Mikki Williden (00:02.434)
Hey everyone, it's Mikki here. You're listening to Mini Mikkipedia on a Monday. And today I want to chat about Omega-3 fatty acids, but not necessarily in the way that you might expect. So we all know the sort of standard story, if you like, that Omega-3s are good for your heart, good for your brain. Take your fish oil, or if you're a vegetarian, take your algae oil. And of course, that evidence is there.

But what I want to focus on today is some of the more surprising, if you like, lesser-known findings from MEGA 3 research. So these are things that genuinely caught my attention when I was looking at recent literature and listening to podcasts. And I think a lot of them may have some practical relevance for you guys, whether you're an active person, whether you're an imperimenopause, whether you're just someone who wants to make informed decisions about supplementation.

Let me take you through what I have found. The first one, which I was reminded of and I really want to share, is that omega-3s can protect against muscle loss during immobilization. So if you've ever had surgery, broken a bone, or been stuck on bed rest, you know how quickly you lose muscle. And we know that the loss of this is driven largely by the suppression of muscle protein synthesis during that period of disuse.

A 2019 study by McGlory and colleagues at McMaster University, which is also where Professor Stu Phillips resides, they published in the Fassib Journal. And that's like a highly revered journal. And they looked at what happens when you supplement with Omega-3s before and during a period of immobilization. So they took 20 young women through two weeks of unilateral leg casting. So putting a leg in a cast.

with one group receiving 5 grams per day of omega-3s and the other getting sunflower oil as a control. They'd started supplementing four weeks before the immobilization began. And the results were striking. The control group lost 14 % of their muscle volume and the omega-3 group just 8%. And after two weeks of recovery, after the cast was removed,

Mikki Williden (02:26.979)
the omega-3 group had fully returned to baseline muscle volume, whereas the control group was still below those pre-immobilization levels. So the mechanism appears to involve the preservation of myofibrilla protein synthesis rates and the protection of mitochondrial respiration during the disuse period. So the omega-3s essentially were maintaining that anabolic signaling machinery while the muscle was inactive.

If you think about the practical implications here, so if you're facing knee surgery, an ACL repair, a hip replacement, or even just a period of reduced activity due to injury, and gosh, who hasn't been there, starting omega-3 supplementation four to six weeks beforehand could meaningfully attenuate that muscle loss. And women are three times more likely to sustain ACL injuries than men. This is particularly relevant for active

women. Look, the amounts aren't small. Five grams is a lot. I take on the regular two grams a day, which I would suggest most people be taking anyway due to the importance of that omega-3 index for the well-known benefits of fish oils. Obviously, check to your doctor. You don't want it interacting with any medications, but a higher dose omega-3 could be good if you're going into surgery.

Now this next one was super interesting. So a Harvard School of Public Health study, which was published in Neurology Journal in 2023, examined blood fatty acid levels in 449 people living with amyotrophic lateral sclerosis, otherwise known as ALS or motor neuron disease. And they followed them for 18 months. So was in almost 450 people. They found that patients with the

highest blood levels of alpha-linolenic acid. That is in fact the plant-based omega-3 acid found in flax seeds, walnuts and chia seeds had a 50 % lower risk of death during the study period compared to those with the lowest levels. Of the 126 participants who died, 33 % were in the lowest ALA group and only 19 % of them were in the highest.

Mikki Williden (04:51.759)
What is particularly interesting with this is that it was from the alpha-linolenic acid, ALA, not the EPA or DHA that showed the strongest association. EPA from fish oil was also associated with reduced mortality risk, but it was ALA that was the standout. I think this challenges the assumption and my assumption that many people also hold that it's the long chain marine forms

are always the most bioactive. So I will say that this is observational. We can't claim causation here at all. So it was just a correlation between blood levels of ALA and mortality. But the researchers noted that their previous work had already linked high ALA intake to a lower risk of developing ALS in the first place, suggesting possible neuroprotective effects that warrant

clinical trial investigation. So that is a finding from those plant-based omega-3s, particularly the ones that are high, obviously, in alpha-linolenic acid, which is something which I often talk to people about when they're choosing their omega-3s. Now, I'll be very transparent. Typically, I will say it's not the plant omega-3s that you want to be actively trying to pursue. It is the fish.

the marine varieties that you want to be having, the ones that are high in that icosapentaenoic or the doccohexanoic acid, EPA and DHA, but here is a really good use case for also including those plant-based sources of the omega-3s. Now, another finding related to omega-3 fatty acids is that with fertility and oocyte quality. So,

This is one I think a lot of my audience may find relevant and it's genuinely sort of under discussed. In 2024, there was a systematic review and a meta-analysis published that pulled data from 13 studies and found that omega-3 intake significantly improved pregnancy rates, both in women undergoing fertility treatment and those conceiving naturally.

