Natural Compounds to Reduce Nitrite in Meat Products
Condition: Colon Cancer
MeSH terms: Colonic Neoplasms
Study type: Interventional
Phase: Phase 1

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      the food additive nitrite has been replaced by natural compounds originating from fruits and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.
    

Detailed description: 
      Rationale:

      The aim of this project is to develop new meat processing technologies, resulting in
      innovative meat products that have low or no nitrite and that have been shown to contribute
      to improved human health. This will be achieved by introducing carefully selected mixtures of
      biologically compounds originating from natural plant extracts. The new meat products will be
      evaluated in a human dietary intervention study to establish their positive effect on cancer
      risk markers in colonic tissues using the newest genomics techniques available.

      Objective:

      This project aims to evaluate the health impact of newly developed low nitrite containing
      meat products using genomics markers in a human dietary intervention study.

      Study design:

      This study has a cross-over design with only healthy volunteers. Each participant will be
      asked to donate a urinal, faecal and blood sample and undergo endoscopy after each
      intervention period. All analyses will be done for each study group separately to examine the
      overall effects of nitrite levels in meat.

      Study population:

      All subjects will be recruited by the University of Maastricht (UM) in the province of
      Limburg, the Netherlands, using advertisements in local newspapers as well as other media.
      Healthy subjects of both sexes will be selected based on predefined inclusion criteria (BMI:
      18-25; > 18 years) and randomly assigned to one of the different experimental groups.

      Intervention (if applicable):

      Subjects will receive a completely controlled diet with 3 different types of meat products
      according to the study design, with either normal levels, low or no added nitrite. After each
      of the three intervention periods of 15 days (300 grams meat per day) blood, urine, saliva,
      mouth wash and faeces will be sampled and stored appropriately at UM for later analysis.
      Additionally, colonic biopsies will be taken by the department of internal medicine (UM) or
      at the hospital of Sittard during an endoscopic examination. To evaluate the impact of
      nitrate in drinking water on the endogenous nitrosation processes in combination with
      processed red meat intake, there will be and extra intervention period of 7 days were
      volunteers will be asked to consume drinking water with high nitrate levels according to the
      Acceptable Daily Intake level (ADI: 3.7mg/kg bodyweight) in combination with 300 grams
      processed red meat per day. Also after this intervention period volunteers will be asked to
      collect a blood and saliva sample and 24h urine and faeces samples. Also, colonic biopsies
      will be taken by the department of internal medicine (UM) or at the hospital of Sittard
      during an endoscopic examination.

      Main study parameters/endpoints:

        -  Formation of N-nitrosocompounds in human faecal and urine samples

        -  Reveal differences in transcriptomic and epigenomic markers after consumption of meat
           products enriched with natural compounds. These markers can be interpreted as an
           indicator of reduced cancer risk.

        -  Correlating gene expression changes to changes in genotoxic endpoints (DNA damage,
           reduction in N-Nitroso compounds (NOC)) to reveal the molecular processes involved in
           cancer risk reduction. The identification of molecular pathways that are crucial in the
           carcinogenic process will demonstrate a causal association between dietary changes and
           markers of carcinogenic risk.
    

Intervention name(s): Processed meat product; White meat wash-out; Processed meat products enriched with natural compounds; 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
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): 300 grams per day during 2 weeks; 300 grams per day during 2 weeks; 300 grams per day during 2 weeks; 3.7 mg nitrate/kg bw per day plus 300 grams of meat for 1 week
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention