When talking about fish oil for mental health, especially depression, to my patients, I always refer to it as a “research merry-go-round.”
One study will show it’s positive for mental health[1] and even for reducing mortality risk.[2] As the merry-go-round continues, there’ll be a contradictory study on mental health[3] that confuses patients and practitioners alike!
In this article, I’m going to try and balance out that view, look at some of the mistakes made in the negative studies and introduce how fish oil can be beneficial for depression and mental health.
Defining the causes of depression is essential when assessing how fish oil might be able to help.
Now more than ever. But why?
A meta-analysis assessing the link between serotonin and depression has ruled that depression may not be a chemical deficiency.[4] Furthermore, the study states that long-term use of antidepressants may reduce serotonin concentration, potentially causing lower levels of serotonin in the treatment process.[5]
It’s fair to say this caused quite a stir. However, this doesn’t then mean that antidepressants don’t work.
A timely reminder that this review was and is not an excuse to stop taking your antidepressants, but it may be an opportunity to evaluate why they are helping and look at complementary interventions based on what you find.
Other origins of depression need to be given equal standing due to this review.
When the meta-analysis came out at the end of July 2022, I first tried to find as many people involved in depression research over the years and their opinions on the review.
One of the prevailing themes was, firstly, none of the researchers were surprised. Secondly, it opens the door to looking into why antidepressants help, which might be through their role in reducing neuroinflammation.[6] It’s reducing neuroinflammation, where fish oil can come into play. Let’s look into this form of inflammation first.
The brain has its own immune system.
And this immune response is handled by specialised immune cells called glia. Microglia are the main focal point we’ll discuss and the primary mediators of the immune response within the brain.
One of their main jobs is to survey the brain and spinal cord and coordinate the signals between the brain and the immune system if any immune action is required.[7]
If immune action is required, say by an infection or injury to the brain, then the inflammation caused by the microglia in response recruits vital immune cells to the site of the problem to do their work.
All of this makes sense. The brain and rest of the central nervous system are crucial at all times, so why not have a specialised immune response to protect them?
Despite the necessity of neuroinflammation for our immune systems, things can get out of control.
As always, stress is one of the things that can make neuroinflammation worse. Especially when the stress is chronic or traumatic, researchers have now been able to link this neuroinflammatory response to the development of conditions such as depression.[8]
To illustrate just how strong this link might be, elevated inflammation,[9] increased microglia activation[10] and evidence of an increased immune response[11] were all detected within specific parts of the brain of depressed suicide victims.
Let’s deconstruct some fish oil basics to understand better how its different parts help the brain.
A vital place to begin is that omega-3 fats occur in many other dietary sources besides their supplemental form in fish oil.
Foods high in omega-3 fats are leafy greens, walnuts, flaxseeds, flaxseed oil, hemp seeds, and oily fish such as salmon, sardines, and tuna.[12]
For our exploration into fish oil, we’ll look at two essential omega-3 fats, eicosapentaenoic acid, also known as EPA and docosahexaenoic acid or DHA.
If you’re new to the current research into fish oil outside of depression and mental health, I will cover that in a different article.
To continue, EPA and DHA play different roles in helping the brain, starting with DHA.
DHA is one of the critical nutrients for the growth of functional development of the brain in infants.[13]
Building on this, research over the years connects DHA deficiency, generated mainly from a dietary deficit in omega-3 fats, to worse how depression worsens cardiovascular syndromes like heart attacks.[14]
To give you a sense of this in the real world, around 200mg of DHA daily from fish or other sources will improve your risk of suddenly dying from a heart attack.[15]
For most, this means having some form of fish daily, which is a long way away for most, hence why supplementation can be necessary because a dietary deficit has been associated with some key changes in the brain and mental health.
Decreases in DHA are also associated with the development of Alzheimer’s disease and cognitive decline. A study from June 2022, a few months ago at the time of writing this, found that higher red blood cell levels of DHA had a positive effect on the prevention of Alzheimer’s disease.[16]
All these effects from one of the fatty acids in fish oil just by correcting diet, and we haven’t even started using it as a potential therapy.
It’s not just deficiencies in DHA that cause issues. Postpartum depression,[17] social anxiety disorder,[18] and bipolar disorder[19] all see lower levels of EPA and DHA.
Not only this, but a study also found that low levels of omega-3 fats predicted a reduced response to standard antidepressant therapy in people with major depressive disorder.[20]
It seems that supplementing with a combination of EPA and DHA on top of correcting a deficiency shows excellent promise for depression and its other associated conditions.
