Dietary Supplements Containing Aegeline and DMAA (1,3-Dimethylamylamine) and their Role in Liver Injury

Aegeline is a constituent of the plant, Aegle marmelos, which has a long history of consumption as a food and traditional medicine. Due to the inclusion in a dietary supplement, OxyELITE Pro, which was apparently associated with liver injury in the fall of 2013 with a suspected cluster in Hawaii, has been the subject of speculation regarding hepatotoxic potential. However, in vitro, animal model and epidemiological data demonstrate a lack of hepatotoxic effects with aegeline. The ingredient, 1,3-dimethylamylamine (DMAA), was also formerly included in OxyELITE Pro and has also been the subject of speculation as to whether it is hepatotoxic. However, randomized controlled trials (RCTs), epidemiological and animal data do not support the notion that DMAA is hepatotoxic. Through an evaluation of the available data, a hypothesis is put forth which better explains the anomalous and contradictory nature of the "outbreak" which was thought to have occurred only in Hawaii and the few subsequent case reports in the mainland United States. Examples of other cases where exclusive reliance upon case reports and a temporal association have led to erroneous assumptions of causality are given. The data do not support a causal role of aegeline, DMAA or OxyELITE Pro in liver injury and instead indicate what may be one of the most prominent cases of a "pseudo-outbreak" and stimulated reporting. This is Part 1 of a 3 part article. Part 1 discusses aegeline and DMAA in detail along with the epidemiology of cases of liver injury purported to be linked with OxyELITE Pro.