Nutrition and coexisting disease

Nutritional consequences
of disease

What’s new?
• Weight loss is a common problem in patients with
cancer; cancer treatments sometimes contribute to the
cachectic state

Mangalam K Sridhar
M E J Lean

• Malnutrition is now recognized as an adverse prognostic
feature of a wide range of chronic non-malignant
diseases such as COPD, cardiac failure, RA and renal
failure; the mechanisms of weight loss are unclear, but
there is evidence of increased cytokine activity (TNFα) in
most cachectic states accompanying chronic disease

Interest in the impact of nutritional factors on the aetiology of disease
has tended to deflect some attention away from the impact of a wide
range of diseases on nutritional status. Diseases can affect all aspects
of nutritional status: appetite, food consumption and diet quality (‘what
we eat’); body and tissue composition (‘what we are’) and capacity to
utilize and metabolize nutrients (‘what we can do’). Weight loss (even in
overweight people) is an important, but not essential, partner to nutritional depletion. Collectively, these impact physical, mental and social
health, and further reduce resistance to other diseases. Identifying and
correcting impaired nutritional status is necessary to break this spiral in
all branches of medical practice.

• Nutritional support may have a role in the malnutrition
associated with these conditions, though evidence for
improved outcome is available for only a few conditions;
hormonal and anticytokine treatments are under trial

acknowledged that diseases as disparate as cancer, rheumatoid
arthritis (RA), chronic obstructive pulmonary disease (COPD) and
heart failure can, via widely differing mechanisms with a common final pathway, cause a state of nutritional depletion with an
adverse effect on functional capacity and on the prognosis of the
underlying illness. This contribution identifies common diseases
that result in nutritional depletion and suggests how they can be
managed. Malabsorption from disorders of the gastrointestinal
tract is discussed in MEDICINE 31:1, 28.

Keywords cancer cachexia; cardiac cachexia; chronic renal failure;
COPD; malnutrition; nutrition; stroke; supplementation

Nutritional status has three components which interact within an
individual. Disease affects the balance of these components.
• What we are (body composition).
• What we eat (internal and external factors).
• What we can do (functional capacity).
 Our functional capacity includes the capacity to obtain foods, to
swallow, absorb, digest and metabolize nutrients. It also includes
all life’s functions which define health including immune function. Impaired nutrition status thus inevitably affects health. Disease, in any body system, has independent effects on what we
eat and what we can do, with the obvious potential for setting up
a vicious cycle of ill-health.
The medical consequences of deranged nutritional status (particularly obesity) have been well studied, but it is only recently
that much attention has been given to the reverse impact of diseases of different organ systems on nutritional status. It is now

Nutritional effects of disease
Cancer cachexia
More than 50% of patients with cancer suffer involuntary weight
loss of more than 5% of body weight over a 6-month period.
Patients with solid tumours are more commonly affected than
those with haematological malignancies. Weight loss is a common presenting symptom of cancer (e.g. in 80% of patients with
upper gastrointestinal tract cancer and 60% with lung cancer).
Cancers can affect both nutrient intake and absorption and also
nutrient utilisation and losses. Cancers may affect the GI tract
directly, but also Involve an inflammatory state. Cytokines produced by the tumour cause anorexia and disrupt intermediate
metabolism, resulting in proteolysis and lipolysis independent of
food intake. The resulting state of nutritional depletion is often
compounded by nausea and vomiting induced by chemotherapy
and radiotherapy, side-effects of other drugs including opiates
(nausea, constipation, altered taste), and depression-induced
aversion to food. Certain chemotherapeutic drugs require folic
acid supplementation. Fatigue, a common and debilitating feature of many cancers, is closely related to weight loss as well as

Mangalam K Sridhar PhD FRCP FRCP(Ed) was Consultant Physician with
Hammersmith Hospitals NHS Trust at Charing Cross Hospital, and
Honorary Senior Lecturer at Imperial College, London, UK. He trained
in respiratory medicine and completed a PhD in Human Nutrition in
Glasgow. Dr Sridhar died tragically young in June 2006. Competing
interests: none declared.

Endocrine disorders
Weight loss including loss of both muscle and fat mass is a
­common presenting feature of type 1 diabetes, and insulin
­therapy in both type 1 and type 2 disease often results in weight
gain. Sulfonylureas and glitazones can also induce weight gain.

M E J Lean MA FRCP is Professor of Human Nutrition at the University of
Glasgow, UK, and Honorary Consultant Physician at Glasgow Royal
Infirmary. Competing interests: none declared.



