What I'd like to discuss next, I find extremely exciting. Why? Well, what I'm about to describe is a compound or I should say a set of compounds that are available over the counter that have been shown to be very effective in reducing the frequency and intensity of headaches. And not just one kind of headache, but multiple types of headaches.

So what I'll describe has been shown to have significant effects in reducing the intensity or frequency of tension type headaches, migraine type headaches, as well as hormone type headaches that are related to the menstrual cycles that I described earlier. Now, there are a lot of data centered around this general topic, but I'm going to focus on three main papers.

What I haven't told you yet, of course, is what is the compound that I'm referring to? What is this over-the-counter compound? Well, it turns out this over-the-counter compound is not just available over the counter, it's also available in food. So it turns out that nutrition can have a very strong impact on the frequency and intensity of headache, although supplementation with this particular compound can accomplish the same thing as well.

What I'm referring to here are omega-3 fatty acids. Many of you are probably familiar with omega-3 fatty acids. These are fatty acids that come in the form of so-called EPA and DHA. And omega-3 fatty acids are commonly distinguished from the so-called omega-6 fatty acids. Omega-6 fatty acids come in a bunch of different foods, and they, of course, can be supplemented as well.

Omega-3 fatty acids come in a bunch of different foods and can be supplemented as well. Common forms of omega-3 fatty acids, or I should say common sources of omega-3 fatty acids in foods include fatty ocean fish, including salmon, salmon skins, sardines, anchovies, things of that sort. Common sources in supplement form are so-called fish oil, capsules, or liquid fish oil.

Again, omega-3 fatty acids. And almost always when we're talking about omega-3 fatty acids, we're talking about a combination of EPA and DHA, but really it is the quantity of EPA omega-3 fatty acids that seems to be the most impactful for the sorts of health metrics that we're going to talk about in a few minutes.

Now, with respect to omega-6 fatty acids, the most typical food sources of omega-6 fatty acids are seed oils. I know nowadays seed oils have become quite controversial. I've given my stance on this in a prior podcast, but I'll just repeat it for those of you that haven't heard it.

I am not of the belief that all seed oils are bad, that they're all inflammatory, that they are killing us or making us sick, that they are the major cause of metabolic dysfunction, et cetera. However, I think it is very clear, and I learned this from Dr. Lane Norton when he was a guest on this podcast and taught us all about nutrition in great depth.

I highly recommend that episode if you're interested in nutrition, that people are consuming a lot more oil generally. And a lot of those oils that people are consuming more of nowadays include a lot of the so-called omega-6 fatty acids. And a lot of those oils are seed oils. The particular omega-6 fatty acid that's going to be relevant for today's discussion is linoleic acid.

And that is common in a lot of seed oils. So again, I'm not going to tell you that seed oils are bad. However, it does seem to be the case that many people are consuming far too many seed oils, and in doing so are consuming far too many calories, and perhaps are consuming too much of the omega-6 fatty acids relative to the omega-3 fatty acids.

Now, with that said, I think there is general agreement among nutritionists and health professionals that we could all stand to get more omega-3 fatty acids, perhaps for cardiovascular health, although that's a little bit debated, but certainly for immune system function, for mood, and for functioning of the brain, and for the potent anti-inflammatory effects of omega-3.

So again, omega-3s can be sourced from food, both animal-based and plant-based. You can simply go online and look up the various food-based sources. But in thinking about headache and different treatments for headache, there are some recent studies exploring how supplementing with omega-3 fatty acids, and in one case, how supplementing with omega-3 fatty acids and deliberately reducing the amount of linoleic acid, the omega-6 fatty acids, how that can impact headache.

So the first study I'd like to describe in reference to the role of omega-3 fatty acids in headache was published in 2018, and the title of the paper is Long-Chain Omega-3 Fatty Acids and Headache in the U.S. Population. There are a number of things that I really like about this study.

A few of those include the fact that they looked at an enormous number of people. That is, they included 12,317 men and women. I like the fact that they included men and women in the study, age 20 or older, and that they broke down the population into categories that included age.

They certainly looked at race and ethnicity. They looked at educational background. They looked at body mass, total energy intake, which is really important. If you think about it, people are going to be eating, and within the things that they eat, they're going to be consuming some omega-3s, hopefully, as well as some omega-6s.

And if they're eating far more, then they're going to get far more of, likely going to get far more of both of those things than they would ordinarily if they were eating a smaller amount. So they controlled for total caloric intake in a way that I find particularly useful for looking at these kind of data.

So the reason they explored omega-3s is worth mentioning. Omega-3 fatty acids are known to have an anti-inflammatory effect. That anti-inflammatory effect is mediated through a couple of different pathways. We won't go into these in too much detail now, but the omega-3 fatty acids, keep in mind, actually make up various parts of cells in the brain and body.

