Effect of Calorie Restriction on Mood, Quality of Life, Sleep, and Sexual Function in Healthy Nonobese Adults: The CALERIE 2 Randomized Clinical Trial

Abstract

Importance: Calorie restriction (CR) increases longevity in many species and reduces risk factors for chronic diseases. In humans, CR may improve health span, yet concerns remain about potential negative effects of CR.

Objective: To test the effect of CR on mood, quality of life (QOL), sleep, and sexual function in healthy nonobese adults.

Design, setting, and participants: A multisite randomized clinical trial (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 [CALERIE 2]) was conducted at 3 academic research institutions. Adult men and women (N = 220) with body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 22.0 to 28.0 were randomized to 2 years of 25% CR or an ad libitum (AL) control group in a 2:1 ratio favoring CR. Data were collected at baseline, 12 months, and 24 months and examined using intent-to-treat analysis. The study was conducted from January 22, 2007, to March 6, 2012. Data analysis was performed from July 18, 2012, to October 27, 2015.

Interventions: Two years of 25% CR or AL.

Main outcomes and measures: Self-report questionnaires were administered to measure mood (Beck Depression Inventory-II [BDI-II], score range 0-63, higher scores indicating worse mood, and Profile of Mood States [POMS], with a total mood disturbance score range of -32 to 200 and higher scores indicating higher levels of the constructs measured), QOL (Rand 36-Item Short Form, score range 0-100, higher scores reflecting better QOL, and Perceived Stress Scale, score range 0-40, higher scores indicating higher levels of stress), sleep (Pittsburgh Sleep Quality Index [PSQI], total score range 0-21, higher scores reflecting worse sleep quality), and sexual function (Derogatis Interview for Sexual Function-Self-report, total score range 24-188, higher scores indicating better sexual functioning).

Results: In all, 218 participants (152 women [69.7%]; mean [SD] age, 37.9 (7.2) years; mean [SD] BMI, 25.1 [1.6]) were included in the analyses. The CR and AL groups lost a mean (SE) of 7.6 (0.3) kg and 0.4 (0.5) kg, respectively, at month 24 (P < .001). Compared with the AL group, the CR group had significantly improved mood (BDI-II: between-group difference [BGD], -0.76; 95% CI, -1.41 to -0.11; effect size [ES], -0.35), reduced tension (POMS: BGD, -0.79; 95% CI, -1.38 to -0.19; ES, -0.39), and improved general health (BGD, 6.45; 95% CI, 3.93 to 8.98; ES, 0.75) and sexual drive and relationship (BGD, 1.06; 95% CI, 0.11 to 2.01; ES, 0.35) at month 24 as well as improved sleep duration at month 12 (BGD, -0.26; 95% CI, -0.49 to -0.02; ES, -0.32) (all P < .05). Greater percent weight loss in the CR group at month 24 was associated with increased vigor (Spearman correlation coefficient, ρ = -0.30) and less mood disturbance (ρ = 0.27) measured with the POMS, improved general health (ρ = -0.27) measured with the SF-36, and better sleep quality per the PSQI total score (ρ = 0.28) (all P < .01).

Conclusions and relevance: In nonobese adults, CR had some positive effects and no negative effects on health-related QOL.

Trial registration: clinicaltrials.gov Identifier: NCT00427193.

Figure 1. CONSORT Diagram

More than 10 000 people expressed interest in the study, and 238 people completed the screening process and were eligible. All 218 participants who started the intervention (calorie restriction [CR], 143; ad libitum [AL], 75) were included in the main study analysis. Adapted from Ravussin et al.

Figure 2. Illustration of Interaction Effects

Estimated changes in the end points for the ad libitum (AL) group are represented by solid circles. Estimated change in the end points for the calorie restriction (CR) group are represented by open circles. Illustrations of a body mass index × treatment × time interaction (A and B) and a sex × treatment interaction (C and D) for the Profile of Mood States (POMS) depression subscale are provided. In addition, a sex × treatment interaction on the sexual arousal subscale of the Derogatis Interview for Sexual Function–Self-report is illustrated (E and F). Error bars indicate SE. ^a Significant differences between the AL and CR groups are denoted at the specified time point, with P = .005 for the difference between the AL and CR overweight participants at month 24 on the POMS depression scale; P = .03 and P = .02 for the difference between the AL and CR men on the POMS depression scale at months 6 and 12, respectively; and P = .04 for the difference between the AL and CR men at month 12on the sexual arousal scale.