The Use of Anabolic Agents in Catabolic StatesMany athletes have said that anabolic steroids facilitate them train tougher and recover faster. They additionally said that that anti-catabolic effects of anabolic steroids had problem creating progress anti-catabopic even anti-catabolic effects of anabolic steroids onto the gains after they were off the medicine. Anabolic might have an anti-catabolic result. Presently, this hypothesis has not been totally proven. Anabolic steroids might block the consequences of hormones like cortisol concerned in tissue breakdown throughout and when exercise.
Anti-Catabolic Effects Of Anabolic Steroids
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We plan to review the current problem of lean mass erosion in catabolic states, caused by injury and critical illness. The available published literature on the pathogenesis of acute catabolic states and the use of anabolic and anticatabolic agents, their indications, mechanism of action, and potential complications was reviewed.
The current understanding and experience of the available anabolic and anticatabolic agents as well as the rationale for the use of each anabolic agent are described. We conclude that the preservation of lean body mass body protein is extremely important in the management of critical care populations, as lean mass loss leads to severe morbidity and increased mortality. Essentially, all of the available anabolic agents stimulate protein synthesis and decrease protein breakdown, but all have different mechanisms of action.
Adequate nutrition, especially protein intake, is essential for any anabolism to occur. Combined anabolic therapy also appears to be advantageous. Although controlling the inflammatory response would also be of major benefit in further controlling protein loss, effective and safe anti-inflammatory agents have not yet become clinically available for this purpose.
There is a very complex relationship between hormones, nutrition and protein synthesis, anabolism, or protein degradation. This is severely disrupted with bodily stress. The stress response to injury, including surgery or any significant illness, can be considered to be a maladaptive or autodestructive process. This process is the result of an excessive catabolic activity due to both a hormonal imbalance and excess inflammation.
This response is activated immediately after a stress insult and peaks around 3 to 5 days postinsult. An inevitable loss of muscle and body protein occurs, which is deleterious to all bodily functions. The magnitude of this autodestructive response is in large part dependent upon the magnitude of the insult and the time course to complete recovery. The impact on the patient can be extremely harmful and can even prove fatal.
So how can this process be controlled? The stress response is characterized by increased and protracted levels of the hormones epinephrine and cortisol, which increase energy demands beyond needs and cause increased protein breakdown, primarily for the production of excess glucose and for energy.
The level of IGF also goes down, leading to a state of insulin resistance, insulin also being an anabolic hormone. Inflammation, a component of any injury or infection, generates products, such as proinflammatory cytokines and oxidants, that will produce further protein degradation.
The degree of acute-phase protein production typically corresponds with the magnitude of the inflammatory response. The lean body mass contains all the proteins present in the body as well as all the water. Two thirds of the protein is found in muscle and skin. The remainder is responsible for organ structure and function, immunity, enzyme activity, and any new tissue formation. As opposed to fat mass, which is basically a storage depot for available calories, there are no stored proteins; all have some significant physiological or metabolic function.
Therefore, any net protein loss is harmful. Breaking down protein over the long-term is maladaptive and autodestructive. The complications of lean mass loss correspond to the amount and rate of lean body mass loss relative to total, assuming total to be not compromised.
It is also important to recognize that the restoration of body protein is at least 4-fold slower than the rate of loss although the use of anabolic agents can accelerate this restoration. It is now clear that controlling the catabolic state, by increasing anabolism and controlling inflammation, is essential to improving the outcome and decreasing complications in the severely injured and critical ill population.
Therefore, the main frontier in critical care is to control both the excess protein loss from hormonal imbalance and the organ damage from inflammation. Providing optimum nutritional support is also essential to keep up with the increased energy caloric and protein demands as well as the increased intake of micronutrients. Typical required protein intake per day is 1. The purpose of this review, however, is to focus on anabolic agents that can assist in controlling protein loss.
Controlling the inflammatory response is something that is yet to be achieved. A number of anabolic and anticatabolic strategies are now available for clinical use.
Several of these agents have been shown to be remarkably effective. Either effect is recognized to be beneficial. Many of the anabolic agents also have anticatabolic properties, often due to down-regulation of cell cortisol receptors. In general, these agents are either amino acids or metabolites that stimulate protein synthesis or hormones with anabolic activity. Sufficient protein intake is essential to support any anabolic activity.
Specific amino acid therapy can lead to an increase in protein synthesis; however, there are no recognized effects on inflammation. Glutamine is the main carrier of nitrogen between various tissues, including skeletal muscle, liver, intestines, and kidney.
The liver uses glutamine as a preferred source of energy. Glutamine is also a precursor, along with cysteine, for the key intracellular antioxidant glutathione, which is produced in the liver and then exported to other organs, especially the lung.
