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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.

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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.

Nutrition and metabolism in burn patients | Burns & Trauma | Full Text

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 In addition, there was a decrease in proinflammatory cytokines, which are activators of inflammation, resulting in a better balance between proinflammatory and anti-inflammatory cytokines. Remarkably, but not unexpectedly, this attenuation of the inflammatory response corresponds with improved cardiac, liver, and renal function. The other beneficial effect of this complex as opposed to other anabolic agents is its effect on normalizing blood glucose levels. Both low and high blood glucose levels, seen with the use of some other anabolic agents, have been well documented to be very deleterious.

Testosterone, whose basic structure is a steroid ring, is the natural endogenous androgen. Testosterone is synthesized primarily in the testicles in males and by the ovaries and adrenal gland in females. Testosterone acts on the cells' androgenic receptors found mainly in skin, muscle, and male sex glands.

Androgenic masculinizing side effects include male sex gland development, male pattern of hair, and mood. Testosterone levels decrease with any severe stress. Testosterone replacement is essential in hypogonadal states to avoid further lean mass loss and the other complications of low testosterone levels. Replacement is typically done by depot injection.

However, beyond replacement therapy, testosterone is not used as an anabolic agent as it has relatively weak anabolic activity compared to its analogs and its androgenic side effects can become problematic. The major complications with its use are a decrease in high-density lipoproteins, some fluid retention, and endrogenic effects. Anabolic steroids refer to the class of drugs produced by modification of testosterone. Modifications were made in the steroid ring because of the short half-life of testosterone and its masculinizing properties.

These changes markedly increased its half-life and decreased its androgenic properties. The mechanisms of action of testosterone analogs are also through activation of the androgenic receptors found in highest concentration in myocytes and skin fibroblasts. Some populations of epithelial cells also contain these receptors. Androgenic receptors were first isolated in the s.

Acute Catabolic State Update in Intensive Care and Emergency Medicine

Stimulation of these receptors leads to a decrease in the efflux of amino acids and an increase in the influx into the cell. A decrease in fat mass is also seen because of the preferential use of fat for fuel. There are no metabolic effects on glucose production. All anabolic steroids increase overall protein synthesis and new tissue formation, as evidenced by an increase in skin thickness and muscle formation. All these agents also have anticatabolic activity, decreasing the protein degradation caused by cortisol and other catabolic stimuli. Oxandrolone is a synthetic anabolic steroid with potent anabolic and anticatabolic activity with minimal androgenic masculinizing properties.

Oxandrolone, a modified form of testosterone, is the only FDA-approved anabolic steroid used for restoring lost body weight. The safety advantage of oxandrolone is that it is cleared by the kidney rather than the liver so hepatoxicity, which is a major problem with other anabolic steroids, is less of an issue. Its anabolic activity is approximately 10 times that of testosterone and its androgenic activity is one tenth that of testosterone.

Currently, this agent is being used clinically not only to restore lost lean mass but also to preserve lean mass loss in catabolic states. Its half-life is 9 to 12 hours. Oxandrolone is given orally twice a day, usually 10 mg per dose.

It has been shown to decrease net catabolism in a number of catabolic states, burns being the most significant. Testosterone analogs act only on androgenic receptors found only in the lean body mass compartment. Testosterone analogs cannot be used in the presence of androgenically sensitive 85 tumors, which include prostate cancer and male breast cancer. Oxandrolone also increases sensitivity to Coumandin, necessitating adjustment in its dosage.

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  7. Studies indicate that anabolic activity is markedly increased in injured men, elderly with and without wounds, steroid-dependent patients, cachexia, HIV, chronic obstructive pulmonary disorder, and cancer chemotherapy with weight loss. HGH is a potent endogenous anabolic hormone that is also anticatabolic, acting on a specific HGH cell receptor. HGH is a large polypeptide with a number of binding proteins and cell-binding sites. Starvation and intensive exercise increase HGH production. Severe, acute, or chronic illness decreases HGH levels.

    Clinical studies have in large part focused on the systemic anabolic and anticatabolic actions of HGH. Populations in which HGH has been shown to have beneficial effects include those with severe burn and trauma, those with HIV infection with wasting, and frail elderly adults. In addition, HGH is being used to slow down the aging process. Increase in lean mass, muscle strength, and immune function has been documented in clinical use.

    Nutrition and metabolism in burn patients

    HGH is approved only for use in children of short stature and is an orphan drug when used for improving protein synthesis. Increased anabolic activity requires ingestion of a high-protein, high-energy diet. As to any direct wound healing effects, skin is a target tissue for HGH, both directly through HGH receptors on the surface of the epidermal cells and indirectly through the action of IGF Exogenously administered HGH has been shown to increase skin thickness in normal humans.

    In addition, HGH has been shown to increase wound collagen content, granulation tissue and wound tensile strength, and the local production of IGF-1 by fibroblasts. These data are derived mainly from animal studies. HGH when provided typically binds with one of its binding proteins.

    HGH has a number of metabolic effects, the most prominent being its anabolic activity but insulin resistance also occurs, which often leads to hyperglycemia, which will increase morbidity.