C. Rationale for Use of Anabolic Agents

Overview

The successful correction of PEM and prevention of a severe protein deficiency in the presence of catabolic illness requires the restoration of the normal protein partitioning process (to restore lean body mass and wound healing). Restoration of the key components of nutrition is essential before considering an anabolic agent.

However, a limiting factor to restoration of lean mass and improving wound healing is the output of the protein synthesis pathway. The rate of synthesis is clearly dependent on:

1) Adequate substrate, amino acids and peptides, as a nitrogen source

2) The biologic activity of protein by-products (peptides) that further increase protein synthesis

3) Overall anabolic drive relative to the catabolic stimulus

Even in the recovery phase, endogenous anabolic activity remains depressed. This is the case in elderly patients, those with chronic illness, or patients with involuntary weight loss. Adequacy of substrate (1.5 g/kg/d protein) may not be sufficient to jump-start a rapid restoration of lean body mass. The machinery is capable of a very rapid rate of protein synthesis that is not age-dependent.

Body composition studies during correction of PEM have demonstrated that a significant portion of weight gain after unintentional weight loss from catabolic disease represents the addition of body fat and extracellular fluid, not added protein mass.

The action of all anabolic agents currently in clinical use is twofold. First, amino acids are driven into the protein synthesis channel in the cell. The metabolic pathways used by anabolic agents may be different, but the outcome is increased protein. The second action is anticatabolic. All anabolic agents appear to decrease protein degradation, possibly by blocking cell cortisal receptors. In the absence of a sufficient anabolic activity, the energy-requiring protein synthesis pathway is underused and excess energy is stored as fat.

Actions of Anabolic Hormones

• Anticatabolic by decreasing loss of amino acids from the protein synthesis pathway

• Anabolic by increasing the rate of protein synthesis

 

Anabolic hormones are being used with increasing frequency in populations with lean mass loss or existing PEM, along with optimal nutrition and the added anabolic stimulus of resistance exercise.

 

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