Mikki Williden (07:16.545)
Odds ratios were 1.74 for fertility treatment, 1.36 for natural conception, and 2.14 for fertilization rate. There was a separate prospective study of 900 women aged 30 to 44 found that those taking omega-3 supplements had 1.83 times the probability of conceiving in a given menstrual cycle. After adjusting for age,

body mass index, and vitamin D status. So the proposed mechanisms here include effects on prostaglandin pathways. So prostaglandin is an inflammatory cytokine that's released, steroidogenesis, follicular oogenesis, and oocyte maturation. In animal models, omega-3 supplementation has even been shown to extend that reproductive lifespan.

we do need to be cautious clearly about extrapolating that to humans. Now just FYI, genesis, when it's used like steroid genesis or folliculogenesis, is that creation of these either hormones or follicular cells. So for women trying to conceive, particularly those potentially in their mid-30s and beyond, this seems like a very low risk, potentially meaningful intervention.

What I would also say, however, with fertility studies, frustratingly, it was quite inconsistent looking on dosing. And this is something that the authors themselves flagged as a limitation for sure. So we don't really have a well-defined fertility-specific dose from the human data yet. And I would just say, looking at, I guess, general supplementation range of EPA and DHA of about one to three grams,

I'd again sort of go, right, can you do two grams a day? So do be mindful that that is a general fish oil recommendation and not one specific to fertility. So we just don't have that lead live data yet. Now, where there was sort of more clear dosing data was actually with dysmenorrhea or period pain. So staying with that woman's health theme, a systematic review and meta-analyses found that supplementing with

Mikki Williden (09:41.264)
300 to 1800 mg of long-chain omega-3s daily for 2 to 3 months significantly reduces both pain severity and the use of pain medication in women with dysmenorrhea. The mechanism here is pretty well understood. Omega-3s compete with arachidonic acid as a substrate, reducing the production of the series 2 prostaglandins.

specifically prostaglandin F2 alpha and E2. And these are the prostaglandins that drive uterine smooth muscle contraction and cramping. So it's essentially the same pathway that non-steroidal anti-inflammatory drugs target, but from the substrate side rather than the enzyme side. given how common dysmenorrhea is and how many women rely on ibuprofen month after month, I think this is definitely a

practical recommendation that we should be chatting to women about. So, and that 300 to 1800 milligrams is in fact, it's about 0.3 grams to 1.8 grams of long chain omega-3s and long chain is the EPA DHA. Now here's one for athletes. Clearly the study caught my eyes for obvious reasons. A 2025 study published in the Frontiers of Nutrition

male endurance athletes and supplemented them with either EPA-rich or DHA-rich omega-3s for 6 weeks. Both groups saw significant increases in their omega-3 index, which I mentioned earlier, and importantly they showed reductions in submaximal exercise heart rate and ratings of perceived exertion compared to placebo. If you can reduce that RPE then honestly you are absolutely winning.

So the EPA rich group received about three grams of fish oils providing 1.8 grams of EPA per day, the remainder being made up of DHA. And the DHA rich group received three grams of algae oil providing two grams of DHA and one gram of EPA. And they were both supplemented for six weeks, as I mentioned earlier. There was a placebo in there as well, it just coconut.

Mikki Williden (12:03.061)
oil at about three grams per day. So there was no significant improvement in time trial performance, but if you think about what a lower heart rate at the same submaximal intensity means, you're going to get this improved cardiac efficiency. For ultra and distance events where you're working at submaximal intensities for hours on end, but like me and the running that I do, and that kind of physiological shift could be meaningful.

even if it doesn't show up in a 24 kilometer time trial. Obviously the study was limited in that it was just male athletes and the researchers rightly noted that women need to be included for future work, but the physiological changes are interesting and do align with the broader literature on omega-3s and cardiac membrane function. There is some level of evidence with early onset dementia and people who are FOE-4 carriers.

Most people know about the omega-3 and Alzheimer's research, but the newer emerging research worth paying attention to is a study found in clinical nutrition December 2025 found that blood omega-3 levels are inversely related to the risk of early onset dementia. So we're not just talking about people who are 80 years and older. know, people in their middle age begin to present with this early onstage dementia.

