophilic and lipophilic molecular aspects. Q10 is found in all organisms and acts as a lipid antioxidant protecting membrane phospholipids from peroxidation and cellular oxidative damage. It is present in all organisms and, in human mitochondria, it functions in the bioenergetic chemistry of human tissue, including gingival (ie, it is involved in production of energy in the mitochondria).2,15
The role of Q10 is primarily to facilitate adenosine triphosphate formation by its involvement in electron transfer in the inner membrane of the mitochondria.16 It also maintains fluidity of membranes, intracellular recycling of radical forms of vitamin C and E, and the protection of membrane lipids against peroxidation. These are cellular protective functions against degradation.
Interestingly, Q10 is present in abnormally decreased cellular levels in people with diseases such as Alzheimer’s disease and other neurodegenerative diseases, some types of malignant neoplastic disease, cardiovascular diseases, and diabetes mellitus. It also may play an important role in the pathogenesis of these diseases.14 Some authors suggest that a Q10 deficiency may be involved with an increased risk of Alzheimer’s disease or vascular dementia.17 There is no established recommended daily allowance of Q10 as there is with vitamin C (another antioxidant), which is 60 mg/day.
COENZYME Q10 AS AN ANTIOXIDANT
Antioxidants delay or prevent oxidation of a substrate. This means that antioxidants act to prevent damage to cellular organelles and to repair enzymes.18 In vitro and in vivo experiments have pointed to the essential role of Q10 as an antioxidant. Additionally, Q10 as a potent antioxidant has been shown to be a precursor in a defensive response to various toxicologic and pathophysiologic assaults. Q10 also acts as an antioxidant in its reduced form, ubiquinol. It has a role in mitochondrial and bacterial respiration in electron transport and proton transfer. Q10 acts to protect membrane phospholipids against peroxidation. As a lipid antioxidant, it regulates membrane fluidity and recycles radical (reactive) forms of vitamin C and vitamin E.
Physiologic peroxide can be lethal for bacteria. It has been shown that bacteria may have gene-controlled production of protective proteins when confronted with low hydrogen peroxide concentrations. The bacterial protective proteins become effective as the concentration of peroxide is increased to a bacteriocidal level. In addition, most mammalian cells have genes that are induced by antioxidants to produce protective proteins. Protective ribosomal proteins are produced after exposure of the cell to antioxidants.
Q10 administration and the restriction of caloric intake in patients have been shown to inhibit age-related changes in cellular protein turnover and structure and extracellular matrix structure. Q10 is used in the treatment of Alzheimer’s disease, amyotrophic lateral sclerosis, fatigue, Friedreich’s ataxia, Huntington’s disease, Parkinson’s disease, cardiomyopathy, hypertension, cardiac ischemic damage, diabetes mellitus, and some malignant neoplasms.14 In diabetes mellitus, endothelial dysfunction (arteriopathy) is a fundamental problem. Q10 functions by interfering with endothelial dysfunction by activating endothelial nitric oxide synthetase and mitochondrial oxidative phosphorylation, which may improve vascularity.14
COENZYME Q10 AND PERIODONTITIS
Periodontitis is an inflammatory disease process resulting from the interaction of a bacterial attack and host inflammatory response.19 The pharmacology of Q10 indicates that it may be an agent for the treatment of periodontitis.
Periodontitis is a disease in which there are multiple molecular players. Free radicals and reactive oxygen species (ROS) are among these. ROS is essential in many molecular metabolic events; however, when overproduced, it can induce cell damage, such as in polymorphonuclear neutrophils (PMNs) during phagocytosis. Periodontal pathogens can induce ROS overproduction and thus may induce collagen and periodontal cell breakdown. When ROS are scavenged by antioxidants, there can be a reduction of collagen degradation.20-23
Because they are the primary cellular body defense against infection, PMNs play a key role in periodontitis. Bacterial products can alter PMN function. Oral treponemes produce factors that inhibit oxygen production by PMNs. Oxygen release by PMNs is part of the host response to infection. Q10 as an antioxidant may play a part in abetting PMNs and reducing collagenous destruction.
There is a deficiency of Q10 in diseased gingiva.24 Oral administration of Q10 increases gingival Q10 and may control advanced periodontitis.3,25 Topical administration to the gingiva as a sole treatment may decrease gingival crevicular flow and probing depths and improve clinical gingival attachment.
