The Use of Antioxidants to Manage Periodontal Diseases

There is considerable, growing interest in the use of antioxidant therapy for a variety of oral conditions, including periodontal disease. Before we can explore how antioxidants may benefit oral health, let's review the basics of oxidative stress first. Oxidation is the process of removing electrons from an atom or molecule. Oxidation describes the loss of electrons by an atom, while reduction describes the gain of electrons by an atom. All metal atoms are characterized by their tendency to be oxidized, meaning that by losing one or more electrons, they then form positively charged ions, called cations. The electrons lost by metal atoms are not destroyed, but are gained by a non-metal atom, which is said to be reduced. As the non-metal atom gains the electrons lost by the metal atom, it forms a negatively charged ion, called an anion. The process of oxidation cannot occur without a corresponding reduction reaction. Oxidation must always be "coupled" with reduction, and the electrons that are "lost" by one substance must always be "gained" by another. Hence, the terms "lost or gained" simply mean that the electrons are being transferred from one particle to another. All forms of life maintain a reducing environment within their cells. Disturbances in this normal redox state can cause toxic effects through the production of reactive oxygen species known as peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress is caused by an imbalance between the production of reactive oxygen species and a biological system's ability to either readily detoxify these reactive intermediates or easily repair the resulting damage. Oxidative stress is an ongoing process that is associated with normal metabolic function, but is influenced by environmental factors and other sources of oxidizing activity. For example, exposure to ultraviolet light, radiation, air pollution, chemicals, and even tobacco and alcohol use increases production of free radicals. In the oral cavity, environmental factors that increase free radical production include exposure to bleaching agents, dental cements, and metal and composite restorative materials. The good news is that the body naturally produces antioxidants to prevent the overproduction of free radicals to prevent cellular damage. One naturally produced antioxidant is glutathione, which is primarily synthesized by the liver; however, all cells in the body are capable of producing glutathione. Glutathione is kept in a reduced form to act as an electron donor to counteract oxidation. Another popular naturally-occurring antioxidant is coenzyme Q10, also known as ubiquinone, found in mitochondria, and in cells of the heart, liver, kidneys and pancreas. It may also be obtained in the diet from meat and seafood, or taken as a dietary supplement. Coenzyme Q10 is involved with a variety of physiologic functions, including ATP production, stimulation of cell growth, inhibition of cell death, regulation of osteoclast formation, and regeneration of other antioxidants. Coenzyme Q10 is used to treat mitrochondrial disorders, heart failure, migraines, cancer and related treatment side effects, and hypertension, and has been shown to improve survival benefit following cardiac arrest. Many dental hygienists recognize that CoQ10 is often taken by patients who use statin medications, which tend to deplete levels of this antioxidant. Other popular dietary sources of antioxidants include vitamins C and E. The body also possesses other natural mechanisms to defend against the damage caused by free radicals, including enzymatic degradation, repair mechanisms to correct damage to cellular DNA, and programmed cellular death if the damage is simply too extensive to repair. Moderate oxidation can trigger apoptosis (programmed cell death), while more intense stresses may cause necrosis (cell death). It is important to mention that while typically we think of free radicals as harmful to the body, there are times when these reactive oxygen species can be beneficial, and in fact necessary, to support certain physiologic functions. For example, reactive oxygen species are used by the immune system as a way to attack and kill pathogens, and are also used in cell signaling mechanisms for cellular communication. Oxidative stress is associated with many diseases of aging, including atherosclerosis, Parkinson's disease and Alzheimer's disease. Chronic inflammation induces oxidative stress (thus, the relationship to periodontitis) and damage to cellular DNA and RNA. If we consider that health depends upon a balance between oxidative stress and antioxidant activity, it is a natural assumption to think that antioxidant use may be beneficial for oral health as well. There are now many oral health products that contain coenzyme Q10, and there is an ongoing debate in the literature as to the benefits of vitamin C on periodontal tissue health. Research supports that oxidative stress leads to increased liver production of advanced glycation end-products, which contributes to a marked increase in hyperglycemia. This relationship helps to explain why we observe poor blood sugar control in patients with diabetes who also have chronic, severe periodontitis. The production of pro-inflammatory chemical mediators in response to the presence of periodontal pathogens also increases oxidative stress. Studies have demonstrated that salivary and plasma levels of antioxidants are lower in patients with periodontal disease, and as the extent of periodontal destruction increases, so too does reactive oxygen species activity with a corresponding decrease in protective salivary antioxidant levels. Both topical and systemic use of coenzyme Q10 has been used as a adjunctive agent for the treatment of periodontitis, either used alone or in combination with vitamins C and E; however, the evidence supporting its use to reduce bleeding and pocket depth is weak and is primarily based on anecdotal reports. Additional research is needed to support the benefits of this intervention. In addition to ongoing research with periodontitis, antioxidant use has been studied in relation to oral cancer, lichen planus, aphthous stomatitis, and cariogenic bacterial growth. There are many published papers investigating the effects of antioxidants; however, collectively, the research is early and more evidence is needed to support how best to deliver antioxidants for managing oral disease. Green tea, as well as black tea, also contains antioxidants, but there is no compelling evidence at this time that demonstrates that consumption of green tea improves periodontal outcomes. REFERENCES Nathan C, Cunningham-Bussel A. Beyond oxidative stress: an immunologist's guide to reactive oxygen species. Nat Rev Immunol. 2013 May;13(5):349-61. Chung HY, Lee EK, Choi YJ, Kim JM, Kim DH, Zou Y, Kim CH, Lee J, Kim HS, Kim ND, Jung JH, Yu BP. Molecular inflammation as an underlying mechanism of the aging process and age-related diseases. J Dent Res. 2011 Jul;90(7):830-40. Pietropaoli D, Tatone C, D'Alessandro AM, Monaco A. Possible involvement of advanced glycation end products in periodontal diseases. Int J Immunopathol Pharmacol. 2010 Jul-Sep;23(3):683-91. Chapple ILC, Matthews JB. The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000. 2007;43:160-232. Sculley DV, Langley-Evans SC. Periodontal disease is associated with lower antioxidant capacity in whole saliva and evidence of increased protein oxidation. Clin Sci. 2003;105:167-172. D'Aiuto F, et al. Oxidative stress, systemic inflammation, and severe periodontitis. J Dent Res. 2010;89:1241-1246. Pendyala G, Thomas B, Kumari S. The challenge of antioxidants to free radicals in periodontitis. J Indian Soc Periodontol. 2008;12:79-83. Chapple IL, Matthews JB. The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000. 2007;43:160-232. San Miguel SM, Opperman LA, Allen EP, Svoboda KK. Use of antioxidants in oral healthcare. Compend Contin Educ Dent. 2011 Mar;32(2):E25-8. San Miguel SM, Opperman LA, Allen EP, Svoboda KK. Reactive oxygen species and antioxidant defense mechanisms in the oral cavity: a literature review. Compend Contin Educ Dent. 2011 Jan-Feb;32(1):E10-5. San Miguel SM, Opperman LA, Allen EP, Zielinski J, Svoboda KK. Antioxidants counteract nicotine and promote migration via RacGTP in oral fibroblast cells. J Periodontol. 2010 Nov;81(11):1675-90.