Appetite and appetite stimulants CLARE SHAW, BSc, SRD, Chief Dietitian, The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK

SHAW C. (1993) European lournal of Cancer Care 2, 121-124 Appetite and appetite stimulants

Poor appetite is a common symptom among cancer patients. It can lead to inadequate food intake, weight loss, physical debilitation and reduced tolerance to anti-neoplastic treatment. Although cancer-induced anorexia is not fully understood, there are some theories relating to its development. Interventions may be aimed at improving nutritional intake to prevent excessive weight loss when poor appetite exists, or it may concentrate on improving appetite by pharmacological means. Appetite should be considered alongside other aspects of symptom control and tackled aggressively when it is contributing to a poor quality of life.

Keywords: cancer and appetite, appetite stimulants, quality of life in cancer.

Appetite is defined by the Oxford English Dictionary as the desire, inclination, natural craving or one’s relish for food.

When examining appetite, it is useful to consider other words which are involved in the complicated picture of eating behaviour. Hunger often refers to the sensation of needmg food, but without the desire or inclination that the word appetite depicts. Satiety is the feeling of satisfaction that is usually associated with the cessation of food intake, whilst anorexia is the absence of appetite. Many of these terms are used when considering the nutri- tional intake and nutritional status of cancer patients.

Control of appetite withn the body is complex and not fully understood. The hypothalamus appears to be the main centre in the brain controlling intake of food and drink. In the early days of research, it was proposed that within the hypothalamus there was a feeding centre, the lateral hypothalamic area, and a satiety centre, the ventromedial nucleus. Ths is now thought to be an c-versimplification of the method of control, but it is

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European Iournal of Cancer Care. 1993, 2, 121-124

accepted that fluctuating levels of neurotransmitters within the hypothalamus are responsible for dluencing the desire to eat (Williams, 1991). Much of this work has been camed out in animal experimentation, where neurotransmitters such as serotonin, beta-endorphin and neuropeptide-Y have been studed.

Levels of neurotransmitters in the brain may alter in response to nerve impulses arriving from the gastrointest- inal tract or the higher centres of the brain, such as the cer- ebral cortex. These inputs from higher centres of the brain can cause mood, indwidual and cultural attitudes, and learned aversions to food to d u e n c e appetite profoundly.

Nutrients within the plasma, such as glucose, amino acids and free fatty acids, may cross the blood-brain barrier, inhibiting or stimulating the formation of neurotransmitters. Hormones such as insulin, produced by the pancreas, and cholecystikinin, one of the peptides produced by the small intestine, are also thought to cross into the hypothalamus and influence appetite. The latter is thought to transmit information to the brain, via the vagus nerve, to modulate behavioural processes related to meal-termination and satiety. Meal size can be reduced when cholecystokinin is administered to both humans and animals (Leibowitz, 1992).

SHAW Appetite and appetite stimulants

Although the control of appetite is complex, many people manage to maintain a food intake level to meet their dietary requirements without huge changes in body weight. It is now well recognized that, in cancer patients, control of appetite may be impaired and that patients may become anorexic. The actual mechanisms involved are not known, but theories surrounding the anorexia of cancer cachexia centre largely on the alterations of nutrients within the plasma-particularly tryptophan. The dietary amino acid tryptophan is a precursor of serotonin or 5- hydroxytryptamine. As a cancer causes plasma albumen to fall, more tryptophan may exist within the plasma as free tryptophan due to a decrease in the bindmg of tryptophan to albumen. Tryptophan taken up in the brain, may be converted to serotonin and, in animal experiments, it has been shown that a rise in brain serotonin is associated with anorexia (Krause et al., 1981 ).

Much interest has arisen in the control and role of cytokine production. In cancer patients cytokines, such as tumour necrosis factor (TNF) and interleukm 1, may act to induce anorexia or may act by stimulating other cytokines such as interleuh-6. Experimental use of cytokmes as biological therapies confirm that these substances have strongly anorexic properties (Gelin &. Lundholm, 1991). Animal experiments have suggested that cytokines may impair the activity of neuropeptide Y, a stimulant of feeding behaviour, and lead to the decrease of appetite in tumour-bearing animals (McCarthy et a]., 1993). In addition to possible metabolic causes for anorexia, anti- cancer treatment may also contribute to loss of appetite and a poor food intake level.

