Short-term time-restricted feeding is safe and feasible in non-obese healthy midlife and older adults

Christopher R Martens, Matthew J Rossman, Melissa R Mazzo, Lindsey R Jankowski, Erzsebet E Nagy, Blair A Denman, James J Richey, Sarah A Johnson, Brian P Ziemba, Yang Wang, Courtney M Peterson, Michel Chonchol, Douglas R Seals, Christopher R Martens, Matthew J Rossman, Melissa R Mazzo, Lindsey R Jankowski, Erzsebet E Nagy, Blair A Denman, James J Richey, Sarah A Johnson, Brian P Ziemba, Yang Wang, Courtney M Peterson, Michel Chonchol, Douglas R Seals

Abstract

Chronic calorie restriction (CR) improves cardiovascular function and several other physiological markers of healthspan. However, CR is impractical in non-obese older humans due to potential loss of lean mass and bone density, poor adherence, and risk of malnutrition. Time-restricted feeding (TRF), which limits the daily feeding period without requiring a reduction in calorie intake, may be a promising alternative healthspan-extending strategy for midlife and older adults; however, there is limited evidence for its feasibility and efficacy in humans. We conducted a randomized, controlled pilot study to assess the safety, tolerability, and overall feasibility of short-term TRF (eating <8 h day-1 for 6 weeks) without weight loss in healthy non-obese midlife and older adults, while gaining initial insight into potential efficacy for improving cardiovascular function and other indicators of healthspan. TRF was safe and well-tolerated, associated with excellent adherence and reduced hunger, and did not influence lean mass, bone density, or nutrient intake. Cardiovascular function was not enhanced by short-term TRF in this healthy cohort, but functional (endurance) capacity and glucose tolerance were modestly improved. These results provide a foundation for conducting larger clinical studies of TRF in midlife and older adults, including trials with a longer treatment duration.

Keywords: Aging; Calorie restriction; Healthspan; Intermittent fasting.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Feasibility of time-restricted feeding. a Compared with normal feeding (NF, black bars), all subjects successfully reduced their feeding window to within the allowed feeding duration (red lines) during time-restricted feeding (TRF, gray bars) resulting in b a reduction in the average daily feeding window. c Subjects were able to maintain a reduction in their daily feeding period throughout the 6-week TRF period with d good overall adherence. There were no adverse changes in e overall diet quality as assessed by the healthy eating index, f energy intake, g estimated energy expenditure, or h body mass. N = 22. Boxes represent median and interquartile range with 95% confidence intervals as whiskers. *p < 0.05. See also Supplementary Table 1, Supplementary Table 2, Supplementary Table 3, and Supplementary Table 4
Fig. 2
Fig. 2
Subjective appetite. Six weeks of time-restricted feeding (TRF) vs. normal feeding (NF) reduced sensations of a hunger but did not alter b desire to eat, c capacity to eat, d fullness, or e stomach fullness despite expected fluctuations between morning (fasted) and evening (fed) conditions. N = 22. Boxes represent median and interquartile range with 95% confidence intervals as whiskers. Data are in millimeters (mm) drawn on a standardized visual-analog scale. *p values < 0.05 based on two-factor repeated measures ANOVA
Fig. 3
Fig. 3
Body composition and bone density. In comparison to normal feeding (NF), time-restricted feeding (TRF) was associated with a a small change in leg fat mass that did not affect total body composition, and b no change in bone mineral density compared with normal feeding (NF). N = 22. Data are mean ± standard error of mean (SEM). *p < 0.05
Fig. 4
Fig. 4
Vascular function and blood pressure at rest. Compared with normal feeding (NF), 6 weeks of TRF did not influence a flow-mediated dilation (FMD), b carotid-femoral pulse wave velocity (PWV), c carotid artery compliance, d carotid intima-media thickness (IMT), e resting systolic blood pressure (SBP), or f resting diastolic blood pressure (DBP). N = 22. Boxes represent median and interquartile range with 95% confidence intervals as whiskers
Fig. 5
Fig. 5
Cardiorespiratory fitness. In comparison to normal feeding (NF), time-restricted feeding (TRF) was associated with a increased distance traveled during a 6-min walk test and b reduced heart rate during light and moderate intensity exercise. N = 22. Boxes represent median and interquartile range with 95% confidence intervals as whiskers. *p < 0.05 based on mixed effects model with repeated measures. See also Supplementary Fig. 2 and Supplementary Table 5
Fig. 6
Fig. 6
Glucose tolerance. Compared with normal feeding (NF), time-restricted feeding (TRF) was associated with a, b a reduction in glucose area-under-the-curve (AUC) during a 2-h OGTT, c, d no changes in insulin levels and the insulin AUC, and e no change in the insulinogenic index (a marker of pancreatic β-cell function). N = 16 participants. Boxes represent median and interquartile range with 95% confidence intervals as whiskers. *p < 0.05 based on mixed effects model with repeated measures
Fig. 7
Fig. 7
Mechanistic biomarkers. Compared with the normal feeding (NF) condition, time-restricted feeding (TRF) was not associated with any changes in a oxidized-LDL levels, b the oxidized-to-total LDL ratio, c interleukin-6 (IL-6), d C-reactive protein (CRP) or plasma ketones including e acetoacetate or f β-hydroxybutyrate. Boxes represent median and interquartile range with 95% confidence intervals as whiskers. See also Supplementary Table 6

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