Miscellaneous Therapies

ZInc supplementation 

Zinc is an essential element for humans as it is vitally important for normal nucleic acid and protein metabolism (McClain et al. 1986). Moderate zinc deficiency has been associated with cell death. Serum hypozincemia and increased urinary zinc excretion are common following head injury and are thought to be an adaptive responsive to inhibit the proliferation of infective organisms. Levels of serum albumin, the major transport carrier for zinc, are also markedly depressed following brain injury and likely help to explain a portion of the reductions in serum zinc levels. Urinary excretion of zinc appears to be proportional to the severity of head injury (Levenson 2005).

Table: Zinc Supplementation in patients with ABI

An RCT was identified that examined the effect of parenteral zinc supplementation following ABI (Young et al. 1996). An improvement in protein synthesis and neurological recovery in patients who received supplementation was reported. Surprisingly, there were no differences in either the serum or cerebrospinal fluid zinc concentrations between the groups.


Based on a single RCT there is Level 1b evidence that zinc supplementation in ABI patients has a positive effect on neurological recovery as measured by the Glasgow Coma Scale. However, no significant improvement in mortality rates could be attributed to zinc supplementation.


Zinc supplementation in the immediate post injury period has been shown to be beneficial in terms of neurologic recovery and visceral protein concentrations in ABI patients. 


Anabolic agents have been proposed as a means to improve lean body mass (Behrman et al. 1995). It has been reported that GH mobilizes fat stores as an energy source and enhances whole body and liver mitochondrial protein stores (Maddaiah et al. 1973; Merimee & Rabin 1973). It is believed that GH exert their effects via insulin-like growth factor-1 (IGF-1), which is synthesized in the liver (Phillips & Vassilopoulou-Sellin 1980). Several studies in non-stressed postoperative patients have demonstrated improvements in nitrogen balance following the use of GH (Manson et al. 1988; Manson & Wilmore 1986; Ponting et al. 1988). The effects of GH on the nutritional parameters of injured patients have not been well established.

Table: Growth Hormone Treatment on Nutrition Post-ABI

In a study conducted by Behrman (1995), GH treatments administered to patients who were completely immobilized did not improve nitrogen balance. The adjuvant recombinant human GH did, however, improve constitutive serum protein concentrations and the patient’s prognostic nutritional index (Behrman et al. 1995). Conversely, another RCT found that individuals who were administered IGF-I/GH had a higher nitrogen balance per day than those in the control group (1.20±0.84 vs. -3.90±0.87, p<0.0001; Hatton et al. 2006). Overall, for patients with TBI there was a sustained improvement in metabolic and nutritional status. A study by Devesa et al. (2013) found that GH administration was useful when provided with proper rehabilitation.


Based on two RCTs, there is conflicting evidence that IGF-I is effective in enhancing growth hormone in those who have sustained an ABI. 


 Growth hormone enhances nutritional repletion, but it unclear as to whether or not it improves nitrogen balance.


Increased nitrogen feeds

Following brain injury, nitrogen losses result from the conversion of endogenous protein to energy with the extra stress demand (Grahm et al. 1989). The attainment of a positive nitrogen balance is complicated because increasing the amount of nitrogen feeding will not be retained, rather it will cause an increased amount of nitrogen excretion (Hadley et al. 1986). Often this positive balance does not occur until the catabolic stimulus begins to subside (Hadley et al. 1986).

Table: Nitrogen Balance

Following a brain injury, the incidence of metabolic changes can influence cell turnover use of substrate and body composition (Twyman 1997). Twyman (1997) noted that urinary urea nitrogen levels increase by a factor of three compared with normal levels within 10 days after severe head injury. On average, about 5 to 10 g of urea nitrogen are excreted daily from an individual; however, patients with ABI lose a mean of 21 g urinary urea in a single day (Twyman 1997). 


Based on a single RCT, there is Level 2 evidence that high nitrogen feedings of approximately 2 g protein/kg are necessary to restore the substantial nitrogen loses that occur post ABI.


 High nitrogen feedings are necessary to restore massive nitrogen loses post-ABI.



Branched-chain amino acids

Branched-Chain Amino Acids (BCAAs), which include leucine, valine and isoleucine, make up roughly 35% of the human body’s essential amino acids and approximately 14% of skeletal muscle amino acids (Aquilani et al. 2005). Following intake of a meal, the amino acid skeletal muscle uptake is comprised of 50% or more BCAAs (Aquilani et al. 2005). Amino acids are not just nutritionally beneficial, but they may also impact cognitive function (Aquilani et al. 2005). It is thought that the BCAAs improve cognitive functioning by providing substrates and increasing brain insulin availability (Aquilani et al. 2005).

Table: Branched-Chain Amino Acid Treatments in ABI patients


There is Level 2 evidence that supplementation of BCAAs in patients with ABI enhances recovery of cognitive function, without negatively effecting tyrosine and tryptophan concentration.


 Supplementation of BCAAs in patients with ABI enhances recovery of cognitive function.