Background Low-density lipoprotein cholesterol (LDL-C) predicts heart disease onset and may be reduced by intermittent fasting. Some studies, though, reported that fasting increased LDL-C; however, no study evaluated LDL-C as the primary endpoint. This randomized controlled trial evaluated the effect of low-frequency intermittent fasting on LDL-C and other biomarkers. Methods Adults ages 21-70 years were enrolled who were not taking a statin, had modestly elevated LDL-C, had ≥1 metabolic syndrome feature or type 2 diabetes, and were not taking anti-diabetic medication (N = 103). Water-only 24-hour fasting was performed twice-weekly for 4 weeks, then once-weekly for 22 weeks; controls ate ad libitum. The primary outcome was 26-week LDL-C change score. Secondary outcomes (requiring p ≤ 0.01) were 26-week changes in homeostatic model assessment of insulin resistance (HOMA-IR), Metabolic Syndrome Score (MSS), brain-derived neurotrophic factor (BDNF), and MicroCog general cognitive proficiency index (GCPi). Results Intermittent fasting (n = 50) and control (n = 53) subjects were, respectively, aged 49.3±12.0 and 47.0±9.8 years, predominantly female (66.0% & 67.9%), overweight (103±24 & 100±21 kg), and had modest LDL-C elevation (124±19 & 128±20 mg/dL). Drop-outs (n = 12 fasting, n = 20 control) provided an evaluable sample of n = 71 (n = 38 fasting, n = 33 control). Intermittent fasting did not change LDL-C (0.2±16.7 mg/dL) versus control (2.5±19.4 mg/dL; p = 0.59), but it improved HOMA-IR (-0.75±0.79 vs. -0.10±1.06; p = 0.004) and MSS (-0.34±4.72 vs. 0.31±1.98, p = 0.006). BDNF (p = 0.58), GCPi (p = 0.17), and weight (-1.7±4.7 kg vs. 0.2±3.5 kg, p = 0.06) were unchanged. Conclusions A low-frequency intermittent fasting regimen did not reduce LDL-C or improve cognitive function, but significantly reduced both HOMA-IR and MSS. Trial registration clinicaltrials.gov, NCT02770313

Aims Animal models repeatedly show fasting increases longevity. Human data, though, are limited to anecdotal claims. This study evaluated the association of routine fasting with survival and, secondarily, with incident major adverse cardiovascular events. Methods and results Cardiac catheterization patients enrolled in the Intermountain INSPIRE longitudinal cohort (n = 2785) during 2013–2015 were followed through March 2019. A fasting survey was completed in n = 2025 (73%) of this cohort and 1957 were included in the final data analysis after 68 participants were removed (24 for data issues and 44 for fasting less than 5 years). Self-reported routine fasting behaviour, years of participation in fasting, and other fasting characteristics were surveyed. Mortality was the primary outcome and incident myocardial infarction (MI), stroke, and heart failure (HF) were secondary. Routine fasters (n = 389, mean age 64 ± 14 years, 34% female) averaged 42 ± 18 years of routine fasting (minimum 5 years). Non-fasters (n = 1568, aged 63 ± 14 years, 36% female) included never fasters (n = 1120 with 0 years of fasting) and previous fasters (n = 448 who averaged 32 ± 21 years of prior fasting but had stopped prior to enrolment). Routine fasters had greater survival vs. non-fasters [adjusted hazard ratio (HR) = 0.54, 95% confidence interval (CI) = 0.36–0.80; P = 0.002] and lower incidence of HF (adjusted HR = 0.31, CI = 0.12–0.78; P = 0.013), but not MI or stroke after adjustment. Conclusions Routine fasting followed during two-thirds of the lifespan was associated with higher survival after cardiac catheterization. This may in part be explained by an association of routine fasting with a lower incidence of HF. Clinical study registration The Intermountain INSPIRE registry https://clinicaltrials.gov/, NCT02450006.

Purpose Transitioning from high school to college generally results in reduced physical activity and weight gain at a rate that is higher than the general population. The purpose of this study was to examine the effects of three progressively higher step recommendations over 24 weeks on changes in body weight and body composition. Methods Ninety-two freshmen college women wore a multifunction pedometer for 24 weeks after being randomly assigned to a daily step level: 10,000, 12,500, or 15,000. Pedometer data were downloaded every two weeks and participants were counseled on meeting their step recommendation. Body weight and body composition were assessed at baseline and 24 weeks. Body composition was assessed by dual X-ray absorptiometry. Results On average, women took 10,786 ± 1501, 12,650 ± 2001, and 13,762 ± 2098 steps per day for the 10,000-, 12,500-, and 15,000-step groups, respectively (F = 15.48, P < 0.0001). Participants gained 1.4 ± 2.6, 1.8 ± 2.1, and 1.4 ± 2.1 kg for the 10,000-, 12,500-, and 15,000-step groups, respectively (F = 37.74, P < 0.0001). Weight gain was not significantly different between groups (F = 0.18, P=0.8385). There was also no difference in fat weight gain (F = 0.41, P=0.7954). Discussion A step recommendation beyond 10,000 does not prevent weight or fat gain over the first year of college. Future research should focus on either intensity of physical activity or the addition of dietary interventions to prevent weight gain during the first year of college.

PurposeThis study assessed β-hydroxybutyrate (BHB) concentration during a short-term fast and the degree to which an initial bout of exercise influences the rate of ketogenesis.MethodsTwenty subjects (11 male, 9 female) completed two 36-h fasts, with one protocol requiring the subject to complete a treadmill exercise session at the beginning of the fast. BHB levels were assessed via portable meter every 2 h, along with mood and hunger ratings. Venipuncture was performed every 12 h.ResultsThe mean (SD) areas under the curve for BHB concentration were 19.19 (2.59) mmol·L−1 (nonexercised) and 27.49 (2.59) mmol·L−1 (exercised), yielding a difference of 8.30 mmol·L−1 between conditions (95% posterior probability interval (PPI), 1.94 to 14.82 mmol·L−1; posterior probability (PP) = 0.99). The mean (SD) times to BHB concentration of 0.5 mmol·L−1 were 21.07 (2.95) h (nonexercised) and 17.5 (1.69) h (exercised), a 3.57-h difference (95% PPI, −2.11 to 10.87 h; PP = 0.89). The differences in area under the curve between conditions were 5.07 μU·mL−1 (95% PPI, −21.64 to 36.18 μU·mL−1; PP = 0.67) for insulin, 97.13 pg·mL−1 (95% PPI, 34.08 to 354.21 pg·mL−1; PP = 0.98) for glucagon, and 20.83 (95% PPI, 4.70 to 24.22; PP = 0.99) for the insulin/glucagon ratio.ConclusionsCompleting aerobic exercise at the beginning of a fast accelerates the production of BHB throughout the fast without altering subjective feelings of hunger, thirst, stomach discomfort, or mood. Insulin and the insulin/glucagon ratio experience a marked reduction within the first 12 h of fasting and was not altered with exercise. Thus, exercising at the beginning of a fast may improve the metabolic outcomes of fasting.

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