Molecular Pathways Related to Short-term Fasting Response

NCT04259879 | Completed

• 1 other identifier: IMD PI0025
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the effect of short-term fasting (36 hours) in gene expression in blood cells in healthy volunteers.

Conditions

Fasting

Keywords

Short-term Fasting; molecular mechanisms; p21; Peripheral blood mononuclear cells (PBMCs); PPARalpha

Outcome Measures

Primary Outcomes (1)

• Changes in gene expression in PBMCs after fasting

  Expression analysis of p21, Pyruvate Dehydrogenase Kinase 4 (PDK4), Carnitine palmitoyltransferase 1 (CPT1), Adipophilin (ADFP) and Solute carrier family 25, member 50 (SLC25A50) were performed in a HT-7900 Fast Real time polymerase chain reaction (PCR). Quantifications were made applying the ΔCt method (ΔCt = \[Ct of gene of interest - Ct of housekeeping\]). The housekeeping genes used for input normalization were β-actin (ACTB) and ribosomal protein lateral stalk subunit P0 (RPLP0).

  Baseline, 24 hours and 48 hours later

Secondary Outcomes (6)

• Changes in Insulin levels in response to fasting

  Baseline, 24 hours and 48 hours later

• Changes in Free Fatty Acids levels in response to fasting

  Baseline, 24 hours and 48 hours later

• Changes ketone bodies in response to fasting

  Baseline, 24 hours and 48 hours later

• Changes in leptin levels in response to fasting

  Baseline, 24 hours and 48 hours later

• Changes in lipid profile in response to fasting

  Baseline, 24 hours and 48 hours later

Study Arms (1)

Fasting

EXPERIMENTAL

The participants will follow a short-term fasting period for 36 hours

Other: Fasting

Interventions

Fasting OTHER

Food intake restriction

Fasting

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women between 18 - 50 years old.
• BMI \>20\<30
• Adequate education level and comprehension of the clinical study
• Willingness to participate in the study as a volunteer and to provide written consent

You may not qualify if:

• BMI \<20 (thinness)
• BMI \>30 (obesity)
• Abnormal low glucose levels after fasting
• Having donated blood less than 8 weeks before starting the study
• Subjects who report special discomfort after previous periods of short fasting
• Diagnosis of type 2 Diabetes mellitus (insulin-dependent)
• Dyslipidemia under pharmacological treatment
• High blood pressure under pharmacological treatment
• Dementia, neurological disease or reduction of cognitive function
• Severe illness (hepatic disease, renal disease, etc
• Taking medications that could affect the lipid and glycemic profiles (statins, fibrate, diuretics, corticoids, anti-inflammatory, hypoglycemic or insulin) 30 days before the beginning of the study.
• Taking medications or substances for weight loss management (15 days before the beginning of the study)
• Pregnancy or lactation

Sponsors & Collaborators

• IMDEA Food: lead
• Centro Nacional de Investigaciones Oncologicas CARLOS III: collaborator

Study Sites (1)

IMDEA Food

Madrid, 28049, Spain

Location

Related Publications (22)

• Antoni R, Johnston KL, Collins AL, Robertson MD. Effects of intermittent fasting on glucose and lipid metabolism. Proc Nutr Soc. 2017 Aug;76(3):361-368. doi: 10.1017/S0029665116002986. Epub 2017 Jan 16.

  PMID: 28091348 BACKGROUND

• Arnason TG, Bowen MW, Mansell KD. Effects of intermittent fasting on health markers in those with type 2 diabetes: A pilot study. World J Diabetes. 2017 Apr 15;8(4):154-164. doi: 10.4239/wjd.v8.i4.154.

  PMID: 28465792 BACKGROUND

• Gotthardt JD, Verpeut JL, Yeomans BL, Yang JA, Yasrebi A, Roepke TA, Bello NT. Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice. Endocrinology. 2016 Feb;157(2):679-91. doi: 10.1210/en.2015-1622. Epub 2015 Dec 14.

