Composite dietary antioxidant index and sleep health: a new insight from cross-sectional study

In this large-scale study of 7274 Americans from NHANES, we discovered that CDAI was non-linearly associated with lower risk of OSA and day sleepiness. At the same time, a linear inverse association between CDAI and insufficient sleep was observed. These findings highlighted the protective effect of antioxidative dietary and provided clinical evidence for the beneficial sleep health from increasing intake of dietary antioxidants.

To date, numerous epidemiological investigations have explored the efficacy of single antioxidant on sleep health, while few studies have focused on the effect of DTAC on sleep disorders. Kanagasabai et al. found that individuals with adequate sleep duration generally had an ideal level of serum vitamin C and other antioxidants profiles in comparison to short or very short sleeper [24]. Observational studies of vitamin A and sleep health are extremely limited and controversial. Natsuko et at. performed a questionnaire survey composed of 3304 Japanese female students and observed that the level of vitamin A intake was linked to disturbed wake–sleep cycle [25], whereas another study discovered there was no significant difference in serum vitamin A levels among adolescent girls with sleepiness comparing with control groups [26]. Although vitamin E was regarded as an important antioxidant, previous studies on vitamin E and sleep have also been controversial. Increased intake of vitamin E was associated with longer sleep time [27] and might reduce memory damage during chronic sleep deprivation [28]. In contrast, a randomized and stratified epidemiological study including 169 mild OSA patients and 83 moderate/severe OSA patients demonstrated that intake of vitamin A, C, D and E was not linked to OSA severity [29]. Interestingly, existing evidence from different observational research consistently supported that carotenoid consumption positively associated with sleep quality, which directly supported our findings in current study. For instance, Stringham et al. showed that healthy adults who were supplemented with 24 mg of macular carotenoid per day experienced improvements in sleep quality [30]. Furthermore, a NHANES 2005–2006 study also found that lower level of serum carotenoid concentration was associated with shorter sleep duration [31]. Despite all this, few studies have evaluated the interaction among different dietary antioxidants on sleep problems. A prior cross-sectional study of 265 diabetic women demonstrated that DTAC was inversely associated with poor sleep quality [11]. Similarly, another cross-sectional study conducted among Iranian post-menopausal women revealed that DTAC was inversely related to sleep disorders and other symptoms related menopause [12].

In present study, we utilized CDAI to comprehensively assess interactive effect of the antioxidants, which was an effective and promising strategy. Our results are generally reasonable. First, oxidative stress constitutes a critical hallmark of sleep disorders. A previous system review indicated that insufficient sleep could activate stress-related neurobiological mechanisms and trigger oxidative processes [32]. An increasing number of epidemiological evidence underlined the adverse effects of oxidative stress in patients with OSA, including the elevated level of intracellular reactive oxygen species (ROS) [33] and decreased level of nitric oxide (NO) or its derivatives [34, 35]. As a matter of fact, unlike other cells, the brain neurons are particularly vulnerable to oxidative stress since they tend to have higher metabolic demands and lower endogenous antioxidant levels [36]. Given that oxidative stress can aggravate impairment to the brain, contributing to the reduction of neurotransmitter concentrations and further affecting sleep quality [37], it is highly plausible that adequate antioxidant dietary may lower the risk of OSA and insufficient sleep via their powerful antioxidant properties.

Second, high-grade inflammation has been acted as a crucial role in the development of OSA [38, 39]. In fact, a prior meta-analysis has demonstrated that sleep disorders and insufficient sleep have elevated levels of c-reactive protein (CRP) and interleukin-6 (IL-6) [24, 40]. A study included three prospective US cohorts suggested that higher anti-inflammatory diet was related to a lower systemic inflammation among 8856 OSA participants [41]. So far, some researchers have verified a negative correlation between DTAC and serum CRP, involving the nuclear transcription factor-κB (NF-κB) pathway [37, 42]. Moreover, two Italian studies based on a two-week intervention with a high DTAC lead to lower CRP levels [43, 44]. Likewise, a population-based cohort study of 3853 Chinese women demonstrated that CDAI was inversely associated with levels of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) [45]. In addition, participants with higher CDAI in our study may consume more vitamins, vegetables and fruits and further display their protective benefits.

Third, glucose metabolism imbalance has been considered as a key risk factor of OSA as well as sleep disorders. A system review suggested that poorly controlled glucose levels could aggravate OSA by impacting central control of respiration and upper airway neural reflexes [37].To some extent, sufficient consumption of antioxidants has associated with lower glucose concentration [46] and improved pancreatic β-cell function [47]. A cohort study of 2694 older people aged more than 59 years old found that higher DTAC was linked to better glucose tolerance [48]. Similar results were found in younger [42] and middle-aged adults [49]. Furthermore, high intake of antioxidants from foods and beverages might provide dietary fiber, magnesium and some enzymes, which were important modifiers in glucose metabolism [50, 51]. Thus, a higher CDAI is related to more intake of these individual antioxidant nutrient, which have beneficial influence on our sleep health.

It is highlighted that non-linear associations between CDAI and the risk of OSA and day sleepiness were found in current study, suggesting the odds of OSA and day sleepiness decreased with the increase of CDAI in a certain range. However, the underlying mechanism of this non-linear relationship still remain unclear. Previous researches reported that dietary zinc and selenium had both properties of antioxidant and prooxidant, which could cause oxidative stress and lose antioxidant capacity when they were out of certain range [52, 53]. Dietary selenium has been linked to increased activation of white blood cells, proliferation and differentiation of immune cells, as well as the production of interferon γ (IFN γ) and other cytokines [54, 55]. Additionally, selenium exerts antioxidant, immunomodulatory and anti-inflammatory effects through the selenoproteins such as selenium-dependent glutathione peroxidase (GPx) [56]. However, an increase in GPx1 activity can potentially disrupt insulin function by excessively suppressing intracellular ROS required for insulin sensitization, ultimately leading to hyperglycemia [57]. Moreover, a meta-analysis of 5 randomized controlled trials has indicated that although selenium administration may improve insulin sensitivity to some extent, no positive effects on lipid profiles or glucose homeostasis have been observed [58]. Thirdly, it is noteworthy that a high dietary antioxidant index is not solely determined by an increased intake of dietary antioxidants, but is also influenced by the consumption of pro-oxidant foods. For instance, red meat, sugary foods, and starches can have pro-oxidant effects due to their high content of advanced glycation end products (AGEs), which are formed during cooking and processing [59]. AGEs can activate inflammatory pathways and generate ROS, which can damage cells and tissues in that counteract the positive effects of antioxidants on the body [60, 61]. These findings offer insight into the antioxidant paradox from various perspectives. Thus, it is possible that excessive intake of zinc and selenium may modify the protective effect of vitamins and carotenoids. More investigations are needed to confirm these dose-response relationship and understand these biological mechanisms.