"We humans have a tendency to take things to the extreme. We over-eat, over-work, overparty,
over-play, and now we even over-Facebook. And then when it is time for people to go
the other way move towards health, they over-exercise, calorie obsess, and over-analyze
whatever they eat.
Regarding food consumption, I remain impressed by how little thought goes into over-eating
pro-inflammatory food calories from sugar, flour, trans-fats, and omega-6 fatty acids; however,
when it comes to eating properly, people start to worry about what is good for them. Why
would we worry so much about what is good, when we had absolutely no worry about what
was bad when we were recklessly eating everything in sight? We humans are a weird bunch.
When it comes to fish oil supplementation, our weirdness continues. If a little fish oil is good,
gallons must be better, correct? The answer is “probably not” in most cases.
If we look at traditional diets, the largest source of fat calories came from saturated and
monounsaturated fatty acids, which contain no or one double bond respectively. The a very
small percentage came from polyunsaturated fatty acids, which contain two or more double
bonds. The greater the number of double bonds in a fatty acid, the greater the chance for a
fatty acid to oxidize. Interestingly, the body only needs a small amount of polyunsaturated fatty
acids and nature happens to provide us with food that only contains small amounts.
EPA and DHA are the omega-3 fatty acids we supplement with in form of fish oil. We can make
EPA and DHA from alpha-linolenic acid, which is found in small amounts in green vegetables
and certain seeds, such as hemps, chia, and flax. EPA and DHA are also found preformed in wild
animals and fish that eat vegetation. It turns out that EPA and DHA have the most double bonds
found in nature.
The fact that we do not get a lot of linolenic acid in most foods, would lead to the assumption
that we might not need a lot of EPA and DHA. In fact we do not get appreciable amounts of EPA
and DHA from animals, save for certain fish, such as salmon. Historically salmon and other wild
fish was consumed by native people who ate no sugar, flour, trans fats and no omega-6 oils
such as corn, safflower, sunflower, cottonseed or peanut oils. These same people were very
active; we are not.
We should follow the historical lead of native people and stay active and avoid sugar, flour,
trans fats, and excess omega-6 oils. We should eat only/mostly natural foods. And the best
evidence suggests that taking 1-3 grams of EPA/DHA per day is reasonable, which is what I
I am not in the habit of taking 5, 10 or more grams of EPA/DHA. This would have been humanly
impossible in past history. However, at times, it might be useful to take heavy doses of
EPA/DHA for short periods. A recent example of this was very high dose EPA/DHA supplementation in 8-24 year olds suffering from major depressive disorder who were not
responding to their selective serotonin reuptake inhibitor (SSRI) (1). The average participant age
was 15.6 years. Twelve subjects were in the low dose group that took 2.4 grams of EPA/DHA.
Eight subjects in the high dose group took 16.2 grams of EPA/DHA. The study period was 10
weeks of supplementation wherein the SSRIs were also taken.
The reason the authors took on this study is because previous studies have shown that
depressed individuals have reduced red blood cell levels of EPA and DHA. The subjects in this
study also had lower levels of EPA/DHA compared to age-matched controls. At the end of the
10-week trial, EPA/DHA levels normalized and symptom remission was observed in 40% of the
low dose group and 100% in the high dose group. This was an open-labeled pilot study with
only 20 subjects and so the authors indicate that larger blinded placebo-controlled trials are
In my opinion, the best natural approach for dealing with depression is to dramatically change
the diet so that pro-inflammatory foods are avoided in favor of anti-inflammatory foods. The
reason is that we now know that depression is a chronic inflammatory state (2-8). The
metabolic syndrome, a pro-inflammatory state, has also been shown to promote depression (9-
11). And finally, compared to an anti-inflammatory diet rich in fish, vegetables and fruit, a proinflammatory
diet heavily loaded with sweetened desserts, deep fried food, processed meat,
and refined grains has been shown to promote depression in middle-aged individuals (12).
The chronic inflammatory state in depression and in general, involves more than just an
imbalance of EPA/DHA that requires heavy omega-3 dosing. In addition to eating an antiinflammatory
diet, supplementation with a multivitamin (13), magnesium (14), omega-3 fatty
acids (15), and vitamin D (16) also offer benefits, as does regular exercise (17).
About the Author
David R. Seaman, DC, MS, is a professor of clinical sciences at the National University of Health
Sciences in Pinellas Park, Florida, where he teaches clinical nutrition and evaluation and
management of the musculoskeletal and cardiorespiratory systems. Dr. Seaman has authored a
book on clinical nutrition for pain and inflammation and has written several chapters and
articles on this topic. He is a consultant for Anabolic Laboratories and is on the Speakers Bureau
1. McNamara RK et al. Detection and treatment of long-chain omega-3 fatty acid deficiency in adolescents
with SSRI-resistant major depressive disorder. PharmaNutrition. 2014;2:38-46.
2. Wium-Andersen MK, Orsted DD, Nielsen SF, Nordestgaard BG: Elevated C-reactive protein levels,
psychological distress, and depression in 73,131 individuals. JAMA Psychiatry 2013, 70:176–184.
3. Khairova RA, Machado-Vieira R, Du J, Manji HK: A potential role for pro- inflammatory cytokines in
regulating synaptic plasticity in major depressive disorder. Int J Neuropsychopharmacol 2009, 12:561–578. 4. Miller AH, Maletic V, Raison CL: Inflammation and its discontents: the role of cytokines in the
pathophysiology of major depression. Biol Psychiatry 2009, 65:732–741.
5. Krishnadas R, Cavanagh J: Depression: an inflammatory illness? J Neurol Neurosurg Psychiatry 2012,
6. Irwin MR: Inflammation at the intersection of behavior and somatic symptoms. Psychiatr Clin N Am 2011,
7. Bonaccorso S, Meltzer HY, Maes M: Psychological and behavioral effects of interferons. Curr Opin
Psychiatry 2000, 13:673–677.
8. Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW: From inflammation to sickness and
depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008, 9:46–56.
9. Heiskanen TH, iskanen K, in kka JJ, Koi umaa- onkanen T, onkalampi K , aatainen K ,
iinam ki T: Metabolic syndrome and depression: a cross-sectional analysis. J Clin Psychiatry 2006, 67:1422–
10. Koponen , Jokelainen J, Kein nen-Kiukaanniemi S, Kumpusalo E, Vanhala M: Metabolic syndrome
predisposes to depressive symptoms: a population-based 7-year follow-up study. J Clin Psychiatry 2008, 69:178–
11. ie ola J, iskanen K, iinam ki , Kumpusalo E: Metabolic syndrome is associated with self-perceived
depression. Scand J Prim Health Care 2008, 26:203–210.
12. Akbaraly TN et al. Dietary pattern and depressive symptoms in middle age. Brit J Psychiatry.
13. Suarez EC. Plasma interleukin-6 is associated with psychological coronary risk factors: Moderation by use
of multivitamin supplement. Brain, Behav, Immunity. 2003;17:296–303.
14. Eby GA, Eby KL. Magnesium for treatment-resistant depression: a review and hypothesis. Med Hypoth.
15. Kiecolt-Glaser JK et al. Depressive symptoms, omega-6:omega-3 fatty acids, and inflammation in older
adults. Psychosomatic Med. 2007;69(3):217-24.
16. Vieth R, Kmball S, Hu A, Walfish PG. Randomized comparison of the effects of the vitamin D3 adequate
intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients. Nutrition Journal
17. Blumenthal JA et al. Exercise and pharmacotherapy in the treatment of major depressive disorder.
Psychosom Med. 2007;69(7):587-96.