12 augustus 2022: Bron: BMJ 2022;376:e066452

Vitamine D-suppletie gedurende vijf jaar, met of zonder omega 3-vetzuren, verminderde auto-immuunziektes met 22%, terwijl omega 3-vetzuursuppletie met of zonder vitamine D het aantal auto-immuunziekten met 15% verminderde. Zo schrijven onderzoekers van de grote VITAL studie in hun studierapport. Gebaseerd op deze twee studies: ClinicalTrials.gov NCT01351805 and NCT01169259  

Vertaling van de conclusies uit het studierapport:

Belangrijkste bevindingen:

  • In dit grote primaire preventieonderzoek bij diverse oudere Amerikanen, resulteerde suppletie met vitamine D in een dosis van 2000 IE/dag gedurende ongeveer vijf jaar, alleen of in combinatie met 1 g/dag omega 3-vetzuren (460 mg eicosapentaeenzuur en 380 mg docosahexaeenzuur) tot een lagere incidentie van bevestigde auto-immuunziekte dan placebo.
  • Suppletie met alleen omega 3-vetzuren verminderde de incidentie van auto-immuunziekten niet statistisch significant. Echter, wanneer deelnemers met een waarschijnlijke auto-immuunziekte werden geïncludeerd, verminderde omega 3-vetzuursuppletie het percentage met 18% in vergelijking met placebo en werd er een significante interactie gevonden in de loop van de tijd, wat wijst op een verhoogd effect na langere duur van de suppletie.
  • Wanneer alleen de laatste drie jaar van de interventie in aanmerking werden genomen, had de vitamine D-groep 39% minder deelnemers met bevestigde auto-immuunziekte dan de placebogroep (P=0,005); terwijl de omega 3-vetzuurgroep 10% minder deelnemers had met bevestigde auto-immuunziekte dan de placebogroep (P=0,54).
  • In deze twee-op-twee-studie verminderde suppletie met zowel vitamine D- als omega 3-vetzuren de auto-immuunziekte met ongeveer 30% vergeleken met alleen placebo.
  • Het aantal deelnemers met individuele auto-immuunziekten was over het algemeen kleiner in de behandelingsgroepen dan in de placebogroepen; auto-immuunziekte van de schildklier (de meest uitdagende om te bevestigen met behulp van medische dossiers) en psoriasis waren uitzonderingen op dit patroon. Deze individuele verschillen waren niet statistisch significant, misschien vanwege het kleine aantal deelnemers met individuele ziekten.
  • De incidentie van reumatoïde artritis was ongeveer 40% lager in de suppletiegroepen dan in de placebogroepen, hoewel gemeld werd dat <40 deelnemers een duidelijke ziekte hadden. Het langer volgen van proefpersonen zal duidelijk maken of deze procentuele verlagingen aanhouden.

Zie deze grafieken uit het studierapport:

Fig 1

Fig 1

Cumulative incidence rates of total autoimmune diseases in the VITAL (vitamin D and omega 3) trial. Hazard ratios are from Cox models controlled for age, sex, race, and randomization group in the opposite arm of the trial

Het volledige studieverslag is gratis in te zien of te downloaden. Klik daarvoor op de titel van het abstract:

Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial

BMJ 2022376 doi: https://doi.org/10.1136/bmj-2021-066452 (Published 26 January 2022)Cite this as: BMJ 2022;376:e066452

Linked Opinion

Vitamin D and fish oil supplements and risk of autoimmune disease

  1. Jill Hahn, postdoctoral fellow123,  
  2. Nancy R Cook, professor14,  
  3. Erik K Alexander, chief of thyroid section5,  
  4. Sonia Friedman, associate professor6,  
  5. Joseph Walter, endpoints coordinator4,  
  6. Vadim Bubes, senior analyst4,  
  7. Gregory Kotler, senior programmer/analyst4,  
  8. I-Min Lee, professor14,  
  9. JoAnn E Manson, professor, chief of division of preventive medicine14,  
  10. Karen H Costenbader, lupus program director2
Author affiliations
  1. Correspondence to: K H Costenbader kcostenbader@bwh.harvard.edu (or @karen_kc123 on Twitter)
  • Accepted 1 December 2021


Objective To investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk.

Design Vitamin D and omega 3 trial (VITAL), a nationwide, randomized, double blind, placebo controlled trial with a two-by-two factorial design.

Setting Nationwide in the United States.

Participants 25 871 participants, consisting of 12 786 men ≥50 years and 13 085 women ≥55 years at enrollment.

Interventions Vitamin D (2000 IU/day) or matched placebo, and omega 3 fatty acids (1000 mg/day) or matched placebo. Participants self-reported all incident autoimmune diseases from baseline to a median of 5.3 years of follow-up; these diseases were confirmed by extensive medical record review. Cox proportional hazard models were used to test the effects of vitamin D and omega 3 fatty acids on autoimmune disease incidence.

Main outcome measures The primary endpoint was all incident autoimmune diseases confirmed by medical record review: rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all others.

Results 25 871 participants were enrolled and followed for a median of 5.3 years. 18 046 self-identified as non-Hispanic white, 5106 as black, and 2152 as other racial and ethnic groups. The mean age was 67.1 years. For the vitamin D arm, 123 participants in the treatment group and 155 in the placebo group had a confirmed autoimmune disease (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, P=0.05). In the omega 3 fatty acids arm, 130 participants in the treatment group and 148 in the placebo group had a confirmed autoimmune disease (0.85, 0.67 to 1.08, P=0.19). Compared with the reference arm (vitamin D placebo and omega 3 fatty acid placebo; 88 with confirmed autoimmune disease), 63 participants who received vitamin D and omega 3 fatty acids (0.69, 0.49 to 0.96), 60 who received only vitamin D (0.68, 0.48 to 0.94), and 67 who received only omega 3 fatty acids (0.74, 0.54 to 1.03) had confirmed autoimmune disease.

Conclusions Vitamin D supplementation for five years, with or without omega 3 fatty acids, reduced autoimmune disease by 22%, while omega 3 fatty acid supplementation with or without vitamin D reduced the autoimmune disease rate by 15% (not statistically significant). Both treatment arms showed larger effects than the reference arm (vitamin D placebo and omega 3 fatty acid placebo).

Study registration ClinicalTrials.gov NCT01351805 and NCT01169259

Ethics statements

Ethical approval

The study protocol was approved by the institutional review board at Partners HealthCare System and monitored by an external data and safety monitoring board.

Data availability statement

Data from this study might be considered for release if the appropriate institutional review board approval and publication clearances have been obtained, and a project is approved by the VITAL oversight committee.


  • Contributors: All authors have contributed substantially to the conception or design of the work, or the acquisition, analysis or interpretation of data; drafting the work or revising it critically for important intellectual content; and final approval of the version published. All authors have agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. JH is the study guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding: This study was funded by the National Institutes of Health grants R01 AR059086, U01 CA138962, R01 CA138962. The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institutes of Health for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Dissemination to participants and related patient and public communities: We disseminate study results to VITAL participants using email and newsletters. We will make great efforts to also disseminate the results to the general public, given that this was a trial in a residential population with results generalizable to older adults. These results were recently presented at the plenary session of the American College of Rheumatology Scientific Convergence 2021 (online annual meeting), and will also be disseminated through press releases.

  • The lead author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

  • Provenance and peer review: Not commissioned; externally peer reviewed.


This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.


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