In addition to contribution from the microbiome, there are other factors that can influence Trp dynamics. Approximately 75-85% (and as high as 95%) of Trp in the body is bound to albumin protein . While only ~5-10% is suspected to be free under normal conditions , because Trp has a higher affinity for the BBB transporter than albumin , it has been estimated that as much as 75% of free Trp can cross the BBB . And whle total Trp usually does not change much, free Trp can change drastically. Changes in peripheral Trp can also cause changes in free Trp in the central nervous system. For example, researchers showed that an intraperitoneal (i.p.) injection of L-Trp resulted in rapid increases in Trp in cerebrospinal fluid and the striatum, which was measured via microdialysis . Furthermore, they found that i.p. injection of L-Trp increased Trp levels in cerebellum to a greater degree than that in striatum, although Trp levels reached a max amount in both regions ~40 min after the injection . Interestingly, there was also an increase in 5-HIAA in the striatum, with a max amount reached 120 min after Trp injection. No changes in 5-HIAA was observed in the cerebellum. Endogenous free Trp levels can also change due to various factors. For example, in a study done by Chaouloff et al. , researchers trained rats to run on a treadmill for 2 hrs. Even though total Trp was not altered, the amount of free Trp in the plasma increased by 70% post-run. The levels of other plasma neutral amino acids were not altered. Interestingly, the amount free brain Trp increased by 80% post-run. Most of the other amino acids did not change and threonine increased only moderately. These studies highlight that there is indeed interesting endogenous Trp dynamics in the brain and periphery and these can be altered by various factors. Collecitvely, this evidence suggest that there are Trp dynamics and these changes in free Trp may alter other neurotransmitter levels (ie serotonin) and thereby alter brain chemistry and behavior.