An overnight fasting regimen commencing at least 3 hours prior to bedtime led to significant improvements in key cardiometabolic measures including nighttime blood pressure, heart rate dipping, and glucose regulation, results from a small but intriguing new study showed.

The findings underscore that “it’s not only how much and what you eat but also when you eat relative to sleep that is important for the physiological benefits of time-restricted eating,” said senior study author Phyllis Zee, MD, director of the Center for Circadian and Sleep Medicine and the chief of sleep medicine in the Department of Neurology at Northwestern University Feinberg School of Medicine in Chicago, in a press statement.

Importantly, the intervention group had a nearly 90% adherence rate, suggesting that sleep-aligned fasting “represents a feasible, nonpharmacological intervention for cardiometabolic disease risk reduction,” Zee and her colleagues noted in the study, recently published in Arteriosclerosis, Thrombosis, and Vascular Biology.

The consumption of food late in the day, in the hours close to bedtime, is known to be associated with a variety of adverse health effects, including weight gain, insulin resistance, and impaired glucose regulation. Conversely, overnight fasting and time-restricted eating have recognized cardiometabolic health benefits.

Aligning Fasting With Individual Sleep Schedules

Research on the issue has been mainly focused on the duration of overnight fasting; therefore, the authors, all with the Northwestern University Feinberg School of Medicine, sought to evaluate the effects of a fasting regimen that was specifically timed to closely align with an individual’s sleep schedule.

“Since sleep timing varies between individuals due to differences in circadian sleep-wake regulation, anchoring the fasting window around each person’s habitual sleep schedule may enhance these sleep-dependent cardiometabolic processes,” they explained in the study.

For the parallel-arm, controlled trial, 39 participants with overweight or obesity, aged 36-75 years, were randomly assigned to complete either an extended overnight fasting intervention of 13-16 hours of fasting, with their last meal timed at least 3 hours before sleep, with no food or beverages with calories in the fasting period or a control condition of maintaining their usual eating routines, with an overnight fast of 11-13 hours.

To minimize differences in other influences on the circadian system, both groups were instructed to dim lights 3 hours prior to bedtime. The median age in each group was 52 years, and about 80% of patients in both groups were female. The median baseline BMI was about 29 vs 33.7 in the intervention group vs the control group.

After a duration of 7.5 weeks, those in the sleep-aligned intervention group that stopped meals within 3 hours of bedtime had meaningful improvements in the co-primary endpoint of diastolic blood pressure dipping (average increase of 3.5% in the day-to-night ratio; P = .019), as well as a greater nighttime heart rate dipping (5%; P = .003) than the control group.

Those findings are important because non-dipping blood pressure patterns — defined as less than 10% reduction in blood pressure from day to night — “are linked to an increased risk of cardiovascular events and target organ damage, independent of blood pressure levels,” the authors wrote.

Importantly, each 5% increase in nighttime blood pressure dipping has been associated with a 17% reduction in cardiovascular events, they noted.

“Furthermore, blunted nighttime heart rate dip has also been linked to all-cause mortality, further supporting [intervention group’s] cardiovascular benefits,” the authors added.

There were no significant differences between the groups in other measures of nighttime systolic blood pressure or daytime changes in systolic or diastolic blood pressure. The intervention group had a significantly greater reduction in nighttime cortisol levels than the control group (P < .007).

The stronger effect of the intervention on diastolic compared with systolic dipping “may reflect the intervention’s effect on reducing sympathetic activation and, consequently, peripheral vascular resistance and cardiac output,” the authors added.

However, the differences could also relate to age-related changes in blood pressure regulation because diastolic blood pressure “becomes more sensitive to autonomic modulation with aging,” they noted.

There were no significant changes in either group in terms of the Matsuda index of insulin sensitivity, which was the other co-primary outcome of the study, and there were also no significant differences in terms of fasting glucose levels.

The authors speculated that the lack of those differences could be explained by the fact that half of the study participants had normal glucose tolerance, and evidence suggests the Matsuda index could have limited sensitivity in capturing insulin changes in longitudinal studies.

However, the intervention group had lower 1-hour oral glucose tolerance test levels and a higher 30-minute insulinogenic index, suggesting improved pancreatic beta-cell function, they said.

Of note, there were no significant differences between the groups in terms of total daily calories, and no differences in change in BMI or waist circumference from baseline to post-intervention.

The observation of significant improvements in cardiometabolic measures only in the intervention group, despite the similar evening light dimming conditions, indicates that the benefits were indeed driven by the sleep-aligned fasting intervention, the authors noted.

Small Study, ‘Robust’ Effect

A key limitation was the study’s small size, but Zee pointed out that the results are nevertheless significant. “The study was relatively small but was sufficiently powered to detect a significant difference,” she told Medscape Medical News.

“What is notable is that the effect was robust enough to be seen in a small to medium sample size,” she added.

While the majority of participants were female, the effect remained after adjusting for sex. “The imbalance is a limitation, but the findings likely generally applicable to both men and women,” she said.

However, the study involved middle- and older-aged adults, and the results may not be generalizable to children or younger adults, Zee noted.

The study received support from the National Heart, Lung, and Blood Institute (R01HL140580) and the National Institute on Aging. Zee reported having no disclosures.