The hallmark of catabolic Involuntary Weight Loss (IWL) is the massive depletion of lean body tissue, which includes muscles, internal organ tissues, blood cells and intracellular and extracellular water. Cancer cachexia and AIDS wasting are but two examples of particularly devastating forms of IWL that compromise quality of life, decrease survival and increase complications and costs of healthcare. If patients with chronic obstructive pulmonary disease (COPD) with weight loss are included, greater than 5 million Americans will be defined as suffering from significant IWL in 2003. This number escalates significantly with the addition of those who experience the age-related weight loss condition known as geriatric sarcopenia.
The loss of lean muscle or tissue contributes to fatigue, impaired functionality in daily activities, deficient immunity and a broad spectrum of conditions that can compromise an individual’s ability to fight the underlying disease and tolerate its treatment. Significant weight loss and specifically, lost muscle, is one of the best predictors of survival in diseases such as cancer, HIV/AIDS, COPD, and in a number of conditions relating to the elderly.
Sudden Weight Loss
Involuntary or unintentional weight loss may be obvious, as in advanced cancer or AIDS, or can be more subtle and insidious. Since two-thirds of US adults are estimated as being overweight or obese, IWL – which is predominantly the loss of muscle or lean body mass – can be ‘hidden’ until reaching an advanced stage. Clinicians are now beginning to understand the devastating effects that IWL can have on patients and have started to refer to this condition as the forgotten ‘vital’ sign.
References:
1.Iannuzzi-Sucich M, Prestwood KM, Kenny AM. “Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women.” J Gerontology A Biological Science Medical Science 2002; 57: M772-7 and, Roubenoff R. “Sarcopenia and its implications for the elderly”. European Journal of Clinical Nutrition, 2000 June; 54 Supplement 3:S40-7.
2.http://www.obesity.org/subs/fastfacts/obesity_US.shtml
The Forgotten “Vital” Sign
Standard ‘vital’ signs for a medical evaluation include temperature, pulse, blood pressure and respiration. They allow the clinician to assess the evident measures or ‘vitality’ of life. And while the ‘vitality’ of the patient may not be ‘measurable’ as such, the appearance of a person experiencing progressive weight loss is usually obvious to any observer – clinician, family or friend.
“Physicians tend to overlook involuntary weight loss while focusing on other more pressing aspects of disease, such as tumor size and metastases in patients with cancer, or viral load and the presence of other infections in AIDS patients. That is why it is appropriately called the “forgotten ‘vital’ sign,” said Dr. Jamie Von Roenn, MD, Professor of Medicine, Northwestern University, Division of Hematology/Oncology, and Department of Medicine Chicago, IL. “Some clinicians may take observable weight loss into account, but they don’t distinguish between the losses of fat versus muscle. The measurement of lean body mass loss and its significance to patient survival is critical to evaluating the whole patient and designing an appropriate treatment regimen,” she added.
The loss of lean muscle or tissue contributes to fatigue, impaired functionality in daily activities, deficient immunity and a broad spectrum of conditions that can compromise an individual’s ability to fight the underlying disease and tolerate its treatment. Significant weight loss and specifically, lost muscle, is one of the best predictors of survival and risk for complication in diseases such as cancer, HIV/AIDS, COPD, and in a number of conditions relating to the elderly.
Recognizing Involuntary Weight Loss
Weight loss and malnutrition can be a strong prognostic factor in a variety of diseases. Attention to weight loss early in the diagnoses of these diseases can help delay this devastating syndrome, and perhaps prevent it altogether. That’s why it’s so important for doctors to remember to pay close attention to this “vital” sign.
Beyond issues of complications and death, IWL impacts both the patient and family. People with IWL often complain that they don’t “feel like themselves.” When they look in a mirror, the frail, skeletal appearance – thin arms and legs, drawn faces and sunken cheeks and eyes – is a constant reminder that they are facing a potentially deadly disease. Depression, a loss of self-esteem and self-confidence are often the result in the change in body shape. People who are depressed and fatigued are less inclined to take steps to improve their health, such as preparing and eating regular nutritious meals and exercising.
