Red Wine Effects Upon Gut Flora and Plasma Levels of Trimethylamine-N-oxide (TMAO) - WineFlora Study

Summary

Recent evidence indicates that Trimethylamine-N-oxide (TMAO) is a pro-atherosclerotic, phosphatidylcholine-dependent metabolite of diet and intestinal flora. Food substrates derive from carnitine and phosphatidylcholine (lecithin), present mainly in eggs, red meat, liver and pork. The intestinal flora pattern that favors the formation of TMAO is very similar to that which predisposes to insulin resistance and obesity: a high proportion between phylum Firmicutes over Bacteroidetes. The intestinal microbiota is sensitive and variable; the use of prebiotics and probiotics can change the relationship between Firmicutes/Bacteroidetes phyla. Red wine (RW), for its composition with polyphenols and possible bactericidal role, may play a role in the intestinal flora modification and could promote proliferation of beneficial bacteria. However, the influence of RW on TMAO is not known. This is the hypothesis to be tested in this trial. METHODS: This is a prospective, crossover, randomized, controlled trial with patients from Heart Institute (InCor), FMUSP and volunteers recruited through press releases. We will evaluate 42 patients, all men, with established atherosclerotic disease. Patients will be evaluated in a crossed manner: each subject receives both treatments, intervention and control (in random order), and they will be divided into 2 groups: A and B. In the first intervention stage, after 2 weeks of washout for all patients , group A receives Red Wine (RW) and group B is the control, abstemious. In the 2nd stage of intervention, after 2 weeks of washout for all patients the groups are inverted: group B receives RW; and group A will be abstemious. In the period with wine intervention, patients will receive 250 mL/day of red wine per day, for 5 days of the week, for 3 weeks. Patients will maintain their usual diet without the use of prebiotics or probiotics, or other polyphenolic derivatives. At the beginning and at the end of each stage, patients will be submitted to serum TMAO and intestinal microbiota evaluation. For the intestinal microbiota evaluation, the new generation sequencing will be used in the highly preserved portion of the 16S subunit of the rRNA gene. The determination of TMAO in plasma will be by liquid chromatography coupled to mass spectrometry. Expected results: It is expected to determine if RW acts on the intestinal flora to the point of influencing plasma TMAO concentration.

Conditions

• Trimethylamine-N-oxide
• Gut Microbiota
• Effects of Red Wine
• Atherosclerosis

Interventions

DIETARY_SUPPLEMENT

Red Wine consumption

After a two weeks washout period,in the intervening period with red wine, patients will receive 250 mL / day of red wine per Day, 5 days a week, for 3 weeks.

OTHER

Period without alcohol consumption

After a two weeks washout period,in the Abstemious period, patients should not consume any kind of alcohol beverages, for 3 weeks

Sponsors & Collaborators

• Fundação de Amparo à Pesquisa do Estado de São Paulo

  collaborator OTHER_GOV

• IBRAVIN

  collaborator UNKNOWN

• University of Sao Paulo General Hospital

  lead OTHER

Principal Investigators

• Protasio L da Luz, Professor · Instituto do Coração - InCor - University of Sao Paulo General Hospital

• Elisa A Haas, MD · Instituto do Coração - InCor - University of Sao Paulo General Hospital

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

45 Years

Max Age

70 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-08-31

Primary Completion

2018-03-22

Completion

2018-04-15