That said, the ratio of EPA in formulas still needs to be represented in higher amounts than DHA. For example, some studies have found that supplementing with EPA, mainly at a dose of 1-2g/d (good supplements will be around 500-700mg equaling two to three capsules daily), was better than placebo and DHA for mild to moderate depression than a combination of EPA and DHA.[21]
So how do EPA and DHA from fish oil differ in their role in depression and neuroinflammation?
Great question.
To put it in simple terms, from my interpretation of the research, EPA is an anti-inflammatory agent, and DHA maintains the functional integrity of the brain.[22] It seems fair to say that this is still being investigated.
Regardless, with the American Psychiatric Association (APA) currently recommending the use of omega-3/fish oil supplementation for depression, impulse control and other psychiatric conditions,[23] if you feel you want to assess whether diet and natural medicine can help, an omega-3 supplement such as fish oil might be an excellent place to start.
Some things to know when starting to use fish oil and the one thing that might stop it from working for you.
One of the first things I recommend to all my patients and you in the broader community is one of the supplements where you need to spend more than you may expect.
Why?
Making a pure fish oil capsule with no heavy metals or other contaminants is expensive. Add in cold pressing and distillation processes that prevent rancid oil from turning into capsules, and in my view, it’s almost impossible to create a cheaper product without cutting corners.
To put one of these manufacturing processes into context, one study assessing supercritical fluid extraction, a way of removing heavy metals from fish oil, saw levels of lead, cadmium, arsenic and mercury reduced by over ninety per cent![24]
The time and dosage taken for fish oil supplementation predict its therapeutic success.
I think this is often the one thing that many patients who say fish oil doesn’t help much for them could do differently in the future.
The first is the minimum time to take before seeing an effect. Different conditions will have different parameters, but I think a rule of thumb for mental health is three months minimum.
This length of time can be astonishing to most, but it does speak to how natural medicine works in the body. In the case of the anti-inflammatory effects of fish oil, these effects can take a long time to change hence why you might not see what you’re looking for even after eight weeks.
The dose is the second place that patients and researchers could do better in the future. The minimum dose for mental health benefits, and in the case of our focus for this article, depression, is a minimum of 1-2g of EPA and around 1g of DHA daily. Unfortunately, this does seem like the lower end of the dose, with other recommendations getting up to nine capsules of fish oil a day for some mental health conditions![25]
In this case, depending on the strength of the EPA and DHA in the formula you’ve chosen, four to six capsules daily for three months will give you the chance of success.
It’s a lot, but hopefully, via reading this article, you will have found that the potential for using fish oil for depression is worth the effort and the cost.
Hope this helps xx
[1] Liao Y, Xie B, Zhang H, et al. Efficacy of omega-3 PUFAs in depression: A meta-analysis [published correction appears in Transl Psychiatry. 2021 Sep 7;11(1):465]. Transl Psychiatry. 2019;9(1):190. Published 2019 Aug 5. doi:10.1038/s41398-019-0515-5
[2] Ma, T., He, L., Luo, Y. et al. Associations of baseline use of fish oil with progression of cardiometabolic multimorbidity and mortality among patients with hypertension: a prospective study of UK Biobank. Eur J Nutr (2022). https://doi.org/10.1007/s00394-022-02889-w
[3] Okereke OI, Vyas CM, Mischoulon D, et al. 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
[4] Moncrieff, J., Cooper, R.E., Stockmann, T. et al. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01661-0
[5] Moncrieff, J., Cooper, R.E., Stockmann, T. et al. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01661-0
