We have determined that the major role of glycine conjugation is to dispose of the end products formed by the gut microbiome through the metabolism of dietary polyphenols. Glycine conjugation facilitates the metabolism of toxic aromatic acids, capable of disrupting mitochondrial integrity. The importance of functional hepatic glycine conjugation has been underestimated in the last few decades. The glycine conjugation capacity of individuals vary significantly. Glycine conjugation is a two-step process and the overall rate of glycine conjugation can be influenced by several factors, including the availability of ATP, Coenzyme A, and glycine; genetic variation in the ATP dependent acid: CoA ligase (ACSM2B) (encoding HXMA) and glycine N-acyltransferase (GLYAT) (encoding GLYAT) genes as well as variable expression of HXMA and GLYAT. We have previously established that the observed variation is not due to genetic variation in GLYAT as the GLYAT gene is highly conserved among humans and polymorphisms with deleterious effects are rare. Due to the high exposure to toxic substrates such as benzoate and aspirin, characterisation of the factors that contribute to the variation in individual glycine conjugation capacity needs to be further investigated.