What is the half‑life of serum albumin in healthy adults, including during pregnancy?

Albumin Half-Life

Physiological Half-Life in Healthy Adults

The half-life of serum albumin in healthy adults is approximately 20 days (range 14-21 days). 1, 2, 3

• The extended half-life results from albumin's interaction with the neonatal Fc receptor (FcRn), which actively recycles albumin and prevents intracellular degradation 4, 5
• In humans, this FcRn-mediated recycling pathway maintains albumin's exceptional circulatory persistence of approximately 21 days 2
• The turnover rate of human serum albumin ranges from 14-20 days, making it one of the longest-lived plasma proteins 1

Structural Requirements for Normal Half-Life

An intact C-terminal end of albumin is essential for maintaining its long half-life. 3

• The last C-terminal leucine residue (L585) is critical for optimal FcRn binding 4, 3
• Enzymatic cleavage of this terminal residue by carboxypeptidase A dramatically reduces the half-life from 20 days to only 3.5 days in humans 4, 3
• This was demonstrated in a patient with acute pancreatitis who had cleaved albumin lacking L585, resulting in a measured half-life of just 3.5 days 3
• A branched aliphatic amino acid or methionine at position 585 is required for optimal receptor binding and cannot be replaced without negatively affecting FcRn engagement 4

Half-Life During Pregnancy

The provided evidence does not contain specific data on albumin half-life changes during pregnancy. Based on general medical knowledge, albumin half-life may be slightly shortened during pregnancy due to increased plasma volume and enhanced metabolic turnover, though the FcRn-mediated recycling mechanism remains intact.

Clinical Implications of Albumin's Half-Life

The 20-day half-life makes albumin useful for monitoring intermediate-term metabolic changes and as a drug delivery platform. 1

For Glycemic Monitoring

• Glycated albumin (GA) reflects glycemic control over approximately 2-3 weeks, specifically the preceding 1-2 weeks 1
• This is in contrast to hemoglobin A1c, which reflects 2-3 months of glycemic control 1
• Conditions affecting albumin turnover alter GA levels independent of glucose control: accelerated turnover (hyperthyroidism, obesity, nephrotic syndrome) falsely lowers GA, while decreased turnover (hypothyroidism, liver cirrhosis) falsely elevates GA 1

For Nutritional Assessment

• Albumin's 20-day half-life makes it less sensitive to acute nutritional changes compared to prealbumin (half-life 2-3 days) or transferrin (half-life 8 days) 1
• This longer half-life means serum albumin reflects nutritional status over weeks rather than days 1

For Drug Development

• Albumin's long half-life is exploited to extend the pharmacokinetics of fused therapeutic molecules 4, 5
• Albumin-binding domains (ABDs) can be used to recruit albumin and extend the half-life of shorter-lived biologics 4-6-fold 6