Efficacy of antioxidants

I read recently that 78 million baby boomers are surging toward the gates of retirement. Many are searching for that magic elixir to keep them healthy and happy, and the search takes them beyond their bank accounts. As a bona fide boomer, I focus on daily exercise and try to follow a low-fat, low-sugar diet. It’s the formula I adhere to in trying to age gracefully and ward off type 2 diabetes and other nasty age-related diseases.

A great friend of mine, Barbara King, also a boomer and an RN, turned me on to a healthier lifestyle. At the time, she was taking a liquid vitamin for about a year called Total Body Formula. Unbeknownst to her, the company recently changed the liquid vitamin formula. From the very first dose, she experienced nausea, diarrhea, vomiting, peripheral neuropathy, hair loss, and night sweats. Barbara was convinced she either had leukemia or lymphoma, and her husband, an internist, started running a battery of medical tests.

It turns out that the new Total Body Formula contained a milligram of selenium (instead of a microgram), and it was the selenium poisoning that was making people like Barbara sick. Barbara told me that the company knew that people were getting sick from the new batch. Instead of recalling it, they issued a falsified certificate, claiming the product was safe. Even the company’s own chemist testified against them in court, and the company is stalling on paying settlements to victims because criminal charges may be filed. (If you search Dateline NBC, Sunday, March 18th, 2012, you can read about the NBC investigation into the laboratory practices of some nutritional supplement companies. Barbara’s story was televised, and she was interviewed by NBC’s Chris Hansen.)

The entire nutraceutical industry is not subject to the strict FDA regulatory regimens as drugs are. Antioxidants are included in this category of natural product compounds, and some have even given them a new name, “antiAGEnts.” Antioxidants are featured in a diversity of consumer packaged goods, including granola bars, vitamin shakes, detox skin care, and anti-aging products.

Antioxidants are now working their way into the oral care industry. Some dental speakers, writers, and clinicians are now promoting salivary antioxidants as a way to regulate oral chemistry and oral health.

So I decided to investigate this topic. As an evidence-based sleuth, I sought assistance from Dr. Sotirios Kotsovilis, a periodontist and researcher, who is familiar with the research surrounding this topic. He is on the staff of Biomedical Research Foundation of the Academy of Athens in Greece, and his research has been published in a variety of journals, including American dental publications.

I corresponded with him about how oxidative stress and antioxidants have engaged considerable interest in the hygiene and periodontal community.

Dr. Kotsovilis reminds us that “the destruction of periodontal tissues may be promoted not only by microorganisms or their products, but also by the host response to the microbial challenge, involving both innate and adaptive immunity. Oxidative stress could possibly be involved in both bacterial- and host-mediated mechanisms of periodontal catastrophe” (see sidebar).

He cited a number of studies that have reported some interesting findings.

“Oxidative stress was demonstrated to be enhanced by advanced glycation/glycosylation end-products, which are products of irreversible non-enzymatic glycosylation of tissue macromolecules (mainly proteins and lipids) occuring in diabetic patients,” Dr. Kotsovilis wrote. “Thus, diabetes-related periodontal destruction was associated with diabetes-induced oxidative stress.”

He also pointed out that patients with periodontal manifestations caused by the Papillon-Lefevre syndrome that “high concentrations of ROS and low levels of antioxidants were identified, suggesting a positive association between oxidative stress and Papillon-Lefevre syndrome-mediated periodontal catastrophe.”

Dr. Kotsovilis said that many of the studies have led to the conclusion that the increased levels of ROS can be “implicated in periodontal inflammation and destruction, both in chronic and aggressive forms of periodontitis, and also that the imbalance in the dynamic equilibrium between oxidant and antioxidant biological activities can be the key factor in the devastating role of ROS in the periodontium.”

This knowledge, since the early 1990s, has stirred interest in antioxidants as a remedy. Dr. Kotsovilis said the in vivo research considered whether antioxidants would:

• Prevent the formation of free radicals (preventive antioxidants)
• Scavenge radicals to prevent or inhibit chain formation (radical-scavenging antioxidants)
• Repair the oxidant-induced tissue damage (repair and de novo enzymes)

He did say something interesting about our own ability to counteract free radicals.

“The human organism possesses natural antioxidants, such as vitamins A, C or E, bilirubin (originating from erythrocytes) or uric acid (produced by the catabolism of purines), aimed at reducing or inhibiting free radical-induced tissue catastrophe. The FoxO family of transcription factors have been shown to bind to β-catenin and subsequently activate transcription of genes associated with the regulation of cell apoptosis, repair of DNA damage or the breakdown of ROS.”