© 2006 Elsevier Ltd. All rights reserved.

cytomegalovirus) and. The protein metabolism of uraemic patients is characterized by a pertubation of this normal response. Temporo-mandibular disease can restrict food choices. HIV enteropathy is a cause of malabsorption and weight loss in the absence of any demonstrable infection in the gut. 60% of HIV patients exhibited features of protein–energy malnutrition. Chronic inflammatory disease (e. Metabolic acidosis and low insulin concentration contribute to and compound this state of negative nitrogen balance. immobility may limit access to food. cryptosporidiosis.g. antibiotic therapy and physiotherapy for respiratory sepsis have had a major role in improving the prognosis of cystic fibrosis – life expectancy for an affected child born in the 1990s is about 40 years. 16% reported a loss of more than 7. sometimes. but about one-third of COPD patients suffer clinically evident derangement of nutritional status. and of the outcome of treatments including lung transplantation. causing extrinsic pressure on the stomach that results in a feeling of satiety at lower levels of food intake • thermogenesis induced by diet and drugs (theophyllines. the body responds to a low-protein diet by suppressing protein and essential amino acid degradation. side-effects of HAART contribute to poor nutritional status. particularly appropriate use of pancreatic enzyme supplements and involvement of dietitians as core members of the cystic fibrosis multidisciplinary team. As many as 25% of those with moderately severe COPD suffer involuntary loss of body weight and/or lean body mass. Advances in management of the nutritional aspects of the disease have also been valuable. Chronic renal failure Under normal circumstances. . Peritoneal dialysis removes ‘middle molecules’. microsporidia. Folic acid supplementation is necessary with isoniazid. The under-lying mechanisms are unclear. wasting with multiple associated nutritional deficiencies continues to be a striking feature of HIV/AIDS in developing countries.g. (Before the advent of HAART. caused by tumour necrosis factor a (TNFα)-driven disruption of insulin receptor signalling. Nutritional status is a predictor of mortality in cystic fibrosis. The muscle wasting is often aggravated by reduced habitual muscle activity and ensuing ‘disuse atrophy’. With advanced rheumatoid arthritis. Total body weight (and body mass index measures based on this value) may be MEDICINE 34:12 Tuberculosis: weight loss is very often a presenting symptom of tuberculosis. Weight loss is common at presentation. 531 © 2006 Elsevier Ltd. Weight loss is related less to the severity of airflow obstruction (forced expiratory volume in 1 second) than to loss of gas exchange (as demonstrated by a decrease in diffusing capacity and transfer coefficient). Factors contributing to the state of negative energy balance in weight-losing patients include: • increased energy costs of breathing • metabolic costs of respiratory tract infections • breathlessness caused by the act of eating • hyperinflation of the lungs. Respiratory disorders Cystic fibrosis: potential causes of malnutrition in cystic fibrosis are: • the pancreatic insufficiency that causes malabsorption • reduced food intake as a result of gastro-oesophageal reflux • the state of wasting associated with the lung disease • occasionally. Weight gain is less common with steroid-sparing medications. All rights reserved. especially with diabetes renal disease. Mycobacterium avium intracellulare. replacement is necessary after dialysis to maintain status. may have a role in muscle wasting in RA and other connective tissue diseases. Protozoal. Poor nutritional status is an independent predictor of mortality and morbidity. Drug-induced side-effects (e. HIV and tuberculosis HIV: the availability of highly-active antiretroviral therapy (HAART) in developed countries has dramatically reduced the incidence of nutritional depletion in HIV/AIDS disease.5% of their pre-morbid body weight. particularly in Africa and Asia. but the loss of muscle and fat mass that characterizes cardiac cachexia is usually evident on physical examination. Other nutritional derangements associated with HIV include hyperlipidaemia and syndrome X (insulin resistance). Cardiac cachexia is associated with a higher mortality. breathless at rest. b-agonists).Nutrition and coexisting disease Magnesium and zinc deficiency may develop. bacterial and viral gastrointestinal infections (e. Weight loss can be a presenting feature of ­hyperthyroidism and adrenal insufficiency (Addison’s disease). and protease inhibitor therapy is associated with a lipodystrophy syndrome. which include ascorbic acid. predominantly emphysema) and ‘blue bloaters’ (obese.  Early diagnosis. altered taste with some angiotensin-converting enzyme inhibitors) may also contribute to weight loss. rheumatoid arthritis and connective tissue disease) Reduced peripheral action of insulin. and 80% suffered the condition at death.) However. and haematinic deficiencies can compound the anaemia of chronic diseases. Weight gain is often a feature of hypothyroidism. 50% of a cohort of patients with cardiac cachexia died within 18 months.g. a distal intestinal obstructive syndrome resulting from the underlying disease or injudicious use of pancreatic supplements. tumour-related steroid hormone secretion) and acromegaly. Cardiac cachexia In a study of unselected patients with heart failure attending an out-patient clinic at a referral centre. a less reliable indicator of nutritional status in these patients because of problems with intermittent fluid retention and diuretic therapy. independent of lung function. anorexia with digoxin. resulting in negative nitrogen balance and loss of lean body mass. COPD: the labelling of patients with COPD as ‘pink puffers’ (thin. states of increased (endogenous or iatrogenic) steroid activity (Cushing’s disease. and this may be used to confirm a clinical diagnosis. cyanosed and predominantly chronic bronchitic) is probably too simplistic. but perturbations of neuroendocrine and immunological homeostasis driven by poor tissue perfusion (tissue hypoxia) appear to mediate the condition. Successful antituberculous chemotherapy results in weight gain in as little as the first few weeks of treatment. and contributes to reduced exercise capacity and greater rates of hospital admission for a given level of lung dysfunction.

