The Antioxidant Status of Smokers
© Juliette Reeves 2005

As dental professionals we are only too aware of the effects of smoking on the periodontium and oral mucosa. Tobacco has long been linked to oral cancer and leukoplakia,. Research over the last 20 years has established a firm association between tobacco use increased prevelence and severity of periodontitis, alveolar bone loss and poor response to traditional therapy including refractory/recurrent disease. The effects of smoking on antioxidant status and activity is receiving increased attention. Smokers typically have depleted antioxidant status and increased lipid peroxidation and free radical activity. Free radical-induced oxidative damage is thought to be involved in the pathogenesis of diseases associated with cigarette smoking, which include the periodontal diseases.

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Smoking and Periodontal Disease

The effect of smoking on periodontal health has been discussed in the dental literature for the last fifty years The first formal studies on smoking and the periodontal diseases began in 1947 and initially focused on gingivitis (2). During the last twenty years a strong association between smoking and periodontal disease has been established. Recent data suggest that the effect of smoking is a direct one and not a serrogate effect, secondary to poor oral hygiene and increased dental plaque accumulation .(3,4)

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Pathogenesis.

There is evidence that cigarette smoking exerts both systemic and local effects. Tobacco smoke contains cytotoxic and vasoconstrictive substances, , which have direct effects on the blood vessels supplying the gingival tissues.(5) This is borne out by reports showing that smokers have less gingival bleeding and inflammation than non smokers. (6,7).
Nicotine also adversely affects fibroblast function and readily penetrates the epithelium of the skin and oral mucosa, resulting in impaired tissue turnover, healing and maintenance of the periodontal attachment.(8) Among the effects of nicotine is the structural alteration of fibroblasts, preventing them from firmly attaching to the root surface. As with other tissues, normal fibroblast function is important for maintenance of the periodontium.

 

Smoking also exerts deleterious effects on bone formation and homeostasis . Nicotine can suppress the proliferation of cultured osteoblasts while stimulating osteoblast alkaline phosphatase activity.(9) This alteration to osteoblasts by nicotine may also affect alveolar bone in tobacco smokers. Indeed, even former smokers have been shown to have less periodontal bone loss than current smokers.(10)

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The Immunosuppressive Effects of Smoking.

The effects of smoking on the immune system are also well documented. These include inhibition of oral neutrophilic polymorphonuclear leukocyte (neutrophil) function, reduced antibody production, and alteration of peripheral blood immunoregulatory T-cell ratios. The suppression of the immune response and alterations in the host functional capacity could significantly compromise this first line of defence. In order for the host to efficiently deal with bacterial infections, fully functional neutrophils are required. It has been well documented that tobacco smoke and its components can have deleterious effects on various neutrophil functions. For example, it has been shown that tobacco smoke can impair the chemotaxis and phagocytosis of both oral and peripheral neutrophils. Nicotine has been shown to depress polymorphonuclear activity (11), resulting in reduced neutrophil activity.

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Antioxidant Nutrients and Immune Function.

Adequate host defence activity critically depends upon the micronutrient status of an individual, in particular the oxidant-antioxidant balance. The oxidative burst is part of the physiological function of phagocytes, which results in a massive production and release of reactive oxygen free radicals which are needed to destroy invading micro-organisms, but which over a prolonged period of time may induce oxidative stress on otherwise healthy tissues. The optimal function of the host defence system depends, therefore, on an adequate supply of antioxidant micronutrients(12).

 

The antioxidant micronutrients are important not only for limiting oxidative stress and tissue damage, but also in preventing increased cytokine production, which is a result of prolonged activation of the immune response. . Dietary antioxidants, and other enzymatic antioxidants such as glutathione peroxidase, superoxide dismutase and catalase, protect the lipid moieties of lipoproteins and other biomembranes against oxidative damage by intercepting oxidants before they can attack the tissues.

 

The first line of defence is superoxide dismutase. As a dismutase two forms of this enzyme exist. The cystolic form requires copper and zinc to function, whilst the mitochondrial form requires manganese. Glutathione in its reduced form is a major endogenous antioxidant and is important for lymphocyte replication. It has been reported that the smoking of a single cigarette is capable of inducing a significant reduction of salivary glutathione concentration(13).

 

Two vitamins, vitamin B6 and riboflavin, and the mineral selenium, participate in the production and maintenance of adequate glutathione. B6 acts as a cofactor in the synthesis of cysteine, needed for glutathione biosynthesis. Riboflavin is a cofactor for glutathione reductase, with selenium being required for both of these activities. Deficiencies in these nutrients can result in reduced cell numbers in lymphoid tissue and produce functional abnormalities in the cell mediated immune response(14).

 

In humans it has been shown that dietary supplementation of vitamin C, the tocopherols and B6, enhances lymphocyte function (14). Cigarette smoking impairs the antioxidant protective action of vitamin C, glutathione and other antioxidants at tissue level. The resulting increased rate of lipid peroxidation and reduced antioxidant status will accelerate the rate of destruction of the periodontium.

More recently the effect of antioxidant micronutrients in the prevention of oxidative damage from smoking has been examined.

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Antioxidant Status of Smokers.