So that is worth noting. And in 2024, a randomized clinical trial specifically targeting people with APOE4 genes, so these highest risk individuals for Alzheimer's from that genetic basis, high dose omega-3 supplementation, maintained neuronal integrity on an MRI and slowed the development of white matter lesions. And that's particularly compelling because these are

question about whether omega-3s can actually deliver structural brain benefits, and this trial suggests that it can in the right population. A 2025 network meta-analyses also showed that long-term high-dose EPA-dominant omega-3s combined with antioxidants showed the highest potential for cognitive benefit among all treatments evaluated for Alzheimer's dementia.

Mikki Williden (14:26.69)
randomized controlled trial looking at the APOE4 carriers, they used a total of 1.65 grams of omega-3s per day, specifically 975 milligrams of EPA and 650 milligrams of DHA. And that was across three years. It's a fairly modest dose.

And what I will note is that the overall group showed no significant benefit, but those APOE4 carriers specifically showed dramatic reductions. And that was visible as early as one year into treatment. So at under two grams a day, it's a pretty modest dose for the benefit that they received. And I will also note for my perimenopausal audience, this is especially relevant given the intersection of estrogen decline.

increase your inflammation in the higher proportion of women who develop Alzheimer's disease. One other benefit that I want to chat about is something to do with colon polyps. And this is obviously in relation to risk of colorectal cancer. So there was a trial called the Seafood Trial published in The Lancet in 2018. It was a multi-center double-blind placebo controlled RCT using two grams

per day of EPA in high-risk individuals who've already had polyps removed through Bell Cancer Screening Program, the NHS. Two grams of EPA is the high dose. The primary endpoint, so the overall adenoma detection rate, wasn't significantly reduced. So do want to be clear about that. However, in the secondary analysis, EPA reduced the number of

adenomas per participant in the left colorectum, and when combined with aspirin there appeared to be this positive interaction. There was a secondary analysis of the same trial published in late 2024 which added an important layer. When they looked at the actual changes in red blood cell EPA levels rather than just the treatment allocation, individuals whose EPA increased by more than 0.5 percentage points had a

Mikki Williden (16:38.416)
30 % reduction in polyp number, regardless of whether that increase came from supplement or dietary intake. So it's that blood level change, not just the pill, that predicted the outcome. There is also other trials that have similar results, including a Vanderbilt observation study that found that regular omega-3 consumption was associated with a 33 reduced risk of colorectal

adenomas in women, though not in men. So that one, of course, is not cause and effect. It is just an observation trial. However, when we're looking across intervention trials, we found that consistently that two grams of EPA per day, this was not a mix of EPA to DHA, was beneficial. So it is a higher EPA dose than most over-the-counter fish oils provide, which is worth flagging.

I do want you to be mindful of that. And the last one, which I think is mechanistically interesting, was a 2024 systematic review and meta-analyses, which found that omega-3 supplementation helped augment whole body protein synthesis rates in both healthy adults and clinical populations. So when they looked specifically at NPS, there was no significant overall effect.

But other meta-analyses consistently report clinically meaningful gains in muscle mass, lower body strength, and functional test performance with omega-3 supplementation. So for anyone concerned about maintaining muscle mass, which should be most of us as we age, this does add another layer to that omega-3 story beyond the anti-inflammatory narrative. So the omega-3s may be working on mitochondrial function and

anabolic sensibility, this may not actually show up in some of these acute MPS measurements. So hopefully you get from this that omega-3 fats have evidence for benefits that go well beyond the standard heart and brain story. We've got protection against disused muscle atrophy, fertility support, period pain reduction, colorectal and bowel cancer, cardiac efficiency gains in endurance athletes. So there's a lot.

Mikki Williden (19:01.115)
there to sort of consider. And I think if we, in terms of practical recommendations, most of this research uses doses in the range of one to five of combined EPA and DHA, with effects typically emerging after about eight to 16 weeks of consistent intake. And the Omega-3 index, which measures EPA plus DHA as a percentage of red blood cell membranes, is increasingly being used as a biomarker.

For context, most countries fall to the low to very low range according to the 2024 Omega 3 World Map update. New Zealand sits in the moderate range, but many individuals will be well below optimal. It should be if they have a target of 8 % or above is desirable. So, whether you get your Omega 3 from fish, high quality fish oil, or algae oil, or if you're plant-based, the key is consistency and

adequate dosing. Alright team, that's it for today. If you enjoyed this, let me know. Share it with someone who is interested. I'm over at xthreads and Instagram @mikkiwilliden, Facebook @mikkiwillidenNutrition, or head to my website, @mikkiwilliden.com. Alright guys, you have the best week. See you later.