CAPÍTULO VI: CONCLUSIONES Y RECOMENDACIONES
6.2. Recomendaciones
Epidemiological evidence links a high intake of saturated animal fats with oral and pharyngeal cancer, at least in males. Though fatty acids can be essential dietary components, there appear to be no reports on the effects of fatty acid deficiency on the oral mucosa.
Vitamins
Vitamins are essential organic dietary factors incapable of being synthesized within the body. Vitamins are classified as water or fat soluble (Table 11.2). They are required in only small amounts; absence can result in a disease state (Table 11.3) and sometimes vitamin excess can cause disease.
Vitamin A (retinol)
Vitamin A is fat-soluble and is found in animal fats, milk, and liver. Vitamin A can also be derived from precursors (carotenes or carotenoids) found in plants, particularly green leafy vegetables. Vitamin A is stored in the liver: reserves can last about 1 year. Natural derivatives of vitamin A, and synthetic analogues of vita- min A, known as retinoids, can modulate epithelial cell differen- tiation, possibly by regulating gene expression.
Hypervitaminosis A
In hypervitaminosis A there is alopecia, peeling of the skin, coars- ening of the hair, and bone pain. Oral features have only rarely been recorded but vitamin A and some analogues such as etreti- nate may cause cheilitis.
Vitamin A deficiency
Vitamin A deficiency is usually dietary in origin. In vitamin A deficiency, the eyes are first affected; night blindness, xeroph- thalmia, and conjunctival ulceration appear. The skin becomes dry and scaly (follicular hyperkeratosis) and the oral mucosa becomes hyperkeratinized, with non-keratinized mucosa chang- ing into keratinized mucosa. Salivary secretory ductal epithelium undergoes metaplasia and there is also a direct effect on the taste buds. Hypovitaminosis A may be found in some patients with
Table 11.2 Classification of vitamins
Fat-soluble Water-soluble
Vitamin A Vitamin B1 (Thiamin) Vitamin D Vitamin B2 (Riboflavin) Vitamin E Vitamin B6 (Pyridoxine)
Vitamin K Vitamin B12
Vitamin C (Ascorbic acid) Folic acid
Pantothenic acid Biotin
Nicotinic acid (Niacin)
Prevention of chemotherapy-induced mucositis
• Pre-treatment use of ice chips • Anti-infective agents—topical
duce some improvement. Hypovitaminosis A also increases the susceptibility of rodents to infection with Candida albicans.
There has been considerable interest in the role of vitamin A in cancers, particularly those of epithelial origin. Both natural pre- cursors (carotenoids) and synthetic analogues (retinoids) may have some protective effect against cancers.
Vitamin B
There are several B vitamins (Tables 11.2 and 11.3): all are water- soluble. Deficiencies may be diet-related or have other causes: oral ulceration and other conditions noted below, may follow.
Vitamin B12 deficiency
The most widely recognized deficiencies are of vitamin B12. This vitamin is found mainly in liver, eggs, meat, and milk: liver stores of this last up to 3 years, and thus deficiency is rarely of dietary origin—except in vegans. Vitamin B12 deficiency is typically seen in pernicious anaemia, where there is deficiency of the gastric intrinsic factor required for the absorption of vitamin B12.
Glossitis and stomatitis may result from vitamin B12 defi- ciency. The tongue tip reddens in the early stages of deficiency, and this eventually spreads with fissuring—the so-called beef tongue—and with papillary atrophy. Angular stomatitis, aph- thae, and erosive lesions may also be seen. Some patients may have Burning Mouth syndrome, even in the absence of recognizable mucosal disease. Oral hyperpigmentation may also be seen. Mucosal changes respond rapidly to replacement therapy.
Vitamin B1 (thiamine, aneurine) deficiency
Vitamin B1 is widely distributed in foods. It is necessary in the formation of the coenzyme thiamine pyrophosphate required for oxidative decarboxylation of pyruvate and a-ketoglutarate, and utilization of pentoses. There is, therefore, in B1 deficiency, a build-up of lactate and pyruvate, interfering with carbohydrate metabolism. Deficiency of vitamin B1 is common in alcoholism and leads to Beriberi, characterized by polyneuritis, muscular weakness, cardiac failure, mental changes and, in children, growth retardation. A role for vitamin B in Burning Mouth syn- drome has been proposed, though these findings have not been confirmed by others. Thiamine deficiency may also shorten the tumour induction time in experimental oral carcinogenesis.
Vitamin B2 (riboflavin) deficiency
Riboflavin is found in leafy vegetables, meat, milk, and fish. It acts in the formation of two coenzymes, flavin adenine dinucleotide and flavin mononucleotide, involved in oxidative metabolism. Deficiency of vitamin B2 is commonly dietary, is especially seen in alcoholics, and leads to seborrhoeic dermatitis, corneal vasculariza- tion, and anaemia, and oral mucosal manifestations similar to those of vitamin B12 deficiency. Angular stomatitis, glossitis and oral ulceration have been recorded in vitamin B2 deficiency.
