How to get depressed quickly

Your grandmother always said that high purity omega-3 oil was “brain food”. Now we are discovering more of the molecular mechanisms that are making grandma’s wisdom from yesteryear into today’s molecular biology breakthroughs.

The newest study that validates grandma’s wisdom will be reported in an upcoming issue of Nature Neuroscience and demonstrates the devastating impact that a lifetime diet that is deficient in omega-3 fatty acids can have on mood and impaired emotional behavior (1).

What enables the brain to make new connections is the endocannabinoid pathway that controls remodeling (i.e. plasticity) of neurons. In particular, the endocannabinoids must interact with their receptors to initiate neuronal remodeling. Without the adequate dietary intake of omega-3 fatty acids, the animals became far more depressed than their genetically identical cousins. The effect of the omega-3 fatty acid deficiency was not a general effect, but localized in the pre-frontal cortex, the area of the brain that is implicated in emotional rewards. Both EPA and DHA were depressed in the pre-frontal cortex. In addition, the levels of arachidonic acid (AA) were significantly increased in the same brain region thereby increasing the extent of neuro-inflammation. An earlier study indicated that it only takes one generation of deficiency of omega-3 fatty acids to increase depression and aggression in rats (2).

This study also helps to explain why high doses of omega-3 fatty acids improve depression in various clinical studies (3-6).

I suspect the mechanism may be the following. The depressed levels of DHA would decrease the fluidity of the neural membrane. This would make it more difficult for the activated endocannabinoid receptor to transmit its signal to the interior of the neuron necessary for the initiation of new neural synthesis. The depression of EPA as well as the increase in AA in the pre-frontal cortex would increase the levels of neuro-inflammation in the brain that would further inhibit the signaling mechanisms necessary to initiate the remodeling of neural tissue.

But to be effective, you must take a therapeutic dose of omega-3 fatty acids. That can be best determined by the AA/EPA ratio in the blood (7). This is because the brain doesn’t make these long-chain fatty acids, but it can readily take them up from the blood.

As usual your grandmother was correct when she called high purity omega-3 oil “brain food”. Her wisdom was in line with epidemiological studies that indicate lowered fish consumption is strongly associated with increased depression (8).


  1. Lafourcade M, Larrieu T, Mato S, Duffaud A, Sepers M, Matias I, De Smedt-Peyrusse V, Labrousse VF, Bretillon L, Matute C, Rodriquez-Puertas R, Laye S, and Manzoni OJ. “Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions.” Nature Neuroscience doi: 10:1038/nn.2736 (2011)
  2. De Mar JC, Ma K, Bell JM, Igarashi M, Greenstein D, and Rapoport SI. “One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats.” J Lipid Res 47: 172-180 (2006)
  3. Rondanelli M, Giacosa A, Opizzi A, Pelucchi C, La Vecchia C, Montorfano G, Negroni M, Berra B, Politi P, and Rizzo AM. “Effect of omega-3 fatty acids supplementation on depressive symptoms and on health-related quality of life in the treatment of elderly women with depression: a double-blind, placebo-controlled, randomized clinical trial.” J Am Coll Nutr 29: 55-64 (2010)
  4. da Silva TM, Munhoz RP, Alvarez C, Naliwaiko K, Kiss A, Andreatini R, and Ferraz AC. “Depression in Parkinson’s disease: a double-blind, randomized, placebo-controlled pilot study of omega-3 fatty-acid supplementation.” J Affect Disord 111: 351-359 (2008)
  5. Stahl LA, Begg DP, Weisinger RS, and Sinclair AJ. “The role of omega-3 fatty acids in mood disorders. Curr Opin Investig Drugs 9: 57-64 (2008)
  6. Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E, Cress KK, and Marangell LB. “Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial.” Arch Gen Psychiatry 56: 407-412 (1999)
  7. Adams PB, Lawson S, Sanigorski A, and Sinclair AJ. “Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression.” Lipids 31: S157-161 (1996)
  8. Hibbeln JR. “Fish consumption and major depression.” Lancet 351: 1213 (1998)

Nothing contained in this blog is intended to be instructional for medial diagnosis or treatment. If you have a medical concern or issue, please consult your personal physician immediately.

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This entry was posted in Zone Health and tagged , , , , by Dr. Barry Sears. Bookmark the permalink.

About Dr. Barry Sears

Dr. Barry Sears is a leading authority on the impact of the diet on hormonal response, genetic expression, and inflammation. A former research scientist at the Boston University School of Medicine and the Massachusetts Institute of Technology, Dr. Sears has dedicated his research efforts over the past 30 years to the study of lipids. He has published more than 30 scientific articles and holds 13 U.S. patents in the areas of intravenous drug delivery systems and hormonal regulation for the treatment of cardiovascular disease. He has also written 13 books, including the New York Times #1 best-seller "The Zone". These books have sold more than 5 million copies in the U.S. and have been translated into 22 different languages.

27 thoughts on “How to get depressed quickly

  1. Dr. Sears – is there a maintenance dosage that you would recommend if the AA/EPA ratio in the blood is not known?

    Also, I have, in the past been a fan of the ZonePerfect bars, but after reading the last few weeks worth of your blogs, etc. have stopped eating them. I would like to try your Zone Bars, but I am not sure I want to buy a whole box of a single flavor without trying them first. Do you have a sample pack or are they sold in retail outlets at all?

  2. I apologize if I have double-posted this, I can’t find my original post.

    I have 2 daughters who have attention problems. My older girl was diagnosed with ADD in 1st grade, and she is now 8th grade and has learned how to work around it. However, my youngest girl has what I perceive to be a bigger problem with attentiveness, which is impacting her grades at school. However, she has passed the screenings that have been done to diagnose ADD, and thus does not actually carry the diagnosis.

