MedicalResearch: What is the background for this study?
Dr. Erickson: In Jan 2012 a paper reported the discovery of irisin, a hormone reportedly lopped off a precursor in muscle and sent through the bloodstream to fat tissue, where it turned white fat into brown fat. Brown fat burns calories, and is what hibernating animals – and even human babies — use to keep warm. Turning on brown fat had exciting promise for obesity, diabetes, etc. Dozens of labs around the world jumped on the discovery and started trials in animals and humans of how irisin levels in blood were altered by exercise and a variety of metabolic challenges.
MedicalResearch: What are the main findings? Early reports.
Dr. Erickson: The follow-up studies from different labs reported a huge range of values for the level of irisin in blood, so they could not all be right. And most of them failed to find any significant effect of exercise. In 2013 two papers criticized the irisin study. A commentary article by Harold Erickson (Adipocyte 2:289-93) reported two substantial flaws in the original study. A research paper by S. Raschke, J. Eckel and colleagues (PloS one 8:e73680) concluded that humans did not make significant amount of irisin. The human gene for irisin has a deleterious mutation in the start codon, and Raschke et al showed that this reduced irisin expression to only 1% the level with the normal start. These two reports may have slowed new labs entering the field, but many groups already invested continued to publish.
MedicalResearch: What are the main findings? New study.
Dr. Erickson: The new study published in Scientific Reports (5:8889) investigated the commercial ELISA kits that most previous studies used to determine irisin levels in blood. These kits were all based on polyclonal antibodies, which had never been investigated for cross-reaction to non-specific blood proteins. The new study found that these antibodies failed to detect any band of the correct size for irisin in the blood from several animal species. Moreover, each antibody strongly stained a variety of non-specific blood proteins. The conclusion was that the ELISA kits used in multiple published studies were reporting levels of non-specific proteins, not irisin.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Erickson: Irisin was never near clinical application. The distant promise of its use in therapy, or as an “exercise pill” is now fading or gone.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Erickson: The field really needs an assay validated to be specific for irisin, and hopefully very sensitive. If this confirmed that humans do not have irisin, as expected from the Raschke study, the field could quietly die.
Irisin – a myth rather than an exercise-inducible myokine
Elke Albrecht, Frode Norheim,Bernd Thiede, Torgeir Holen,Tomoo Ohashi,
Lisa Schering,Sindre Lee,Julia Brenmoehl, Selina Thomas,Christian A. Drevon,
Harold P. Erickson& Steffen Maak
MedicalResearch.com Interview with:, & Harold P. Erickson Ph.D (2015). ‘Exercise Pill’ Irisin Appears To Be A Myth