FAQ Episode 88: Omega-3s and their role in reducing inflammation and migraine
Frequently Asked Questions about Natural Migraine Relief
Understanding the role of neurogenic inflammation is a key to understanding multiple neurological disorders, including migraine. In this post we will review the role of two common classes of fatty acids in our diet, how they can either reduce or promote migraine headaches, and specific steps you can take to prevent adding this factor to others that would push your “migraine reserve capacity” past its limits.
Our industrialized diet: featuring the dueling omegas
Our dietary fat intake tends to be too low in the omega-3 fatty acids: EPA (eicosapentaenoic) and DHA (docosahexaenoic)-typically found in seafood, and too high in the omega-6 fatty acid LA (linoleic acid), commonly found in vegetable oils, also called seed oils.
Each of these fatty acids can be converted into oxylipins that influence both the initiation, as well as, the perception of pain. The neurogenic inflammation initiated down this cascade by neuropeptide release from peripheral pain-sensing fibers will cause plasma protein leakage, blood vessel expansion and activation of pain pathways. The oxylipins derived from EPA and DHA can reduce pain, while those derived from LA may increase it. The process is related both to the absolute amounts of omega-3 EPA and DHA, as well as the omega-6 linoleic fatty acids in your diet, but even more so, the ratio between them.
How omega fats in the diet affect migraine
Let’s review several studies from the literature that document the beneficial effect of omega-3 fatty acids on migraine headaches.. See the footnotes for documentation on each of the following findings:
A study from the Journal of Adolescent Health showed that 2 months supplementation with 1 g of omega-3 fatty acids significantly decreased the frequency of headaches and also patients reported 74% reduction in the duration of their headaches.1
A study from the British Journal of Medicine2 looked at 182 people who had migraines for 5 to 20 days each month. They were were randomly assigned to consume one of three diets for 16 weeks: a diet with increased EPA and DHA and a linoleic acid level the same as the average U.S. intake; a diet with increased EPA and DHA and reduced linoleic acid; or a control diet with levels of EPA, DHA, and linoleic acid the same as average U.S. intakes. The study used a modified double-blind design; the dietitian who counseled the participants knew which diet each individual was assigned to, but the other study staff and the participants did not. They measured both quality of life indicators, as well as levels of 17-hydroxy docosahexaenoic acid (17-HDHA), a precursor of pain-reducing oxylipins, in samples of blood plasma. Participants on the diet with increased EPA and DHA and decreased linoleic acid had fewer days with headache per month than those on the diet with increased EPA and DHA and average linoleic acid. Levels of the protective 17-HDHA levels also increased in participants on the modified diets, compared with the control diet. This is interesting as it is a “rubber meets the road” connection of an improved omega-3/omega-6 ratio to reduced neuroinflammation.
A meta-analysis of five randomized controlled trials published in Nutrition Reviews3 revealed that fatty acid supplementation improved clinical outcomes in individuals with migraine. The pooled data showed significant reductions in headache intensity, headache duration, and headache frequency.
Another meta-analysis looking at 13 randomized controlled trials, published in Nutritional Neurosciences showed that added dietary omega-3s reduced the duration of migraine headaches suffered per month.4
If you would like to take a deep dive on the immunology and biochemistry of how omega fats affect neuroinflammation (and its a long list!), I would refer you to a Frontiers in Neurology article: Neuroimmunological effects of omega-3 fatty acids on migraine: a review5. It covers how omega-3s modulate of at least 14 key inflammatory factors, some of which I briefly list under this same footnote.
Taking Action: Making the omega factor work for you
Let me start by doing my broken-record thing: “I believe that all migraine headaches have more than one root cause adding up to push you past your migraine threshold.” Any one intervention, like the one we’re discussing might be, for you, a 10%, 30% or even 50% player. But it is unlikely, on its own, to be “the 100% answer to your migraine problem.” I’ve had some patients where omega-3 supplementation made a HUGE difference, and others here it added little benefit, as best we could tell. If you have elevated inflammatory lab markers (c-reactive protein, ESR, fibrinogen level) or have another inflammatory based disorder (see this post’s last paragraph) you may be a good candidate for omega altering therapy.