That's right. The membrane that, remember I talked before about how steroid hormones can go through the different membranes of the cells, the outer membrane and the inner membrane, a lot of those actual membranes, the structural constituents of neurons and other cells are actually made up of or include certain fatty acid, long chain fatty acids.

And the omega-3 fatty acids are important for the actual construction of those tissues, as well as having anti-inflammatory effects through things like limiting prostaglandins and other things that can cause inflammation. Okay, so there are a bunch of different ways that omega-3 fatty acids can be useful. They refer in this study to an earlier study that looked at the so-called analgesic effect, the pain relieving effect.

Analgesic means pain relieving effect of omega-3 fatty acids in what had been a randomized control trial. And in that previous paper, what they found was that diets high in omega-3s and low in omega-6s. Okay, so high three, low six. And as compared to diets that were just reduced omega-6s, they found a greater analgesic effect of increasing omega-3s while also reducing omega-6 fatty acids.

So in the context of the seed oil discussion, although keeping in mind that omega-6s can come from other sources as well, if omega-6s were just reduced on their own, there wasn't as great an effect in terms of reducing pain and inflammation as there was when omega-3 fatty acids were deliberately increased and omega-6 fatty acids were reduced.

Again, in all of these studies, because these are the ones in which they controlled things well, as we say, they are holding constant the caloric intake. So it's not just that you're removing fat, eating less fat, there's actually a removal of certain fats and fatty acids and a replacement of those with omega-3 fatty acids.

In one case, in the other case, it's just a reduction in omega-6s and you're using other food types and macronutrients to offset that reduction in calories caused by reducing omega-6s. The basic takeaway that they're relying on marching into the study is that increasing omega-3s and reducing omega-6s seems to be beneficial for reducing pain.

And indeed, in this study, they find something quite similar, which is that when you hold caloric intake constant and when you look at omega-6s, whether or not you decrease omega-6 fatty acids or not, you find is that increasing omega-3 fatty acids in the diet, so either consumed through food sources or by supplementation, was associated with a lower prevalence of severe headache or migraine.

So severe tension type headache or migraine. So this is promising and points to the fact that long-chain omega-3 fatty acids are likely to have either a pain-reducing, and there's evidence for that, and/or an inflammation-reducing effect that can significantly reduce the severity of headache in both tension type headache and in migraine.

So that's the first study. The second study is a more recent study, it was published in 2021, that used a, I would say, a more or less similar type of overall design as the one I referred to earlier. The title of this paper is "Dietary Alteration of," what they call N3, but those are omega-3 and N6, omega-6, sorry for the shift in nomenclature, I didn't write the paper, "Dietary Alteration of Omega-3 and Omega-6 Fatty Acids for Headache Reductions in Adults with Migraine." And this was a randomized control trial.

Randomized control trials involve having people be in one condition, where they do one thing, and then they get swapped randomly into another condition. So they serve as their own internal control, and that controls for all sorts of things like differences in sex, differences in age, differences in health background, and any number of other variables as best as one can.

In this study, they had people either ingest a diet that had increased omega-3s, so increased EPA and DHA, or increased EPA and DHA and reduced amounts of linoleic acid, okay? So that's going to reduce omega-6s. Or a control diet in which they had people taking, well, it's essentially the average intake of omega-3s and omega-6s.

And you can probably already guess what the general results of this study are going to be. The general results were that there were reductions in headaches, okay? The really cool thing is, is it was a massive reduction in headache, okay? They refer to it as a robust reduction in headache, in particular for the subjects that increased their omega-3s and reduced the amount of linoleic acid that they took.

The other thing that I really like about this study is that while they don't know the exact underlying mechanism for the effect, they did spend some time delineating what it is that the omega-3 and omega-6 fatty acids are likely doing to either offset or exacerbate headache. Now, I didn't say that omega-6 fatty acids exacerbate headache, but it does seem that people who ingest more linoleic acid and omega-6 are experiencing more inflammation.

And that is evident in a bunch of different conditions. One, for instance, is increases in things like CGRP. CGRP is a molecule that's associated with a calcium signaling pathway. It's involved in vasodilation, the expansion of the blood vessels and capillaries. And that's known, as I mentioned earlier, to exacerbate certain forms of headache, okay?

There are also forms of headache that can be caused by vasoconstriction. We'll talk about one very dramatic example, perhaps, as we get toward the end. It's a very uncommon example, but it's called thunderclap headache. And trust me, you do not want a thunderclap headache. In any case, in this paper, they didn't study mechanism directly, but they're resting on this known analgesic, anti-pain, as well as known anti-inflammatory pathways related to increasing omega-3 intake, and simultaneously resting on the idea, or I think we now can say conclusion, that omega-6 fatty acids, in particular linoleic acid, can increase inflammation by way of increasing things like CGRP, vasodilation, and some other pathways related to the so-called inflammatory cytokine pathways.

