Home > Blog > Fish Oil & Depression – How Much and for How Long? – Part 4

Fish Oil & Depression – How Much and for How Long? – Part 4

by Kathy Mankofsky R.D., L.D on July 27, 2012

Guest Blog by Kathy Mankofsky R.D., L.D.

In part 1, part 2 and part 3, we saw that EPA Omega-3 helps with depression. And DHA doesn’t.

Fish Oil Depression Part 4

Great! So the more EPA you take the better you feel, right?

Not so!

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:

  • depression
  • anxiety
  • sleep
  • libido
  • suicidality

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.’

‘Desirable side-effects’

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.


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.

fish consumption correlates with depression

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

Epidemiological studies (like thisthis, this, this, this, this, and this – enough?) indicate an association between low dietary intake of fish and depression.

Biochemical studies (this one and this one) show that depletion of Omega 3 fats in the blood correlates with the severity of the depression.

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…
Do not stop taking your current medication without consulting your doctor.
Do not change dosage of medication without medical supervision.
Do not self-diagnose or make medical decisions without your doctor.
Omega 3 may be taken in addition to prescription medicines for depression and it may have an additive benefit.

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:

  1. Puri, Basant K, & Boyd, Hilary. The Natural Way to Beat Depression The groundbreaking discovery of EPA to change your life, London, Hodder & Stroughton, 2004.
  2. Servan-Schreiber, David. The Instinct To Heal, Holtzbrinc. Paris, 2004.
  3. Ilardi, Stephen S. The Depression Cure, Cambridge, MA. Da Capo Press, 2009.


  1. 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.
  2. 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.
  3. Hibbeln JR. Fish consumption and major depression. The Lancet, Volume 351, Issue 9110, Page 1213, 18 April 1998
  4. 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.
  5. 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.
  6. 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.
  7. 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


DISCLAIMER: This website is for your education and general health information only. The ideas and suggestions contained on this website are not to be used as a substitute for medical advice, diagnosis or treatment from your doctor for any health condition or problem. Users of this website should not rely on information provided on this website for their own health problems. Any questions regarding your own health should be addressed to your own physician.

Fish Oil Labels Kathy Mankofsky RD, LD is a registered and licensed dietitian. She has studied Omega-3s extensively. She lives in St. Louis, Missouri.

pharmaceutical grade fish oil

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{ 12 comments… read them below or add one }

Margie September 7, 2012 at 9:29 am

Hi Kathy,

I have taken Fish oil for several years but I won’t buy it anymore not for now anyway. According According to Time magazine people are over harvesting the little fish and creating an imbalance in the oceans. I have seen this with the herbs that are on the endangered list because people over harvested them.
What are your thoughts.

Margie Lewis
Herbalist & Iridologist


Vin Kutty September 30, 2012 at 8:29 pm

Hi Margie, overfishing is a problem and you make a good point. But overfishing depends on the area of fishery and the species. Some species are overfished while others are not. We use an ecologically friendly source of oil from Alaska. All our oils are Marine Stewardship Council approved as sustainable. Still, the long-term solution is to make Omega-3 from non-fish sources like algae, yeast etc.


sunil August 15, 2013 at 6:49 am

kindly let me know where will i get omega 3 capsules with only EPA


Vin Kutty August 15, 2013 at 6:21 pm

Hi Sunil – we will have an EPA-only Omega-3 formula available on this website by mid-September 2013. It will also be available on Amazon.com for customers outside the US.


Jenny Kallis September 19, 2013 at 5:59 am

Hi Vin,
I have been a loyal taker of Omega 3 for years. In recent times I saw an Eastern Medicine doctor because my achilles tendons are achy when I get up. He had me increase my Omega intake. A great added benefit started to take place: my anxiety (which I had always felt in the morning when I wake) disappeared. I was thrilled. I take a lot of Omega for this benefit. …then I decided to experiment and try a less expensive brand of Omega (actually a fish oil) and just double my intake. Despite my doubling the intake to get the same amount of EPA, my anxiety has crept back in a bit (not completely but it’s there…like an uninvited ghost).
1. Can you take too many Omega 3 and does it become a waste because it just gets eliminated.
2. Does your brand come from non-fish sources as you suggested above is the best formula?
I am very curious to switch brands again and see if the anxiety disappears.
Looking forward to hearing from you.


Vin Kutty September 19, 2013 at 1:46 pm

Hi Jenny – you can take too much Omega-3. My unofficial cut off is 4000 mg of Omega-3 per day. I don’t think most people need more than that. If you do, it is time to cut back on Omega-6 fats and watch your diet.

No, OmegaVia is made from fish. The best Omega-3 are marine sources.

More here: http://www.omegavia.com/supplements-for-depression-anxiety/


kiki February 6, 2014 at 1:30 am

I would like you to to let me know if my hair loss has anything to do with EPA consumption. I have been taken 1000 mg pure EPA for three years and my hair keep on shedding during this time. I currently take EPO 1000 mg/day. Is this going to help?
Thank you in advance


Vin Kutty February 7, 2014 at 7:52 pm

Hi Kiki – I assume you mean EPO – Evening Primrose Oil and not EPA (Omega-3 from fish). EPO is not known for causing hair loss – there are several other causes. Are you a vegetarian? Do you eat egg yolk? You should! You may be Vitamin B12 deficient. So there are many reasons. But I doubt it has much to do with EPO or EPA.


Amanda March 4, 2014 at 3:43 am

I do not agree that more epa is not better! I used to take only 1000 mg of Minami PlusEPA, my OCD is better controlled with 3000 mg of PlusEPA–6 capsules a day. Each person is different. Some of us get along better with more than 2 grams of EPA per day!


Vin Kutty March 4, 2014 at 4:57 pm

Hi Amanda – I’m not surprised. We are, after all, different. The ‘more is not better’ notion still applies because while you found your effective dose at 3000 mg, that does not mean 5000 mg would be better. At does much higher than, say, 5000 mg per day, you need to start thinking about the oxidative stress that much Omega-3 can add to your body.

The study I cited said much more than 1000 mg of UNOPPOSED EPA showed reduced returns. That was an average of a large group of people. Frankly, I was a bit surprised. I would have thought, after talking to hundreds of people who take EPA for mood, that 2000 mg would have been the most effective.


Amanda March 15, 2014 at 1:56 am

Thank you for commenting! I am interested in trying Omegavia EPA to see if I could save some money I am currently spending around 100 dollars a month on Minami PlusEPA per month. The same amount of Omegavia would cost me just over 43 dollars a month. I wish I could read more testemonials about the Omegavia EPA working for other poeple for their depression. I saw some reviews on your website but alot of the testemonials were about lowering triglycerides. Can you share, have you read very many testemonials of Omegavia EPA really helping people’s mood/depression? Thank you


Vin Kutty March 15, 2014 at 5:41 pm

Hi Amanda – we just recently introduced the EPA 500 product (in later 2013). While there are hundreds of new people taking the product for depression, we’ve only received feedback from a few customers so far. If/when they give us permission to share their testimonials, we will post them on the site. But frankly, if you can find any EPA-only product, they will all do the same thing. The brand does not matter that much – it is the ingredient within that matters.

I suggest you give it a try and see how you do. Even if we had dozens of testimonials to share in another year or two, that still does not show how you would personally respond to EPA therapy. If EPA has worked for you in the past, then this EPA 500 product will also.


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