Title: Biochemical Markers of Protein Status
Key words: Albumin, amino acids, transferrin, retinaol-binding protein, insulin-like growth factor (IGF-1)
Date: July 2000
Category: 14. Measurement
Author: Dr van Rhijn
Biochemical Markers of Protein Status
Biochemical markers of protein status can be measured precisely, and are independent of the size of the individual. However, the currently available indices1 all have limitations, as discussed below.
Commonly used markers
Serum albumin, one of the first prognostic2 markers to be used, decreases (reduced production) during protein-energy malnutrition. Albumin has a long half-life (21days), responds slowly to altered protein intake, and even marasmic children can have normal albumin and serum protein levels. The low levels seen in kwashiorkor, oncology3 & haemodialysis4 patients may be due to the plasma dilution effects of oedema rather than a real effect. Albumin is an acute-phase protein, raised in trauma and infections, which often accompanies malnourished patients5 and has prognostic significance6.
The ratio of essential amino acids to nonessential amino acids is decreased in protein deficiency, but its sensitivity to PEM is limited as it is affected by recent food intake. The methodology is expensive and difficult.
Serum transferrin has been investigated7 as a protein marker of nutritional status and its smaller body pool and short half-life (10 days) may be more sensitive to protein status. It is inversely correlated with Fe status, affected by acute-phase response with reduced serum concentrations in inflammatory states, liver disease, exogenous protein loss (nephritic syndrome) and haemolytic anaemia. It is therefore of limited use in assessing nutritional status but it may be used to evaluate any nutritional support8 given and may have prognostic significance.
Pre-albumin, synthesised in the liver, has an even shorter half-life (2 days), a very small pool size and responds rapidly to recent dietary intake. It is sensitive to hyperthyroidism, inflammation and liver disease during which serum levels decrease rapidly (redistribution & reduced synthesis). Measuring CRP helps to exclude acute phase reaction but as it is irresponsive to energy deficiency, its usefulness as a measure of nutritional status is limited10 although it is useful in assessing response to nutritional treatment 11.12.
Retinol-binding protein, responsible for Vit A transport, has a very short half-life (12 h), very low serum concentrations and is difficult to measure. It is sensitive to acute-phase responses, Vit A & Zn deficiency, hyperthyroidism and renal function. It responds, like pre-albumin to recent dietary intake (use to evaluate nutritional therapy13) rather than reflecting nutritional status per se14.
The low molecular weight, liver produced, protein bound polypeptide (IGF-1), a regulator of cell growth, has a half-life of a few hours and is relatively unaffected by acute-phase response15. Serum IGF-1 concentrations correlate well with albumin and transferrin16 in malnourished patients (reduced synthesis17), but not to anthropometry18. Being affected by growth hormone, kidney & liver disease, undernutrition19 (protein and energy intake20) and its wide reference range render its usefulness in assessing nutritional status limited.
There no single universally accepted objective blood biochemical marker of protein-status due to poor specificity21 and sensitivity to other factors22, especially inflammation23. Serum concentration changes in short half-life proteins24, in the absence of acute phase reaction and hydration changes, indicates a change in nutritional status.