  PMID: 26653760 BACKGROUND

• Halberg N, Henriksen M, Soderhamn N, Stallknecht B, Ploug T, Schjerling P, Dela F. Effect of intermittent fasting and refeeding on insulin action in healthy men. J Appl Physiol (1985). 2005 Dec;99(6):2128-36. doi: 10.1152/japplphysiol.00683.2005. Epub 2005 Jul 28.

  PMID: 16051710 BACKGROUND

• Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res Rev. 2017 Oct;39:46-58. doi: 10.1016/j.arr.2016.10.005. Epub 2016 Oct 31.

  PMID: 27810402 BACKGROUND

• Varady KA, Bhutani S, Church EC, Klempel MC. Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults. Am J Clin Nutr. 2009 Nov;90(5):1138-43. doi: 10.3945/ajcn.2009.28380. Epub 2009 Sep 30.

  PMID: 19793855 BACKGROUND

• Vasconcelos AR, Yshii LM, Viel TA, Buck HS, Mattson MP, Scavone C, Kawamoto EM. Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment. J Neuroinflammation. 2014 May 6;11:85. doi: 10.1186/1742-2094-11-85.

  PMID: 24886300 BACKGROUND

• Tinkum KL, Stemler KM, White LS, Loza AJ, Jeter-Jones S, Michalski BM, Kuzmicki C, Pless R, Stappenbeck TS, Piwnica-Worms D, Piwnica-Worms H. Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival. Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):E7148-54. doi: 10.1073/pnas.1509249112. Epub 2015 Dec 7.

  PMID: 26644583 BACKGROUND

• Safdie FM, Dorff T, Quinn D, Fontana L, Wei M, Lee C, Cohen P, Longo VD. Fasting and cancer treatment in humans: A case series report. Aging (Albany NY). 2009 Dec 31;1(12):988-1007. doi: 10.18632/aging.100114.

  PMID: 20157582 BACKGROUND

• Raffaghello L, Safdie F, Bianchi G, Dorff T, Fontana L, Longo VD. Fasting and differential chemotherapy protection in patients. Cell Cycle. 2010 Nov 15;9(22):4474-6. doi: 10.4161/cc.9.22.13954. Epub 2010 Nov 15.

  PMID: 21088487 BACKGROUND

• Lee C, Raffaghello L, Brandhorst S, Safdie FM, Bianchi G, Martin-Montalvo A, Pistoia V, Wei M, Hwang S, Merlino A, Emionite L, de Cabo R, Longo VD. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med. 2012 Mar 7;4(124):124ra27. doi: 10.1126/scitranslmed.3003293. Epub 2012 Feb 8.

  PMID: 22323820 BACKGROUND

• Di Biase S, Lee C, Brandhorst S, Manes B, Buono R, Cheng CW, Cacciottolo M, Martin-Montalvo A, de Cabo R, Wei M, Morgan TE, Longo VD. Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity. Cancer Cell. 2016 Jul 11;30(1):136-146. doi: 10.1016/j.ccell.2016.06.005.

  PMID: 27411588 BACKGROUND

• Pietrocola F, Pol J, Vacchelli E, Rao S, Enot DP, Baracco EE, Levesque S, Castoldi F, Jacquelot N, Yamazaki T, Senovilla L, Marino G, Aranda F, Durand S, Sica V, Chery A, Lachkar S, Sigl V, Bloy N, Buque A, Falzoni S, Ryffel B, Apetoh L, Di Virgilio F, Madeo F, Maiuri MC, Zitvogel L, Levine B, Penninger JM, Kroemer G. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance. Cancer Cell. 2016 Jul 11;30(1):147-160. doi: 10.1016/j.ccell.2016.05.016.

  PMID: 27411589 BACKGROUND

• Ruderman NB. Muscle amino acid metabolism and gluconeogenesis. Annu Rev Med. 1975;26:245-58. doi: 10.1146/annurev.me.26.020175.001333. No abstract available.