Many Q10 studies were performed 15 to 30 years ago without the benefit of modern experimental design and may not be highly credible based on contemporary evidenced-based review criteria.26 In a review of research up to 1995, the results found limited data, no grounds for claims made, evidence that some data had inadequate statistical analysis, and that Q10 may have “no place in periodontal treatment.”27,28 However, in 1976, Wilkinson and colleagues reported significant positive results by monitoring crevicular fluid flow, pocket depth, calculus, and plaque scores in a double-blind study by treating measurable pockets with systemic Q10.15
In 1994, Hanioka and colleagues reported on 10 male periodontal patients aged 35 to 61 years with periodontal pockets > 4 mm at the facial aspect.3 Thirty facial periodontal pocket sites were selected. The pockets were topically treated with Q10 alone and had no mechanical periodontal therapy of any type for the first 3 weeks. This treatment showed no effect. This phase was followed by subgingival and conventional debridement with some sites receiving weekly Q10 topical treatment for an additional 3 weeks. In all sites, there was a reported reduction of plaque index (Silness and Loe), crevicular fluid flow, probing depths, and attachment loss. However, only the sites treated with Q10 exhibited significantly decreased modified gingival index scores (Lobene), bleeding on probing, and peptidase activity of periodontal pathogens. The authors concluded that Q10 improves adult periodontitis and may be an effective sole periodontal treatment or used in combination with nonsurgical therapy.
Although Q10 may have been viewed as an alternative medication, it is used routinely, both topically and systemically, by many believing dentists and periodontists. These practitioners titrate the patients’ systemic dosing based on clinical response parameters, such as bleeding on probing and pocket depth, and usually without testing for Q10 plasma levels (personal communication, Sal Squatrito DMD, April 2006).
Q10 has been used with several other drugs and natural products in the treatment of Ehlers-Danos syndrome.1 The rationale of new therapies in this and other disorders are based on concepts of increasing evidence that poor nutrition may play a major factor in the disease pathogenesis. Many symptoms are characteristic of nutritional deficiencies and there may be synergistic actions of appropriate combinations of nutritional supplements that promote normal tissue function and healing. Q10 may act as an antioxidant to relieve oxidative stress in periodontitis and reduce collagenous destruction.
Coenzyme Q10 has been and is now being used to treat a variety of diseases. Based on new concepts of synergism with nutritional supplements and host response, Q10 may possibly be effective as a topical and/or systemic sole or adjunctive treatment for periodontitis either as a stand-alone biological or in combination with other synergistic antioxidants (ie, vitamin C and vitamin E). Randomized, blinded clinical trials for the outcomes of topical and systemic administration of Q10 are needed to affirm or refute the usefulness of Q10 as a therapeutic agent for periodontitis.
References1. Mantle D, Wilkins RM, Preedy V. A novel therapeutic approach strategy for Ehlers-Danlos syndrome based on nutritional supplements. Med Hypotheses. 2005;64(2):279-283.
2. Battino M, Bullon P, Wilson M, et al. Oxidative injury and inflammatory periodontal diseases: the challenge of anti-oxidants to free radicals and reactive oxygen species. Crit Rev Oral Biol Med. 1999;10(4):458-476.
3. Hanioka T, Tanaka M, Ojima M, et al. Effect of topical application of coenzyme Q10 on adult periodontitis. Mol Aspects Med. 1994;15 (suppl):s241-s248.
4. Battino M, Ferreiro MS, Quiles JL, et al. Alterations in the oxidation products, antioxidant markers, antioxidant capacity and lipid patterns in plasma of patients affected by Papillon-Lefevre syndrome. Free Radic Res. 2003;37(6):603-609.
5. Battino M, Ferreiro MS, Bompadre S, et al. Elevated hydroperoxide levels and antioxidant patterns in Papillon-Lefevre syndrome. J Periodontol. 2001;72(12):1760-1766.
6. Hsieh C, Inoshita E, Hanioka T, et al. Changes in coenzyme Q-dependent enzyme activities in the inflamed gingiva of dogs. J Osaka Univ Dent Sch. 1983;23:93-98.
7. Hansen IL, Iwamoto Y, Kishi T, et al. Bioenergetics in clinical medicine. IX. Gingival and leucocytic deficiencies of coenzyme Q10 in patients with periodontal disease. Res Commun Chem Pathol Pharmacol. 1976; 14(4): 729-738.
