Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Serge Hercberg

ORCID ID

Contact details

U557 Inserm (UMR Inserm/Inra/Cnam)
5 rue Vertbois
Paris
75003
France

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

SU.FOL.OM3 Study

Study hypothesis

Definitive proof that supplementation with B-vitamins or omega-3 fatty acids will lead to a reduced cardiovascular diseases morbidity and/or mortality is still scarce. The currently available intervention trials did either not have a study design that allows this conclusion or the results need to be reproduced before they can be regarded as definitive. (NB the trials with B vitamins evaluated mostly the effect on intermediate end-points).

Secondary intervention trials with hard endpoints and B-vitamin supplementation have recently started, but not all of these trials used a combination B vitamins and most trials used pharmacological doses. This has the disadvantage that the results will be difficult to translate into dietary advice. In addition, recent research has indicated that supplementation with 5-methyl tetrahydrofolate (5-methyl-THF), the most abundant natural folate vitamin, is safe and lowers homocysteine levels. This form of folate, in contrast to folic acid, does not lead to circulating unmetabolized folic acid. Unmetabolized folic acid is hypothesized to mask the hematological manifestations of a vitamin B12 deficiency, thereby predisposing subjects to irreversible neurological damage. Stable 5-methyl-THF was not available when other intervention studies started and therefore they all use folic acid.

Taking all this information together, there is a need for a large double-blind placebo-controlled randomized intervention trial evaluating the effect of supplementation with B-vitamins (exchanging folic acid for 5-methyl-THF) and n-3 fatty acids in nutritional doses on hard cardiovascular endpoints. Therefore, we propose the following intervention study in which participants are SUpplemented with natural FOLate, vitamin B6 and B12 and/or OMega-3 fatty acids: the SU.FOL.OM3 study.

Ethics approval

1. Ethics Committee of Paris-Cochin (Comité Consultatif pour la Protection des Personnes se prêtant à la Recherche Biomédicale) (ref: CCPPRB n°1933)
2. National Committee of information and liberty (La Commission Nationale de l'Informatique et des Libertés [CNIL]) (ref: CNIL n° 901230)

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Prevention

Patient information sheet

Condition

Cardio and neurovascular diseases

Intervention

5-methyl-THF (560 µg), vitamin B6 (3 mg) and B12 (20 µg) and/or omega-3 supplements (600 mg with an eicosapentaenoic acid [EPA]:docosahexaenoic acid [DHA] ratio of 2:1) versus placebo

Intervention type

Supplement

Phase

Not Specified

Drug names

Folate, vitamins B6 and B12 and Omega 3 Fatty Acids

Primary outcome measures

Combination of myocardial infarction, cerebral vascular ischemic accident or cardiovascular deaths

Secondary outcome measures

1. Hospitalisation for coronary diseases
2. Hospitalisation for cardiac diseases
3. Hospitalisation for vascular diseases
4. Total mortality
5. Cardiovascular mortality
6. Myocardial infarctions
7. Acute coronary syndrome without necrosis
8. Ischemic cerebral vascular accidents
9. Arteriopathies
10. Venous thrombosis
11. Cancers

Overall trial start date

15/04/2003

Overall trial end date

30/06/2009

Reason abandoned

Eligibility

Participant inclusion criteria

1. Participants should have experienced a coronary or cerebral event during 1 to 12 months before baseline. A coronary or cerebral event is defined as:
a. Myocardial infarction (validated and documented by a combination of clinical, enzymatic, or electrocardiogram [ECG] parameters)
b. Acute coronary syndrome without necrosis (validated and documented by a combination of clinical, enzymatic or ECG parameters)
c. A cerebral vascular ischemic accident (defined by criteria validated in epidemiological studies)
2. The participants should be 45-80 years at baseline

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

2,400

Participant exclusion criteria

1. Age <45 years or >80 years
2. Cardiovascular pathology not well defined
3. Patients that are incapable of understanding the study protocol
4. Patients with a pathology that might interfere with homocysteine or omega-3 fatty acid metabolism, in particular those that use methotrexate for the treatment of a cancer or rheumatoid arthritis and chronic renal failure (plasma level of creatinine >200 µmol/l or creatinine clearance <40 ml/min)
5. Patients with a non-cardiovascular pathology with a suspected survival time less than the 5 years period of the study (solid cancer, evolved dementia, leukemia etc.)

