Background The effect of macronutrient composition on total energy expenditure (TEE) remains controversial, with divergent findings among studies. One source of heterogeneity may be study duration, as physiological adaptation to lower carbohydrate intake may require 2 to 3 wk. Objective We tested the hypothesis that the effects of carbohydrate [expressed as % of energy intake (EI)] on TEE vary with time. Methods The sample included trials from a previous meta-analysis and new trials identified in a PubMed search through 9 March 2020 comparing lower- and higher-carbohydrate diets, controlled for EI or body weight. Three reviewers independently extracted data and reconciled discrepancies. Effects on TEE were pooled using inverse-variance-weighted meta-analysis, with between-study heterogeneity assessed using the I2 statistic. Meta-regression was used to quantify the influence of study duration, dichotomized at 2.5 wk. Results The 29 trials ranged in duration from 1 to 140 d (median: 4 d) and included 617 participants. Difference in carbohydrate between intervention arms ranged from 8% to 77% EI (median: 30%). Compared with reported findings in the prior analysis (I2 = 32.2%), we found greater heterogeneity (I2 = 90.9% in the reanalysis, 81.6% in the updated analysis). Study duration modified the diet effect on TEE (P < 0.001). Among 23 shorter trials, TEE was reduced on lower-carbohydrate diets (−50.0 kcal/d; 95% CI: −77.4, −22.6 kcal/d) with substantial heterogeneity (I2 = 69.8). Among 6 longer trials, TEE was increased on low-carbohydrate diets (135.4 kcal/d; 95% CI: 72.0, 198.7 kcal/d) with low heterogeneity (I2 = 26.4). Expressed per 10% decrease in carbohydrate as %EI, the TEE effects in shorter and longer trials were −14.5 kcal/d and 50.4 kcal/d, respectively. Findings were materially unchanged in sensitivity analyses. Conclusions Lower-carbohydrate diets transiently reduce TEE, with a larger increase after ∼2.5 wk. These findings highlight the importance of longer trials to understand chronic macronutrient effects and suggest a mechanism whereby lower-carbohydrate diets may facilitate weight loss.

Background The inverse association between physical activity and coronary heart disease (CHD) risk has primarily been shown in studies of middle-aged and older adults. Evidence for the benefits of frequency, type, and volume of leisure-time physical activity in young women is limited. Methods We conducted a prospective analysis among 97,230 women aged 27-44 years at baseline in 1991. Leisure-time physical activity was assessed biennially by questionnaire. Cox proportional hazards models were used to examine the associations between physical activity frequency, type, and volume and CHD risk. Results During 20 years of follow-up, we documented 544 incident CHD cases. In multivariable-adjusted models, the hazard ratio (HR) (95% confidence interval [CI]) of CHD comparing ≥ 30 to < 1 MET-hours/week of physical activity was 0.75 (0.57, 0.99) (p, trend = 0.01). Brisk walking alone was also associated with significantly lower CHD risk. Physical activity frequency was not associated with CHD risk when models also included overall activity volume. Finally, the association was not modified by body mass index (BMI, kg/m2) (p, interaction =0.70). Active women (≥ 30 MET-hrs/wk) with BMI < 25 kg/m2 had 0.52 (95% CI: 0.35, 0.78) times the rate of CHD compared to women who were obese (BMI ≥ 30 kg/m2) and inactive (physical activity < 1 MET-hrs/wk). Conclusions These prospective data suggest that total volume of leisure-time physical activity is associated with lower risk of incident CHD among young women. Additionally, this association was not modified by weight, emphasizing that it is important for normal weight, overweight, and obese women to be physically active.