The Continued Mismeasurement of Plasma Serotonin: A Systematic Review

Studies reporting on the analysis of free plasma (platelet-poor plasma, PPP) serotonin (5-hydroxytryptamine, 5-HT) in plasma obtained from healthy humans have been systematically reviewed. The review covered the period from 2010 to July 2024 and is a follow-up of a similar review published in 2011 which found that nearly all published reported of PPP 5-HT were clearly and markedly erroneously high. This problem has persisted unabated with nearly all retrieved 47 reports from the past 14 years also apparently being erroneously high. Possible causes and consequences of the problem are discussed along with potential approaches to improving the analysis and reporting of plasma 5-HT. Most of the errors appear to arise from pre-analytical problems that occur during the preparation of PPP due to residual platelets and/or due to the release of platelet 5-HT. The large number of fields interested in plasma 5-HT and the disparate publication venues appear to have contributed to a general lack of awareness of the difficulties with analyzing plasma 5-HT. The reporting of erroneous plasma 5-HT values has led to unsupported conclusions about possible alterations in plasma 5-HT and about the role of plasma 5-HT across a wide range of biomedical research areas.