Meat-based Versus Pesco-vegetarian Diet and Colorectal Cancer

NCT03416777 | Completed DMC

• 1 other identifier: MeaTIC-INTIMIC
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer (CRC) is strongly affected by diet, with red and processed meat increasing risk. To understand the role of microbiome in this phenomenon and to identify specific microbiome/metabolomics profiles associated with CRC risk, will be studied: 1) healthy volunteers fed for 3 months with: a high-CRC risk diet (meat-based MBD), a normalized CRC risk diet (MBD plus alpha-tocopherol, MBD-T), a low-CRC risk diet (pesco-vegetarian, PVD). At the beginning and at the end of the intervention, gut microbiome profiles (metagenomics and metabolomics), and CRC biomarkers (genotoxicity, cytotoxicity, peroxidation in faecal water; lipid/glycemic indexes, inflammatory cytokines, oxidative stress), 2) Colon carcinogenesis: the same diets will be fed (3 months) to carcinogen-induced rats or to Pirc rats, mutated in Apc, the key gene in CRC; faecal microbiome profiles, will be correlated to carcinogenesis measuring preneoplastic lesions, colon tumours, and faecal and blood CRC biomarkers as in humans; 3) To further elucidate the mechanisms underlying the effect of different microbiomes in determining CRC risk, faeces from rats fed the experimental diets will be transplanted into carcinogen-induced germ-free rats, measuring how microbiome changes correlate with metabolome and disease outcomes. The results will provide fundamental insight in the role of microbiome in determining the effect of the diet, in particular red/processed meat intake, on CRC risk

Conditions

Nutrition Aspect of Cancer; Diet Modification; Cancer of Colon

Keywords

vegetarian; meat; fish

Outcome Measures

Primary Outcomes (1)

• DNA damage

  Decrease (\<25%) of DNA damage by faecal water (genotoxicity), using comet assay in a cellular model

  3 months

Secondary Outcomes (4)

• Microbiome and metabolomics profiles

  3 months

• Peroxidation

  3 months

• Inflammatory parameters

  3 months

• Oxidative stress

  3 months

Study Arms (3)

Meat-based diet (MBD)

ACTIVE COMPARATOR

Behavioral intervention with diet including 4 servings per week of red meat, 3 servings per week of processed meat, and 1 servings per week of poultry, for a total amount of 900 g per week of meat.

Behavioral: Meat-based diet

Meat-based alpha-tocopherol (MBD-T)

EXPERIMENTAL

Behavioral intervention including diet with 4 servings per week of red meat, 3 servings per week of processed meat, and 1 servings per week of poultry, for a total amount of 900 g per week of meat with a dietary supplement of 100 mg/day of alpha-tocopherol in the form of tablet

Dietary Supplement: Meat-based diet supplemented with alpha-tocopherol (MBD-T)

Pesco-vegetarian (PVD)

EXPERIMENTAL

Behavioral intervention with diet excluding fresh and processed meat, poultry but including 3 servings per week of any type of fish, excluding shellfish

Behavioral: Pesco-vegetarian diet

Interventions

Meat-based diet BEHAVIORAL

Diet including 4 servings per week of red meat (1 serving = 150 g), 3 servings per week of processed meat (1 serving = 50 g), and 1 servings per week of poultry (1 serving = 150 g), for a total amount of 900 g per week of meat.

Also known as: MBD

Meat-based diet (MBD)

Meat-based diet supplemented with alpha-tocopherol (MBD-T) DIETARY_SUPPLEMENT

Dietary intervention like the MBD with supplementation of alpha-tocopherol at a dosage of 100 mg/die. Available evidence suggests that alpha-tocopherol may help prevent colon cancer by decreasing the formation of mutagens arising from the oxidation of faecal lipids, by decreasing oxidative stress in the epithelial cells of the colon and by molecular mechanisms that influence cell death, cell cycle and transcriptional events (Pierre 2013, Bastide 2016, Bastide 2017, Diallo 2016). It is important to note that 200 mg/day of tocopherol was administered to 20,000 women for 10 years without side effects (Lee et al.,2005).

Also known as: MBD-T

Meat-based alpha-tocopherol (MBD-T)

Pesco-vegetarian diet BEHAVIORAL

Diet excluding fresh and processed meat, poultry but including 3 servings per week of any type of fish, excluding shellfish (1 serving = 150 g), for a total amount of 450 g per week. Diet will contain other sources of proteins (e.g. eggs, dairy, legumes/beans). There is suggestive evidence that fish and vegetable consumption has protective effects against CRC (Vieira et al., 2017).

Also known as: PVD

Pesco-vegetarian (PVD)

Eligibility Criteria

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

You may qualify if:

• clinically healthy (both sexes)
• age \>18 years and ≤ 50 years.
• The study population will be selected with an age ranging from 18 to 50 years because after 50 years the risk for CRC shows a significant increase in incidence. In fact, more than 90% of the people diagnosed with the disease are older than 50, with the average age at the time of diagnosis being 64 (Amersi et al., 2005). With respect to gender, its role in the development of colorectal cancer remains unclear (Amersi et al., 2005).

You may not qualify if:

• Presence of current illness or unstable conditions
• Current or recent (past 2 months) use of antibiotics or probiotics
• Pregnancy or intention to become pregnant in the next 12 months or lactation
• Current smoking habit
• Current or recent (past 2 months) adoption of a vegetarian diet

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria Careggi: lead

Study Sites (1)

Unit of Clinical Nutrition, University Hospital of Careggi

Florence, 50134, Italy

Location

Related Publications (12)

• Femia AP, Luceri C, Soares PV, Lodovici M, Caderni G. Multiple mucin depleted foci, high proliferation and low apoptotic response in the onset of colon carcinogenesis of the PIRC rat, mutated in Apc. Int J Cancer. 2015 Mar 15;136(6):E488-95. doi: 10.1002/ijc.29232. Epub 2014 Oct 6.