[6] Hashioka S. Antidepressants and neuroinflammation: Can antidepressants calm glial rage down?. Mini Rev Med Chem. 2011;11(7):555-564. doi:10.2174/138955711795906888
[7] DiSabato DJ, Quan N, Godbout JP. Neuroinflammation: the devil is in the details. J Neurochem. 2016;139 Suppl 2(Suppl 2):136-153. doi:10.1111/jnc.13607
[8] DiSabato DJ, Quan N, Godbout JP. Neuroinflammation: the devil is in the details. J Neurochem. 2016;139 Suppl 2(Suppl 2):136-153. doi:10.1111/jnc.13607
[9] Janelidze S, Mattei D, Westrin Å, Träskman-Bendz L, Brundin L. Cytokine levels in the blood may distinguish suicide attempters from depressed patients. Brain Behav Immun. 2011;25(2):335-339. doi:10.1016/j.bbi.2010.10.010
[10] Schnieder TP, Trencevska I, Rosoklija G, et al. Microglia of prefrontal white matter in suicide. J Neuropathol Exp Neurol. 2014;73(9):880-890. doi:10.1097/NEN.0000000000000107
[11] Torres-Platas SG, Cruceanu C, Chen GG, Turecki G, Mechawar N. Evidence for increased microglial priming and macrophage recruitment in the dorsal anterior cingulate white matter of depressed suicides. Brain Behav Immun. 2014;42:50-59. doi:10.1016/j.bbi.2014.05.007
[12] Tur JA, Bibiloni MM, Sureda A, Pons A. Dietary sources of omega 3 fatty acids: public health risks and benefits. Br J Nutr. 2012;107 Suppl 2:S23-S52. doi:10.1017/S0007114512001456
[13] Horrocks LA, Yeo YK. Health benefits of docosahexaenoic acid (DHA). Pharmacol Res. 1999;40(3):211-225. doi:10.1006/phrs.1999.0495
[14] Amin AA, Menon RA, Reid KJ, Harris WS, Spertus JA. Acute coronary syndrome patients with depression have low blood cell membrane omega-3 fatty acid levels. Psychosom Med. 2008;70(8):856-862. doi:10.1097/PSY.0b013e318188a01e
[15] Horrocks LA, Yeo YK. Health benefits of docosahexaenoic acid (DHA). Pharmacol Res. 1999;40(3):211-225. doi:10.1006/phrs.1999.0495
[16] Sala-Vila A, Satizabal CL, Tintle N, et al. Red Blood Cell DHA Is Inversely Associated with Risk of Incident Alzheimer’s Disease and All-Cause Dementia: Framingham Offspring Study. Nutrients. 2022;14(12):2408. Published 2022 Jun 9. doi:10.3390/nu14122408
[17] De Vriese SR, Christophe AB, Maes M. Lowered serum n-3 polyunsaturated fatty acid (PUFA) levels predict the occurrence of postpartum depression: further evidence that lowered n-PUFAs are related to major depression. Life Sci. 2003;73(25):3181-3187. doi:10.1016/j.lfs.2003.02.001
[18] De Vriese SR, Christophe AB, Maes M. Lowered serum n-3 polyunsaturated fatty acid (PUFA) levels predict the occurrence of postpartum depression: further evidence that lowered n-PUFAs are related to major depression. Life Sci. 2003;73(25):3181-3187. doi:10.1016/j.lfs.2003.02.001
[19] Su KP, Matsuoka Y, Pae CU. Omega-3 Polyunsaturated Fatty Acids in Prevention of Mood and Anxiety Disorders. Clin Psychopharmacol Neurosci. 2015;13(2):129-137. doi:10.9758/cpn.2015.13.2.129
[20] Cussotto S, Delgado I, Oriolo G, et al. Low omega-3 polyunsaturated fatty acids predict reduced response to standard antidepressants in patients with major depressive disorder. Depress Anxiety. 2022;39(5):407-418. doi:10.1002/da.23257
[21] Liao Y, Xie B, Zhang H, et al. Efficacy of omega-3 PUFAs in depression: A meta-analysis [published correction appears in Transl Psychiatry. 2021 Sep 7;11(1):465]. Transl Psychiatry. 2019;9(1):190. Published 2019 Aug 5. doi:10.1038/s41398-019-0515-5
[22] Devassy JG, Leng S, Gabbs M, Monirujjaman M, Aukema HM. Omega-3 Polyunsaturated Fatty Acids and Oxylipins in Neuroinflammation and Management of Alzheimer Disease. Adv Nutr. 2016;7(5):905-916. Published 2016 Sep 15. doi:10.3945/an.116.012187
[23] Nasir M, Bloch MH. Trim the fat: the role of omega-3 fatty acids in psychopharmacology. Ther Adv Psychopharmacol. 2019;9:2045125319869791. Published 2019 Aug 27. doi:10.1177/2045125319869791
[24] Hajeb P, Jinap S, Shakibazadeh Sh, Afsah-Hejri L, Mohebbi GH, Zaidul IS. Optimisation of the supercritical extraction of toxic elements in fish oil. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2014;31(10):1712-1722. doi:10.1080/19440049.2014.942707
[25] Freeman MP, Hibbeln JR, Wisner KL, et al. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry [published correction appears in J Clin Psychiatry. 2007 Feb;68(2):338]. J Clin Psychiatry. 2006;67(12):1954-1967. doi:10.4088/jcp.v67n1217
