Guest Blog by Kathy Mankofsky R.D., L.D.
Great! So the more EPA you take the better you feel, right?
EPA Omega-3: Less is more?
A study by Doctors Peet & Horrobin showed significant positive results at 1000 mg EPA and no improvement with 4000 mg of EPA.
The study included patients who had persistent depression, despite ongoing treatment with prescription antidepressants. They used pure EPA (ethyl eicosapentanoate) vs placebo for 12 weeks, in addition to the unchanged background medication. The patients were given pure EPA and no DHA.
The authors acknowledge that the most popular prescription antidepressant (Prozac), improves depression symptoms by 50% in only 56% of those who complete the treatment and that new methods of treating depression are needed. Hence their study.
Results: symptoms improved on all 3 depression rating scales with the 1000 mg EPA. There was significant improvement in:
The group that received 4000 mg EPA showed trends towards improvement that were non-significant. The authors did not expand on why ‘more wasn’t better.’
The authors note that both depression and cardiovascular disease are associated with low blood EPA levels. EPA may be a benefit to depressed patients who are also at risk for cardiovascular disease.
The study states that EPA lowers triglyceride levels, inhibits platelet aggregation (clumping together of blood cells), and inhibits cardiac arrhythmia (irregular heartbeats). Inflammatory cytokines (hormone-like substances that come from Omega-6 breakdown) made from Arachidonic Acid (AA) are consistently elevated in depression. EPA can compete with AA to decrease inflammatory cytokines. In other words, EPA decreases inflammation (it’s anti-inflammatory). This may be the common factor in both depression and cardiovascular disease.
Conclusion: 1000 mg EPA was effective in treating depression in patients who previously remained depressed despite antidepressant therapy. The most significant changes occurred at weeks 8 and 12.
My Comment: It is puzzling that 4000 mg of EPA per day did not show benefits. The technical term for this is ‘non-linear dose response.’ That means more is not better and that doses higher than ideal will not give you greater results. Based on this study and the one we discuss below, I’d suggest 1000 to 2000 mg of ‘unopposed’ EPA per day. (Unopposed EPA = mg EPA – mg DHA.)
So what is an effective dose of Omega-3?
And how long does it take?
Let’s look at two studies from the 2011 meta-analysis.
The 2002 Nemets et al. Study (Study 1): Nemets et al, led a study of patients with major depression. They gave 2000 mg EPA per day vs placebo. This was in addition to their ongoing antidepressant therapy.
The effect of EPA Omega-3 was significant after 2 weeks of treatment.
In the EPA group, at week 3 the core symptoms of depression such as depressed mood, feelings of guilt, worthlessness and insomnia had all improved.
Results: The benefits with 2000 mg EPA-Omega-3 were highly significant at week 3 compared with poor results with placebo. Note that the ‘placebo’ group was already taking prescription antidepressants.
The Peet and Horrobin Study (Study 2) mentioned above: improvement was seen on all 3 depression rating scales with the 1000 mg EPA.
Results: 1000 mg EPA was effective in treating depression in patients who previously remained depressed despite adequate antidepressant therapy. The most significant changes occurred at weeks 8 and 12.
Studies Show Effective Dose for Depression
|Effective Dose||Time to See Benefit|
||2000 mg EPA||3 weeks|
||1000 mg EPA||8 – 12 weeks|
- It appears from these 2 studies that 1000 to 2000 mg EPA is an effective dose for depression.
- It typically takes 3-12 weeks to see improvements in core symptoms of major depression.
Both of these studies were done on people who were already taking antidepressants. But they were all ‘non-responders’ – in other words, they didn’t get better on Prozac. This is not surprising since only a third to half of all people who take prescription antidepressants notice any benefit. Improvements in mood, sleep, anxiety etc. were not noticed until EPA was introduced. One can not conclude that the results of this study was from EPA alone. That may be the case since we already know that antidepressant drugs had no positive effect on this subject pool. But that’s not what the studies conclude. To conclusively say that EPA alone cured depression, these studies would have to be repeated on depressed persons who are NOT on antidepressants.
THE MORE FISH THE LESS DEPRESSION
Did your grandma from the old country ever say ‘We never had depression back in my time?’
Well, she may have had a point.
They ate differently. Diet changes everything. (And walking 5 miles to school in the snow probably didn’t hurt either.)
A study in the Greek islands in 2009 found that the more frequent the fish consumption, the lower the prevalence of depression.
