Schubel 2018.

Study characteristics
Methods	Multiple‐arm randomised controlled trial
Participants	150 participants based in Germany aged between 35 and 65 with a BMI ≥25 and <40 Inclusion criteria: women and men BMI≥ 25kg/m2 and < 40kg/m2 age 35 to 65 years Exclusion criteria diagnosed diabetes mellitus HbA1c levels ≥6.5% and/or fasting plasma glucose levels >126 mg/dl known hepatic or renal dysfunction, or severely increased gamma‐glutamyl transpeptidase, glutamate oxaloacetate transaminase, glutamic‐pyruvic transaminase, creatinine, urea and/or uric acid levels history of cancer within the past10 years, known eating disorders (e.g. bulimia nervosa, anorexia nervosa, binge‐eating) increased or decreased thyroid‐stimulating hormone levels severe bleeding tendency medication for immunosuppression or modulation of fat metabolism participation in an intervention study within the past three months current pregnancy or were pregnant or breastfeeding during the past 12 months
Interventions	3‐arm trial Intervention (n = 49): ICR group were advised to restrict their energy intake on 2 self‐selected nonconsecutive days per week to 25% of the individual energy requirement. The remaining 5 days of the week were based on a eucaloric balanced diet Comparators ( n=49, n = 52): continuous energy restriction arm and control/ad libitum feeding arm
Outcomes	Lipid profile, glucose, CRP
Notes	All arms were included in analysis. Funding: the HELENA Trial was funded by the Helmholtz Association of German Research Centers (Cross Program Topic: Metabolic Dysfunction). MRI examinations were performed in and financed by the Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg. The financing of the MRI was also supported by the Stiftung zur Förderung der Erforschung der Zivilisationserkrankungen, Baden‐Baden, Germany. CMU was funded by the Huntsman Cancer Foundation, Salt Lake City, UT and by NIH grant U01 CA 206110. Type of paper: full‐text publication ICR‐ Intermittent calorie restriction
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The web‐based software RANDI2 was used to generate the random allocation sequence."
Allocation concealment (selection bias)	High risk	Participants were assigned by stratified block randomisation with a fixed block size. This means that the executors can predict the next assignment, and this is clearly incompatible with allocation concealment.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Because the HELENA Trial was a dietary intervention study, it was not feasible for participants or all study personnel to be blinded to the group assignment.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The technical staff was blinded for downstream laboratory work and data management.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants were included in intention‐to‐treat analysis; dropout rates were also low at 4 out of 49 participants (8.2%) in the intermittent calorie restriction group and 2 out of 52 participants (3.8%) in the control group.
Selective reporting (reporting bias)	Low risk	The vast majority of pre‐specified outcomes (ClinicalTrials.gov: NCT02449148) were reported in the Results section, with the exception of some secondary outcomes such as effect on quality of life.
Other bias	Low risk	Nothing to note.