Rebuttal from Saurabh S Thosar, Nicole P Bowles, and Andrew W McHill

In this debate, Drs. Ritchie and Broussard argue that insufficient sleep is primarily responsible for the increased risk for metabolic disease in shift workers. They have systematically highlighted the deleterious effects of sleep loss on cardiometabolic health, to which we agree. However, their argument that sleep loss is the primary driver for poor health in shift-work is somewhat undercut by the fact that they based their reasoning on studies that 1) are unable to separate the effects of circadian misalignment and insufficient sleep, 2) are unclear about the distinction between insufficient and disrupted sleep, which potentially act through separate mechanisms, 3) postulate circadian misalignment as the mechanism for metabolic dysfunction in shift workers, and 4) only investigate the acute effects of sleep loss (Åkerstedt, 2003; Broussard et al., 2015; Anothaisintawee et al., 2016; Brouwer et al., 2020; Peñalvo et al., 2021).

To address the authors’ claim that shift work and sleep are inextricably linked, we point to work in their argument that either controls for sleep duration while investigating circadian misalignment or demonstrates the metabolic impact of circadian misalignment independent of sleep. Meta-analysis by (Anothaisintawee et al., 2016) concluded that shift work remains associated with increased risk for metabolic disease even after controlling for traditional risk factors, including physical activity, smoking, dietary choices, and alcohol consumption. While the investigators of the meta-analysis control for likely culprits, they do not control for circadian misalignment, an inherent insidious trait of shift-work and impossible to separate. Moreover, this meta-analysis also found that long sleep is associated with a higher relative risk of developing diabetes compared to short sleep, which may refute Drs. Ritchie and Broussard’s argument.

As we previously argued, human volunteers typically consume excess calories in the presence of insufficient sleep, with the majority of those excess calories being consumed in the late evening hours (Nedeltcheva et al., 2009; Markwald et al., 2013; Spaeth et al., 2013). Though such evidence doesn’t directly point to circadian misalignment as the mechanism, per se, subsequent work has demonstrated that such a shift in the time of energy intake is associated with an increased risk for obesity when controlling for sleep (McHill et al., 2017). Importantly, recent data in humans suggest limiting eating to daytime (circadian alignment) under experimental conditions of shift work, which results in some degree of sleep loss even in near-perfect sleeping conditions (67.8% sleep efficiency), mitigates metabolic dysfunction (Chellappa et al., 2021).

In conclusion, although shift-work results in insufficient and/or impaired sleep, extensive evidence suggests that the inherent circadian misalignment under conditions of shift work is most responsible for the increased risk of metabolic disease.