Peer-reviewed scientific studies have come to opposite conclusions on whether the mercury exposure from amalgam fillings causes health problems. A 2004 systematic review conducted by the Life Sciences Research Office, whose clients include the FDA and NIH, concluded that "the current data are insufficient to support an association between mercury release from dental amalgam and the various complaints that have been attributed to this restoration material". A peer-reviewed Journal of the Canadian Dental Association article holds that "it seems likely that humans may have evolved with a threshold level for mercury below which there is no response or observable adverse health effects". Another review published in 2005 by the Freiburg University Institute for Environmental Medicine found that "mercury from dental amalgam may lead to nephrotoxicity, neurobehavioural changes, autoimmunity, oxidative stress, autism, skin and mucosa alterations or non-specific symptoms and complaints", that "Alzheimer's disease or multiple sclerosis has also been linked to low-dose mercury exposure", and that "removal of dental amalgam leads to permanent improvement of various chronic complaints in a relevant number of patients in various trials."