Casting a Wider Net with Omega-3s: From CVD Prevention to Longevity Intervention
- jmr042
- Apr 4
- 4 min read
For decades, fish oil capsules, brimming with omega-3 fatty acids, were the poster child of an “integrative” medical approach that stressed the importance of supplementing important basic nutrients especially when diet fell short. And you can’t get more basic or important than the omega-3s, a family of polyunsaturated fatty acids classified as “essential” because the body doesn’t make them -- you’d die if you didn’t consume them as food, in the case of the omega-3s, the richest sources being fatty fish like salmon, herring and sardines.
Fish oil supplements are loaded with two especially important omega-3s, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), that look to provide an anti-inflammatory benefit, enhancing cell membrane structure and fluidity and cell-to-cell communication. Several decades of mostly observational studies seem to bear out this good-news fish story – both the consumption of fish and fish oil supplements were correlated with better cardiovascular and neurological health, even lower rates of depression and cancer.
But in more recent years, a handful of randomized controlled trials – basically, giving one group of people fish oil supplements and another group a placebo and measuring the difference in health outcomes over time -- have mostly failed to find these benefits.
So why in the world am I still recommending most of my patients take at least 1 gram of fish oil daily?
For starters, there were a number of problems with these negative, randomized controlled trials. RCTs should only be considered the gold standard of medical evidence if their design sidesteps confounding biases and blind spots. Not the case here. Most of these negative studies looked at people at high cardiovascular risk, meaning that many were taking statins, blood pressure drugs and aspirin, drugs that can mask a positive effect produced by fish oil alone. More fundamentally, many of these studies made no effort to account for the omega-3 blood levels of the participants at the start of the study. It stands to reason that most of the health benefits of fish oil supplementation would accrue to people with low blood omega-3 levels – their diets didn’t include much or any fish and/or their bodies were less efficient at incorporating the omega-3s they did consume into their tissues. But those benefits would be at least partially washed out in the study data by the little or no benefit experienced by the people who already had healthy omega-3 levels.
I should also add that not all the fish oil RCTs paint such a dismal picture. In the 2018 VITAL trial that lasted five years, the study group consuming a gram of fish oil daily had 28% fewer heart attacks; those who had the least amount of fish in their diet had a 40% reduction in heart attacks. (The endpoint that the researchers failed to reach was a statistically significant reduction in a composite measure -- heart attacks, stroke and deaths from cardiovascular disease – so, technically speaking, the study was negative.) In the 2019 REDUCE-IT trial, the group consuming a highly purified form of EPA saw a 26% reduction in that composite measure, a positive result.
But the real hook of the omega-3 story for me is the growing body of studies on its potential impact on aging. A 2021 randomized controlled study in Molecular Psychiatry showed that, following a social stress test, higher levels of omega-3 tracked with a lower expression of stress and inflammatory molecules (think cortisol, TNFalpha, IL-6), and increased telomerase, critical for telomere length preservation and repair. In a Nutrients review of studies examining omega-3s and telomeres, including 11 human studies, supplementation generally correlated with longer telomere lengths. Other studies avail themselves of the epigenetic clocks to show how omega-3 supplementation alters the epigenetic chemical markers that affect the expression of genes involved in managing inflammation and oxidative stress. And in a study this year in Nature, researchers found that omega-3, in combination with vitamin D and exercise, had slowed the “rate of aging” by more than three months over a three year period, according to our best epigenetic “clocks.”
So, is there proof positive that taking fish oils drive down cardiovascular risk and slows aging? No. Should we wait for a better RCT to be done? Also no. If I’m wrong and fish oil doesn’t do much good, the possible harm of taking it is extremely small, although at mega-doses, issues with bleeding have been reported.
If anything, I’m more bullish on fish oil supplementation because fish oil testing has become more readily available, thanks to OmegaCheck offered by Quest and Labcorp which measures a snapshot of omegas in serum. Even more usefully, Omegaquant’s Omega-3 Index test measures them in red blood cells, a better indicator of tissue levels. While an Index of 8% or higher is ideal, in the U.S., not a nation of ardent fish eaters, the average is 4% or below, at least suggestive of higher heart disease risk and quite possibly accelerated aging.
Fair to say "personalized" medicine has found its way to everyday nutrition. I use blood tests to measure my patients’ vitamin D levels and fruit and vegetable intake, following a straightforward protocol: test, supplement as indicated, monitor, and adjust as necessary. To this I’ve added a quarterly check of omega-3s.
While definitive proof of fish oil’s health impact remains elusive, the growing body of evidence, and ease of omega-3 testing, make it a risk worth taking. Given the minimal risk of harm and a sea of potential benefits, fish oil could be considered a cornerstone of nutritional health, combating inflammation, supporting heart health, and pushing back against the aging process itself.
Ogłuszka M, Lipiński P, Starzyński RR. Effect of Omega-3 Fatty Acids on Telomeres-Are They the Elixir of Youth? Nutrients. 2022 Sep 9;14(18):3723. doi: 10.3390/nu14183723. PMID: 36145097; PMCID: PMC9504755.
Madison, A. A., Belury, M. A., Andridge, R., Renna, M. E., Shrout, M. R., Malarkey, W. B., Lin, J., Epel, E. S., & Kiecolt-Glaser, J. K. (2021). Omega-3 supplementation and stress reactivity of cellular aging biomarkers: An ancillary substudy of a randomized, controlled trial in midlife adults. Mol. Psychiatry, 26(7), 3034-3042. https://doi.org/10.1038/s41380-021-01077-2
Wu, D., Jia, Y., Liu, Y., & Shang, M. (2024). Dose–response relationship of dietary omega-3 fatty acids on slowing phenotypic age acceleration: A cross-sectional study. Front. Nutr., 11, 1424156. https://doi.org/10.3389/fnut.2024.1424156
JoAnn E Manson and Shari S Bassuk et al. Principal results of the ViTamin D and OmegA-3 Trial (VITAL) and updated meta-analyses of relevant vitamin D trials. J Steroid Biochem Mol Biol. 2020. Apr:198:105522. doi: 10.1016/j.jsbmb.2019.105522. Epub 2019 Nov 13.
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