Vitamin B6 (pyridoxine) deficiency
Vitamin B6 is found in meat and vegetables and is involved in the formation of pyridoxal phosphate and pyridoxamine phosphate,
particularly found in alcoholism, pregnancy, and the use of some drugs; e.g. isoniazid. Deficiency of vitamin B6 leads to dermatitis and peripheral neuropathy and oral mucosal manifestations similar to those of vitamin B12 deficiency—with angular stomatitis and generalized stomatitis and sometimes ulceration.
Pantothenic acid deficiency
Pantothenic acid is needed for the synthesis of coenzyme A, nec- essary for several metabolic pathways. There is a report of glossi- tis in possible pantothenic acid deficiency.
Nicotinic acid (niacin: nicotinamide) deficiency
Wheat, nuts, meat, and fish are rich sources of nicotinic acid. The active derivative of nicotinic acid, nicotinamide, is necessary for the production of NAD and NADP for oxidative metabolism. Deficiency of nicotinic acid is seen mainly in the West in alco- holics, and causes pellagra (dermatitis and neurological distur- bances), oral mucosal erythema, and papillary atrophy of the tongue. There may be a burning sensation in the tongue, and hypersalivation and angular stomatitis.
Vitamin C (ascorbic acid)
Vitamin C is water soluble and found especially in fresh fruits (mainly in citrus fruits) and vegetables: potatoes are a common source in the West. Deficiency is because of dietary lack of vitamin C.
Vitamin C is involved in the hydroxylation of proline in colla- gen synthesis, and deficiency leads to defective collagen with cap- illary fragility, a haemorrhagic state, anaemia, and follicular hyperkeratosis and gingival changes. Vitamin C deficiency can also occasionally predispose to angular stomatitis and oral ulcera- tion. There is a tenuous association between vitamin C and a pro- tective effect against oral, pharyngeal, and oesophageal cancers.
Vitamin D
Vitamin D is the general name for a group of fat-soluble sterols. Vitamin D is found in fish, eggs, and milk products, and ultravio- let light converts the skin precursor 7-dehydro-cholesterol to vita- min D. Cholecalciferol from dietary sources is converted into 25-hydroxycholecalciferol in the liver and this is converted in the kidneys to the active form 1,25-dihydroxycholecalciferol. Vitamin D affects calcium and phosphate metabolism. Oral mucosal effects have not been described but vitamin D may affect parotid function.
Vitamin E
Vitamin E is the general name for a group of fat-soluble toco- pherols. Prematurely born, low birth weight infants are generally considered to be marginally vitamin E-deficient. However, although subclinical or biochemical vitamin E deficiency was seen in plasma and buccal mucosal cells in healthy, premature infants in the first 6 weeks of life, the other cells showed no such defi- ciency during the study and the authors concluded that these infants do not need routine vitamin E supplementation (Kaempf and Linderkamp 1998).
No oral mucosal disorders appear to have been recorded in vitamin E deficiency. However, there may be a relationship to
TABLE 11.3 Aspects of vitamin and mineral intake
Vitamin/ Source Active form Mode of action Deficiency state— Deficiency state— Cause of Outcome of Mineral general oral deficiency Excess
Vitamin A Animal fats, Derived from Modulates epithelial Night blindness Affects on taste buds Malabsorption Headache,
milk, Liver caretonoids cell differentiation Xeropthalmia Inadequate diet convulsions
(Leafy green Dry, scaly skin hepatotoxicity, teratogenicity,
vegetables skin peeling
coarse hair Vitamins
Vitamin B1 Fortified flours Thiamine Formation of Beri-beri-polyneuritis, Role in Burning Alcoholism Not known
(Thiamine) and cereals; diphosphate/ coenzyme to muscle weakness, Mouth syndrome Inadequate diet
milk, eggs, yeast pyrophosphate facilitate carbohydrate cardiac failure,
extract, fruit metabolism mental changes
Growth retardation in young people
Vitamin B2 Milk, cheese, Riboflavine Metabolism of Seborrhoeic dematitis, Angular stomatitis; Alcoholism Not known
(Riboflavine) eggs, fish, coenzymes in corneal vascularisation, glossitis, oral Inadequate diet
fortified cereals, oxidative anaemia ulceration Drugs
liver, kidney, metabolism
whole grains, leafy vegetables
Vitamin B6 Liver, meat, fish, Pyridoxal Formation of Dermatitis, Angular stomatitis, Alcoholism, Peripheral
(Pyridoxine) whole grain phosphate coenzymes in amino neuropathy ulceration pregnancy, neuropathy
cereals, milk,. acid metabolism drugs
Peanuts
Vitamin B12 Liver, eggs, Requires gastric Affects development Macrocytic anaemia; Papillary atrophy Vegan diet Not known
(Cobalamin) meat, milk intrinsic factor of rapidly dividing villus atrophy; Apthae; Burning Inadequate diet
for absorption cells – oral mucosa, glossitis, stomatitis Mouth syndrome;
blood cells oral hyper-
pigmentation
Pantothenic acid Synthesis of Glossitis
co-enzyme A in metabolic pathways
Nicotinic acid Wheat, nuts, Nicotinamide Production of NAD Pellagra—dermatitis Oral mucosal Alcoholism Vasodilatatiion
(Niacin) meat, fish, and NADP for and neurological erythema, papillary (In the West)
dairy products, oxidative metabolism disturbances atrophy of tongue,
