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

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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.

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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

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VitaminDWiki - Vitamin D and Omega-3 category

374 Omega-3 items in category Omega-3 helps with: Autism (9 studies), Depression (29 studies), Cardiovascular (31 studies), Cognition (48 studies), Pregnancy (39 studies), Infant (24 studies), Obesity (13 studies), Mortality (5 studies), Breast Cancer (6 studies), Smoking, Sleep, Stroke, Longevity, Trauma (12 studies), Inflammation (18 studies), Multiple Sclerosis (9 studies), VIRUS (12 studies), etc

   See also - Overview: Omega-3 many benefits include helping vitamin D

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

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

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VitaminDWiki - Depression summary

• Low vitamin D is associated with most types of depression, Including: Seasonal Affective Disorder. manic depression, bipolar disorder, dysthymia, Depression during/after pregnancy, Seniors, Suicide
• Seasonal Affective Disorder is treated by both bright light and Vitamin D because both make serotonin
• Supplementing with Vitamin D (or getting more sun) decreases most types of depression as well as drugs
• Omega-3, Magnesium, and St. Johns' Wort also decrease depression
  • Speculate that some combination (Vit D, Omega-3, Mg, St John's) will decrease depression even more
  • Note: Both Omega-3 and Magnesium increase the amount of vitamin D which gets to tissues
• Omega-3 and Vitamin D each treat many mental health problems - April 2018
• Antidepressants reduce cellular Vitamin D, increasing fractures, CVD, etc. - Oct 2022
• There are 240 items in the Depression category in VitaminDWiki

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A few of the VitaminDWiki pages with OMEGA-3 INDEX in the tile

• Some Omega-3 index references
• Omega-3 index - good level needed 2.4 grams of regular Omega-3 - Grassroots Nov 2018
• Omega-3 index replaces the Omega-6 to Omega-3 ratio – March 2018
• Depression after childbirth 5 X less likely if good Omega-3 index – April 2019
• Higher Omega-3 index (4 to 8 percent) associated with 30 percent less risk of coronary disease (10 studies)
• 4X fewer COVID-19 deaths in those having high Omega-3 index – Jan 6, 2021