Antioxidants & Oral Health
What your patients need to know
Health news never sleeps.
It’s global and around the clock, driven by rapidly expanding news, Internet, and social media outlets. The latest “discovery” in treating or preventing disease—proven or not—spreads quickly through the channels and dominates the headlines. That is, until word of the next major discovery breaks.
It often falls on oral healthcare providers to separate the science from the spin, to help our patients develop their health literacy and critical eye. Because dental team members are well versed in evidence-based dentistry and peer-reviewed research, they can offer their patients more grounded information.
Research about the benefits of antioxidants for oral health is one example. To assist in patient education, this month Inside Dental Assisting features an excerpt from a literature review on this timely topic.
Antioxidants in Oral Healthcare
The use of specific antioxidants in the proper combination can provide natural protection from environmental and inherent free-radical exposure. Antioxidants neutralize damaging free radicals that produce disease states. It has been suggested that the negative effects of nicotine could be reversed by antioxidants.1
Antioxidants are available from different sources, including vitamins, minerals, enzymes, and hormones, as well as food and herbal supplements. The supplements may exist in bar, capsule, drops, liquid, powder, gel, and tablet forms. As an alternative medicine, herbal therapy is a treatment modality to remedy many medical and dental conditions. Antioxidants have also been used in combination with dried, fresh, and blended herbal paste. The majority of herbal supplements include green tea catechins,2 aloe vera, star anise oil, myrrh gum, calendula extract, ammonium glycyrrhizate (from licorice root), fennel oil, and neem extracts.3,4
Most recently, dental manufacturers and distributors have incorporated antioxidant supplements into toothpastes, mouth rinses/mouthwashes, lozenges, fluoride gels and dentifrices, oral sprays, breath fresheners, and other dental products for the control of gingival and periodontal diseases. The rapidly advancing field of dental pharmacotherapeutics has paved the way for the development of a wide array of antioxidants that have beneficial clinical effects.4 However, it is important to understand, given the inherent unstable nature of antioxidants, that simply adding an antioxidant to an oral preparation may not be an effective treatment.
Leaf and Berry Extracts
Many other extracts have been used in studies to demonstrate antioxidative potential. A recent study concluded that the lactoferrin and black tea polyphenols had protective effects against carcinogen activation, DNA damage, cell proliferation, invasion, and angiogenesis in an experimental oral carcinogenesis model.5
A phytochemical is found in black raspberries, which are a rich, natural source of vitamins and minerals. Specifically, the active compounds in black raspberries include vitamins A, C, and E, folic acid, calcium, selenium, beta-carotene, ellagic acid, coumaric acid, and quercitin, besides different anthocyanins and phytosterols. Freeze-dried black raspberries prevent the growth of oral, esophageal, and colon cancer in rodents, and human trials have shown a decreased expression of molecular biomarkers of dysplasia.6 However, the antioxidant levels of freeze-dried black raspberries are not reliable enough to warrant their commercial use.