  PMID: 25257656 BACKGROUND

• Bastide NM, Naud N, Nassy G, Vendeuvre JL, Tache S, Gueraud F, Hobbs DA, Kuhnle GG, Corpet DE, Pierre FH. Red Wine and Pomegranate Extracts Suppress Cured Meat Promotion of Colonic Mucin-Depleted Foci in Carcinogen-Induced Rats. Nutr Cancer. 2017 Feb-Mar;69(2):289-298. doi: 10.1080/01635581.2017.1263745. Epub 2017 Jan 17.

  PMID: 28094544 BACKGROUND

• Caderni G, Femia AP, Giannini A, Favuzza A, Luceri C, Salvadori M, Dolara P. Identification of mucin-depleted foci in the unsectioned colon of azoxymethane-treated rats: correlation with carcinogenesis. Cancer Res. 2003 May 15;63(10):2388-92.

  PMID: 12750256 BACKGROUND

• Irrazabal T, Belcheva A, Girardin SE, Martin A, Philpott DJ. The multifaceted role of the intestinal microbiota in colon cancer. Mol Cell. 2014 Apr 24;54(2):309-20. doi: 10.1016/j.molcel.2014.03.039.

  PMID: 24766895 BACKGROUND

• Pierre F, Peiro G, Tache S, Cross AJ, Bingham SA, Gasc N, Gottardi G, Corpet DE, Gueraud F. New marker of colon cancer risk associated with heme intake: 1,4-dihydroxynonane mercapturic acid. Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2274-9. doi: 10.1158/1055-9965.EPI-06-0085.

  PMID: 17119057 BACKGROUND

• Gueraud F, Tache S, Steghens JP, Milkovic L, Borovic-Sunjic S, Zarkovic N, Gaultier E, Naud N, Helies-Toussaint C, Pierre F, Priymenko N. Dietary polyunsaturated fatty acids and heme iron induce oxidative stress biomarkers and a cancer promoting environment in the colon of rats. Free Radic Biol Med. 2015 Jun;83:192-200. doi: 10.1016/j.freeradbiomed.2015.02.023. Epub 2015 Mar 3.

  PMID: 25744414 BACKGROUND

• De Filippis F, Pellegrini N, Vannini L, Jeffery IB, La Storia A, Laghi L, Serrazanetti DI, Di Cagno R, Ferrocino I, Lazzi C, Turroni S, Cocolin L, Brigidi P, Neviani E, Gobbetti M, O'Toole PW, Ercolini D. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut. 2016 Nov;65(11):1812-1821. doi: 10.1136/gutjnl-2015-309957. Epub 2015 Sep 28.

  PMID: 26416813 BACKGROUND

• De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14691-6. doi: 10.1073/pnas.1005963107. Epub 2010 Aug 2.

  PMID: 20679230 RESULT

• Albanese D, De Filippo C, Cavalieri D, Donati C. Explaining diversity in metagenomic datasets by phylogenetic-based feature weighting. PLoS Comput Biol. 2015 Mar 27;11(3):e1004186. doi: 10.1371/journal.pcbi.1004186. eCollection 2015 Mar.

  PMID: 25815895 RESULT

• Pierre FH, Martin OC, Santarelli RL, Tache S, Naud N, Gueraud F, Audebert M, Dupuy J, Meunier N, Attaix D, Vendeuvre JL, Mirvish SS, Kuhnle GC, Cano N, Corpet DE. Calcium and alpha-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers. Am J Clin Nutr. 2013 Nov;98(5):1255-62. doi: 10.3945/ajcn.113.061069. Epub 2013 Sep 11.

  PMID: 24025632 RESULT

• Dinu M, Ristori S, Pagliai G, Lotti S, Meriggi N, Nerini A, Chevolleau S, Bowman J, Caderni G, Colombini B, Gerard P, Giovannelli L, Gueraud F, Marcucci R, Pierre F, De Filippo C, Sofi F. Effects of meat-based, meat-based with alpha-tocopherol, and pesco-vegetarian diets on biomarkers associated with colorectal cancer risk: a randomized behavioral intervention trial. Sci Rep. 2025 Dec 8;16(1):1502. doi: 10.1038/s41598-025-31410-6.

  PMID: 41361349 DERIVED

• Sofi F, Dinu M, Pagliai G, Pierre F, Gueraud F, Bowman J, Gerard P, Longo V, Giovannelli L, Caderni G, de Filippo C. Fecal microbiome as determinant of the effect of diet on colorectal cancer risk: comparison of meat-based versus pesco-vegetarian diets (the MeaTIc study). Trials. 2019 Dec 9;20(1):688. doi: 10.1186/s13063-019-3801-x.

  PMID: 31815647 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

alpha-Tocopherol

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Tocopherols; Vitamin E; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Alessandro Casini, MD

  University of Florence

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: In this trial blinding of participants and investigators will not be possible because of obvious differences between the intervention diets
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Clinical Nutrition

Model Details: Randomized parallel open dietary intervention study with 3 arms of intervention

Study Record Dates

• First Submitted: January 8, 2018
• First Posted: January 31, 2018
• Study Start: June 1, 2019
• Primary Completion: December 31, 2019
• Study Completion: April 30, 2021
• Last Updated: July 30, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)