  PMID: 1096762 BACKGROUND

• Cahill GJ Jr, Owen OE, Morgan AP. The consumption of fuels during prolonged starvation. Adv Enzyme Regul. 1968;6:143-50. doi: 10.1016/0065-2571(68)90011-3. No abstract available.

  PMID: 5720334 BACKGROUND

• Nuttall FQ, Almokayyad RM, Gannon MC. Comparison of a carbohydrate-free diet vs. fasting on plasma glucose, insulin and glucagon in type 2 diabetes. Metabolism. 2015 Feb;64(2):253-62. doi: 10.1016/j.metabol.2014.10.004. Epub 2014 Oct 8.

  PMID: 25458830 BACKGROUND

• Nuttall FQ, Almokayyad RM, Gannon MC. The ghrelin and leptin responses to short-term starvation vs a carbohydrate-free diet in men with type 2 diabetes; a controlled, cross-over design study. Nutr Metab (Lond). 2016 Jul 22;13:47. doi: 10.1186/s12986-016-0106-x. eCollection 2016.

  PMID: 27453716 BACKGROUND

• Merl V, Peters A, Oltmanns KM, Kern W, Born J, Fehm HL, Schultes B. Serum adiponectin concentrations during a 72-hour fast in over- and normal-weight humans. Int J Obes (Lond). 2005 Aug;29(8):998-1001. doi: 10.1038/sj.ijo.0802971.

  PMID: 15917861 BACKGROUND

• Bouwens M, Afman LA, Muller M. Fasting induces changes in peripheral blood mononuclear cell gene expression profiles related to increases in fatty acid beta-oxidation: functional role of peroxisome proliferator activated receptor alpha in human peripheral blood mononuclear cells. Am J Clin Nutr. 2007 Nov;86(5):1515-23. doi: 10.1093/ajcn/86.5.1515.

  PMID: 17991667 BACKGROUND

• Lopez-Guadamillas E, Fernandez-Marcos PJ, Pantoja C, Munoz-Martin M, Martinez D, Gomez-Lopez G, Campos-Olivas R, Valverde AM, Serrano M. p21Cip1 plays a critical role in the physiological adaptation to fasting through activation of PPARalpha. Sci Rep. 2016 Oct 10;6:34542. doi: 10.1038/srep34542.

  PMID: 27721423 BACKGROUND

• Prokesch A, Graef FA, Madl T, Kahlhofer J, Heidenreich S, Schumann A, Moyschewitz E, Pristoynik P, Blaschitz A, Knauer M, Muenzner M, Bogner-Strauss JG, Dohr G, Schulz TJ, Schupp M. Liver p53 is stabilized upon starvation and required for amino acid catabolism and gluconeogenesis. FASEB J. 2017 Feb;31(2):732-742. doi: 10.1096/fj.201600845R. Epub 2016 Nov 3.

  PMID: 27811061 BACKGROUND

• Tinkum KL, White LS, Marpegan L, Herzog E, Piwnica-Worms D, Piwnica-Worms H. Forkhead box O1 (FOXO1) protein, but not p53, contributes to robust induction of p21 expression in fasted mice. J Biol Chem. 2013 Sep 27;288(39):27999-8008. doi: 10.1074/jbc.M113.494328. Epub 2013 Aug 5.

  PMID: 23918930 BACKGROUND

MeSH Terms

Conditions

Fasting; Intermittent Fasting

Interventions

Angptl4 protein, mouse

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior

Study Officials

• Pablo J Fernandez-Marcos, PhD

  IMDEA Food

  PRINCIPAL INVESTIGATOR

• Manuel Serrano Marugán, PhD

  Spanish National Cancer Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study was an Interventional study. There were three evaluations: the basal one was an initial evaluation after overnight fasting, the second evaluation 24 hours later (36 hours fasting) and the third one 24 hours post-refeeding.

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 7, 2020
• Study Start: April 7, 2016
• Primary Completion: May 18, 2016
• Study Completion: June 15, 2016
• Last Updated: February 17, 2020

Record last verified: 2020-01

Locations

ES (1)