Considerable evidence also has revealed that flavonoids possess antioxidant and anti-inflammatory properties that reduce inflammatory molecule expression in macrophages and monocytes within the gingival connective tissues. Some flavonoids such as luteolin, quercetin, and genistein have regulated the nitric-oxide production of LPS-stimulated human gingival fibroblasts. Luteolin is involved with LPS signaling pathways, decreasing the activation of various mitogen-activated protein kinase (MAP kinase) family members, and prevents inflammatory mediator expression.7
Ferulic acid is also a component of raspberries and is active against free radicals such as ROS. Animal studies and in vitro studies suggest that ferulic acid may have direct antitumor activity against breast and liver cancer, and can help in the fight against the effect of carcinogenic compounds like benzopyrene and 4-nitroquinoline 1-oxide. Ferulic acid has pro-apoptotic (programmed cell death) effects that will damage the cancer cells.8-11
The topical combinations of ascorbic acid, vitamin E, and ferulic acid may diminish oxidative stress and prevent the formation of thymine dimers (damage caused by ultraviolet light) in skin.12
Vitamins and Supplements
Recent studies have indicated that vitamin E may have therapeutic effects in treating and preventing periodontal pathology.13,14 Vitamin E is a powerful lipid-soluble antioxidant that is valuable in decreasing wound-healing time.15
To determine whether free radicals have an effect on the normal process of the cell cycle and whether vitamin E inhibits cell damage, normal human oral epithelial cells were treated with hydrogen peroxide (H2O2) in culture in the presence or absence of vitamin E.16 Cultures exposed to H2O2 showed characteristic features common among premalignant epithelial lesions. Therefore, the conclusion is that vitamin E may have the potential to reduce oxidative damage caused by hydroxyl radicals.16
Another vitamin supplement that is essential is folic acid. Low serum folate levels have been associated with an increased risk of periodontal disease in older adults as shown in a recent population-based, cross-sectional study.17 The role of folic acid in combination with oral hygiene measures was investigated in a 1-year follow-up study on epileptic children treated with phenytoin (an anticonvulsant). This study led to the conclusion that the combined effects of systemic folic acid and phenytoin slow down the onset and decrease the incidence and severity of phenytoin-induced gingival overgrowth.18
Single Purified Antioxidant Molecules
Resveratrol was shown to have potential benefits in preventing or counteracting cellular damage, cancer, aging, and many other diseases.19 Resveratrol is found in green vegetables, citrus fruit, and red grape wines.20 Resveratrol was potentially effective for treating neuronal death, neurological dysfunction, or other neurodegenerative genetic disorders such as Huntington’s and Alzheimer’s disease.21
The combinations of topical antioxidants such as phloretin, vitamin C, and ferulic acid prevent many signs of premature aging and correct existing photodamage in skin.22,23 Phloretin has the ability to control the level of reactive oxygen species (ROS) throughout skin layers. Other functional activities include its capacity to prevent the mutation that occurred in skin cells and to participate in cultures with rapid cell turnover.24
Conclusion
This review identifies novel and current therapeutic protective agents in recent studies and provides some foundation to anticipate and prepare for future challenges and opportunities. Some of these single antioxidants when applied to cells possess anti-angiogenic, anti-inflammatory, antiviral, and/or anti-tumor properties. It is possible that combined antioxidant supplements will provide greater protective effects against free-radical damage to human gingival and periodontal tissues than individual antioxidants. The increasing evidence from studies of combinations of antioxidants has raised hopes that these products can be useful in the treatment of dental diseases.
Excerpt from San Miguel SM, et al. Use of Antioxidants in Oral Healthcare. Compend Contin Educ Dent. 2011;32(2). https://www.dentalaegis.com/cced/2011/03/use-of-antioxidants-in-oral-healthcare.
References
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2. Cabrera C, Artacho R, Giménez R. Beneficial effects of green tea—a review. J Am Coll Nutr. 2006;25(2):79-99.
3. Abebe W. An overview of herbal supplement utilization with particular emphasis on possible interactions with dental drugs and oral manifestations. J Dent Hyg. 2003;77(1):37-46.
4. Carnelio S, Khan SA, Rodrigues G. Definite, probable or dubious: antioxidants trilogy in clinical dentistry. Br Dent J. 2008;204(1):29-32.
5. Letchoumy PV, Mohan KV, Stegeman JJ, et al. In vitro antioxidative potential of lactoferrin and black tea polyphenols and protective effects in vivo on carcinogen activation, DNA damage, proliferation, invasion, and angiogenesis during experimental oral carcinogenesis. Oncol Res. 2008;17(5):193-203.
6. Stoner GD, Wang LS, Zikri N, et al. Cancer prevention with freeze-dried berries and berry components. Semin Cancer Biol. 2007;17(5):403-410.
7. Gutierrez-Venegas G, Kawasaki-Cardenas P, Arroyo-Cruz SR, Maldonado-Frias S. Luteolin inhibits lipopolysaccharide actions on human gingival fibroblasts. Eur J Pharmacol. 2006;541(1-2):95-105.
