Introduction

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Poor nutrition is associated with one-third of all cases. Antioxidant nutrients are assuming more importance in cancer research, including cancers of the oral cavity. As a profession it is important that we update our knowledge of current information on antioxidant nutrients and their possible role as chemopreventive agents in the development and treatment of oral cancer. Incorporating nutrition education into our daily practice is part of the preventive message.  

 

Part One of this series looked at the role of dietary antioxidants as chemopreventive agents in oral cancer. This article will review the role of antioxidant enzymes such as glutathione peroxidase and superoxide dismutase in oral cancer development and the micronutrients involved in the synthesis of those enzymes. The effect of inflammation in cancer development and the role of  anti inflammatory metabolites from essential fatty acids in the diet is also reviewed. Practical dietary advice for avoiding weight loss and protein malnutrition linked with the treatment and progression of oral cancer is also presented. 

 

Antioxidant Enzymes  

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The antioxidant enzymes are important in cancer prevention and treatment as they limit cell injury induced by reactive oxygen species.  

 

Glutathione, a tripeptide found in a variety of foods, may function as an anticarcinogen by acting as an antioxidant and by binding with cellular mutagens. Glutathione is a major endogenous low molecular weight antioxidant and is important for lymphocyte replication. The smoking of a single cigarette is capable of inducing a significant reduction of salivary glutathione concentration.(3) Glutathione requires adequate selenium and sulphur amino acids from the diet for synthesis.  The sulphur amino acids methionine and cysteine are found in most sulphur rich foods such as cabbage, cauliflower, onions and garlic.

 

Malnutrition is characterized by marked tissue depletion of anti-oxidant nutrients, including glutathione peroxidase, a key extracellular anti-oxidant enzyme as well as a modulator of T-cell activation. In its reduced form Glutathione (GSH) and its precursor cysteine inhibit activation of the nuclear transcription factor NFkB and have been shown to be protective against chemically induced oral cancer and leukoplakia.  

 

Other trace minerals important in the synthesis of antioxidant enzymes include zinc, copper and manganese. These are part of the antioxidant enzyme Superoxide Dismutase (SOD). Two forms of this enzyme exist, the cystolic form requires copper and zinc to function, whilst the mitochondrial form requires manganese.  SOD converts the oxygen free radical “superoxide” into the less harmful hydrogen peroxide. Studies have shown SOD to be essential enzymes that eliminate reactive oxygen species, in squamous cell cancers of the lung, larynx and oral cavity. Cancer cells are generally low in the enzymatic activities of both forms of superoxide dismutase. In general, in oral squamous cell carcinomas, the mucosal basal cells displayed lower antioxidant enzyme levels and primary tumour cells displayed lower antioxidant enzyme staining intensities than did their normal cell counterparts. (4)  Deficiencies of trace minerals, therefore, will compromise the adequate synthesis of the antioxidant enzymes.   

 

Selenium

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Selenium is a trace element, important for the antioxidant defences of the body as an integral component of metalloprotein enzymes. It is a component of selenoproteins, which have important enzymatic functions(5,6). Deficiency of selenium is accompanied by loss of immunocompetence. An inverse relationship between selenium intake and cancer mortality has been documented(7)  Vitamin A, riboflavin and selenium supplementation have been shown to produce a concomitant regression of precancerous lesions present on the palate. Complete remission of white, red and combination lesions was seen in 57% of subjects on supplements, whereas 8% of the placebo group showed a positive response.(8) Selenium is also a key component of enzymatic antioxidants such as superoxide dismutase, catalase and glutathione peroxidase, thus implicating selenium status as an important antioxidant in the prevention of oral cancer.  

 

Essential Fatty Acids

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Chronic inflammation, resulting in chronic phagocytic activity is one of the major endogenous sources of free radicals and is associated with the development of cancer.(9)  Prostaglandins are potent mediators of the immuno-inflammatory pathways. The pro inflammatory prostaglandins (e.g. PGE2) and other metabolites of Arachidonic Acid (AA) are released in response to tissue damage. Inhibition of prostaglandins by pharmacological agents has been demonstrated to enhance immunocompetence, and to suppress growth of tumours in animals and humans.  

 

The anti inflammatory prostaglandins (PGE1 and PGE3) antagonise the excess production of PGE2 and other AA metabolites. Adequate intake of the essential fatty acid precursors of PGE1 and 3 can manipulate the activity of PGE2.  GLA (gammalinolenic acid) and EPA (eicosapentaenoic acid) block the mobilisation and synthesis of certain leukotrienes from AA and compete with AA to prevent the synthesis of inflammatory metabolites(10,11).   On the basis of research conducted to date, if a deficiency of essential fatty acids leads to the inability to synthesise anti-inflammatory prostaglandins and both GLA and EPA have been shown to increase the synthesis of PGE1 and PGE3, then ingesting adequate amounts of essential fatty acids would appear to play an important part in host resistance to cancer development. 

 

Research has shown how vitamins C and E also exert a dose-dependent effect on AA release and PGE2 synthesis in  human gingival fibroblasts and oral squamous carcinoma cells. A combination of the two vitamins had a consistent dose-dependent inhibitory effect on AA and PGE2.(12) The in vivo significance of these findings requires further investigation. 

 

Protein Malnutrition

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Over 40% of cancer patients actually die from malnutrition, not from the cancer. Cancer generates chemicals that lower appetite while increasing calorie needs. The net effect is that many cancer patients begin to lose weight.  

 

Malnutrition, particularly protein-energy malnutrition, which invariably involves concurrent deficiencies of the antioxidant micronutrients, promotes salivary gland hypofunction, impaired immunity, and an early shift in the oral microbial ecology toward a dominance of anaerobic organisms. The immune suppression, which includes impaired cytokine function as well as a diminished acute-phase response to infections, has a negative impact on the resistance to oral cancer. 