Causes of Involuntary Weight Loss
The mechanism associated with IWL can vary from disease to disease and among individuals. In general, however, there are two main factors responsible for progressive IWL:
- Inadequate intake of protein and calories to meet the requirements of the individual.
This decrease in intake can be due to poor appetite (anorexia), or impediments to intake such as problems with swallowing, digestion or absorption. Decreased intake can result from a patient’s disease and/or treatment. For example, in patients with cancer, swallowing may be a problem due to tumors in the mouth, throat or other parts of the gastrointestinal tract. In other cases, powerful treatments, such as radiation and surgery, and side effects from chemotherapeutic or AIDS drugs, can result in nausea and vomiting and a diminished appetite. These conditions make it impossible to take in the nutrients the patient needs. - Metabolic changes in the patient.
If intake was the whole picture in IWL related to cancer and AIDS, patients would recover if they somehow were given more calories, either through more appetizing meals or tube feeding. But increasing calories and protein alone seldom helps. Metabolic changes can occur in a number of medical conditions and by a variety of different mechanisms. Such changes can be mediated by hormones or by hormone-like proteins made by the body in response to specific conditions such as presence of infection, severe trauma or injury, cancer, or other catabolic conditions. These substances modulate a number of different types of cell functions and are often associated with decreases in muscle and other protein synthesis and/or increases in muscle or protein breakdown. One of the major effects of these metabolic changes is a disproportionate loss of muscle.
Risks of Involuntary Weight Loss
Weight loss itself can be deadly, especially lean body mass (LBM). Loss of about 40% of LBM can be fatal because LBM is the site of 99% of the body’s metabolic functions. Several reports have consistently found that as many as one in five patients with cancer will die from weight loss, malnutrition and its complications. Despite the appreciation of weight loss as a prognostic factor (of health) for more than seven decades, only recently is there a growing understanding of the science of involuntary weight loss and therapeutic options. In the 1930s, IWL of more than 10% was noted to increase complications and risk of death in surgical patients. In the 1970s, this was quantified with 10% loss as significant if it occurred within a period of six months with similar risks of 7.5% loss in three months, 5% in one month or 2% loss in one week. Work in AIDS has shown similar findings, with adverse outcomes with weight loss as little as 3%.
IWL in small amounts is significant for a number of reasons. The significant loss of lean body mass may complicate medical conditions which include decreased muscles required for breathing and coughing, decreased extremity muscle mass and function, decreased immunity and less functional organs with impaired tolerance of medications used to treat the underlying diseases.
Beyond issues of complications and death, IWL impacts both the patient and family. People with IWL often complain that they “don’t feel like themselves.” When they look in a mirror, the frail, skeletal appearance—thin arms and legs, drawn faces and sunken cheeks and eyes—is a constant reminder that they are facing a potentially deadly disease. Depression, a loss of self-esteem and self-confidence, is often the result in the change in body shape. People who are depressed and fatigued are less inclined to take steps to improve their health, such as preparing and eating regular nutritious meals and exercising.
Involuntary Weight Loss FAQ
1. What is involuntary weight loss?
Cancer cachexia and AIDS wasting are but two examples of particularly devastating forms of involuntary weight loss (IWL) that result in compromised quality of life, decreased survival, increased complications and increased costs of healthcare. This loss of functional tissue contributes to fatigue, impaired functionality in daily activities, deficient immunity and a broad spectrum of conditions that can compromise an individual’s ability to fight the underlying disease and tolerate its treatment.
Beyond issues of complications and death, IWL impacts both the patient and family in terms of ‘quality of life.’ People with IWL often complain that they “don’t feel like themselves”. When they look in a mirror, the frail, skeletal appearance—thin arms and legs, drawn faces and sunken cheeks and eyes—is a constant reminder that they are facing a potentially deadly disease. Depression, a loss of self-esteem and self-confidence are often the result of the change in body shape. People who are depressed and fatigued are less inclined to take steps to improve their health, such as preparing and eating regular nutritious meals and exercising.