Ann Int Med 2006. but long-term use may be limited by adverse effects on ­immunocompetence. eds. and studies have shown that. All rights reserved.g. Treatment of protein energy malnutrition in chronic non-malignant disorders. but none has been shown to improve ­mortality or morbidity from the underlying illness in large randomized controlled trials. Sweeney C. poor mobility. ◆ Stroke Stroke commonly leads to profound tiredness and depression. Meta-analysis: protein and energy supplementation in older people. Management of nutritional depletion in disease Specific treatment of the conditions discussed above varies. Further reading Akner G. James W P T. poor nutritional status can result from a general deterioration of mental and physical status. Garrow J S. enabling estimation of total calorie and protein intake • Identify correctable impediments to re-nutrition and regular food intake (e. Hormonal manipulation: progestogens (particularly megestrol). Nutrition and lung health. Avenell A. More proactive use of enteral (nasogastric and percutaneous gastrostomy) feeding techniques have rendered malnutrition less common in patients who have suffered a stroke. but in others (e. Potter J.g. The syndrome of cardiac cachexia. Human nutrition and dietetics. Edinburgh: Churchill Livingstone. Appropriate nutritional support has improved prognosis in some conditions (e. Proc Nutr Soc 1999.Nutrition and coexisting disease Anticytokine treatment (particularly with anti-TNF agents) is undergoing extensive trials in disease-related cachectic conditions. as well as affecting swallowing. A large Swedish study and a meta-analysis has shown that oral nutritional supplements can improve nutritional status and seem to reduce mortality and complications for undernourished elderly patients in the hospital. taking into account the increased energy needs arising from the disease processes in addition to basal energy requirements • If nutritional support is used. accurate technique and calibrated scales • Consider support from a dietitian. Recent studies have also indicated a potential role for creatine supplementation in improving health related quality of life in patients with COPD. including RA. extensive references. Lancet Oncol 2000. in appropriate cases. no evidence was found to support routine supplementation for older people at home or for well-nourished older patients in any setting.) Bruera E. Nutritional supplements provided in conjunction with exercise therapy and other rehabilitation measures appear to have a more beneficial effect than supplementation alone in conditions such as cardiac and respiratory cachexia.) Akner S D. 85: 51–66. 58: 303–8. nutritional support may improve the outcome of medical interventions. MEDICINE 34:12 532 © 2006 Elsevier Ltd. (This issue is devoted to cachectic syndromes in chronic illness. including rehabilitation after hip fracture. cardiac cachexia. cystic fibrosis). ad libitum use of proprietary supplements without adequate monitoring is unlikely to be beneficial • Pharmacological measures to stimulate anabolism (megesterol. 144: 37–48. Am J Clin Nutr 2001. particularly with a view to obtaining a full and accurate dietary history. However. Int J Cardiol 2002. but the evidence that this improves outcome is not uniformly favourable. anticytokine agents) can be used under specialist supervision or as part of a clinical trial Nutritional supplementation (enteral or parenteral) may seem an appropriate treatment for malnutrition in chronic disease. Sharma R. It appears to be a promising treatment for the future. recurrent physical illness and depression all contribute. replace emetogenic drugs with less unpleasant alternatives. 1999. evidence for the benefit of supplementary nutritional therapy alone is equivocal.) Nutrition in the elderly In the elderly. (A summary of links between nutrition and lung disease. but there are general principles underlying the management of nutritional depletion in these diseases. RA). The ethics of refeeding in patients with cerebrovascular disease are a difficult issue. 1: 138–47. it is best to seek the help of a dietitian. . growth hormone. antidepressants for depressionrelated anorexia. antibiotics for sepsis-related catabolic states) • Consider enteral or parenteral nutritional support. Practice points • When dealing with patients with a chronic illness. supplemental oxygen for breathlessness on eating. Cederholm T. Cachexia and asthenia in cancer patients. (A review of the treatments available for improving nutritional status in patients with chronic disease. The long-term safety of hormonal treatment remains unproven. Malnutrition in the elderly is known to adversely affect both physical and cognitive abilities. 74: 6–24. loss of taste sensation. using a standardized. but it is worth noting that poor nutritional status remains a potentially remediable cause of poor outcome in stroke. Milne A C. Sridhar M K. growth hormone. testosterone analogues and insulin-like growth factor 1 all have a beneficial impact on nutritional status in chronic disease.g. ask for a history of weight loss • Measure body weight at each consultation.