Abstract

Aims

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 and results

Adults aged 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-h fasting was performed twice weekly for 4 weeks and 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). 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% and 67.9%), and overweight (103 ± 24 and 100 ± 21 kg) and had modest LDL-C elevation (124 ± 19 and 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) vs. 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.

Details

Title
Randomized controlled trial of once-per-week intermittent fasting for health improvement: the WONDERFUL trial
Author
Bartholomew, Ciera L 1 ; Muhlestein, Joseph B 2 ; May, Heidi T 3 ; Le, Viet T 4 ; Galenko, Oxana 3 ; Kelly Davis Garrett 5 ; Brunker, Cherie 6 ; Hopkins, Ramona O 7 ; Carlquist, John F 2 ; Knowlton, Kirk U 8 ; Anderson, Jeffrey L 2 ; Bailey, Bruce W 1 ; Horne, Benjamin D 9 

 Department of Exercise Sciences, Brigham Young University, Provo, UT, USA 
 Intermountain Medical Center Heart Institute, 5121 S. Cottonwood St., Salt Lake City, UT 84107, USA; Cardiology Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA 
 Intermountain Medical Center Heart Institute, 5121 S. Cottonwood St., Salt Lake City, UT 84107, USA 
 Intermountain Medical Center Heart Institute, 5121 S. Cottonwood St., Salt Lake City, UT 84107, USA; Rocky Mountain University of Health Professions, Provo, UT, USA 
 Neuropsychology, Intermountain Medical Center, Salt Lake City, UT, USA; Center for Aging, University of Utah, Salt Lake City, UT, USA 
 Geriatric Medicine, Department of Internal Medicine, Intermountain Medical Center; Division of Geriatrics, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA 
 Pulmonary Division, Department of Internal Medicine, Intermountain Medical Center, Salt Lake City, UT, USA; Psychology Department and Neuroscience Center, Brigham Young University, Provo, UT, USA 
 Intermountain Medical Center Heart Institute, 5121 S. Cottonwood St., Salt Lake City, UT 84107, USA; Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego, La Jolla, CA, USA 
 Intermountain Medical Center Heart Institute, 5121 S. Cottonwood St., Salt Lake City, UT 84107, USA; Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA 
Publication year
2021
Publication date
Sep 2021
Publisher
Oxford University Press
e-ISSN
27524191
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3191358863
Copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.