2. How often do patients experience involuntary weight loss?
Given the numbers of individuals with just three conditions—cancer, chronic obstructive pulmonary disease (COPD) and AIDS—IWL is experienced by more than five million Americans in a given year. This does not include the numbers of individuals older than 65 years who experience moderate to severe geriatric sarcopenia (muscle deficiency) and those with major trauma.
For cancer, it is estimated that more than 1.3 million Americans will be newly diagnosed during 2003 and approximately 560,000 will die of their cancer or its complications. While estimates vary, 60-90% of patients with cancer will experience significant weight loss at some point during the course of their cancer.
It is estimated that there are approximately 16 million people with COPD while prevalence of significant IWL in this group is estimated to be approximately 25%. This translates to approximately 4 million people with significant IWL.
While the number of people in the U.S. who are HIV+ or who have AIDS is significantly smaller than those with cancer or COPD and while weight loss in this population is a less obvious problem in the US today than in the 1980s and early 1990s, in HIV/AIDS patients, IWL is still seen—even in the era of highly active antiretroviral therapy. It is estimated that approximately 18% of HIV/AIDS patients experience significant IWL. Furthermore, loss of lean body mass (LBM) is observed in people with HIV/AIDS, even if individuals have weight that is stable or increased.
3. Isn’t losing weight a good thing?
For most people it is. With obesity at epidemic levels, many people need to drop excess fat. But in conditions such as cancer, AIDS and COPD, the loss of weight is a sign of a metabolic malfunction in which lean body mass (LBM)—the muscles, organs, the immune system and blood cells—are lost as well. LBM depletion results in the gaunt and drawn, sickly appearance so common in cancer and AIDS wards, and if not treated, can be deadly.
4. Why does this happen?
The mechanism associated with IWL can vary from disease to disease and among individuals. In general, however, there are two main factors responsible for progressive IWL:
1. Inadequate intake of protein and calories to meet the requirements of the individual. This decrease in intake can be due to poor appetite (anorexia), or impediments to intake such as problems with swallowing, digestion or absorption. Decreased intake can result from a patient’s disease and/or treatment. For example, in patients with cancer, swallowing may be a problem due to tumors in the mouth, throat or other parts of the gastrointestinal tract. In other cases, powerful treatments, such as radiation and surgery, and side effects from chemotherapeutic or AIDS drugs, can result in nausea and vomiting and a diminished appetite. These conditions make it impossible to take in the nutrients the patient needs.
2. Metabolic changes in the patient. Metabolic changes can occur in a number of medical conditions and by a variety of different mechanisms. Such changes can be mediated by hormones or by hormone-like proteins made by the body in response to specific conditions such as presence of infection, severe trauma or injury, cancer or other catabolic conditions. These substances modulate a number of different types of cell functions and are often associated with decreases in muscle and other protein synthesis and/or increases in muscle or protein breakdown. One of the major effects of this metabolic change is a disproportionate loss of muscle.
5. How serious is IWL?
Weight loss itself can be deadly. The significant loss of LBM may cause medical conditions which include decreased muscles required for breathing and coughing, decreased extremity muscle mass and function, decreased immunity and less functional organs with impaired tolerance of medications used to treat the underlying disease.
Loss of about 40% of lean body mass can be fatal because it is the site of 99% of the body’s metabolic functions. Several reports have consistently found that as many as one in five patients with cancer will die from weight loss, malnutrition and its complications. Despite the appreciation of weight loss being used as a prognostic factor for more than seven decades, only recently is there a growing understanding of the science of IWL and therapeutic options available to treat the condition.
Beyond issues of complications and death, IWL impacts the quality of life both the patient and family. People with IWL often complain that they “don’t feel like themselves.” When they look in a mirror, the frail, skeletal appearance—thin arms and legs, drawn faces and sunken cheeks and eyes—is a constant reminder that they are facing a potentially deadly disease. Depression, a loss of self-esteem and self-confidence are often the result of the change in body shape. People who are depressed and fatigued are less inclined to take steps to improve their health, such as preparing and eating regular nutritious meals and exercising.