One portion increase of fish per week was associated with .58 times lower likelihood of having depression.
Hibbeln (1998) found that there is a correlation between high fish consumption and lower annual prevalence of major depression across many countries.
In this study, the author argues that Omega-3 may be a required nutrient to prevent depression. He proposes that we may need to increase Omega-3 intake to match blood levels with subjects from Japan. In Japan, where they have a high intake of Omega-3 in their diet, the lifetime prevalence rates of depression are several fold lower than the US.
Low levels of EPA Omega-3 are found in the blood of those who are depressed.
Researchers in China conducted a study relating low blood levels of EPA and suicide attempts. They studied 100 suicide-attempt cases versus 100 control patients who were injured by accidents.
Results: Their finding suggests that low EPA levels in the tissues were a risk factor for suicide attempt. (A suicide attempt indicates severe depression.)
A French study of 1390 depressed elderly patients on antidepressants found that plasma EPA was inversely associated with severity of depression.
In other words, lower EPA level in their blood was associated with more severe depression symptoms.
Many studies point to Omega-3 deficiency
Placebo controlled studies (generally considered the gold standard) show that EPA Omega-3 (ethyl eicosapentanoate) is effective in treating depression.
All 3 types of studies suggest that a lack of Omega-3 in the diet is associated with depression.
Much of the evidence that we have reviewed here supports the Omega-3 hypothesis of depression. The Omega-3 hypothesis of depression states that having low levels of Omega-3 can trigger depression.
Evidence suggests that Omega-3 fats play a role in certain cases of depression.
- EPA Omega-3 from fish oil appears to help with depression while DHA does not
- 1000 to 2000 mg of ‘unopposed’ EPA per day in combination with antidepressants showed significant improvement in depression
- Unopposed EPA= mg EPA – mg DHA
- It typically takes 3-12 weeks to see improvements in depression symptoms
- Fish oil EPA Omega-3 also helps with cardiovascular disease risk factors
Next up: how to change your diet and supplement routine to help with depression.
If you are taking a prescription medicine for depression…
Depression can be caused by factors other than Omega-3 or nutritional deficiency. If this is your case, Omega-3 may not help you.
Your body still needs regular supplies of DHA for various functions, especially if you are pregnant!
References and Suggested Reading:
- Puri, Basant K, & Boyd, Hilary. The Natural Way to Beat Depression The groundbreaking discovery of EPA to change your life, London, Hodder & Stroughton, 2004.
- Servan-Schreiber, David. The Instinct To Heal, Holtzbrinc. Paris, 2004.
- Ilardi, Stephen S. The Depression Cure, Cambridge, MA. Da Capo Press, 2009.
- Nemets B, et al. Addition of Omega-3 Fatty Acid to Maintenance Medication Treatment for Recurrent Unipolar Depressive Disorder .Am J Psychiatry 2002;159:477-479.
- Bountziouka V.et al. Long-term fish intake is associated with less severe depressive symptoms among elderly men and women: the MEDIS (MEDiterranean ISlands Elderly) epidemiological study. J Aging Health. 2009 Sep;21(6):864-80.
- Hibbeln JR. Fish consumption and major depression. The Lancet, Volume 351, Issue 9110, Page 1213, 18 April 1998
- Huan M, et al. Suicide attempt and n-3 fatty acid levels in red blood cells: a case control study in China. Biol Psychiatry. 2004 Oct 1;56(7):490-6.
- De Vriese SR, et al. In humans, the seasonal variation in poly-unsaturated fatty acids is related to the seasonal variation in violent suicide and serotonergic markers of violent suicide. Prostaglandins Leukot Essent Fatty Acids. 2004 Jul;71(1):13-8.
- Feart C, et al. Plasma eicosapentaenoic acid is inversely associated with severity of depressive symptomatology in the elderly: data from the Bordeaux sample of the Three-City Study. Am J Clin Nutr. 2008 May;87(5):1156-62.
- McNamara RK. Evaluation of docosahexaenoic acid deficiency as a preventable risk factor for recurrent affective disorders: Current status, future directions, and dietary recommendations. Prostaglandins, Leukotrienes and Essential Fatty Acids Volume 81, Issue 2 , Pages 223-231, August 2009.
Photo credit: Garrison Photography
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|Kathy Mankofsky RD, LD is a registered and licensed dietitian. She has studied Omega-3s extensively. She lives in St. Louis, Missouri.|