The effect of cigarette smoking on the serum vitamin C status of smokers has been researched over the last forty years. Early studies by McCormick (15),established that each cigarette smoked destroys an average of 25mg of vitamin C. Further study in the 70’s and 80,s by Pelletier (16) and Cheraskin et al(17) suggested that smokers need twice as much vitamin C intake as non-smokers to maintain comparable blood levels. This may in part be due to the fact that smoking adversely affects absorption and utilisation of vitamin C. More recent studies have confirmed that the radical scavenger vitamin C reacts sensitively to oxidative stress induced by cigarette smoke in human plasma, and that plasma vitamin C levels are reduced in smokers compared to non-smokers(18). The same is also true of total carotenes(19)and alpha-tocopherol ( vitamin E). (20,21)

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Recent study has also suggested that smoking adversely affects preferences for Vitamin C rich foods, and that dietary antioxidant intake is significantly lower in smokers than non smokers (22,23). Smokers had the lowest dietary vitamin C intake and serum levels compared to those who had never smoked (22) This inverse association was independent of age,sex, body weight, race and alcohol consumption. Beta-carotene intake was also significantly reduced compared to non- smokers with an almost 60% lower fruit intake observed in smokers (23).

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That lipid peroxidation appears higher in smokers than non- smokers is borne out by data from a number of recent studies.(20 21). Reilly et al(24) carried out a study to examine the production of 8-epi-prostaglandin (PG) F2 alpha, a stable product of lipid peroxidation in vivo, and its modulation by aspirin and antioxidant vitamins in chronic cigarette smokers. Aspirin treatment failed to suppress urinary levels of 8-epi-PGF2 alpha excretion. . A combination of vitamins C and E led to a reduction in urinary levels of 8-epi-PGF2 alpha excretion. The authors concluded, therefore, that elevated levels of 8-epi-PGF2 alpha in smokers may be modulated by antioxidant therapy or by quitting smoking.

Do et al(25) also suggested a strong correlation between the decline in ethane output in smokers after supplementation of vitamins A.C. and E. They concluded that antioxidant vitamin supplementation resulted in attenuation of smoking related lipid peroxidation. Cross et al(26) were able to show that exposure of human plasma to cigarette smoke causes lipid peroxidation, and that endogenous ascorbic acid protects against lipid peroxidation.

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Dietary Antioxidant Micronutrients

Of the micronutrients, Vitamins A.C.E, and minerals selenium and zinc have important influences on immune responses. Increasing attention is also being given to the antioxidant activity of the carotenoids, particularly lycopene.

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Vitamin A is a fat-soluble nutrient, which occurs in two forms: preformed vitamin A (Retinol in animal tissues) and provitamin A (from the synthesis of Beta-Carotene). Vitamin A is needed in the production of secretory IgA. This antibody protects mucous membrane throughout the body from bacterial invasion and allergic assaults. Vitamin A can also stimulate the thymus, thereby increasing the number of circulating lymphocytes. Vitamin A is one of the few vitamins that has the potential of toxicity at relatively low therapeutic levels. It has also been shown to be teratogenic. There is no reported toxicity to beta-carotene and for this reason beta carotene is the recommended form.

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Vitamin C exhibits and enormous array of chemical and metabolic functions, that are mainly associated with its oxidation-reduction activity. It is an important water- soluble nutrient capable of intercellular free radical scavenging activity. Vitamin C improves host defence mechanisms by stimulating T-cell migration and aiding phagocytosis.

Vitamin E is an essential micronutrient, by definition, as the body cannot synthesise the tocopherol group and thus it must be provided by the diet. The intra cellular activity of vitamin E makes it the first line of defence against lipid peroxidation, protecting cell membranes through its free radical-scavenging activity.

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Selenium is a vital component of the body’s antioxidant defence system. The free-radical quenching activity of glutathione peroxidase (GSHPx) is dependant on adequate selenium. GSHPx has four selenium atoms per molecule. If adequate selenium is not available, this level will not be reached and production of GSHPx will be impaired. Selenium compounds in foods are easily reduced by heat, processing and cooking. The refining of grains reduces selenium content by 50 to 75 percent.Zinc is an essential trace element of significant biological importance inclusive of cell membrane integrity, epithelial cell turnover ,connective tissue and immune system regulation.

 

Studies show Zinc deficiency leads to T-cell depletion, phagocytic activity is lowered, and sulcular epithelial permeability is increased. It has been concluded that Zinc deficiency may cause oxidative damage to cell membranes. (28)

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Carotenoids are the naturally occurring pigments, which are synthesized by plants and are responsible for the bright colours of various fruits and vegetables. Over 500 specific carotenoids have been identified, however, only a small number ofcarotenoids are found in significant quantities in human blood and tissues. The major ones are Alpha-Carotene, Beta-Carotene, Lutin, Zeaxanthin, Cryptoxanthin and Lycopene. Carotenoids are effective quenchers of singlet oxygen, with Lycopene exhibiting the highest singlet oxygen quenching activity. The antioxidant action of lycopene has proven more effective than any other carotene. Currently there are no specific government recommendations for lycopene or total carotenoid intake.

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Thus smoking may induce or exacerbate various forms of periodontal disease by direct or local damage to the periodontal tissues, and/or by altering the host inflammatory-immune response. Tobacco may also impair the normal repair mechanisms in the periodontal tissues, and disrupt fibroblast and osteoblast function.

Tobacco smoking severely depletes the body of important antioxidant micronutrients needed for effective functioning of the host immune response. This is especially so in the case of vitamin C, beta-carotene and alpha tocopherol, which are known to be vastly depleted in smokers in comparison to non-smokers.

In recommending smoking cessation to our patients, it clear that adequate dietary intake of antioxidant micronutrients is of equal priority. This is especially so for our patients who continue to smoke. It is also clear that specific food choices are needed to facilitate delivery of these essential nutrients.

 
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