Is Albumin an Acute Phase Reactant?
Yes, albumin is a negative acute-phase reactant, meaning its serum concentration decreases during inflammation, infection, or tissue injury. 1, 2
Mechanism of Action During Inflammation
- Inflammatory cytokines directly suppress hepatic albumin synthesis in the liver, even when protein and caloric intake are adequate. 2, 3
- This downregulation occurs at the individual hepatocyte level, with some liver cells completely ceasing albumin production while others maintain normal synthesis, creating a patchy pattern of albumin production during acute inflammation. 4
- The suppression of albumin synthesis represents a reprioritization of hepatic protein production toward positive acute-phase proteins (such as C-reactive protein, fibrinogen, haptoglobin, and ceruloplasmin) during inflammatory states. 1, 3
Clinical Behavior During Acute Inflammation
- Within 24 hours of an acute inflammatory insult (such as elective surgery or trauma), plasma albumin concentrations fall markedly without any change in whole body nutritional status. 1
- Postoperative states typically show a 10-15 g/L decrease in albumin due to inflammatory cytokine activity and transcapillary albumin loss. 3
- Serum albumin concentrations are inversely correlated with C-reactive protein (CRP) and other positive acute-phase proteins. 2, 3, 5
Contrast with Positive Acute-Phase Reactants
- While albumin decreases during inflammation, positive acute-phase proteins (CRP, α1-acid glycoprotein, ferritin, ceruloplasmin, fibrinogen, serum amyloid A, and haptoglobin) increase in concentration. 1, 2, 6
- This inverse relationship is so consistent that CRP should be measured simultaneously with albumin to properly interpret albumin levels in any clinical context. 1, 7
Critical Clinical Implications
- Low albumin does not automatically indicate malnutrition—it primarily reflects systemic inflammation in most hospitalized patients. 3, 7, 8
- The American Society for Parenteral and Enteral Nutrition explicitly states that serum albumin is an indicator of inflammation, not malnutrition. 3, 7
- Albumin's long half-life (20 days) means it responds slowly to both nutritional changes and resolution of inflammation. 1, 7
Common Pitfalls to Avoid
- Assuming hypoalbuminemia is solely due to malnutrition when inflammation is the primary driver in most acute and chronic disease states. 3, 7
- Failing to measure inflammatory markers (particularly CRP) when interpreting low albumin values, which prevents accurate clinical assessment. 1, 7
- Attempting to "correct" low albumin with nutritional supplementation or intravenous albumin infusions while inflammatory suppression of hepatic synthesis persists—this approach is ineffective and potentially harmful. 3
Comparison with Prealbumin
- Prealbumin (transthyretin) is also a negative acute-phase reactant with a shorter half-life (2-3 days versus 20 days for albumin). 1, 7
- Despite its shorter half-life, there is insufficient evidence to conclude that prealbumin is more sensitive or accurate than albumin as a nutritional marker, and both are equally limited by their response to inflammation. 1, 7
- The presence of acute or chronic inflammation limits the specificity of both prealbumin and albumin as nutritional markers. 1