After briefly considering the mechanisms of appetite control, it is necessary to consider how important appetite is to the cancer patient. In 1981, a study in Ramsey County, Minnesota, reveals that 84% of cancer patients questioned experienced loss of appetite; 58% nausea and vomiting; 48% dry mouth; and 48% difficulty in swallowing (Gallagher-Allred, 1989). Other studies have reported 40-50% of cancer patients experiencing anorexia and 28% of patients reported that loss of appetite was a symptom of their disease which caused major distress (Von Meyenfeldt et al., 1988). It is apparent from such stuhes that appetite and problems associated with eating are perceived by patients as being major factors which inhibit a normal lifestyle.

When anorexia is present, it is important to identlfy whether the problem is the patient’s, the family’s or both. Often, the patient’s anorexia is more problematic for the family than for the patient h s e l f (Holden, 1991 ). It is the weight-loss associated with anorexia that is often of more c,oncem to the patient, as this may contribute to poor mobhty, apathy in rehabilitation, increased risk of

pressure sores and the reinforcement of the perception of being a weight-losing cancer patient. Identdying how patients feel about appetite, enables us to describe two categories of cancer patients.

THE PATIENT WHO CANNOT OR WILL NOT EAT

For this patient, the loss of appetite is a source of anxiety and conflict within the family. An American study identified that the care-giver’s anxiety is usually more pronounced in the female than the male carer, and that the intake of food and fluid taken is used as a barometer of the patient’s overall condltion (Holden, 1991 1. Patients who fall into this category find anorexia of less concern than other problems and would prefer to have their farmly members focus less energy on encouraging them to eat. It may be more appropriate to offer the patient little or even no food unless he requests it. The family and carers need to be supported throughout this shh towards acknowl- edging the patient’s comfort and needs. This is most appropriate in patients with an advanced stage of the disease for whom the burdens of eating and drinking may outweigh the benefits of doing so.

THE PATIENT WHO CAN AND WANTS TO EAT, BUT HAS DIFFICULTY EATING SUFFICIENT AMOUNTS

Such patients may be helped to eat, and the importance of improving appetite and enabling them to eat better cannot be overestimated.

If anorexia is due to correctable causes and the patient has a predlcted Me expectancy of several months, the correctable causes should be treated aggressively. Treat- ment should also be aggressive when anorexia appears to be an isolated symptom, and the consequence is malnu- trition that could compromise the quality and quantity of the patients’ remaining days.

DIETARY INTERVENTION

Dietary advice as a means of intervention has not been shown to improve appetite, but may help the patient achieve a better energy intake without necessanly advocating large portions of food. Advice can be given concerning the frequency of eating, with small meals taken more frequently, often providing a more acceptable method of achieving a moderate food intake level. Ths may be particularly important when the patient experi- ences early satiety, defined as the desire to eat, but the inability to eat more than a few mouthfuls (Theologides,

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1976). Patients may report that they fill easily, despite having a good initial appetite. Up to 62% of cancer

the oesophagus into my stomach and literally at that moment perceived a keen appetite. (Pavlov, 1910)

patients may experience this eating difficulty (Annes et al., 1992).

Current healthy eating guidelines are not appropriate for the palliative-care patient with a poor appetite. A low fat, low sugar, high-fibre diet provides food that is bulky and has a low energy density. Patients may be discouraged from using low fat or low calorie foods and, therefore, obtain the maximum amount of energy from small portions of appropriate food. Practical advice concerning specific eating difficulties, such as a dry mouth, chewing or swallowing problems, weight loss or early satiety, can be obtained from a number of booklets aimed specifically at cancer patients (Royal Marsden Hospital Patient Information Series, 1989; BACUP, 1992). Referral to a hetitian may help patients with a particularly poor food intake as dietary advice may be tailored to the patient’s likes and dislikes. Advice may also be given on appropriate and imaginative ways of u s i n g dletary supplements, many of which may be prescribed for cancer cachexia.

