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Omega-3 did not prevent depression (they failed to reduce Omega-6, which blocks Omega-3) – RCT Dec 2021


Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores – A Randomized Clinical Trial

JAMA. 2021;326(23):2385-2394. doi:10.1001/jama.2021.21187 (PDF is behind a paywall)
Olivia I. Okereke, MD, SM1,2,3; Chirag M. Vyas, MBBS, MPH1; David Mischoulon, MD, PhD1; et al Grace Chang, MD, MPH4; Nancy R. Cook, ScD3,5; Alison Weinberg, MA5; Vadim Bubes, PhD5; Trisha Copeland, MS, RD5; Georgina Friedenberg, MPH5; I-Min Lee, MBBS, ScD3,5; Julie E. Buring, ScD3,5; Charles F. Reynolds III, MD6; JoAnn E. Manson, MD, DrPH2,3,5

Objective To test effects of omega-3 supplementation on late-life depression risk and mood scores.

Design, Setting, and Participants A total of 18 353 adults participated in the VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention) ancillary study to VITAL, a randomized trial of cardiovascular disease and cancer prevention among 25 871 US adults. There were 16 657 at risk of incident depression (no previous depression) and 1696 at risk of recurrent depression (previous depression, but not for the past 2 years). Randomization occurred from November 2011 through March 2014; randomized treatment ended on December 31, 2017.

Interventions Randomized 2 × 2 factorial assignment to vitamin D3 (2000 IU/d), marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid and 375 mg of docosahexaenoic acid) or placebo; 9171 were randomized to omega-3 and 9182 were randomized to matching placebo.

Main Outcomes and Measures Prespecified coprimary outcomes were risk of depression or clinically relevant depressive symptoms (total of incident + recurrent cases); mean difference in mood score (8-item Patient Health Questionnaire [PHQ-8] depression scale).

Results Among 18 353 participants who were randomized (mean age, 67.5 [SD, 7.1] years; 49.2% women), 90.3% completed the trial (93.5% among those alive at the end of the trial); the median treatment duration was 5.3 years. The test for interaction between the omega-3 and the vitamin D agents was not significant (P for interaction = .14). Depression risk was significantly higher comparing omega-3 (651 events, 13.9 per 1000 person-years) with placebo (583 events, 12.3 per 1000 person-years; hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P = .03). No significant differences were observed comparing omega-3 with placebo groups in longitudinal mood scores: the mean difference in change in PHQ-8 score was 0.03 points (95% CI, −0.01 to 0.07; P = .19). Regarding serious and common adverse events, the respective prevalence values in omega-3 vs placebo groups were major cardiovascular events (2.7% vs 2.9%), all-cause mortality (3.3% vs 3.1%), suicide (0.02% vs 0.01%), gastrointestinal bleeding (2.6% vs 2.7%), easy bruising (24.8% vs 25.1%), and stomach upset or pain (35.2% vs 35.1%).

Conclusions and Relevance Among adults aged 50 years or older without clinically relevant depressive symptoms at baseline, treatment with omega-3 supplements compared with placebo yielded mixed results, with a small but statistically significant increase in risk of depression or clinically relevant depressive symptoms but no difference in mood scores, over a median follow-up of 5.3 years. These findings do not support the use of omega-3 supplements in adults to prevent depression.


Personal note by the founder of VitaminDWiki

For years I took Omega-3 supplements without feeling any benefits
I got an low-cost Omega-3 index test and found that I was low
Omega-6 restricts the amount of Omega-3 that the body can use
Omega-6 lowers the Omega-3 index test results

  1. I changed my brand of Omega-3 to one which is more bio-available (Coromega)
  2. I reduced my consumption of Omega-6
  3. I now have a good Omgea-3 index (=6) and also now feel the benefits

VitaminDWiki - Vitamin D and Omega-3 category

398 Omega-3 items in category Omega-3 helps with: Autism (7 studies), Depression (28 studies), Cardiovascular (34 studies), Cognition (50 studies), Pregnancy (40 studies), Infant (33 studies), Obesity (14 studies), Mortality (7 studies), Breast Cancer (5 studies), Smoking, Sleep, Stroke, Longevity, Trauma (12 studies), Inflammation (18 studies), Multiple Sclerosis (9 studies), VIRUS (12 studies), etc
CIlck here for details

VitaminDWiki - studies in both of the categories of Depression and Omega-3


VitaminDWiki - Depression Intervention (Vitamin D. Omega-3...)


VitaminDWiki - Depression summary

Some recent publications


14+ VitaminDWiki pages with OMEGA-6 in the title

This list is automatically updated

Items found: 17
Title Modified
Hypothesis – Bipolar Disorder will be reduced if add Omega-3 while reducing Omega-6 – Oct 2016 06 Dec, 2023
Lecithin increased Omega-3 and decreased Omega-6 (in rats) - July 2016 17 Jul, 2023
Omega-6 blocks Omega-3 etc. -many studies 17 Jul, 2023
Omega-6 increase may have increased the risk of many other diseases - Jan 2022 05 Feb, 2022
Omega-3 did not prevent depression (they failed to reduce Omega-6, which blocks Omega-3) – RCT Dec 2021 22 Dec, 2021
High-dose Omega-3 fought COVID in 2 hospital trials (6x reduction in ICU, reduced time) – Masterjohn Oct 2021 14 Oct, 2021
4X fewer COVID-19 deaths in those having high Omega-3 index – Jan 6, 2021 13 Jan, 2021
Omega-3 index of 6 to 7 associated with best cognition in this study – Nov 2019 10 Nov, 2019
Prenatal Omega-3 somewhat reduced child allergies (should also reduce Omega-6) – RCT June 2018 17 Apr, 2019
Omega-3 index replaces the Omega-6 to Omega-3 ratio – March 2018 16 Apr, 2018
Why Alzheimer’s studies using Omega-3 have mixed results – quality, dose size, Omega-6, genes, etc. March 2018 18 Mar, 2018
People felt less aggression after just 6 weeks of Omega-3 – RCT Dec 2017 03 Mar, 2018
Supplementation while pregnant and psychotic – 20 percent Omega-3, 6 percent Vitamin D – June 2016 20 Jan, 2018
Hypothesis – Omega-6 to Omega-3 ratio increases obesity – Nov 2015 23 Oct, 2016
ADHD 2 times more likely if poor Omega-6 to Omega-3 ratio – meta-analysis May 2016 07 Jun, 2016
Huge increases in Omega-6 to Omega-3 ratio increase risk of obesity, etc. – March 2016 14 Mar, 2016
Schizophrenia treated by 6 months of Omega-3 – RCT Nov 2015 28 Nov, 2015

Created by admin. Last Modification: Monday July 17, 2023 23:20:56 GMT-0000 by admin. (Version 7)