Always be looking at the big picture to understand your own contributory root cause factors, and how to integrate them in a plan that is best suited to your story. Please take a look at my FAQ Table of Contents to review topics on other root cause factors that may be helpful in addressing in this process.
Augmenting your omega-3 levels: Three considerations
Looking for direct food sources. Healthy dietary sources rely primarily on the omega-3 content of fish products. The studies we reviewed above generally used ~1000-1500 mg/day of omega-3s. Some common food sources include:
-Mackerel: A 3-ounce serving can contain over 1,000 mg of omega-3s.
-Salmon: A 3.5-ounce serving typically provides 1-2 grams of omega-3s.
-Herring: Around 1.5 grams per 3-ounce serving.
-Canned Salmon: Can contain 500-1000 mg of omega-3s per 150g serving.
-Canned Tuna: Offers 300-500 mg per 150g serving.
Although most canned sources are tested for mercury or PCB contamination, this isn’t true for all fish. In general, wild caught fish tend to be cleaner than farm raised.
To obtain omega-3 without fish, focus on incorporating plant-based sources like flaxseeds, chia seeds, walnuts, hemp seeds, algal oil, and soybeans into your diet. These sources provide ALA (alpha-linolenic acid), which your body can convert to EPA and DHA, the omega-3 fatty acids found in fish
Supplementing with omega-3 nutritionals
As most of us don’t eat fish daily, a focused nutritional supplement might be the most effective way of ensuring a therapeutic level of omega-3 support. Start by looking at the label. It will generally include “Total Omega 3s” and then a further breakdown of DHA and EPA components. I would advise that you look for a 1000 mg total of EPA+ DHA per serving. This might require a higher “Total Omega-3” number, usually 30% more. So you might need 1500 mg per serving (on the front label) to get 1000 mg per day of the EPA+DHA total (on the back label.) I would avoid products which do not specifically list the EPA and DHA ingredients.
Reduce vegetable/seed oils to reduce the omega-3/omega-6 ratio.
It’s not just the omega-3s that buy benefit, but also an improvement of the omega-3/omega-6 ratio! This means that we should seek a reduction of the pro-inflammatory linoleic acid content of food. For most of us, that means reducing the vegetable oil component found in processed food. Also known as seed oils, these are cooking oils derived from the seeds of plants. They can be extracted from canola, corn, cottonseed, soybean, sunflower, safflower, grapeseed, and rice bran. They are often used in deep-fried foods, fast food, and packaged snacks. Avoiding these processed foods would be the best place to start your omega journey. The next would be to consider using oils relatively low in omega-6 such as butter, coconut oil, lard, palm oil, and olive oil for routine cooking purposes.
To keep it simple, overhauling your omega-3s as a pathway to reducing migraine would include:
Reducing processed fats in your diet (less omega-6s). Chose whole foods like nuts, seeds, or animal products like eggs and chicken for omega-6 content.
Choose more high omega-3 content fish entrees or cooking oils for day to day use.
Take 1000 mg of a EPA+DHA total supplement (~1500 mg of ‘total Omega-3s’) daily with a meal to achieve a therapeutic effect that is hard to achieve by diet alone.
Cautionary considerations
Fortunately, taking additional omega-3s through diet or supplementation is generally very safe. Here are a few circumstances that could merit avoiding or moderating additional omega supplementation:
As mentioned above, the quality of both dietary and store supplements can vary. Investigate the source of your oils, whether they come with gills or a gelcap.
omega-3s can degrade with time, becoming oxidized-or what we would call rancid. Look for an expiration date on the bottle, and avoid or discard supplements with an unpleasant odor or taste.
A well known effect of fish oil is to reduce platelet aggregation and decrease the speed at which blood clots, which can be beneficial for some conditions but can also increase the risk of bleeding in susceptible individuals.., Consult with your personal physician if you have a blood clotting disorder, are taking aspirin or other ‘blood thinning’ medications or are considering a major medical procedure.
Omega-3 doses greater than 1 gram a day have been associated in a higher rate of atrial fibrillation for those with known heart disease, diabetes or high triglycerides. Consider staying under 1000 mg of total omega-3/day dosing.