Although le tary advice may help to improve energy

To date, there are no studies demonstrating that alcohol promotes appetite or weight gain in the terminally ill. Studies have also failed to show that ethanol can stimulate appetite. In large quantities ethanol may actually depress appetite (Davidson & Passmore, 1986). However, when people take alcohol as an alcoholic beverage not as ethanol alone, there do seem to be advantages. Experiments examining the drinking of alcoholic beverages have often failed to show an increased food intake, but they have demonstrated that alcohol adds calories to meals and does not displace them (Kerr, 1992). Alcoholic drinks do, indeed, stimulate gastric acid secretion and this may be associated with an urge to eat, although accurate data on this subject is laclung. Psychological factors are probably the most important when considering alcohol as an appetite stimulant. Eating is a socially facilitated beha- viour and, for some patients, an alcoholic beverage may help to provide a convivial atmosphere, which in turn may enhance food intake.

intake and, therefore, help prevent further weight loss, it is often appetite itself which is considered of most importance by the patient. It may, therefore, be appro- priate to use appetite stimulants to help the patient‘s desire to eat.

Medication

Steroids, such as dexamethasone, may be used in low doses to stimulate appetite (Loprinzi et al., 1992). More

APPETITE STIMULANTS

recently, there has been the use of megetrol acetate and medroxyprogesterone acetate. These drugs are used in the treatment of hormone-responsive tumours, such as breast

Alcohol or prostate cancer. They were noted to cause weight gain

The use of alcohol as an appetizer dates back to the eighteenth century, although early literature suggests that alcoholic aperitifs work non-specifically ‘through sheer force of habit or perhaps imagination’. Ivan Pavlov’s work on dlgestion in the early 1900s included a few comments on the appetite enhancing effect of alcohol (Kerr, 1992). First, he claimed that alcohol prior to a meal ‘assists in alleviating the pressing strain of daily anxieties’ (Pavlov W Thompson, 1910). Secondly, he claimed that the presence of bitter or sour substances in certain beverages improved appetite by gustatory stimulation. Thirdly, by inference, the sight of a desired beverage and its brief irritating action on gastrointestinal mucosa could provoke both salivary flow and gastric secretion, which in turn could cause a desire to eat. After an illness which caused him to lose his appetite, Pavlov experimented on himself to see the effects of alcohol

Fearing that I should break down, I resolved . . . to en- deavour to create an appetite by swallowing a mouthful of wine. 1 felt it quite distinctly pass along

in such patients and, as a result, their use in palliative-care patients was examined. A number of studies have shown the benefit of megestrol acetate or medroxy progesterone acetate over a placebo to improve appetite, subjective energy levels, well-being and objective anthropometric measurements, such as weight and skin-fold thickness. The drug appears to be well tolerated with few side-effects and, therefore, provides a useful tool in persistently anorexic patients (Bruera, 1990; Tchekmedyian et a]., 1992).

Animal studies have suggested that the next step forward in the development of appetite stimulants may be in drugs that alter the level of brain serotonin. Blocking the rise in brain serotonin may provide a way of stimulating appetite in cancer-induced anorexia (Lee & Clifton, 1992).

Vitamins

Thiamin (vitamin B1) has been shown to enhance appetite in elderly women who were marginally thiamin-deficient.

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Although this study did not recruit cancer patients; vitamin status should be considered in patients who have had a poor dietary intake for any period of time (Smidt et a]., 1991). An unpublished study carried out at The Royal Marsden Hospital showed the value of a multivitamin supplement in improving appetite, when given to anorexic cancer patients for a period of 4 weeks.

Loss of appetite is a troublesome symptom experienced by the majority of cancer patients. It is often seen as a certain sign of impending death and a source of consider- able anxiety. Good symptom control of pain, nausea, vomiting and other gastrointestinal complaints in addition to psychological support may go a long way to improve appetite. For those patients who continue to be persis- tently anorexic, there are clearly other means at our dis- posal to try and overcome this distressing symptom. The palhative-care team should approach this subject sensi- tively to ensure that it does not become a burden to the patient, but that both patient and care-givers are aware that anorexia may be tackled along with other symptoms. Appetite should only be as important to us as it is to the palliative-care patient, but for those who enjoy eating, the aim is that they continue to do so for as long as is possible.