6. Why is it called “the forgotten ‘vital’ sign”?
Standard ‘vital’ signs for a medical evaluation include temperature, pulse and respiration. They allow the clinician to assess the evident measures or ‘vitality’ of life. Unfortunately, physicians tend to overlook IWL while focusing on other more pressing aspects of disease, such as tumor size and metastases in patients with cancer, or viral load and the presence of other infections in AIDS patients. Some clinicians may take observable weight loss into account, but they may not distinguish between the losses of fat versus muscle. The measurement of LBM and its significance to patient survival is critical to evaluating the whole patient and designing an appropriate treatment regimen. The active assessment and treatment of this as the “forgotten ‘vital’ sign” must be made a standard part of healthcare in the 21st century.
7. What are the common treatments used for IWL?
Methods to support weight gain and muscle anabolism include meeting the body’s protein and energy requirements, resistance exercise and various medications that can aid in protein retention and either increase protein synthesis and/or decrease protein breakdown. In the case of anorexia, which can lead to progressive weight loss, an obvious approach is to increase protein and calorie intake to meet the body’s requirements.
Medications that improve a patient’s food intake include corticosteroids, and US Food and Drug Administration (FDA) approved agents for appetite stimulation.
Two oral medications approved for appetite stimulation in AIDS-related weight loss include megestrol acetate and dronabinol. Both have been shown to improve appetite in people with weight loss associated with AIDS or cancer. However, use of dronabinol has not been shown to be associated with weight gain.
Megestrol acetate is an effective appetite stimulant and its use has been associated with increased weight and improved sense of well-being in patients with either AIDS or cancer. If weight gain and quality of life were the only issues, this would be a successful approach to IWL.
Recombinant human growth hormone is an injectable medication approved for AIDS wasting or cachexia. It has both anabolic and anticatabolic effects and its use is associated with increase in weight and increase in LBM. However, routine use of recombinant human growth hormone is limited by the fact that it must be injected on a daily basis, is significantly more expensive than appetite stimulants, and can be associated with such side effects as joint stiffness, fluid retention and various changes in blood chemistries such as blood glucose levels, liver function tests and blood lipids (i.e. cholesterol and triglycerides).
In the context of weight, the oral medication oxandrolone is indicated as an adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma, and in some patients who, without definite pathophysiologic reasons, fail to gain or to maintain normal weight and to offset the protein catabolism associated with prolonged administration of corticosteroids.
Importance of Treatment
With involuntary weight loss (IWL), the loss of lean muscle or tissue contributes to fatigue, impaired functionality in daily activities, deficient immunity and a broad spectrum of conditions that can compromise an individual’s ability to fight the underlying disease and tolerate its treatment. Significant weight loss and specifically, lost muscle, is one of the best predictors of survival and risk for complication in diseases such as cancer, HIV/AIDS, COPD, and in a number of conditions relating to the elderly.
Beyond issues of complications and ability to function in daily activities, IWL impacts both the patient and the family. People with IWL often complain that they “don’t feel like themselves.” When they look in the mirror, the frail, skeletal appearance- thin arms and legs, drawn faces and sunken cheeks and eyes-is a constant reminder that they are facing a potentially deadly disease. Depression, a loss of self-esteem and self-confidence, is often the result in the change in body shape. People who are depressed and fatigued are less inclined to take steps to improve their health, such as preparing and eating regular nutritious meals and exercising.
While the adverse effects of IWL on quality of life and survival have been recognized, what is known about the economic implications of involuntary weight loss is somewhat limited by lack of well-designed pharmacoeconomic studies. However, the following is known: involuntary weight loss and malnutrition are associated with slower healing, increased complications, and longer length of stay in hospital, increased unscheduled hospitalizations, and higher rates of morbidity and mortality across a broad spectrum of medical diagnoses as evidenced by the following:
In a 1990s study which took into consideration clinical conditions, average length of stay (LOS) and charges per hospital admission to predict the effect of early nutritional intervention on LOS and the potential for hospital cost savings, it was estimated that when the model was applied at the national level, acute care hospitals could save at least $6 billion annually by providing timely, minimal nutritional intervention to appropriately selected patients.
