The effects of intermittent calorie restriction on metabolic health: Rationale and study design of the HELENA Trial.
Mechanistic studies suggest benefits of intermittent calorie restriction (ICR) in chronic disease prevention that may exceed those of continuous calorie restriction (CCR), even at equal net calorie intake. Despite promising results from first trials, it remains largely unknown whether ICR-induced metabolic alterations reported from experimental studies can also be observed in humans, and whether ICR diets are practicable and effective in real life situations. Thus, we initiated the HELENA Trial to test the effects of ICR (eu-caloric diet on five days and very low energy intake on two days per week) on metabolic parameters and body composition over one year. We will assess the effectiveness of ICR compared to CCR and a control diet over a 12-week intervention, 12-week maintenance phase and 24-week follow-up in 150 overweight or obese non-smoking adults (50 per group, 50% women). Our primary endpoint is the difference between ICR and CCR with respect to fold-changes in expression levels of 82 candidate genes in abdominal subcutaneous adipose tissue biopsies (SATb) during the intervention phase. The candidate genes represent pathways, which may link obesity-related metabolic alterations with the risk for major chronic diseases. In secondary and exploratory analyses, changes in metabolic, hormonal, inflammatory and metagenomic parameters measured in different biospecimens (SATb, blood, urine, stool) are investigated and effects of ICR/CCR/control on imaging-based measures of subcutaneous, visceral and hepatic fat are evaluated. Our study is the first randomized trial over one year testing the effects of ICR on metabolism, body composition and psychosocial factors in humans.
German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Ruth
R
Schübel
German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Mirja E
ME
Graf
Heidelberg University Hospital, Diagnostic and Interventional Radiology, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Johanna
J
Nattenmüller
German Cancer Research Center (DKFZ), Division of Medical and Biological Informatics, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Diana
D
Nabers
German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Disorn
D
Sookthai
German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Laura F
LF
Gruner
German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Theron
T
Johnson
Heidelberg University Hospital, Diagnostic and Interventional Radiology, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Christopher L
CL
Schlett
Heidelberg University Hospital, Diagnostic and Interventional Radiology, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Oyunbileg
O
von Stackelberg
National Center for Tumor Diseases (NCT), Liquid Biobank, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany.
Romy
R
Kirsten
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120 Heidelberg, Germany.
Nina
N
Habermann
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Mario
M
Kratz
Heidelberg University Hospital, Diagnostic and Interventional Radiology, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Hans-Ulrich
HU
Kauczor
Department of Population Health Sciences, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112-5550, USA; Huntsman Cancer Institute, Salt Lake City, 2000 Circle of Hope, Salt Lake City, UT 84112-5550,USA.
Cornelia M
CM
Ulrich
German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Rudolf
R
Kaaks
German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. Electronic address: t.kuehn@dkfz.de.
Tilman
T
Kühn
D000328:Adult; D000368:Aged; D001823:Body Composition; D031204:Caloric Restriction / Q000379:methods*; D005215:Fasting / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000628:therapy*; D050177:Overweight / Q000378:metabolism / Q000628:therapy; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism
Adipose tissue; Calorie restriction; Gene-expression; Intermittent fasting; Metabolism; Obesity