References

Armes P. J., Plant H. J., Allbright A., Silverstone T. and Slevin M.L. [ 1992) A study to investigate the incidence of early satiety in pa-tients with advanced cancer. British Iournal of Cancer, 65, 481484.

BACUP (1992) Diet and the Cancer Patient. Available from BACUP, 3 Bath Place, Rivington Street, London EC2A 3JR.

Bruera E., Macmillan K., Kuehn N., Hanson J. & MacDonald R.N. (1990) A controlled trial of megestrol acetate on appetite, caloric intake, nutritional status and other symptoms in patients with advanced cancer. Cancer, 66, 1279-1282.

Davidson S. and Passmore R. (1986) In: Human Nutrition and Dietetics (ed. R. Passmore and M.A. Eastwood), p. 73. Churchill Livingstone, London.

Gallagher-Allred C.R. (1989) Nutritional care of the terminally ill. Aspen Publications Inc. Maryland.

Gelin J. & Lundholm K. (1991) Cancer cachexia, what are the mediators? Topics on Supportive Care in Oncology, 3,4-5.

Holden C.M. (1991) Anorexia in the terminally ill cancer patient: the emotional impact on the patient and family. Hospital Journal, 7[3), 73-84.

Kerr D. (1992) Alcohol and palliative care. Palliative Medicine, 6,

Krause R., Humphrey C., von Meyenfeldt M., James H. & Fischer J.E. (1981) A central mechanism for anorexia in cancer: A hypothesis. Cancer Treatment Reports, 65, Suppl5, 15-21.

Lee M.D. & Clifton P.G. (1992) Partial reversal of fluoxetine anorexia by the 5-HT antagonist metergoline. Psychopharma- cology (Berlin), 107, 359364.

Leibowitz S.L. [ 1992) Neurochemical-neuroendocrine systems in the brain controlhg macronutrient intake and metabolism. Trends in Neurosciences, 15, 491497.

Loprinzi C.L., Goldberg R.M. & Bumham N.L. (1992) Cancer associated anorexia and cachexia. Implications for drug therapy. Drugs, 43, 499-506.

McCarthy H.D., McKibbin P.E., Perkins A.V., Linton E.A. & Williams G. (1993) Alterations in hypothalmic neuropeptide Y and cortioctrophin-releasing factor in anorexic tumour-bearing rats. American Journal of Physiology, 264, E638-E643.

Pavlov I. & Thompson W. (1910) The Work of the Digestive Glands.

Smidt L.J., Cremin F.M., Grivetti L.E. & CMord A.J. (1991) Influence of thiamin supplementation on the health and general well-being of an elderly Irish population with mar- ginal thiamin deficiency. Iournal of Gerontology,46, M16-22.

Theologides A. (1976) Anorexia-producing intermediary metabo- lites. American Journal of Clinical Nutrition, 29, 552-558.

Royal Marsden Hospital Patient Information Series 1989. Over- coming Eating Difficulties: a guide for cancer patients No 9. Available from Haigh and Hochland Ltd, International University Bookshelves, The Precinct Centre, Oxford Road, Manchester M13.

Tschekmedyian N.S., Hickman M., Siau J., Greco F.A., Keller J., Browder H. & Aisner J. (1992) Megestrol acetate in cancer anorexia and weight loss. Cancer, 69, 1268-1274.

Der Aalst A.C.M.J. & Soeters P.B. (1988) The management of weight loss and malnutrition in cancer patients. Bailliere's Clinical Gastroenterology, 2, 869-885.

Williams G., McKibbin P.E. & McCarthy H.D. (1991) Hypotha- lamic regulatory peptides and the regulation of food intake and energy balance: signals or noise? Proceedings of the Nutrition Society, 50, 527-544.

183-201.

Von Meyenfeldt M.F., Fredriv E. W.H.M., Haagh W

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