Nutrition and coexisting disease

Nutritional consequences
of disease

Whats 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 (TNF) in
most cachectic states accompanying chronic disease

Abstract
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 lifes 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
anaemia.

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.

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Nutrition and coexisting disease

Magnesium and zinc deficiency may develop, especially with

diabetes renal disease.
Weight gain is often a feature of hypothyroidism, states of
increased (endogenous or iatrogenic) steroid activity (Cushings
disease, tumour-related steroid hormone secretion) and acromegaly. Weight loss can be a presenting feature of hyperthyroidism
and adrenal insufficiency (Addisons disease).

a less reliable indicator of nutritional status in these patients

because of problems with intermittent fluid retention and diuretic
therapy, but the loss of muscle and fat mass that characterizes
cardiac cachexia is usually evident on physical examination. The
under-lying mechanisms are unclear, but perturbations of neuroendocrine and immunological homeostasis driven by poor tissue perfusion (tissue hypoxia) appear to mediate the condition.
Drug-induced side-effects (e.g. anorexia with digoxin, altered
taste with some angiotensin-converting enzyme inhibitors) may
also contribute to weight loss.

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, a distal intestinal obstructive syndrome resulting
from the underlying disease or injudicious use of pancreatic
supplements.
Early diagnosis, 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. Advances in management of the nutritional aspects of the disease have also been valuable, particularly
appropriate use of pancreatic enzyme supplements and involvement of dietitians as core members of the cystic fibrosis multidisciplinary team. Nutritional status is a predictor of mortality in
cystic fibrosis, independent of lung function, and of the outcome
of treatments including lung transplantation.

Chronic inflammatory disease (e.g. rheumatoid arthritis

and connective tissue disease)
Reduced peripheral action of insulin, caused by tumour necrosis
factor a (TNF)-driven disruption of insulin receptor signalling,
may have a role in muscle wasting in RA and other connective tissue diseases. The muscle wasting is often aggravated by reduced
habitual muscle activity and ensuing disuse atrophy. Weight
loss is common at presentation. Weight gain is less common with
steroid-sparing medications. With advanced rheumatoid arthritis, immobility may limit access to food. Temporo-mandibular
disease can restrict food choices, and haematinic deficiencies can
compound the anaemia of chronic diseases.
Chronic renal failure
Under normal circumstances, the body responds to a low-protein
diet by suppressing protein and essential amino acid degradation. The protein metabolism of uraemic patients is characterized
by a pertubation of this normal response, resulting in negative
nitrogen balance and loss of lean body mass. Metabolic acidosis
and low insulin concentration contribute to and compound this
state of negative nitrogen balance. Peritoneal dialysis removes
middle molecules, which include ascorbic acid; replacement is
necessary after dialysis to maintain status.

COPD: the labelling of patients with COPD as pink puffers (thin,

breathless at rest, predominantly emphysema) and blue bloaters (obese, cyanosed and predominantly chronic bronchitic) is
probably too simplistic, but about one-third of COPD patients
suffer clinically evident derangement of nutritional status. As
many as 25% of those with moderately severe COPD suffer
involuntary loss of body weight and/or lean body mass. 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). Poor nutritional status is an independent predictor
of mortality and morbidity, and contributes to reduced exercise
capacity and greater rates of hospital admission for a given level
of lung dysfunction. 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, 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,
b-agonists).

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. (Before
the advent of HAART, 60% of HIV patients exhibited features of
proteinenergy malnutrition, and 80% suffered the condition at
death.) However, wasting with multiple associated nutritional
deficiencies continues to be a striking feature of HIV/AIDS in
developing countries, particularly in Africa and Asia. Protozoal,
bacterial and viral gastrointestinal infections (e.g. cryptosporidiosis, microsporidia, Mycobacterium avium intracellulare, cytomegalovirus) and, sometimes, side-effects of HAART contribute
to poor nutritional status. HIV enteropathy is a cause of malabsorption and weight loss in the absence of any demonstrable
infection in the gut. Other nutritional derangements associated
with HIV include hyperlipidaemia and syndrome X (insulin resistance), and protease inhibitor therapy is associated with a lipodystrophy syndrome.