Dr. Kotsovilis concluded that “using antioxidants as part of the treatment of inflammatory conditions, including chronic or aggressive periodontitis, appears to be reasonable and scientifically sound.”

But he warned that the efficacy of such therapeutic methods should be documented by appropriate preclinical and clinical studies, backed up with strong systematic reviews and meta-analyses.

I also asked Dr. Kotsovilis about the trend toward natural antioxidant remedies such as mouthrinses, gels, pastes, gum, or lozenges. He replied that “some experimental data tend to suggest good prospects for antioxidant-based periodontal therapy.”

But he added that the “few clinical trials on these products ... reported limited beneficial effects or no beneficial effects on the human inflamed periodontium.”

Dr. Kotsovilis added, “As far as I am aware, there are no systematic reviews that address the efficacy of antioxidants in periodontal therapy. Therefore, the aforementioned studies have never been subjected to quality assessment. Considering also the low number of studies available, I think it appears reasonable to conclude that the current evidence to support the use of natural antioxidant remedies, such as mouthrinses, gels, pastes, gum or lozenges, is insufficient.”

He said we must remember that commercial topical antioxidant remedies should be evaluated in terms of:

• “... every commercial product supposed to have the aforementioned effects should have been thoroughly tested by appropriate well-conducted animal studies, as well as trials in periodontitis patients before it is released for commercial use...”
• “... the efficacy of any product of this type should be not only statistically significant, but also clinically significant. It is a common phenomenon nowadays that many treatment modalities, used as adjuncts to conventional periodontal therapy, provide statistically significant added clinical benefits, but of too limited clinical importance (for example, improvements of probing pocket depth or clinical attachment level of less than 0.5 mm). In such cases, clinicians should always be puzzled about the cost-to-benefit ratio of the use of such treatment modalities in daily clinical practice.” RDH

References

Abou Sulaiman AE, Shehadeh RM. Assessment of total antioxidant capacity and the use of vitamin C in the treatment of non-smokers with chronic periodontitis. J Periodontol 2010; 81(11): 1547-1554.

Asman B, Bergström K, Wijkander P, Lockowandt B. Influence of plasma components on luminol-enhanced chemiluminescence from peripheral granulocytes in juvenile periodontitis. J Clin Periodontol 1986; 13(9): 850-855.

Asman B, Engström PE, Olsson T, Bergström K. Increased luminol enhanced chemiluminescence from peripheral granulocytes in juvenile periodontitis. Scand J Dent Res 1984; 92(3): 218-223.

Aurer-Kozelj J, Kralj-Klobucar N, Buzina R, Bacic M. The effect of ascorbic acid supplementation on periodontal tissue ultrastructure in subjects with progressive periodontitis. Int J Vitam Nutr Res 1982; 52(3): 333-341.

Chandra RV, Prabhuji ML, Roopa DA, Ravirajan S, Kishore HC. Efficacy of lycopene in the treatment of gingivitis: a randomised, placebo-controlled clinical trial. Oral Health Prev Dent 2007; 5(4): 327-336.

Gogebashvili NN, Dzhashi LM, Datunashvili IV, Intskirveli NA, Kiparoidze LI. Influence of antioxidant phenovin and immunomodulator Una de gato on free radical oxidation at parodontitis. Georgian Med News 2009; 18(169): 32-35.

Harpenau LA, Cheema AT, Zingale JA, Chambers DW, Lundergan WP. Effects of nutritional supplementation on periodontal parameters, carotenoid antioxidant levels, and serum C-reactive protein. J Calif Dent Assoc 2011; 39(5): 309-312, 314-318.

Henry CA, Winford TE, Laohapund P, Yotnuengnit P. Neutrophil chemi-luminescence and opsonic activities of young people with periodontitis in Thailand. Arch Oral Biol 1984; 29(8): 623-627.

Kazarina LN, Kuzin VB, Ellarian LK, Tepaev DV. Influence of gel Metrogil Denta and curative toothpaste Mexidol Dent activ on indices of periodontal status and lipid peroxidation in patients with chronic generalized catarrhal gingivitis. Stomatologiia (Mosk) 2007; 86(4): 19-21.

Mishchenko VP, Silenko IuI, Khavinson VKh, Tokar DL. The effect of periodontal cytomedin on lipid peroxidation and hemostasis in spontaneous periodontitis in rats. Stomatologiia (Mosk) 1991; 70(5): 12-14.

Muñoz CA, Kiger RD, Stephens JA, Kim J, Wilson AC. Effects of a nutritional supplement on periodontal status. Compend Contin Educ Dent 2001; 22(5): 425-428, 430, 432, 440.