 

Patients with oral cancer usually have protein-energy malnutrition, largely due to an inadequate dietary intake(13) . This may  be due to a combination of factors. Treatment of oral cancer usually involves maxillofacial surgery which in itself  makes eating and drinking difficult. Other treatments such as radiotherapy may cause xerostomia and dysphagia  and if chemotherapy is used then nausea is also a recurring problem.   A high protein diet therefore is indicated for the cancer patient and this may be achieved by following the practical dietary advice below. In patients with renal failure specialist dietary advice will be needed.  

 

Practical Dietary Advice.

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Well-established guidelines have been researched and laid down regarding the prevention of oral cancer. These include consuming a diet rich in whole grains, raw fruits and vegetables, at least five portions daily. Include cruciferous vegetables, such as cauliflower, broccoli, and cabbage.  Avoid smoking and lower saturated fat intake, increase dietary fibre and avoid obesity. Adequate intake of cold pressed  unsaturated oils and  essential fatty acids also appear to be of value. Avoid or lower alcohol consumption. Lower intake of salt-cured, smoked, or nitrite-containing foods and moderate intake of red meat.  

For patients being treated for cancer and particularly for those who have had surgery the following guidelines will be helpful in avoiding weight loss and malnutrition.  

 

Don't drink fluids or have soup before a main meal as this will fill the stomach with foods that are low in calorie density. Eat on a large plate, thus avoiding food portions that appear overwhelming. Have small portions, and come back for more. People eat more when dining in groups than by themselves.  

 

Avoid fizzy drinks as these are filling, instead, try diluted apple juice or ginger tea. Ginger helps to relieve nausea, ginger tea can be drunk hot or cold.  

 

When planning a meal make sure the foods chosen are energy and nutrient dense. For example Iceberg lettuce is the most common salad bar offering, but is low in nutrient value relative to most other vegetables. Choose the healthier fruits, vegetables and whole-grain foods. As a guide: the deeper the colour of the vegetable, the more nourishing it is. Dark greens are better than pale greens, dark orange sweet potatoes are better in carotene content than white potatoes, and so on. In nature, cauliflower is a dark green vegetable, until human intervention ties the leaves around the developing flower to deprive it of sunlight.  

 

Many patients undergoing treatment, however, find eating very difficult. To solve that problem, a nutrient rich shake or smoothies  can be helpful., This can incorporate many nutrients in powder and juice form, thus helping to avoid malnutrition. It is also smooth making it , easier to swallow and lubricating the throat. Depending on the calorie requirements of the patient,  this shake can be used  in addition to or instead of some meals.  

 

Conclusion

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Detection and prevention of oral cancer is an integral part of our daily practice and remain the goals of the dental profession in our  efforts to reduce the impact of this disease our patients.  Concurrent abuse of tobacco products worsens dental disease and heightens the risk of developing oral cancer. Poor dietary intake of protective micronutrients is also a significant risk in cancer development. Encouraging and educating our patients in the importance of good dietary intake of fresh fruits and vegetables and the role that dietary antioxidants play in cancer prevention, is an integral part of the preventive message.   

 

 

References

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1.Moore SR, Johnson NW, Pierce AM, Wilson DF. The epidemiology of mouth cancer: a review of global incidence. Oral Diseases 2000;6(2):65-74.  

 

2.  www.dentalhealth.org.uk  

 

3.Zappacosta. B., Persichilli.S., DeSole.P., Mordente.A., Giardina.B. : Effect of smoking one cigarette on antioxidant metabolites in the saliva of healthy smokers.  Arch Oral Biol 44(6): 485-8 Jun 1999  

 

4.Yang J, Lam EW, Hammad HM, Oberley TD, Oberley LW. Antioxidant enzyme levels in oral squamous cell carcinoma and normal human oral epithelium. J Oral Pathol Med. 2002 Feb;31(2):71-7.    

 

5.Hughes D. Dietary antioxidants and human immune function. Nutrition Bulletin 2000;25:35-41.  

 

6. Rayman M. The importance of selenium to human health. Lancet 2000;356:233-41.  

 

7. Schrauzer GN, White DA, Schneider CJ. Cancer mortality correlation studies. III. Statistical association with dietary selenium intakes. Bioinorganic Chemistry 1977;7:35-56.  

 

8. Krishnaswamy K, Prasad MP, Krishna TP, Annapurna VV, Reddy GA A case study of nutrient intervention of oral precancerous lesions in India. European Journal of Cancer. Part B, Oral Oncology1995 Jan31B: (1)41-8    

 

9.Collins RH, Feldman M, Fordtran JS. : Colon cancer, dysplasia and surveillance in patients with ulcerative colitis. A critical review. New England Journal of Medicine 1987;316:1654-8.  

 

10. Horrobin D.F : The regulation of prostaglandin biosynthesis: negative feedback mechanisms and the selective control of formation 1 and 3 prostaglandin series: relevant to inflammation and immunity. Medical Hypothesis 1980 6(7):687-709.  

 

11. Lands WE,. Byrnes MJ.: The influence of ambient peroxides on the conversion of EPA to prostaglandins. Progress in Lipid Research 1982 20:287-90.  

 

12. el Attar TM, Lin HS. : Effect of vitamin C and vitamin E on prostaglandin synthesis by fibroblasts and squamous carcinoma cells. Prostaglandins Leukot Essent Fatty Acids. 1992 Dec;47(4):253-7.    

 

13.  Dawson ER, Morley SE, Robertson AG, Soutar DS: Increasing dietary supervision can reduce weight loss in oral cancer patients. Nutr Cancer. 2001;41(1-2):70-4.