Natural Compounds to Reduce Nitrite in Meat Products

NCT04138654 | Completed Phase 1 DMC

• 1 other identifier: NL43956.068.13
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

The PHYTOME project (Phytochemicals to reduce nitrite in meat products) is a major European Union (EU) co-funded research project that aims to develop innovative meat products in which the food additive nitrite has been replaced by natural compounds originating from fruits and vegetables. These biologically active compounds, also referred to as phytochemicals, are known to contribute to improved gut health and are added to the meat as natural extracts. In a number of meat products, carefully selected combinations of natural antioxidants and other biologically active compounds occurring in vegetables, fruits and natural extracts such as coffee and tea, will be added during meat processing. Some of these compounds possess an antimicrobial activity allowing them to replace nitrite, whereas others possess a natural red colour that may contribute to the desired appearance of the products. Also, some of these compounds are known to protect colonic cells against damaging effects of cancer causing agents that may be formed in the large intestine after meat consumption. The PHYTOME project will develop new technologies to introduce the natural extracts during processing to different types of meat products. These techniques will guarantee good sensory quality of the product as well as microbiological safety. Once these techniques have been developed and optimized at laboratory scale, the new type of products will be produced on an industrial scale. The health promoting effects of these products will be evaluated in a human dietary intervention study with healthy volunteers. After consumption of a fully controlled diet with either relatively high amounts of the traditional meat products or products produced following the new concept, faeces and colonic material will be collected and investigated for markers of colorectal cancer risk. These investigations will be performed in close collaboration with Research Institutes in the United Kingdom, Belgium, Italy and Greece, and will make use of the newest genomics techniques that are available.

Conditions

Colon Cancer

Outcome Measures

Primary Outcomes (2)

• Change in N-nitroso compound (NOC) levels in faeces and urine measured as apparent total nitroso compounds (ATNC) between baseline levels at the start of the intervention and each intervention period

  The faecal and urinal level of NOC is measured as Total Apparent Nitroso Compounds (ATNC) and used indicator of colonic endogenous nitrosation. It is known to significantly increase following strictly controlled diets high in red or processed meat.

  At baseline, at 2 weeks, at 4 weeks, at 6 weeks, and at 7 weeks

• Change in whole genome gene expression analyses in colonic biopsies and blood between baseline levels and each intervention period (transcriptomics)

  Colon biopsies and blood will be analysed for transcriptomic responses to the dietary changes. This will provide information on gene expression changes in the colon epithelium that may be linked with other parameters such as faecal NOC levels. This will also identify molecular pathways that can link dietary composition to processes involved in cancer development.

  At baseline, at 2 weeks, at 4 weeks, and at 6 weeks

Secondary Outcomes (5)

• Change in urinary nitrate and creatine levels between baseline levels at the start of the intervention and each intervention period.

  At baseline, at 2 weeks, at 4 weeks, at 6 weeks, and at 7 weeks

• Genotyping of DNA

  At baseline

• Change in DNA methylation analyses of DNA isolated from colonic biopsies and blood (epigenetics) between baseline levels at the start of the intervention and each intervention period

  At baseline, at 2 weeks, at 4 weeks, at 6 weeks

• Change in enzyme activity of nitrate reductase in saliva between baseline levels at the start of the intervention and each intervention period

  At baseline, at 2 weeks, at 4 weeks, at 6 weeks, and at 7 weeks

• Change in the microbiome in feacal samples and in saliva between baseline levels at the start of the intervention and each intervention period

  At baseline, at 2 weeks, at 4 weeks, at 6 weeks, and at 7 weeks

Other Outcomes (3)

• Change in faecal water genotoxicity between baseline levels at the start of the intervention and each intervention period

  At baseline, at 2 weeks, at 4 weeks, at 6 weeks

• Change in O6-CMG in colonic biopsies between baseline levels at the start of the intervention and each intervention period

  At baseline, at 2 weeks, at 4 weeks, at 6 weeks

• Change in O6-MeG in colonic biopsies between baseline levels at the start of the intervention and each intervention period

  At baseline, at 2 weeks, at 4 weeks, at 6 weeks

Study Arms (2)

Normal nitrite levels

EXPERIMENTAL

Processed meat products enriched with natural compounds will contain normal nitrite levels.

Dietary Supplement: Processed meat product; Dietary Supplement: White meat wash-out; Dietary Supplement: Processed meat products enriched with natural compounds; Dietary Supplement: Drinking water containing nitrate up to acceptable daily intake level (ADI = 3.7 mg/kg bw) in combination with 300 grams of processed meat, white meat or processed meat enriched with natural compounds

Reduced nitrite levels

EXPERIMENTAL

Processed meat products enriched with natural compounds will contain reduced nitrite levels

Dietary Supplement: Processed meat product; Dietary Supplement: White meat wash-out; Dietary Supplement: Processed meat products enriched with natural compounds; Dietary Supplement: Drinking water containing nitrate up to acceptable daily intake level (ADI = 3.7 mg/kg bw) in combination with 300 grams of processed meat, white meat or processed meat enriched with natural compounds

Interventions

Processed meat product DIETARY_SUPPLEMENT

300 grams per day during 2 weeks

Normal nitrite levels; Reduced nitrite levels

White meat wash-out DIETARY_SUPPLEMENT

300 grams per day during 2 weeks

Normal nitrite levels; Reduced nitrite levels

Processed meat products enriched with natural compounds DIETARY_SUPPLEMENT

300 grams per day during 2 weeks

Normal nitrite levels; Reduced nitrite levels

Drinking water containing nitrate up to acceptable daily intake level (ADI = 3.7 mg/kg bw) in combination with 300 grams of processed meat, white meat or processed meat enriched with natural compounds DIETARY_SUPPLEMENT

3.7 mg nitrate/kg bw per day plus 300 grams of meat for 1 week

Normal nitrite levels; Reduced nitrite levels

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy with a Body Mass Index (BMI) between 18-25, male or female
• Between 18-70 years old

You may not qualify if:

• Alcohol abuse up to 6 months before participation in this research
• Current aberrations or insufficiency of kidney, liver, gut, heart or lungs
• Current presence of persistent inflammation in the gut or liver
• Current endocrine or metabolic aberrations
• Current anaemia or infection
• HIV infection or hepatitis
• Use of antibiotics and other medication over the last 3 months
• Current smokers
• Vegetarians
• Pregnant women
• Participants of other intervention studies during this intervention period.

Sponsors & Collaborators

• Maastricht University: lead

Study Sites (1)

Toxicogenomics

Maastricht, (Click to Select US State), 6200MD, Netherlands

Location

Related Publications (38)

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  PMID: 33785324 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Poultry

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)

Meat; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2014
• First Posted: October 24, 2019
• Study Start: April 17, 2014
• Primary Completion: June 30, 2015
• Study Completion: December 1, 2015
• Last Updated: October 24, 2019

Record last verified: 2014-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)