Table 2.

Plasma and urinary levels of conventional markers of protein status

Subject of measurement	Rationale	Usage
Plasma protein levels: albumin, transthyretin (formerly called prealbumin), and retinol binding protein	These proteins are selectively synthesized by the liver. Therefore, it is generally believed that their rate of synthesis parallels the supply of amino acids. In the case of inflammation, plasma levels of these proteins do not indicate nutritional status	Transthyretin measurements can be used to assess the efficacy of nutrition support [75], while albumin measurements can be used to assess the risk of complications associated with malnutrition. When used for this purpose, albumin may be used alone [76] or, ideally, as an index to be considered in combination with variations in body weight over time (nutritional risk index [77] in adults, geriatric nutritional risk index [78] in geriatric patients)
Urinary 3-methylhistidine (3MH)	3MH is derived from histidine with a post-transcriptional methylation at position 3. This amino acid is present mainly in myofibrillar proteins and, to a smaller extent, in intestinal smooth muscles. Following proteolysis, released 3MH is not reincorporated into proteins since there is no codon for this amino acid. Instead, 3MH is further eliminated into urine	There is a correlation between the 24-hour excretion of 3MH and myofibrillar proteolysis. Since the former will be dependent upon muscle mass, 3MH excretion must be expressed as a ratio to urinary creatinine. It has been clearly demonstrated that muscle myofibrillar proteins account for the entire increase in 3MH excretion during hypercatabolic states [79]. In chronic malnutrition, urinary 3MH is low due to restriction adaptation, and improvement in the nutritional state leads to an increase of this parameter because elevated protein synthesis leads to an increase in proteolysis
Plasma phenylalanine	Phenylalanine is mainly catabolized in the liver, and not in the muscle. The arteriovenous difference in phenylalanine concentration is a marker of muscle proteolysis. Unfortunately, arterial puncture is an invasive procedure, and is associated with technical problems that complicate the use of this marker. In addition, interpretation of the data requires that blood flow is measured simultaneously. Alternatively, plasma phenylalanine can be measured as a marker of protein turnover. Some authors have suggested measuring the phenylalanine:tyrosine ratio for this purpose	It has been shown [80] that plasma phenylalanine correlates well with nitrogen balance in burn patients. At present, there are insufficient data available to recommend the use of plasma phenylalanine or of the phenylalanine:tyrosine ratio as a reliable marker of protein turnover
Plasma citrulline	The amino acid citrulline is not included in proteins and it is almost absent in food. In the general circulation, most citrulline is formed in enterocytes and is mostly catabolized in the kidneys [81]. Of note, citrulline in the liver is strictly compartmentalized within periportal hepatocytes [61] and the liver neither takes citrulline up nor releases it, except in patients with liver cancer [82]	Following the pioneering work by Crenn and colleagues [83] in patients with short bowel syndrome, plasma citrulline has been validated as a marker of gut functional mass in a number of clinical situations (see [84] for a recent review)