Enterocytes prefer to use glutamine instead of glucose as their primary energy source. The availability of glutamine is now recognized as a rate-limiting step in muscle protein synthesis, and the rate of protein turnover in muscle depends in part on the availability of glutamine. In addition, there is a well-recognized glutamine deficiency state within 48 hours of a severe injury or illness and glutamine then becomes an essential amino acid.
Increasing glutamine intake appears to have both anticatabolic and anabolic effects. Glutamine supplementation at the level of 0. The major anabolic and anticatabolic property of glutamine is likely because of increased availability for protein synthesis in a postinjury deficiency state.
Another potentially important anabolic action of glutamine is stimulating HGH release. There is not yet a unanimous opinion as to which critically ill patient populations benefit from glutamine supplementation. Certainly, it is effective in trauma patients but the effect is less clear in patients with sepsis. The mechanism of action of OKG is not clearly understood, but it appears to act by the enhanced secretion of anabolic hormones and the increased synthesis of metabolites, glutamine, polyamines, and arginine.
It is recommended that high-dose glutamine not be given in the presence of liver failure due to increased production of ammonia. Arginine has been shown to have a wide variety of potentially beneficial metabolic effects in the injured or critically ill patient population.
One mechanism may be stimulation of the release of HGH. In addition, there is clearly an increase in lymphocyte production and therefore an immune system stimulation effect. Improved wound healing, as evidenced by increased collagen deposition, has also been well described in experimental studies.
Clinical data on healing or infection control is much less convincing. There are no studies on the advantages or disadvantages of arginine supplementation in critical illness at the present time, although there are a number of important products on the market with increased arginine content.
More clinical studies, verifying the efficacy of arginine as an anabolic agent other than increased wound collagen deposition, still need to be performed. It has been shown, in a number of clinical trials, to decrease catabolism in normal man and in the elderly after exercise.
The mechanism of action appears to be related to the fact that leucine depletion, during stress, increases catabolism and providing the HMB metabolism, blocks this response. In addition, HMB has been shown, in several clinical trials, to increase the restoration of lean mass in conjunction with exercise, felt to be the result of its anticatabolic effect.
Glutamine, arginine, and HMB were combined in a nutritional supplement JUVEN that showed a decrease in catabolism and an increase in lean mass in catabolic states HIV, cancer, and elderly weight loss in 3 randomized controlled studies.
However, the role of each amino acid in the anabolic actions of the combined product is not known. Insulin is a naturally occurring endogenous polypeptide hormone best known for controlling blood glucose levels by increasing glucose uptake at the cell level.
Its mechanism of action is complex but mainly involves transport of amino acids, glucose, and fat into the cell while decreasing the efflux of amino acids from the cell. Its anticatabolic effect relates to a decrease in proteolyses. The anabolic activity is mainly seen in the protein content of muscle and skin in the lean mass compartment. The anabolic response to insulin decreases with aging while most other anabolic agent activity is not age related.
Increased re-epithelialization of skin graft donor sites was reported in one clinical trial in burn patients. Several animal studies have demonstrated increased collagen production with insulin and increasing the level of insulin administered to mice with diabetes improved all phases of healing.
However, the effects of insulin on wound healing have not been well studied in man. The major complication with its use as an anabolic agent is hypoglycemia, requiring rigorous monitoring of glucose levels. Also, because of its short half-life, a continuous parenteral insulin infusion is especially utilized.
There are no recognized effects of insulin on the inflammatory phase of the stress response. Insulin will also cause fat production in liver if excess glucose is also present.
IGF-1 is a naturally occurring large polypeptide that has hormone-like properties. IGF-1 is produced by a variety of wound cells, such as fibroblasts and platelets. The IGF receptor on the cells is expressed in many different tissues and active peptide is bound, in plasma, by IGF-binding proteins.
There are no clinical studies showing anti-inflammatory activity with IGF Also, an IGF-1 infusion loses its anabolic activity with long-term use. The attenuation of stress-induced hypermetabolism is a favorable property of IGF The clinical trials using an IGF-1 infusion have focused on demonstrating increased anabolic activity.
Increased protein synthesis and nitrogen retention has been reported in burns, head injury, and HIV-induced catabolic states. The major problem with its use is the risk of hypoglycemia low glucose. Also problematic is the need for a continuous intravenous infusion, requiring that glucose levels be monitored. Low-dose infusions are not effective. The ideal dose has not yet been determined. As expected, many properties remain similar to those of IGF-1 and insulin.
However, the half-life is increased from minutes to more than 12 hours. Exogenous IGF infusion, over time, appears to lead to an attenuation of its anabolic effects. There is a significant increase in protein synthesis anabolism and anticatabolic properties persist and remain constant with long-term administration.
Increased wound healing has also been demonstrated, much like that for IGF