And there's a whole discussion nowadays of what's called the inflammatome. So the basic takeaway is that if you are interested in reducing headache, it may be beneficial, at least according to these two studies, and another one I'll talk about in a moment, to increase amounts of omega-3 fatty acids.

And that can be done, again, through the ingestion of foods. Although, based on the dosages that we'll talk about in a moment, increasing omega-3 fatty acids by taking liquid form fish oil, which is perhaps the most cost-effective way to supplement omega-3s, or capsules, which is perhaps the most efficient way to supplement omega-3s, will lead to a level of one gram or more of EPA per day.

Again, that's the EPA form in particular. So if you're, for instance, taking supplemental fish oil, or you're getting your omega-3s from food, and you're getting what you determine to be 2,000 milligrams or two grams per day of omega-3s, keep in mind that's going to include EPA and DHA. And it does seem that getting above one gram per day of EPA omega-3 fatty acids, either through food or supplements or both, is going to be the critical threshold for reductions in the frequency and intensity of headaches that include both tension headaches and migraine headaches.

Now, some people will find, actually, that ingesting far more omega-3 fatty acids, generally through supplementation, but again, can be accomplished through foods as well, can also be beneficial for other things such as mood. And indeed, there's a whole literature related to effects of ingesting one to three grams, again, three grams per day of EPA.

So that's going to require quite a high intake of omega-3s in whatever form or supplement you decide to take those into your body. But that can improve mood and so forth. The basic range that I was able to find in the meta-analysis, so meta-analyses are where a researcher will look at the results of a bunch of different studies focused on the same thing, look at the different strength of those studies.

They'll do all sorts of cool statistical gymnastics, like remove the most potent study, the one that had the greatest effect, and see whether or not there's still an effect of some treatment. Or for instance, they will swap in and out different studies and different combinations to see whether or not any one study is really leading to the conclusion that a given treatment does something.

In any case, in the meta-analyses of omega-3 fatty acids for the treatment of headache, and that includes all the different kinds of headache, they found in exploring a huge range of omega-3 supplementation ranging from 200 milligrams all the way up to 2,000 milligrams per day, it really was at the one gram or higher dosage per day where the significant impact in reducing headache frequency and intensity was found.

And just very briefly, earlier I mentioned that not only has omega-3 fatty acid supplementation been shown to be effective in reducing the frequency and intensity of headache in tension type and migraine type headache, but it's also been shown to improve outcomes for premenstrual syndrome related headaches. These are what we referred to earlier as hormone-based headaches.

Again, the low estrogen, low progesterone associated with certain phases of the menstrual cycle as well as other phases of the menstrual cycle are often associated with headache. In a study entitled "Effect of Omega-3 Fatty Acids on Premenstrual Syndrome, a Systematic Review and Again, Meta-Analysis," what they found, and here I'm paraphrasing the conclusion, was that omega-3 fatty acids could, yes, effectively reduce the severity of PMS symptoms.

And one of the symptoms in particular that they found that was reduced was the pain-related symptoms associated with headache. And they actually had some very nice hypotheses as to why that likely would be. And in fact, point out that in earlier studies, omega-3 fatty acids have actually been considered as non-steroidal anti-inflammatory drugs in some cases.

And indeed, there are prescription forms of omega-3 fatty acids. And I highlight that not because I think people need to run out and get the prescription form of omega-3 fatty acids. They're actually quite hard to obtain and quite expensive. But because I think oftentimes when we're talking about something like omega-3 fatty acids, the fact that they are available over the counter in a supplement or by liquid or available in food for that matter, leads many people to conclude that, oh, this is supplementation.

This is something that it's going to have relatively weak or minor impact on things like headache or other health metrics. But let's just say that the fact that it exists as a prescription drug in its highest potency form, at least in my opinion, points to the potency of omega-3 fatty acids in dealing with analgesic effects, that is reducing pain and anti-inflammation, as well as some of the known cardiovascular improvements that are associated with increasing omega-3 fatty acid intake.

Put simply, omega-3s are not just something that comes from food or supplements. They are also being marketed as prescription drugs. So I do think they need to be considered as quite potent. And at least as far as these papers that again, include meta-analyses of many other papers and data sets, indicate that supplementing with omega-3 fatty acids to a point where you're getting above one gram per day of EPA is not just going to be beneficial for treating and reducing the frequency and intensity of one particular type of headache, but many types of headaches.

And when you combine hormonal headaches, tension headaches, and migraine headaches, you account for more than 70% of the total types of headaches that are out there. The effects of omega-3s on cluster headaches and some of the other types of headaches, at least to my knowledge, have not been evaluated.

There's no reason to think that omega-3s would not be beneficial for those types of headaches. But at least as far as the data sets we talked about here are concerned, it is clear. Omega-3 fatty acids are going to be a very potent way to reduce pain and to reduce inflammation in ways that can reduce the frequency and the intensity of different kinds of headache.

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