If you have any version of joint hypermobility, either inborn or secondary to past trauma. As some migraines can be worsened by cervical spine instability, it's possible that using fish oil supplements might make them worse. If this happens, discontinue their use and consult your personal physician or chiropractor.
Potential collateral benefits of omega-3s
When one considers the broad array of biochemical and immunological interventions provided by omega-3 fatty acids, its not surprising that clinical trials for multiple medical problems have shown the beneficial effect of dietary supplementation with fish oils. It can help to manage multiple inflammatory and autoimmune diseases in human, including rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis, lupus erythematosus, M.S. and migraine headache. If you have a personal or family history of one or more of these, you may find that optimizing the ratio of omega-3 to omega-6 balance could provide overlapping benefits.
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The information in this newsletter is for educational and informational purposes only. It is not intended as medical advice, nor should it be used as a substitute for professional healthcare guidance, diagnosis, or treatment.
Always seek the advice of your doctor or a qualified healthcare provider before making any changes to your health routine, starting new treatments, or addressing specific medical concerns.
This content does not create a doctor-patient relationship. While I make every effort to ensure accuracy, the information provided may not apply to your unique situation.
Supplementation with omega-3 polyunsaturated fatty acids in the management of recurrent migraines in adolescents. Zeev Harel, et.al. J Adolesc Health 2002 Aug;31(2):154-61. https://pubmed.ncbi.nlm.nih.gov/12127385/
Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial Christopher E Ramsden, et. al. BMJ 2021;374 doi:https://doi.org/10.1136/bmj.n1448
Impact of Fatty Acid Supplementation on Migraine Outcomes: A Systematic Review and Meta-analysis. García-Pérez-de-Sevilla G et.al. Nutr Rev. Published online January 17, 2025. doi:10.1093/nutrit/nuae219
Effects of omega-3 fatty acids on the frequency, severity, and duration of migraine attacks: A systematic review and meta-analysis of randomized controlled trials Leila Maghsoumi-Norouzabad et.al. 018 Nov;21(9):614-623. doi: 10.1080/1028415X.2017.1344371. Epub 2017 Jun 30. Abstract at: https://pubmed.ncbi.nlm.nih.gov/28665211/
Neuroimmunological effects of omega-3 fatty acids on migraine: a review Ting-Bin Chen et.al. Front. Neurol., 05 May 2024 Sec. Headache and Neurogenic Pain Volume 15 - 2024 | https://doi.org/10.3389/fneur.2024.136637 includes 97 pertinent citations that cover how omega-3s affect:
the cyclooxygenase and lipoxygenase enzymatic pathway,
production of Resolvins (which inhibits the production of inflammatory cytokines in microglial cells and has anti-inflammatory effects.
inhibition of production of inflammatory proteins such as TNF-α, IL-1, IL-6, IL-8 and IL-12 in various cell types including endothelial cells, monocytes, macrophages and dendritic cells. The inhibition of proinflammatory cytokines from macrophages has a beneficial inhibitory effect in autoimmune diseases in vivo.
by phosphorylating the inhibitor of kappa B (IkB) (less NFkB activity)
by reducing the activity of mitogen-activated protein kinases (MAPKs).
by promoting PPAR-ϒ. The PPAR-Υ is a transcription factor that has anti-inflammatory function and can directly regulate the expression of inflammatory genes.
signaling G protein-coupled receptors (GPCRs), like GPR120, which are localized in the cell membrane and can bind to omega-3 fatty acids. This binding results in the activation of cell signaling pathways responsible for reducing the response of macrophages, decreasing phosphorylation of IkB (more NFkB activity) and production of TNF-α and IL-6.
targeting the lipopolysaccharide (LPS) surface receptor, which suppresses NFkB activity and the production of inflammatory cytokines in microglia.
anti-inflammatory effects of due to a DHA metabolite, named NeuroprotectinD1, which inhibits the expression of cytokines induced by Aβ peptides in microglia.
reduction of oxidative stress and NO in microglial cells with secondary neuroprotective effects.