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Objective: We examined the effects of megestrol acetate versus placebo and progressive resistance physical exercise on weight, lean muscle mass, quality of life, ability to exercise, proinflammatory cytokines, and anti-inflammatory cytokines, and their correlations with one another., Design: We organized a prospective 20-week, randomized, double-blind, placebo-controlled pilot trial of hemodialysis patients., Setting: This study took place at the Outpatient Unit of the Northport Veteran Affairs Medical Center., Subjects: We studied nine male hemodialysis patients who had two or more of the following: albumin level <4.0 g/dL, total cholesterol <150 mg/dL, protein catabolic rate <0.8 g/kg/day, and predialysis serum urea nitrogen <60 mg/dL. Their ages were 50 to 83 years. Two were diabetic, and seven were nondiabetic., Interventions: Interventions included megestrol acetate (MA) or placebo 800 mg oral daily for 20 weeks, along with weight resistance physical therapy with weights twice a week before dialysis. Patients were followed prospectively for an additional 4 weeks., Main Outcome Measurements: Weight, body composition, activities of daily living, ability to exercise, and plasma cytokine levels were measured., Results: At 24 weeks, the MA group had a statistically significant weight gain (11.1-pound increase vs. 1.5-pound decrease for the placebo group, P = .018), body fat gain (6.2-pound increase vs. a 0.4-pound decrease for the placebo group, P = .044) and fat-free mass gain (5-pound increase vs. a 1.2-pound decrease in the placebo group). The MA group also had a greater tendency toward increased appetite and sense of well-being. The MA group showed a greater improvement in ability to exercise (mean change in rate of perceived exertion (RPE), 4.7) vs. the placebo group (mean change in RPE vs. 0.5, P = .02). Elevated cytokine levels were evident at baseline in both groups. In all patients, increases in weight, fat-free mass, sense of well-being, appetite, and ability to exercise were negatively correlated with tumor necrosis factor receptor subunit p75 (P < .05). There was a trend toward all of these parameters to be negatively correlated with tumor necrosis factor receptor subunit p55, although only sense of well-being was statistically significant (P < .05)., Conclusion: In a pilot trial in dialysis patients, MA showed significant benefits in improving weight and ability to exercise. Cytokine changes were correlated with weight gains and increases in fat-free mass.

Cachexia is a hypercatabolic condition that is often associated with the terminal stages of many diseases, in which the patient's resting metabolic rate is high and loss of muscle and fat tissue mass occur at an alarming rate. The patient also usually has concurrent anorexia, amplifying the wasting syndrome that is cachexia. The greater the extent of cachexia (regardless of underlying disease), the worse the prognosis. Efforts to treat cachexia over the years have fallen short of satisfactorily reversing the wasting syndrome. This article reviews the pathophysiology of cachexia, enumerating the different pro-inflammatory cytokines that contribute to the syndrome and attempting to illustrate their interwoven pathways. We also review the different treatments that have been explored, as well as the recent literature addressing the use of anti-cytokine therapy to treat cachexia.

Anticachexic or antisarcopenic medications are prescribed worldwide for geriatric patients with poor appetite and associated weight loss. They represent a valuable treatment option for managing cachexia. However, the well-publicized adverse reports about these medications in acquired immunodeficiency syndrome (AIDS) and in the cancer population has led to some concern and much subsequent discussion over the safety of these medications being used in geriatric population. This review looks at the evidence in relation to the benefits and risks of these medications and discusses what we know about their use in the geriatric population.

The aim is to review major clinical trials that have used megestrol acetate (MA) in the treatment of cachexia across several disease states. A review of general usage and potential side-effects are discussed. A theory that the newly approved nanocrystal formation of MA can better deliver this potent medication for treatment will also be reviewed.

Objectives: To evaluate the effect of proinflammatory cytokines, their receptors, and nutritional indicators (at baseline and after 12 weeks of megestrol acetate (MA) treatment) upon long-term survival in geriatric cachectic patients without active acute infections, inflammation, or cancer., Design: Randomized clinical trial with placebo or MA treatment for 12 weeks and then follow-up for more than 4 years., Setting: Veterans Affairs nursing home in Northport, New York., Participants: Nursing home patients with weight loss of 5% of usual body weight over the previous 3 months or body weight 20% below ideal body weight., Intervention: Random assignment of placebo or MA oral suspension 800 mg/d to the eligible patients for 12 weeks., Measurements: White blood cell counts, prealbumin, plasma cytokine levels (or their receptors), including tumor necrosis factor receptor (TNFR), soluble subunits (TNFR-p55 and TNFR-p75), interleukin (IL)-6, soluble IL-2 receptor, and C-reactive protein at baseline and 12 weeks after treatment., Results: There was no difference in survival between the MA and placebo groups. Considering possible confounders, initial IL-6, initial TNFR-p75 levels, and final neutrophil percentage were associated with elevated mortality, whereas higher initial prealbumin, initial albumin, final prealbumin, final albumin, and final weight gain were associated with decreased death., Conclusion: In geriatric weight-loss patients with cachexia, certain cytokines and nutritional indicators were effective in predicting long-term mortality, regardless of treatment with MA. Interventions to modify levels of these cytokines or their receptors and improvement in nutritional status by weight gain might be helpful in ameliorating undetected chronic inflammation and thus might prolong the survival of these nursing home residents.

The Society for Sarcopenia, Cachexia, and Wasting Disease convened an expert panel to develop nutritional recommendations for prevention and management of sarcopenia. Exercise (both resistance and aerobic) in combination with adequate protein and energy intake is the key component of the prevention and management of sarcopenia. Adequate protein supplementation alone only slows loss of muscle mass. Adequate protein intake (leucine-enriched balanced amino acids and possibly creatine) may enhance muscle strength. Low 25(OH) vitamin D levels require vitamin D replacement.

Establishes the role of proinflammtory cytokines in geriatric cachexia. Examples of proinflammatory cytokines involved in cachexia; Association of cytokine concentration reduction with weight gain; Relation between geriatric cachexia and increased concentrations of negative regulatory cytokines.