Malnutrition and weight loss are associated with prolonged average length of hospital stay. In a number of studies across a variety of medical conditions, the patients average length of stay was consistently 5-10 days longer in malnourished patients.
In surgical patients, weight loss was shown to be predictive of postoperative complications (wound infection, wound dehiscence, intra-abdominal infection, septicemia and pneumonia) in patients with stomach cancer who underwent total removal of surrounding lymph nodes.
References:
1.Berstein LH et al. “Financial Implications of malnutrition.” Clinical Lab Medicine; 1993: 13:491-507.
2.Reilly JJ, Hull SF, Albert N, ET AL: “Economic impact of malnutrition: A model system for hospitalized patients.” Journal of Parental and Enteral, Medicine; 1988; 12:371-376.
3.Shaw-Stiffel TA et al. “Effect of nutritional status and other factors on length of stay after major gastrointestinal surgery.” Nutrition; 1993: 9:140-145.
4.Binderow, S.R et al. “Laboratory parameters as predictors of operative outcome after major abdominal surgery in AIDS- and HIV-infected patients.” American Surgeon; 1993: 59:754-757.
5.Bellantone, R. et al. “Validity of serum albumin, total lymphocyte count, and weight loss in predicting postoperative nutrition-associated complications.” Nutrition; 1990;6: 264-266. Wallace J.I, Schwartz RS, LaCroix AZ, et al.: “Involuntary weight loss in older outpatients: Incidence and clinical significance.” Journal of the American Geriatric Society; 1995: 43:329-337.
Exercise
Exercise is extremely important and should be included in any plan for a patient to prevent and treat involuntary weight loss. Exercise helps ensure optimum results of any pharmacologic therapies by helping the body maintain and restore lean body mass (LBM). Inadequate exercise (or other factors) may be responsible for disproportionate fat vs. lean body mass. While LBM has been linked to survival, fat mass has not.
Studies of individuals who attended scheduled exercise sessions noted improvements in their health. Other studies have concluded that individuals can experience significant increases in neuromuscular strength and cardiorespiratory fitness. Still others have also determined that exercise may activate the immune system. However, overtraining can suppress immune function. People fighting involuntary weight loss should consult with their physician and choose one that best fits their needs, physical abilities and overall schedule.
Resistance exercise, not aerobic exercise, is considered the best form or exercise to build lean muscle tissue. Free-weight training, resistance bands, exercise-machine weight training, etc., are among the most popular kinds of resistance exercise programs.
Although, under normal circumstances, aerobic activity should be included as part of the exercise program, the goal is to increase lean muscle tissue; therefore, it is highly recommended that focus be on resistance exercise or training with light weights. What is correct for an individual is the level of exercise wherein there may be some soreness but not fatigue. The patient should listen to his/her body and exercise accordingly. Before beginning any exercise program, patients should have a complete physical examination and consult a certified exercise trainer or physical therapist.
References:
1.Macarthur RD, Levine SD, Birk TJ. Supervised exercise training improves cardiopulmonary fitness in HIV-infected persons. Med Sci Sports Exerc. 1993 Jun; 25(6):684-8
2.Rigsby LW, et.Al. Effects of exercise training on men seropositive for the human immunodeficiency virus-1. Med Sci Sports Exerc. 1992 Jan;24 (1):6-12
Medications
Methods to support weight gain and muscle anabolism include meeting the body’s protein and energy requirements, resistance exercise, various medications that can aid in protein retention and either increase protein synthesis and/or decrease protein breakdown.
In the case of anorexia, which can lead to progressive weight loss, an obvious approach is to increase protein and calorie intake to meet the body’s requirements. Medications that improve a patient’s food intake include corticosteroids, and US Food and Drug Administration (FDA) approved agents for appetite stimulation. Corticosteroids may be associated with short-term increases in appetite (two to four weeks) for people with disease-related weight loss. However, any weight gain is generally related to fluid retention and use of corticosteroids is associated with progressive loss of Lean Body Mass (LBM).
