from http://journals.sagepub.com/doi/pdf/10.1177/2326409817707771 Coenzyme Q10 in the Treatment of Mitochondrial Disease Journal of Inborn metabolic disease 2017 Viruna Neergheen, MSc, Annapurna Chalasani, MSc,Luke Wainwright, MSci, MRes, Delia Yubero, PhD, Raquel Montero, PhD, Rafael Artuch, MD, PhD,and Iain Hargreaves , PhD extract: Absorption and Bioavailability of CoQ10 Formulations Although all cells of the body apart from red blood cells are capable of synthesizing CoQ10, the body also receives CoQ10from dietary sources such as meat, fish, and some vegetables,with an estimated intake of 3 to 5 mg per day. In view of its similar physicochemical properties to that of vitamin E, CoQ10 appears to follow an analogous pattern of digestive uptake. Gastric digestion releases dietary CoQ10 from the food matrix, secretions from the pancreas, and bile and then facilitates micelle formation leading to absorption of the solubilized lipid in the small intestine. Coenzyme Q10 is then incorporated into chylomicrons and transported via the lymphatic system into the circulation. Following absorption from the gastrointestinal (GI) tract, CoQ10 is reduced into its ubiquinol form which is thought to occur in the enterocytes of intestine prior to its entry into the lymphatic system. After release into the circulation, chylomicron remnants are readily taken up by the liver, where ubiquinol is repackaged into lipoproteins, primarily, low-density lipoproteins, and then rereleased into the circulation. In general, tissues with a high-metabolic turnover or energy demand, such as the heart, kidney, liver, and muscle, contain relatively high concentrations of CoQ10, and it is thought that most of this CoQ10 pool is synthesized in such tissues. Approximately 95% of plasma and 61% to 95% of tissue CoQ10 are present in the reduced, ubiquinol form. The brain and lungs are exceptions with 25% of total CoQ10 being found as ubi- quinol. This may reflect the higher degree of oxidative stress in these 2 tissues. In cases of primary and secondary CoQ10 deficiency, acquisition of CoQ10 from the diet may be insufficient to meet cellular requirements as intestinal absorption of CoQ10 is very limited and supplementation may be a consideration. An important factor to consider which may influence the clinical response to CoQ10 supplementation is the type of CoQ10 formulation employed, as this will have an important bearing on absorption and bioavailability. In view of their superior absorption, the use of gel and oil-based formulations of CoQ10 has been recommended in preference to tablets in the treatment of patients with mitochondrial disorders. Recently, a study by Martinefski et al reported that liquid emulsion improved the bioavailability of CoQ10 with respect to solid formulations. Following administration, CoQ10 takes approximately 6 hours to reach its maximal plasma concentration. Subsequently, a second plasma CoQ10 peak is often observed at about 24 hours, which has been attributed to enterohepatic recycling as well as redistribution to the circulation. Once administered, the circulatory half-life of CoQ10 has been reported to be approximately 36 hours requiring a 2-week period of cessation of treatmentbefore it returns to its baseline level following 4 weeks of supplementation. There is a lot of debate at present as to whether formulations of ubiquinol have a better absorption from the GI tract than those of CoQ10. It has been estimated that the GI absorption of ubiquinol is 3 to 4 times greater than that of CoQ10. However, since upon absorption from the GI tract, CoQ10 undergoes reduction to ubiquinol, the purported superior bioavailability of ubiquinol formulations to that of CoQ10 may in part be attributable to the matrix in which the quinol is encapsulated. Furthermore, there is limited data available from patient studies and no clear indications of dosage compatibility. Interestingly, ubiquinol treatment, in contrast to an equivalent dosage of CoQ10, was reported to increase the CoQ10 status of mitochondria from the cerebrum of a mouse model of CoQ10 deficiency due to a COQ9 mutation. The results of this study may therefore have important implications for the treatment of the cerebral presentations of CoQ10 deficiency. The efficiency of absorption of CoQ10 formulations has been reported to decrease as the dosage increases with a suggested block of GI absorption above 2400 mg, and split doses have been recommended in preference to a single dose. Dietary fat together with grapefruit juice consumption have been reported to improve the absorption of CoQ10. In contrast, ingestion of high-dose vitamin E together with CoQ10 may impede the absorption of CoQ10 resulting in lower plasma levels of the quinone, possibly as a result of competition during the GI absorption process.