8. Wilkinson EG, Arnold RM, Folkers K, et al. Bioenergetics in clinical medicine. II. Adjunctive treatment with coenzyme Q in periodontal therapy. Res Commun Chem Pathol Pharmacol. 1975;12(1):111-1123.
9. Iwamoto Y, Nakamura R, Folkers K, Morrison RF. Study of periodontal disease and coenzyme Q. Res Commun Chem Pathol Pharmacol. 1975;11(2):265-271.
10. Mizuno K, Takada I, Watanabe R, et al. [Effect of TCO-27 (coenzyme Q7) on periodontal disease]. Aichi Gakuin Daigaku Shigakkai Shi. 1974;11(4):372-382.
11. Matsumura T, Saji S, Nakamura R, Folkers K. Evidence for enhanced treatment of periodontal disease by therapy with coenzyme Q. Int J Vitam Nutr Res. 1973;43(4):537-348.
12. Crane FL, Hatefi Y, Lester RL, et al. Isolation of a quinone from beef heart mitochondria. Biochim Biophys Acta. 1957;25(1): 220-221.
13. Shunk CH, Linn BO, Wong EL, et al. Coenzyme Q. II. Synthesis of 6-farnesyl and 6-phytyl derivatives of 2,3-dimethoxy-5-methylbenzylquionone and related analogs. J Am Chem Soc. 1958;80:47-53.
14. Dhanasekaran M, Ren J. The emerging role of coenzyme Q-10 in aging, neurodegeneration, cardiovascular disease, cancer and diabetes mellitus. Curr Neurovasc Res. 2005; 2(5):447-459.
15. Wilkinson EG, Arnold RM, Folkers K. Bioenergetics in clinical medicine. VI. Adjunctive treatment of periodontal disease with coenzyme Q10. Res Commun Pathol Pharmacol. 1976;14(4):715-719.
16. Fernandez-Ayala DJ, Lopez-Lluch G, Garcia-Valdes M, et al. Specificity of coenzyme Q10 for a balanced function of respiratory chaín and endogenous ubiquinone biosynthesis in human cells. Biochem Biophys Acta. 2005; 1706(1-2):174-183.
17. Bragin V, Chemodanova M, Dzhafarova N, et al. Integrated treatment approach improves cognitive function in demented and clinically depressed patients. Am J Alzheimers Dis Other Demen. 2005;20(1):21-26.
18. Allison C. Antioxidants drug targeting. In: Sies H, ed. Antioxidants in Disease Mechanisms and Therapy. Advances in Pharmacology. 1997; Vol. 38. San Diego, CA: Academic Press; 273-291.
19. Altman LC, Baker C, Fleckman P, et al. Neutrophil-mediated damage to human gingival epithelial cells. J Periodont Res. 1992; 27(1):70-79.
20. Chapple IL. Reactive oxygen species and antioxidants in inflammatory periodontal diseases. J Clin Periodontol. 1997;24(5): 287-296.
21. Aman B, Wijkander P, Hjerpe A. Reduction of collagen degradation in experimental granulation tissue by vitamin E and selenium. J Clin Periodontol. 1994;21(1):45-47.
22. Ellis SD, Tucci MA, Serio FG, et al. Factors for progression of periodontal diseases. J Oral Pathol Med. 1998;27(3):101-105.
23. Waddington RJ, Moseley R, Embery G. Periodontal disease mechanisms. Reactive oxygen species: a potential role in the pathogenesis of periodontal diseases. Oral Dis. 2000;6:138-151.
24. Nakamura R, Littarru GP, Folkers K, et al. Deficiency of coenzyme Q10 in gingival of patients with periodontal disease. Int J Vit Nutr Res. 1973;43:84-92.
25. Nylander M, Nordlund M. Clinical effects on periodontal status after given oral supplement of ubiquinone. Swed J Biol Med. 1991;1:6-11.
26. Newman M. Levels of evidence. J Evidence Based Dent. 2005;5(4): 6A.
27. Watts TL. Coenzyme Q10 and periodontal treatment: is there any beneficial effect? Br Dent J. 1995;178(6):209-213.
28. Lister RE. Coenzyme Q10 and periodontal disease. Br Dent J. 1995;179(6): 200-201.