Herein, we demonstrated feasibility of a 14-day, 10-hour time-restricted eating intervention among cancer survivors with persistent cancer-related fatigue, as well as initial efficacy. The intervention was very well received, and the vast majority of participants stated that they will continue a time-restricted eating in some fashion. This intervention was safe, and participants reported clinically meaningful improvements in their fatigue using uni- and multidimensional fatigue questionnaires. These results support further testing of a 10-hour time-restricted eating intervention vs. usual care and time- and attention-control interventions to alleviate cancer-related fatigue in cancer survivorship.
Adherence was excellent, with 86% adhering at least 80% of the days, and an average eating window of 9 hours, 20 minutes. This is in line with other studies that have evaluated adherence to 8-10-hour time-restricted eating regimens. For example, healthy participants adhered to a 10-12-hour window (self-selected) 6.5 ± 0.5 days/week during a 12-week-long study (92% adherence, n = 19) [7]. Adults with type 2 diabetes adhered to a 9-hour eating window (10:00–17:00) 20 ± 7 out of 28 days of the intervention (average 72% adherence, n = 19) [10]. Obese adults adhered to an 8-hour eating window (10:00–18:00) 5.6 ± 0.3 days/week for 12 weeks (80% adherence, n = 23) [24]. Further, people with metabolic syndrome adhered at least 5.0 ± 2.2 days/week over a 12-week intervention (72–81% weekly adherence, n = 37). While our study was only 14 days long, other studies have demonstrated consistent adherence over time periods up to 12 weeks [24, 25].
Our results build upon literature showing that cancer survivors with persistent cancer-related fatigue are willing and able to adhere to behavioral interventions to address their fatigue. Currently, behavioral interventions such as exercise and psychosocial interventions (e.g., cognitive behavioral therapy) are more effective to combat fatigue than the available pharmaceuticals [26], and effective nutritional interventions are emerging [27]. Behavioral interventions are desirable because they have a plethora of health benefits and few side effects. Time-restricted eating, specifically, is appealing because it is free-of-charge and does not require specialized equipment, thereby making it widely accessible [8]. Our adherence rate of 90% was slightly higher than many other studies that evaluate behavioral interventions among cancer survivors. For example, exercise interventions tend to have adherence rates of 54–78% among cancer survivors [28]. Dietary interventions tend to have more variable adherence, with rates ranging from less than 50–100%, depending on how adherence is calculated [27]. Notable examples include adherence of 81% at 12 weeks for a Mediterranean diet intervention [29] and 73–94% for food group goals in a 12-week ‘Fatigue Reduction Diet’ study [30], both of which were conducted among survivors with persistent cancer-related fatigue.
Time-restricted eating has the potential to improve several pathophysiological mechanisms that underlie cancer-related fatigue. First, time-restricted eating may be able to alleviate fatigue by entraining circadian rhythms. Circadian rhythms are 24-hour biological cycles that work in synchrony to regulate hormone secretion, the sleep/wake cycle, and metabolic processes. Cancer and cancer treatment have been shown to disrupt circadian rhythm, which can lead to sleep disturbances and fatigue [31–34]. Circadian rhythm is affected by external cues—zeitgebers—that include light exposure, sleep, physical activity, and nutrient timing [6]. Consistent animal and human data demonstrate that aberrant eating patterns disrupt circadian rhythm (i.e., disruption of expression of genes that show strong diurnal oscillations) [6]. Only about 10% of people eat within a window less than 12 hours [14], and a consistent, shorter window of eating, for example 10 hours, may help entrain the circadian clock and improve metabolic homeostasis with broad health consequences [6, 7]. In addition, bright light therapy, which aims to regulate circadian processes, has shown benefits for cancer-related fatigue [35]. Second, cancer and cancer treatments can interfere with metabolism including glucose, lipid, and redox homeostasis, hormone regulation, and mitochondrial function, possibly causing or exacerbating cancer-related fatigue [5, 36, 37]. Time-restricted eating can regulate glucose metabolism and metabolic hormones in people with chronic conditions [6, 7, 24]. It can be combined with other dietary interventions that prescribe the amount and/or composition of the diet (e.g., [9]). Other suggested mechanisms underlying cancer-related fatigue include chronic inflammation, disruption of the hypothalamus-pituitary-adrenal (HPA) axis, neuroendocrine functions, and psychological distress [5, 37]. There is preliminary evidence that time-restricted eating can regulate and/or improve some of these functions via circadian or independent processes [8, 38]. The effects of time-restricted eating on circadian rhythm have yet to be measured and the relationships between cancer- and treatment-related pathology, persistent psychological distress, circadian rhythm, and cancer-related fatigue are not yet fully elucidated, but this is a rich area for future research.
The results of this study should take into account both its strengths and limitations. It is one of the first studies testing time-restricted eating in the cancer population, and the first, to our knowledge, to apply it to address chronic fatigue and supportive care outcomes. Our study is limited in that it was small and conducted in mostly older breast cancer survivors, so generalizability should occur with prudence. Also, recruitment occurred during 2020–2021; it is unknown how the COVID-19 pandemic impacted the feasibility of recruitment and participants’ ability to adhere to time-restricted eating. However, because our study was conducted completely remotely, our methods may be used for follow-up multisite studies and studies in rural and other hard-to-reach populations. Lastly, our study was only 14 days long and time-restricted eating interventions that report health benefits are usually at least 8 weeks [6, 8]; it is unknown how adherence will change over a longer study period.