yeast extracts, hypersalivation,
179
Preventing mucosal disease through nutrition
Vitamin D osteomalacia
Vitamin E Vegetable oils, Tocopherol Antioxidant Inadequate diet Nausea
(Tocopherols) wholegrain cereal,
eggs, margarine
Vitamin K Green vegetables, Naphthaquinone Carboxylation of Hypoprothrombinaemia, Gingival Malabsorption, Hyperbilirubinaemia
liver derivative glutamic acid bleeding bleeding parenteral nutrition,
residues on factors Post-extraction anticoagulants
II, VII, IX, and X, haemorrhage
as well as proteins C and S, all involved in blood clotting
Folic acid Green vegetables, Tetra-hydrofolate Synthesis of Megaloblastic changes Chronic hyperplastic/ Poor intake, Not known
(Pteroylglutamic liver, yeast purine and in haemopoietic and atrophic candidiasis mucosal malabsorption
acid) pyrimidine bases other cells lesions increased
Villus atrophy demands, drugs
Iron Meat Transported as Oxygen transport, Hypochromic, Glossitis, angular Poor diet, None known
transferrin intra-cellular microcytic stomatitis, Burning malabsorption,
respiration anaemia Mouth syndrome, blood loss
Plummer—Vinson sore tongue,
syndrome apthae, candidiasis
Zinc Meat Essential in some Skin lesions None known Inadequate diet Lethargy
Cheese enzyme systems Alopecia acrodermatitis
Wheat Weight loss enteropathica
carcinogenesis, since vitamin E, like α-carotene, is antioxidant and appears to inhibit experimental oral carcinogenesis and, in humans, higher serum vitamin E levels appear associated with a decreased risk of oral cancer.
Vitamin K
Vitamin K is a fat-soluble naphthaquinone derivative found in green vegetables. Malabsorption, parenteral nutrition, and antico- agulants cause deficiency.
The oral mucosal manifestations of vitamin K deficiency can include gingival bleeding and post-extraction haemorrhage.
Folic acid
Folic acid (pteroylglutamic acid) is biologically inactive: folates are the active water-soluble forms. Dietary folate, present in green vegetables, liver, and yeast, is converted to the active tetra- hydrofolate, which is involved in synthesis of purine and pyrimi- dine bases, after absorption in the small intestine. Folate deficiency is typically because of a diet deficient in green vegeta- bles, and can arise within a relatively short period of time, since body stores last less than 3 months. Alcoholism and some cyto- toxic drugs and phenytoin are other relatively common causes of deficiency of folate at the cellular level.
Folate deficiency leads to impaired synthesis and repair of DNA with megaloblastic change in haemopoietic and other cells. Buccal epithelial cells show changes similar to those in vitamin B12 deficiency.
Some patients with chronic hyperplastic candidiasis may be folate deficient. Folate-deficient individuals may also suffer from chronic atrophic candidiasis but the restoration of serum folate to normal levels rarely has any beneficial effect indicating that folate deficiency in itself may not be an aetiological factor.
The oral manifestations of vitamin deficiencies are summarized in Table 11.3.
Iron
Dietary iron is found mainly in meat. Iron is vital to oxygen trans- port and intracellular respiration, being inherent in some enzymes. Most iron is present in haemoglobin; some is stored in macrophages in the liver and spleen as ferritin and haemosiderin. Iron is transported as transferrin.
Deficiency can arise from dietary or absorptive causes, but usu- ally is a consequence of chronic blood loss—typically because of menorrhagia (Table 11.4). Iron deficiency affects rapidly dividing cells such as bone marrow and oral mucosa. A hypochromic microcytic anaemia results. The serum iron and serum ferritin levels are low.
Oral mucosal manifestations of iron deficiency are common and include glossitis, angular stomatitis, and Burning Mouth syndrome. Atrophic glossitis is found in up to 40 per cent of iron deficient patients and angular stomatitis in 15 per cent. About one third of patients have a sore tongue. Manifestations respond within a few weeks to replacement therapy. Aphthae may be seen. Iron deficiency may play a role in the oral carriage of Candida species and may be one reason why oral candidal carriage is more prevalent in females than males.
There is a possible role for iron deficiency in carcinogenesis in view of the premalignant potential of the Plummer–Vinson syn- drome. This syndrome, consisting of iron deficiency, dysphagia and post-cricoid oesophageal stricture may be accompanied by glossitis and angular stomatitis, and may be associated, in up to 15 per cent, with carcinomas of the post-cricoid pharynx, oesophagus, stomach, and occasionally mouth. However, any significant role for iron deficiency in oral carcinogenesis has yet to be established and, in animal models, iron deficiency has had only equivocal effects on chemical oral carcinogenesis.
Zinc
Zinc is involved in several enzyme reactions. Deficiency of zinc is usually dietary, or due to the inherited disorder acrodermatitis enteropathica. It can have many general effects (Table 11.5) but, as far as the oral mucosa is concerned, zinc deficiency does not cause atrophy—at least in animals.