Cardiac cachexia
In a study of unselected patients with heart failure attending an
out-patient clinic at a referral centre, 16% reported a loss of more
than 7.5% of their pre-morbid body weight. Cardiac cachexia is
associated with a higher mortality; 50% of a cohort of patients
with cardiac cachexia died within 18 months. 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. Successful antituberculous chemotherapy results
in weight gain in as little as the first few weeks of treatment,
and this may be used to confirm a clinical diagnosis. Folic acid
supplementation is necessary with isoniazid.
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Nutrition and coexisting disease

Anticytokine treatment (particularly with anti-TNF agents)

is undergoing extensive trials in disease-related cachectic conditions. It appears to be a promising treatment for the future,
but long-term use may be limited by adverse effects on
immunocompetence.

Stroke
Stroke commonly leads to profound tiredness and depression,
as well as affecting swallowing. More proactive use of enteral
(nasogastric and percutaneous gastrostomy) feeding techniques
have rendered malnutrition less common in patients who have
suffered a stroke. The ethics of refeeding in patients with cerebrovascular disease are a difficult issue, but it is worth noting
that poor nutritional status remains a potentially remediable
cause of poor outcome in stroke.

Further reading
Akner G, Cederholm T. Treatment of protein energy malnutrition in
chronic non-malignant disorders. Am J Clin Nutr 2001; 74: 624.
(A review of the treatments available for improving nutritional
status in patients with chronic disease; extensive references.)
Akner S D, Sharma R. The syndrome of cardiac cachexia. Int J Cardiol
2002; 85: 5166.
(This issue is devoted to cachectic syndromes in chronic illness,
including RA.)
Bruera E, Sweeney C. Cachexia and asthenia in cancer patients. Lancet
Oncol 2000; 1: 13847.
Garrow J S, James W P T, eds. Human nutrition and dietetics.
Edinburgh: Churchill Livingstone, 1999.
Milne A C, Avenell A, Potter J. Meta-analysis: protein and energy
supplementation in older people. Ann Int Med 2006; 144: 3748.
Sridhar M K. Nutrition and lung health. Proc Nutr Soc 1999; 58: 3038.
(A summary of links between nutrition and lung disease.)

Nutrition in the elderly

In the elderly, poor nutritional status can result from a general
deterioration of mental and physical status; loss of taste sensation,
poor mobility, recurrent physical illness and depression all contribute. Malnutrition in the elderly is known to adversely affect
both physical and cognitive abilities, and studies have shown
that, in appropriate cases, nutritional support may improve the
outcome of medical interventions, including rehabilitation after
hip fracture. 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. However, no evidence
was found to support routine supplementation for older people at
home or for well-nourished older patients in any setting.

Management of nutritional depletion in disease

Specific treatment of the conditions discussed above varies, but
there are general principles underlying the management of nutritional depletion in these diseases.

Practice points
When dealing with patients with a chronic illness, ask for a
history of weight loss
Measure body weight at each consultation, using a
standardized, accurate technique and calibrated scales
Consider support from a dietitian, particularly with a view
to obtaining a full and accurate dietary history, enabling
estimation of total calorie and protein intake
Identify correctable impediments to re-nutrition and
regular food intake (e.g. replace emetogenic drugs with
less unpleasant alternatives, supplemental oxygen for
breathlessness on eating, antidepressants for depressionrelated anorexia, antibiotics for sepsis-related catabolic states)
Consider enteral or parenteral nutritional support, taking into
account the increased energy needs arising from the disease
processes in addition to basal energy requirements
If nutritional support is used, it is best to seek the help of a
dietitian; ad libitum use of proprietary supplements without
adequate monitoring is unlikely to be beneficial
Pharmacological measures to stimulate anabolism
(megesterol, growth hormone, 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,
but the evidence that this improves outcome is not uniformly
favourable. Appropriate nutritional support has improved prognosis in some conditions (e.g. cystic fibrosis), but in others (e.g.
cardiac cachexia, RA), evidence for the benefit of supplementary
nutritional therapy alone is equivocal. 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. Recent studies have also indicated a potential role
for creatine supplementation in improving health related quality
of life in patients with COPD.
Hormonal manipulation: progestogens (particularly megestrol),
growth hormone, testosterone analogues and insulin-like growth
factor 1 all have a beneficial impact on nutritional status in
chronic disease, but none has been shown to improve mortality
or morbidity from the underlying illness in large randomized
controlled trials. The long-term safety of hormonal treatment
remains unproven.

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2006 Elsevier Ltd. All rights reserved.