Nitrate INFORMER Nitrosamine Study
Condition: Health Risk Behaviors
Study type: Interventional

Summary: 
      Nitrate is a controversial component of vegetables, meat, and drinking water. The now
      well-established benefits of nitrate, through the enterosalivary nitrate-nitrite-nitric oxide
      (NO) pathway, on cardiovascular risk factors and long-term cardiovascular disease risk are
      tarnished by a continuing concern about a link between nitrate ingestion and cancer. This can
      result in misguided advice to avoid consumption of high-nitrate leafy green vegetables by
      both the media and the scientific literature. A recent media headline stated, "Cancer alert
      over rocket: trendy salad leaves exceed safe levels of carcinogenic nitrates in one in every
      ten samples". One scientific review stated, "the presence of nitrate in vegetables, as in
      water and generally in other foods, is a serious threat to man's health". Controversy in the
      literature, and gaps in the knowledge are leading to confusing messages around vegetables
      that may play a critical role in cardiovascular health.

      The major dietary sources of nitrate are vegetables, meat, and drinking water. Source of
      nitrate could be a crucial factor determining whether the consumption of nitrate is linked
      with beneficial (such as improving cardiovascular health) versus harmful (N-nitrosamine
      formation) effects. For example, unlike meat and water-derived nitrate, vegetables contain
      high levels of vitamin C and/or polyphenols that may inhibit the production of
      N-nitrosamines. So far, no study has investigated the formation of N-nitrosamines after
      consumption of these different sources in humans.

      A pilot study will be conducted to determine that endogenous N-nitrosamine formation is
      observed after ingestion of meat with added nitrate and nitrite and that consumption of
      vegetables with the meat containing added nitrate and nitrite will inhibit the production of
      N-nitrosamines.
    

Detailed description: 
      Study design:

      A crossover study design will be used with a 1-week washout period. Each participant will
      complete the scheduled study visits for one of the dietary interventions which will be
      assigned in random order. Following the washout, the participants will then complete the
      scheduled study visits for the remaining intervention. Participants will be provided with a
      low nitrate and N-nitrosamine meal on the preceding evening of each study visit. These meals
      will be consistent across all study visits. Participants will be asked to refrain from
      drinking coffee and any alcoholic beverage and doing any exercise 24 hours prior to the study
      visit.

      Dietary interventions:

      Meat with added nitrate: Prosciutto/pancetta/Parma ham/salami (all derived from pork)
      prepared by a commercial butcher with sodium nitrate as an additive.

      Meat with added nitrate plus vegetables: The same intervention described above consumed
      together with mixed vegetables.

      Assessments:

      At each clinic visit, baseline samples of urine will be collected for measurement of
      N-nitrosamines, nitrate, and nitrite. After the intervention, all urine within the first 240
      minutes and then subsequent 20-hour period will be collected for measurement of
      N-nitrosamines, nitrate, and nitrite.
    

Intervention name(s): Meat with added nitrate; Meat with added nitrate plus vegetables
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Prosciutto/pancetta/Parma ham/salami (all derived from pork) prepared by a commercial butcher with the sodium nitrate and nitrite as an additive.; The same intervention as of intervention "meat with added nitrate" consumed together with mixed vegetables.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: prospective, mono-centre, randomised, controlled, crossover study
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention