Shift work refers to working time arrangements that differ significantly from society's traditional working hours (e.g., 9 a.m.−5 p.m.), or even night work that is completely reversed (1). It cannot be ignored that disruption of circadian rhythms caused by the inability to adapt to shift work may be a major trigger of sleep disturbances (2), cardiovascular disease (3), stroke (4), metabolic syndrome (5), mood problems (6), cancer (7), and sudden death (8). Furthermore, shift work negatively impacts job performance (9), driving safety (10), and health outcomes during pregnancy (11). The best way to avoid shift work disorders altogether is probably to eliminate shift changes. However, owing to the pressures of life, only a small percentage of people can do this. Thus, identifying effective, safe, and acceptable prevention and treatment modalities to maintain health in the long term for shift workers is important.

The prevention and treatment of shift work disorder is mostly a stepwise approach, which is generally conducted in a parallel and multimodal manner. This approach includes pharmacological interventions such as sedative-hypnotics, wake promoters, and dietary supplements (DSs) (12) and includes non-pharmacological therapies such as bright light, napping, physical exercise, and sleep education (13). DSs have been widely available for people with sleep disturbances because of their additional benefits of being more affordable and easier to implement (14), but their therapeutic potential in the field of shift work disorder (SWD) remains to be determined.

In addition, questions concerning the applicability of measurements obtained after simulated shifts of healthy people to the real world prompted this study. Excessive stress due to work and social relationships in real life can lead to a vicious cycle of circadian rhythm disruption (15). Therefore, in our review, we deliberately excluded trials with simulated shifts to better reflect the clinical efficacy of DSs in the real world. The aim of this review was to assess the efficacy and safety of DSs for shift workers.

This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Supplementary File 1) (16). This prospective meta-analysis is registered in the International Prospective Register of Systematic Reviews (PROSPERO) and the registration number is CRD42021273558. This review had no direct patient or public involvement.

The purpose of this review was to explore the potential role of DSs in improving sleep quality, daily functioning, and mood among shift workers. The key findings of this systematic review and meta-analysis indicated that, compared with placebos, DSs demonstrated a statistically significant difference in improving sleep quality and daytime function for participants. However, the change in psychomotor vigilance and mood was not significant. Perhaps the most important finding was that although a limited number of studies reported the presence of adverse events such as sleepiness, dizziness, and headache, all adverse effects were mild and transient, and the differences between the DS and the control groups were not statistically significant. No participants withdrew from the studies because of adverse events. In subgroup analyses, high-quality studies showed that DSs had a clear clinical effect, but low-quality studies showed no difference. It is interesting to consider that there was no difference in the efficacy of DS in either the melatonin or non-melatonin subgroups, this change in outcome may be related to the reduced sample size of the subgroups.

To the best of our knowledge, this study is the first systematic review and meta-analysis to examine the effects of DSs on SWD in real working environments. In a recent systematic review (12) of pharmacological interventions for SWD, the clinical efficacy of melatonin and that of caffeine were assessed. The findings suggested that melatonin may improve sleep length after night shifts, but may not improve other sleep quality parameters, whereas pre-shift caffeine increased alertness during the night shift. Investigators in another review (31) similarly concluded that caffeine may be an effective intervention for improving performance in shift workers. However, both studies lacked high-quality evidence and did not involve other types of dietary supplements. Consistent with these reviews, we reiterated the positive impact of DSs on sleep quality and work performance among shift work populations. SWDs are often accompanied by changes in mood (32); therefore, in our study, we evaluated the effect of DSs on the emotional state. However, we did not find that DSs had a better effect on mood in SWD than did placebos.

Uncertainty about the action mechanism of DSs may be the primary cause contributing to their limited promotion because they affect sleep quality, endogenous melatonin metabolism, positive regulation of the sleep–wake cycle, and alterations in inflammatory conditions closely associated with insomnia (33). For example, probiotics are believed to bring health benefits to patients with insomnia through the activity of the gut–brain axis (34). The mechanisms regarding the role of vitamins and herbs in sleep are similar and are probably associated with anti-inflammatory and antioxidant activity (35, 36). Of note, this area of research has received increasing attention because links between SWD and many major diseases of modern society have been established (32).

Compared with other intervention options, safety and adherence are also issues to consider when choosing DSs. Pharmacological hypnotics and wake-promoting drugs have a low safety profile and significant adverse effects; thus, the ingestion of drugs to manage SWD may not meet with widespread acceptance (37). Light therapy has been used effectively in SWD, but the time needed for bright light treatment may conflict with work tasks, and light exposure in the surrounding environment may be difficult to control. The application of laboratory-based knowledge to the real world can be problematic (2, 13). Our results suggested that consumption of DSs was comparatively safe with no serious adverse events. Researchers in a previous systematic review (38) on the safety of DSs drew a similar conclusion and proposed that the evaluation of DSs use and their safety should be regularly included in clinical trials. In addition, most of the studies we included did not address follow-up; therefore, the long-term efficacy of DSs has yet to be determined. Future research is urged to incorporate adequate follow-up with a long-term duration.

Despite the partially encouraging results of our study, several limitations should be noted. First, heterogeneity existed in the main outcome indicators, and through a meta-regression, we identified the year of publication, occupation, and study quality as possible sources. An attempt to analyze subgroups by year of publication and occupation unfortunately failed, as no grouping pattern was found for them. We were only able to select the types of DSs and study quality for subgroup analysis based on clinical characteristics, but there was still some heterogeneity. The findings were also interesting in the results of the sensitivity analysis. The outcome of sleep quality remained stable, as demonstrated in Figure 4, although we found that the statistical significance of the differences changed after removing several studies (19, 23, 29, 30), possibly because of differences in the study quality or sample size of these and other trials. Second, despite our efforts to conduct a comprehensive search of the literature, some relevant studies may have been missed because they were in languages other than English, which limited the amount of the included literature. Our systematic review did not include studies in Chinese, even though herbs are very popular in China. As the quality of clinical studies published in Chinese improves, future meta-analyses may include more trials using Chinese herbal medicine for SWD. Finally, populations in work-shift situations need prolonged attention. However, the included studies lacked follow-up information, thereby resulting in a lack of basis for evaluating the long-term efficacy of DSs.

Our meta-analysis showed that DSs improved sleep quality and daytime function in shift workers, but they had no significant effect on psychomotor vigilance and mood. Thus, DSs could potentially be valuable clinically in improving sleep quality and daytime function in shift workers. Unfortunately, the small amount of the literatures included for each type of dietary supplement does not allow us to know how the different DSs compare. More high quality multi-arm and crossover designed RCTs are needed in the future to enable us to update the findings of this meta-analysis in time and provide the best options for dietary supplement management for shift workers.

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.

YW and CZ: writing—original draft. YW, XH, CZ, and DS: methodology. XH: software. RW: supervision and validation. QZ and HL: writing—review and editing. QZ: conceptualization. HL: team management and coordination. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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