    Since it is the DHA that plays the role (will leave the scientific explanation out of this), would my daughter(s) benefit from a fish oil that has a larger concentration of DHA?

    • Actually DHA has very little impact on ADHD. This is because ADHD is more strongly correlated with cellular inflammation in the brain, and EPA has a greater impact in reducing that cellular inflammation than DHA. Unfortunately, EPA is rapidly oxidized in the brain (DHA is not) meaning that you have to maintain high levels of EPA in the blood to reduce cellular inflammation in the brain. Our published studies on use of high-dose fish oil in ADHD confirm this (Sorgi et al J Nutr 13:16 (2007)).

  3. Please explain the benefits of EPA vs. DHA, I see that most concentrate fish oil is old with a 2:1 ratio, respectively. Thank you.

  4. EPA has most of the anti-inflammatory properties, DHA has most of the structural properties. You need both. However, if your goal is the reduction of cellular inflammation, having more EPA than DHA will get you closer to your goal.

    I worked with most of the major fish oil manufacturers several years to optimize their production process to produce a 2:1 ratio of EPA and DHA at the lowest possible price. That’s why we use it in OmegaRx.

  5. Dr. Sears, I love that your blogs are an attempt to educate us about the neurosciences of the bodies’ functions. However I find them a bit technical and often am left scratching my head going “huh?” Any way you make them a little simpler to understand? After all, the real goal of scientists is to make science accessible!

    • It’s really hard since nutrition is so complex and becoming more so every day. I try to make the science digestible (pardon the pun) without turning into mush.

      Bottom line, follow anti-inflammatory diet, take your fish oil and make sure you are consuming a lot of polyphenols and you will become thinner, happier, and smarter. That’s the emotional appeal that is supported by the intellectual science of the blogs.

  6. Dr. Sears, I have been a Zoner for a while. Can you explain to me the EPA and the DHA which of your products have it and what is the best way to get all the good benefits of them.

    • All the fish oil products have the same levels of EPA (400 mg of EPA per gram of oil) and DHA (200 mg of DHA per gram of oil). The best way to get the benefits is to take it every day. If you follow an anti-inflammatory diet rich in polyphenols, then you will maximize the results.

  7. Dear Dr. Sears,
    Are Eskimos, Swedish, Norwegians, etc. who eat lots of cold water fish ever depressed? They must be eating buckets of fish oil.

    • Unlike the Swedes and Norwegians, the Eskimos don’t eat a lot of excess carbohydrates. That’s why the early epidemiological studies of the Eskimos indicated they had little, if any, depression. Once you start eating too many high glycemic carbohydrates, all the benefits of fish oil quickly erode.

  8. Let’s not forget Bertie and Jeeves, the immortal characters created by P.G. Wodehouse! Bertie was constantly ascribing the superior intelligence of his manservant to the regular inclusion of fish in his diet!

  9. Dr Sears, A teenage family member was recently diagnosed with APD (Auditory Processing Disorder) after many years of being tagged ADD and taking the usual medications that did nothing. In your blog, you discuss brain plasticity and Omega 3 for mood. Is there any benefit to him taking it for this type of problem? Thanks so much.

    • Nancy, I am curious about APD, can you tell me how it was diagnosed? My youngest has an attention problem but is passing ADD screening, and the school psychologist brought up the possibility of this being APD. Can you share your experience with it?

      And, Dr. Sears, I would also be interested in hearing whether fish oil can be of benefit to someone with APD–is it a cellular inflammatory condition like ADD?

      • APD is often misdiagnosed as ADHD or forms of autism. I suspect that an underlying cause might be cellular inflammation in the brain causing disruption of signaling patterns. Following an anti-inflammatory diet rich in omega-3 fatty acids certainly can’t hurt.

  10. Der Sears, First let me complement you. Your research and spread of information about Omega 3′s is probaly the single most effective way to improve health in this country that we have at this time. Your message is also valuable because it helps persons to become engaged in their own health maintainence.
    I have a question: Can omega 3′s help in brain trauma if that person is also on coumadin or an anti-coagulant prior to falling an sustaining head trauma and bleeding within the cranial vault? I was impressed that your capsules were helpful in recovery from brain trauma in a doulble blind study recfntluy published but wonder is these could be used if there is a bleeding tendency in the patient Sibncerely ,M.Ing,MD

    • When dealing with brain trauma patients, we always check the AA/EPA ratio to ensure its not too low to prevent clotting, but not high to continually fuel the cellular inflammation in the brain that will prevent the healing process. As a prophylatic measurement if one is taking a blood thinning agent, they should be also be continually monitoring the AA/EPA ratio.

      We now have a finger stick method for doing that type of testing, but with all blood testing, this only available to physicians.

  11. DR. Greetings,
    I’m currently taking your fish oil etc. but would like to list the other meds I’m on and ask if there is a conflict as I have not really Felt the positive effects of these packets after these three weeks. , you know what, I can’t trust the privacy of any internet sites anymore so forget it.

  12. Dr. Sears, I think we really need ”the testimonial” section that your used to include, why is it taking so long to reopen it?
    it’s important for the majority to read about other people’s experiences
    thank you, Luis.

  13. Dr. Sears,
    My son has been diagnosis with ADD lately, he’s been taking 4 caps (240 caps per bottle) of Omega 3Rx for over year, You said 10 to 12 grs of fish oil can be the optimal amount, with a zone diet, so how many caps he has to take every day to make it 10 or 12 grs and how many blocks of protein, carbs and fats he is supposed to have now if I increases the omega 3 dossage?. And how often do i have to check his AA/EPA ratio and which is the lab you nowadays you recomend? Thank you very much

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