Epidemiological evidence on the association between macronutrient intake and excessive daytime sleepiness (EDS) is scarce. Using data from the North West Adelaide Health Study, we aimed to determine the association between iso-caloric substitution of macronutrients and EDS. Data from 1997 adults aged ≥ 24 years were analyzed. Daytime sleepiness was measured using the Epworth Sleepiness Scale, a score ≥ 11 was considered EDS. Dietary intake data were collected using a food frequency questionnaire. We determined absolute and relative energy intake based on consumption of saturated and unsaturated fats, protein, and carbohydrate. Odds ratios (ORs) were used to determine the associations using log-binomial logistic regression with and without iso-caloric substitution methods, and models were adjusted for confounders. The prevalence of EDS in the sample was 10.6%. After adjusting for potential confounders, substituting 5% energy intake from protein with an equal amount of saturated fat (OR = 1.57; 95% CI: 1.00–2.45) and carbohydrate (OR = 1.23; 95% CI: 0.92–1.65) increased the odds of EDS. When carbohydrate was substituted with saturated fat (OR = 1.27; 95% CI: 0.93–1.59), the odds of EDS were increased. The odds of EDS were lower when saturated fat was substituted with unsaturated fat (OR = 0.74; 95% CI: 0.51–1.06), protein (OR = 0.63; 95% CI: 0.41–0.99) or carbohydrate (OR = 0.79; 95% CI: 0.57–1.08). While these results were consistent over different iso-caloric substitution methods, inconsistent results were found with standard regression. While substitution of fat and carbohydrate with protein was inversely associated with EDS, substitution of protein with fat and carbohydrate was positively associated with EDS. Randomized trials are needed to confirm if dietary interventions can be used to improve daytime alertness in those with EDS.
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