Two oral medications approved for appetite stimulation in AIDS-related weight loss include megestrol acetate and dronabinol. Megestrol acetate is a synthetic derivative of the female hormone progesterone and dronabinol is a synthetic derivative of the tetrahydrocannabinol, the active ingredient of marijuana. Both have been shown to improve appetite in people with involuntary weight loss (IWL) associated with AIDS or cancer. However, use of dronabinol has not been shown to be associated with weight gain. Megestrol acetate is an effective appetite stimulant and its use has been associated with increased weight and improved sense of well-being in patients with either AIDS or cancer. If weight gain and quality of life were the only issues, this would be a successful approach to IWL.
Megestrol acetate is used for weight gain with either little or no increase in LBM at recommended doses. The use of megestrol acetate may also cause loss of LBM if not combined with replacement of testosterone combined with resistance exercise. No published data have addressed the effect of dronabinol on LBM.
Recombinant human growth hormone is an injectable medication approved for AIDS wasting or cachexia. It has both anabolic and anticatabolic effects and its use is associated with increase in weight and LBM. However, routine use of recombinant human growth hormone is limited by the fact that it must be injected on a daily basis, is significantly more expensive than appetite stimulants, and can be associated with such side effects as joint stiffness, fluid retention, and various changes in blood chemistries i.e. blood glucose levels, liver function tests and blood lipids such as cholesterol and triglycerides.
The oral medication oxandrolone is indicated as an adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma, and in some patients who, without definite pathophysiologic reasons, fail to gain or to maintain normal weight and to offset the protein catabolism associated with prolonged administration of corticosteroids.
Oxandrolone is a synthetic derivative of testosterone. Derivatives of testosterone are known as anabolic androgenic steroids and, while generally well tolerated in men or women, can have side effects that can include fluid retention and various changes in blood chemistries i.e. liver function tests and blood lipids such as cholesterol and triglycerides.
Studies of oxandrolone in either healthy volunteers or in people with a variety of conditions associated with IWL have demonstrated the following:
- Oxandrolone increased muscle protein synthesis,
- Increased nitrogen (a breakdown product of protein) retention,
- Increased weight, and
- Increase in LBM.
Interestingly, many of the studies performed using oxandrolone have used an integrated approach to weight gain in IWL, including actively addressing protein requirements as well as including a variety of different types of resistance exercise. In a randomized double blind, placebo-controlled study performed in HIV+ subjects at the University of California at Berkeley and published in the Journal of the American Medical Association (JAMA) in 1999, both gain in total body weight and lean body mass weight was significantly greater in subjects treated with oxandrolone compared with placebo.Similar results have been demonstrated in community-based clinical settings in cancer, HIV/AIDS, and chronic obstructive pulmonary disease as well as in other academic studies in geriatric sarcopenia.
The goal of any program in the treatment of involuntary weight loss is to successfully prevent the continued loss of lean body mass, help the patient add lean body mass, and allow the patient to become self sufficient with the highest quality of life and the greatest chance of survival.
References:
1.Fisher A, Abbaticola M, the Oxandrolone Study Group. The effects of oxandrolone on body weight and composition in patients with HIV-associated weight loss. Presented at: 5th Conference on Retroviruses and Opportunistic Infections. February 1-5, 1998; Chicago, IL.
2.Tchekmedyian S, Von Roenn J, Ottery F, for the M0241 Study Group. Patients with aerodigestive tract cancer and pre-existing weight loss: weight, body composition, performance status, quality of life, and laboratory parameters with oxandrolone use. Paper presented at: 44th Annual ASTRO Meeting; October 6-10, 2002; New Orleans, La.
3.Yeh SS, DeGuzman B, Kramer T. Reversal of COPD-associated weight loss using the anabolic agent oxandrolone. Chest 2002;122:421-428
4.Strawford A. Bargien T. Van Loan M, et al. Resistance exercise and supraphysioloic androgen therapy in eugonadel men with HIV-related weight loss: a randomized controlled trial. JAMA 1999;281:1282-1290.