European Primary Care Cardiovascular Society

Does low-frequency intermittent fasting reduce LDL-c?

Randomized controlled trial of once-per-week intermittent fasting for health improvement: the WONDERFUL trial

Literature - Bartholomew CL, Muhlestein JB, May HT, et al. - Eur Heart J Open. 2021 Sep 3;1(2):oeab026. doi: 10.1093/ehjopen/oeab026

Introduction and methods


Although intermittent fasting can improve several lipid and lipoprotein parameters [1], it is not clear what the effect is on LDL-c. While some studies have reported that intermittent fasting increased the LDL-c level [2-4], no study has used LDL-c as the primary endpoint.

Aim of the study

The study aim was to evaluate the effect of low-frequency intermittent fasting on the levels of LDL-c and other biomarkers compared with an ad libitum diet.


In this RCT, 103 patients (aged 21–70 years) were recruited from Intermountain hospitals and clinics in the USA and from local community volunteers. They had to have modestly elevated LDL-c levels (90–189mg/dL for ages 21–39 years, or 90–159mg/dL for ages 40–70 years, or >90mg/dL in anyone who had used statins and stopped due to intolerance or contraindications), ≥1 metabolic syndrome feature or T2DM, and no chronic disease diagnoses, and they should not be taking statins (or had an indication for statin therapy) or antidiabetic medications. The participants were randomized (1:1 ratio) to intermittent fasting, which consisted of only drinking water for 24 hours twice weekly for 4 weeks and then once weekly for 22 weeks, or an ad libitum control diet (consisting of the usual food intake) for 26 weeks. The intermittent fasting group was allowed to eat ad libitum between the fasting days. The investigators anticipated a 15% drop-out rate.


The primary outcome was the change in LDL-c level from baseline to 26 weeks. Secondary outcomes (requiring prespecified Bonferroni-corrected P≤0.01) were 26-week changes in the homeostatic model assessment of insulin resistance (HOMA-IR), metabolic syndrome score (MSS), level of brain-derived neurotrophic factor (BDNF), and MicroCog general cognitive proficiency index (GCPi).

Main results


In an RCT with 71 participants with modestly elevated LDL-c levels, a low-frequency intermittent fasting regimen did not decrease LDL-c levels or improve markers of cognitive function compared with an ad libitum control diet. However, it did lower insulin resistance (as measured by the HOMA-IR) and the MSS.


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Find this article online at Eur Heart J Open.

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