8. Kampa M, Alexaki VI, Notas G, et al. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action. Breast Cancer Res. 2004;6(2):R63-74.
9. Lee YS. Role of NADPH oxidase-mediated generation of reactive oxygen species in the mechanism of apoptosis induced by phenolic acids in HepG2 human hepatoma cells. Arch Pharm Res. 2005;28(10):1183-1189.
10. Lesca P. Protective effects of ellagic acid and other plant phenols on benzo[a]pyrene-induced neoplasia in mice. Carcinogenesis. 1983;4(12):1651-1653.
11. Mori H, Kawabata K, Yoshimi N, et al. Chemopreventive effects of ferulic acid on oral and rice germ on large bowel carcinogenesis. Anticancer Res. 1999;19(5A):3775-3778.
12. Srinivasan M, Sudheer AR, Menon VP. Ferulic Acid: therapeutic potential through its antioxidant property. J Clin Biochem Nutr. 2007;40(2):92-100.
13. Chapple IL, Matthews JB. The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000. 2007;43:160-232.
14. Battino M, Bullon P, Wilson M, Newman H. 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.
15. Barbosa E, Faintuch J, Machado Moreira EA, et al. Supplementation of vitamin E, vitamin C, and zinc attenuates oxidative stress in burned children: a randomized, double-blind, placebo-controlled pilot study. J Burn Care Res. 2009;30(5):859-866.
16. Royack GA, Nguyen MP, Tong DC, et al. Response of human oral epithelial cells to oxidative damage and the effect of vitamin E. Oral Oncol. 2000;36(1):37-41.
17. Yu YH, Kuo HK, Lai YL. The association between serum folate levels and periodontal disease in older adults: data from the National Health and Nutrition Examination Survey 2001/02. J Am Geriatr Soc. 2007; 55(1):108-113.
18. Prasad VN, Chawla HS, Goyal A, et al. Folic acid and phenytoin induced gingival overgrowth—is there a preventive effect. J Indian Soc Pedod Prev Dent. 2004;22(2):82-91.
19. Brisdelli F, D’Andrea G, Bozzi A. Resveratrol: a natural polyphenol with multiple chemopreventive properties. Curr Drug Metab. 2009;10(6):530-546.
20. Savio M, Coppa T, Bianchi L, et al. The resveratrol analogue 4,4’-dihydroxy-trans-stilbene inhibits cell proliferation with higher efficiency but different mechanism from resveratrol. Int J Biochem Cell Biol. 2009;41(12):2493-2502.
21. ElAttar TM, Virji AS. Modulating effect of resveratrol and quercetin on oral cancer cell growth and proliferation. Anticancer Drugs. 1999;10(2):187-193.
22. Rezk BM, Haenen GR, van der Vijgh WJ, Bast A. The antioxidant activity of phloretin: the disclosure of a new antioxidant pharmacophore in flavonoids. Biochem Biophys Res Commun. 2002;295(1):9-13.
23. Lin FH, Lin JY, Gupta RD, et al. Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin. J Invest Dermatol. 2005;125(4):826-832.
24. Valenta C, Cladera J, O’Shea P, Hadgraft J. Effect of phloretin on the percutaneous absorption of lignocaine across human skin. J Pharm Sci. 2001;90(4):485-492.
About the Authors
Symone M. San Miguel, DMD, PhD
Postdoctoral Fellow
Biomedical Sciences
Texas A&M Health Science Center
Baylor College of Dentistry
Dallas, Texas
Lynne A. Opperman, PhD
Professor of Biomedical Sciences
Texas A&M Health Science Center
Baylor College of Dentistry
Dallas, Texas
Edward P. Allen, DDS, PhD
Adjunct Professor
Department of Periodontics
Texas A&M Health Science Center
Baylor College of Dentistry
Dallas, Texas
Kathy K.H. Svoboda, PhD
Professor of Biomedical Sciences
Texas A&M Health Science Center
Baylor College of Dentistry
Dallas, Texas
