Anabolic hormones are necessary to maintain the increased protein synthesis required for maintaining LBM, including wound healing, in conjunction with the presence of adequate protein intake. However, endogenous levels of these hormones are decreased in acute and chronic illness and with increasing age, especially in the presence of a large wound. Because the lost LBM caused by the stress response, aging, and malnutrition retards wound healing, the ideal use of these agents is to more effectively restore anabolic activity. There are also data that indicate a direct wound healing stimulating effect for some of these hormones.
Finally, controlling catabolism by producing anabolism by agents, many being endogenous, has been shown in the presence of adequate protein intake to increase net body anabolism, which, in turn, will improve overall protein synthesis including the wound.
HGH has a number of metabolic effects (Table ). The most prominent is its anabolic effect. HGH increases the influx and decreases the efflux of amino acids into the cell. Cell proliferation is accentuated, as are overall protein synthesis and new tissue growth. HGH also stimulates IGF-1 production by the liver, and some of the anabolism seen with HGH is that produced by IGF-1, another anabolic agent.,
The effect on increasing fat metabolism is beneficial in that fat is preferentially used for energy production, and amino acids are preserved for use in protein synthesis. Recent data indicate that insulin provides some of the anabolic effect of HGH therapy. At present, the issue as to the specific anabolic effects attributed to HGH versus that of IGF-1 and insulin remains unresolved.
A number of clinical studies have demonstrated the ability of exogenous delivery of anabolic hormones to increase net nitrogen retention and overall protein synthesis. Wound healing has also been reported to be improved.* However, it remains unclear as to how much of the wound healing is the result of an overall systemic anabolic effect, or whether there is a direct effect on wound healing. Anabolic hormones for which data are available are listed in Table .
IGF-1 is a large polypeptide that has hormone-like properties. The IGF-1, also known as somatomedin-C, has metabolic and anabolic properties similar to insulin. Practically speaking, this agent is not as much used for its clinical wound healing effect or anabolic activity as HGH or IGF. The main source is the liver, where IGF synthesis is initiated by HGH. Decreased levels are noted with a major body insult.,
In summary, use of HGH in conjunction with adequate nutrition and protein intake clearly results in increased anabolic activity and will positively impact wound healing by increasing protein synthesis in catabolic populations.
It is now well recognized that the hormonal environment, so critical to wound healing, can be beneficially modified.,, In general, restoration or improvement in net protein synthesis and, therefore, in wound healing, is the result of 2 hormonal processes. The first is an attenuation of the catabolic hormonal response, and the second is an increase in overall anabolic activity, recognizing that adequate nutrition is being provided. Any hormonal manipulation that decreases the rate of catabolism would appear to be beneficial for wound healing. Blocking the cortisol response would seem to be intuitively beneficial and, as stated, growth hormone and testosterone analogues decrease the catabolic response to cortisol.
Increased anabolic and wound healing benefits have also been shown for the conditionally essential amino acids, glutamine, and arginine. Both of these amino acids characteristically decrease with activation of the stress response leading to a deficiency state well recognized to impede protein synthesis and overall anabolism.*. Replacement therapy has been shown in both circumstances to increase net anabolism.
The hormone insulin is known to have anabolic activities in addition to its effect on glucose and fat metabolism. In a catabolic state, exogenous insulin administration has been shown to decrease proteolysis in addition to increasing protein synthesis.,, The anabolic activity appears to mainly affect the muscle and skin protein in the LBM compartment. An increase in circulating amino acids produced by wound amino acid intake increases the anabolic and anticatabolic effect in both normal adults and populations in a catabolic state.
There are now well-recognized micronutrients that are necessary for anabolic activity and that can actually improve net protein synthesis (Table ). These components include the amino acids glutamine and arginine already described. A variety of vitamins and microminerals are also involved in this process.
The micronutrients required for anabolic and anticatabolic activity and protein synthesis are described in Table *. These elements have properties considered to be directly involved with protein synthesis and as cell protectors through potent antioxidant properties. Oxidants are a major source of cell toxicity with wound inflammation, and antioxidant activity is essential for the wound healing process to continue. Vitamin C and glutathione, products of glutamine, are water-soluble antioxidants. (Table ) Other vitamins and minerals with antioxidants activity are described in Table .
A number of clinical trials,,, mainly in burn patients, have demonstrated the stimulation of protein synthesis, decreased protein degradation, and a net nitrogen uptake, especially in skeletal muscle. The positive insulin effect on protein synthesis decreases with aging. There are much less data on the actions of insulin on wound healing over and above its systemic anabolic effect. The main complication is hypoglycemia.