Silenko IuI, Mishchenko VP, Tokar DL, Khavinson VKh, Popsuïko GI. The effect of periodontal cytomedin on free-radical lipid oxidation and on antiaggregation activity in the periodontium in chronic stress. Stomatologiia (Mosk) 1994; 73(4): 6-8.

Silenko IuI, Mishchenko VP, Tokar DL, Khavinson VKh, Zhukova MIu. The mechanism of the therapeutic effect of periodontal cytomedin on the course of experimental periodontitis. Stomatologiia (Mosk) 1991; 70(4): 13-15.

Vogel RI, Lamster IB, Wechsler SA, Macedo B, Hartley LJ, Macedo JA. The effects of megadoses of ascorbic acid on PMN chemotaxis and experimental gingivitis. J Periodontol 1986; 57(8): 472-479.

Woolfe SN, Kenney EB, Hume WR, Carranza FA Jr. Relationship of ascorbic acid levels of blood and gingival tissue with response to periodontal therapy. J Clin Periodontol 1984; 11(3): 159-165.

Dr. Kotsovilis: The science behind free radicals

“As we know from basic chemistry, free radicals were discovered by Moses Gomberg in 1900. Although great confusion exists with respect to the definition of “free radicals,” we can define them in the most general sense as atoms, ions, or molecules that are able to exist at an independent state and which contain one or more unpaired electrons. This definition of “free radicals” is the most general possible, because it is not restricted by their charge. Thus, free radicals, as defined above, might be positively charged (e.g. NAD+•), negatively charged (e.g. O2-•) or electrically neutral (e.g. OH•).

“The above-mentioned definition is compatible with pertinent observations in biological systems, where free radicals are contained at an independent state, having positive, negative or no charge. In such systems, free radicals are extremely important, because most of them are highly chemically reactive and can cause severe destruction in cells and tissues. The “free-radical theory of aging” is now a popular theory, based on the observations made by Rebbeca Gershman and Denham Harman as far back as six decades ago, attributing aging of multicellular organisms to the accumulation of free radical-induced tissue damage over time.

“Reactive oxygen species (ROS) are oxygen-based free radicals. Examples are superoxide radical (O2-•), hydroperoxyl radical (HOO•), hydroxyl radical (OH•), hydrogen peroxide (H2O2), ozone (O3) or hypochlorous acid (HOCl). These are derivatives of the physiological metabolism of molecular oxygen (O2) and are able to cause unwanted side reactions, leading to cell damage and/or death through various mechanisms, such as damage or alteration of small organic biomolecules, proteins (including enzymes), nucleic acids, fatty acids or lipids, activation of genes related to transcription factors, and others.

“As a result of these biological activities, ROS have been associated with the development of many conditions, such as inflammatory diseases, cardiovascular diseases, diabetes, cancer, neurological disorders (Parkinson’s, Alzheimer’s etc.), liver damage, and others. Therefore, this type of tissue damage is oxidative.

“Oxidative stress could be defined as an imbalance of the dynamic equilibrium between the production of ROS and the ability of a biological system to prevent or repair the destruction caused by ROS.

“Because ROS have been associated with the development of inflammatory diseases, the hypothesis that ROS could be related to the pathogenesis of periodontitis appears to be reasonable. In the mid-1980s, the first studies were published in the periodontal literature implicating ROS in the pathogenic mechanisms of juvenile periodontitis (now termed “aggressive periodontitis”). These studies (Asman et al. 1984, 1986; Henry et al. 1984) concluded that in juvenile periodontitis patients, peripheral polymorphonuclear leukocytes (PMNs) can release ROS in the extracellular fluid, which — if not counteracted/neutralized by protective antioxidant mechanisms of the organism (for example, by scavengers or superoxide dismutase) — are able to subsequently induce periodontal tissue catastrophe, thus contributing to periodontal disease pathogenesis. As we know, the physiological role of these ROS is to eliminate microorganisms contained in the phagosome during the defense process of phagocytosis.”

Lynne Slim, RDH, BSDH, MSDH, is an award-winning writer who has published extensively in dental/dental hygiene journals. Lynne is the CEO of Perio C Dent, a dental practice management company that specializes in the incorporation of conservative periodontal therapy into the hygiene department of dental practices. Lynne is also the owner and moderator of the periotherapist yahoo group: www.yahoogroups. com/group/periotherapist. Lynne speaks on the topic of conservative periodontal therapy and other dental hygiene-related topics. She can be reached at [email protected] or www. periocdent.com.