Recruitment start date

15/04/2003

Recruitment end date

30/06/2009

Locations

Countries of recruitment

France

Trial participating centre

U557 Inserm (UMR Inserm/Inra/Cnam)
Paris
75003
France

Sponsor information

Organisation

INSERM - Direction of Clinical Research (France)

Sponsor details

101 rue de Tolbiac
Paris
75003
France

Sponsor type

Research organisation

Website

http://www.inserm.fr

Funders

Funder type

Industry

Funder name

National Institute for Health and Medical Research (INSERM) (France)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

French National Institute for Agricultural Research (INRA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Ministry of the Higher Education and Research (France)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Pierre Fabre

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Eprova

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Danone Vitapole/Lu

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Unilever Bestfoods France

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Candia/ Yoplait

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2003 publication on background and rationale of the SU.FOL.OM3 study in http://www.ncbi.nlm.nih.gov/pubmed/14625623
2. 2008 protocol in http://www.ncbi.nlm.nih.gov/pubmed/18544171
3. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/21115589
4. 2012 cancer prevention results in http://www.ncbi.nlm.nih.gov/pubmed/22331983
4. 2012 blood pressure results in http://www.ncbi.nlm.nih.gov/pubmed/21801476
6. 2012 depressive symptoms results in http://www.ncbi.nlm.nih.gov/pubmed/22648722
7. 2013 biomarker results in: http://www.ncbi.nlm.nih.gov/pubmed/23582589

Publication citations

  1. Results

    Galan P, Kesse-Guyot E, Czernichow S, Briancon S, Blacher J, Hercberg S, , Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial., BMJ, 2010, 341, c6273.

  2. Cancer prevention results

    Andreeva VA, Touvier M, Kesse-Guyot E, Julia C, Galan P, Hercberg S, B vitamin and/or ω-3 fatty acid supplementation and cancer: ancillary findings from the supplementation with folate, vitamins B6 and B12, and/or omega-3 fatty acids (SU.FOL.OM3) randomized trial., Arch. Intern. Med., 2012, 172, 7, 540-547, doi: 10.1001/archinternmed.2011.1450.

  3. Blood pressure results

    Szabo de Edelenyi F, Vergnaud AC, Ahluwalia N, Julia C, Hercberg S, Blacher J, Galan P, Effect of B-vitamins and n-3 PUFA supplementation for 5 years on blood pressure in patients with CVD., Br. J. Nutr., 2012, 107, 6, 921-927, doi: 10.1017/S0007114511003692.

  4. Depressive symptoms results

    Andreeva VA, Galan P, Torrès M, Julia C, Hercberg S, Kesse-Guyot E, Supplementation with B vitamins or n-3 fatty acids and depressive symptoms in cardiovascular disease survivors: ancillary findings from the SUpplementation with FOLate, vitamins B-6 and B-12 and/or OMega-3 fatty acids (SU.FOL.OM3) randomized trial., Am. J. Clin. Nutr., 2012, 96, 1, 208-214, doi: 10.3945/ajcn.112.035253.

  5. Biomarker results

    Ahluwalia N, Blacher J, Szabo de Edelenyi F, Faure P, Julia C, Hercberg S, Galan P, Prognostic value of multiple emerging biomarkers in cardiovascular risk prediction in patients with stable cardiovascular disease., Atherosclerosis, 2013, 228, 2, 478-484, doi: 10.1016/j.atherosclerosis.2013.03.017.

  6. Galan P, de Bree A, Mennen L, Potier de Courcy G, Preziozi P, Bertrais S, Castetbon K, Hercberg S, Background and rationale of the SU.FOL.OM3 study: double-blind randomized placebo-controlled secondary prevention trial to test the impact of supplementation with folate, vitamin B6 and B12 and/or omega-3 fatty acids on the prevention of recurrent ischemic events in subjects with atherosclerosis in the coronary or cerebral arteries., J Nutr Health Aging, 2003, 7, 6, 428-435.

  7. Galan P, Briancon S, Blacher J, Czernichow S, Hercberg S, The SU.FOL.OM3 Study: a secondary prevention trial testing the impact of supplementation with folate and B-vitamins and/or Omega-3 PUFA on fatal and non fatal cardiovascular events, design, methods and participants characteristics., Trials, 2008, 9, 35, doi: 10.1186/1745-6215-9-35.

Editorial Notes