Meal timing as a modifiable behavior associated with coronary heart disease and DNA methylation

Background

The association between chrononutrition and cardiovascular health is an emerging field and mechanisms remain uncertain. We aimed to assess weather meal timing is associated with the risk of coronary heart disease (CHD) and stroke, and to identify epigenetic marks as potential underlying mechanism.

Methods

Using data from the Spanish prospective GCAT cohort, we fitted multivariable Cox proportional-hazards models to examine associations between time of first and last meal, nighttime fasting duration, number of eating occasions, and intervals between waking and first meal and between last meal and bedtime, with CHD and stroke incidence. Additionally, we conducted an epigenome-wide association study (EWAS) on blood DNA methylation assessed at baseline with the Illumina EPIC2 array, using robust regression models.

Results

Among 6988 adults (58% women, median age 52y [IQR: 47-58]), 115 CHD and 60 stroke events occurred over a median follow-up of 6 years. A later time of last meal was associated with a higher risk of CHD events (HR for 1 hour increase: 1.35; 95% CI: 1.04–1.76), while a longer interval between the last meal and bedtime and longer nighttime fasting were associated with lower risk (HR: 0.78 [0.62–0.99] and HR: 0.85 [0.721–0.99] respectively). No associations were found with stroke. The EWAS conducted in a subcohort of 665 subjects identified 20 suggestive cytosine-phosphate-guanine loci (CpGs) associated with meal timing and nighttime fasting (P < 10⁻⁵), of which 6 had been previously linked to cardiometabolic traits such as BMI, cholesterol, and inflammation.

Conclusions

Earlier last meals and longer nighttime fasting were associated with reduced CHD risk and suggestively associated with differential DNA methylation at several CpG sites, some related to cardiometabolic health. These findings support meal timing as a potentially modifiable behavioral factor and may inform innovative public health strategies for cardiovascular prevention.

Key messages

• Meal timing may represent a modifiable behavioural factor and a potential target for public health strategies to prevent coronary heart disease.

• A later last meal is associated with higher coronary heart disease risk, whereas longer nighttime fasting appears protective, highlighting the role of meal timing in cardiovascular health.