From animal cage to aircraft cabin: an overview of evidence translation in jet lag research.

Recent laboratory experiments on rodents have increased our understanding of circadian rhythm mechanisms. Typically, circadian biologists attempt to translate their laboratory-based findings to treatment of jet lag symptoms in humans. We aimed to scrutinise the strength of the various links in the translational pathway from animal model to human traveller. First, we argue that the translation of findings from pre-clinical studies to effective jet lag treatments and knowledge regarding longer-term population health is not robust, e.g. the association between circadian disruption and cancer found in animal models does not translate well to cabin crew and pilots, who have a lower risk of most cancers. Jet lag symptoms are heterogeneous, making the true prevalence and the effects of any intervention difficult to quantify precisely. The mechanistic chain between in vitro and in vivo treatment effects has weak links, especially between circadian rhythm disruption in animals and the improvement of jet lag symptoms in humans. While the number of animal studies has increased exponentially between 1990 and 2014, only 1-2 randomised controlled trials on jet lag treatments are published every year. There is one relevant Cochrane review, in which only 2-4 studies on melatonin, without baseline measures, were meta-analysed. Study effect sizes reduced substantially between 1987, when the first paper on melatonin was published, and 2000. We suggest that knowledge derived from a greater number of human randomised controlled trials would provide a firmer platform for circadian biologists to cite jet lag treatment as an important application of their findings.