Omega-3s & Mortality
This Week’s Research Highlight
Background
Interest in the effects of omega-3 fatty acids dates back to around the 1970s. It was known at the time that polyunsaturated fatty acids, generally derived from plant sources, lowered cholesterol, while saturated fatty acids from animals tended to elevate atherogenic blood lipids. In the minds of some researchers, this raised a question: how would the body respond to an animal source of polyunsaturated fatty acids, like those found in cold-water fish?
They decided to put it to the test by feeding study participants a staggering half cup of salmon oil daily. Sure enough, the salmon oil lowered cholesterol, compared to saturated fat, and had some other intriguing effects on biomarkers in these subjects. Later on, an analysis of stored blood samples from participants in the Physicians’ Health Study revealed that men with the highest levels of long-chain omega-3s in their blood had 90% lower odds of dying from sudden cardiac death. This is when omega-3s really got on the map as a modifiable risk factor for cardiovascular disease.
However, research investigating the effects of omega-3s on health have resulted in conflicting findings — some quite favorable, while others have “failed.” The reasons for this are complex, but one major problem is that fatty acid concentrations are not always measured objectively. Instead, researchers rely upon self-reported dietary data, which can obviously be fraught with error.
However, more recent observational studies have used blood samples to assess levels of omega-3s, as a reliable and objective measure of omega-3 consumption, and we can learn quite a bit from such research.
Study
Researchers conducted a meta-analysis of 17 prospective cohort studies — the gold standard of epidemiological study design. Basically, people who were free of any major medical diagnoses were recruited and they were followed over a period of years to see how levels of omega-3 fatty acids in their blood affected their risk of dying during the study.
All of the participants were older adults, with an average age at baseline of 65 years (range of mean ages across cohorts was 50–81 years). They were followed for an average of 16 years (range from 5-32 years), so plenty of time to observe effects on mortality in these aging cohorts.
The researchers measured levels of alpha linolenic acid (ALA), the omega-3 found in plants, like walnuts, flax, chia seeds, etc, as well as the long-chain omega-3 fatty acids that naturally occur in seafood and algae. These include:
- Eicosapentaenoic acid (EPA)
- Docosahexaenoic acid (DHA)
- Docosapentaenoic acid (DPA)
As you can see from this diagram, the impact of circulating eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) on the risk of dying from any cause during the study was generally found to be beneficial in the 17 contributing studies. (Boxes that are to the left of the dotted line above the hazard ratio of 1 indicate reduced mortality risk.)
The researchers collected and pooled the individual-level data from these studies — encompassing a total of 42,466 individuals. They also took into account a wide array of potential confounding variables, including age, sex, race, BMI, education, occupation, marital status, smoking, physical activity, alcohol, and health.
After adjusting for confounders, the researchers found a significant association between higher levels of long-chain omega-3 fatty acids (EPA, DHA, DPA) and all-cause mortality. When they compared individuals with the highest quintile of these fatty acids to the lowest, they found that the risk of dying from any cause during the follow-up period was reduced by 15-18%.
Importantly, ALA was not found to be significantly associated with all-cause mortality. This is a key distinction because ALA, and the foods that contain them, are commonly conflated with EPA/DHA and the marine sources of omega-3s. If you watch health influencers, you’ll often hear them suggest consuming walnuts or flaxseed as a way to acquire omega-3s instead of seafood.
Now, alpha-linolenic acid is a healthy fat source. In fact, the famous Lyon Diet-Heart Study achieved remarkable reductions in heart attacks by providing study participants with a margarine that was made with ALA. But for most people, it is not a sufficient substitute for EPA and DHA. You see, ALA can be converted into EPA and DHA, but the conversion rate sucks, at least for the majority of humans. Depending on your genetics, it might be as low as 5%. Consequently, you cannot rely wholly on ALA for your omega-3 needs.
But what precisely drives the increase in longevity associated with long-chain omega-3s?
Mechanisms
The cardiovascular benefits of both EPA and DHA are well established, as are the underlying mechanisms.
Both EPA and DHA are linked to improvements in platelet function. Specifically, they make platelets less sticky, which reduces the risk of harmful clots. EPA and DHA also serve as precursors for lipid mediators known as specialized pro-resolving mediators (SPMs), which are involved in the resolution phase of inflammation. SPMs help stabilize coronary plaques and promote repair processes for damaged blood vessels.
But when the research team for this meta-analysis zeroed in on cause-specific mortality, they noticed something interesting. The long-chain omega-3s were indeed associated with reduced cardiovascular mortality, much as we might expect. But they were also linked to lower cancer mortality, as well as deaths due to other causes (ranging from suicide, accidents, neurodegenerative diseases, and so on). This suggests that these fatty acids are beneficial across multiple domains, beyond the heart — perhaps influencing systems that you wouldn’t necessarily expect to be affected by omega-3 fatty acids.
And indeed, science suggests that omega-3s may be beneficial for muscle health, especially as we get older. When older adults who show signs of anabolic resistance are supplemented with omega-3s, their muscle-building response to an infusion of amino acids is doubled. You can imagine that this would help prevent sarcopenia, and the resultant frailty associated with age-related muscle loss.
Long-chain omega-3s, especially DHA, also seem to be critical for the brain. In older adults without dementia, lower levels of DHA in the blood are linked to smaller brain volume, as well as poorer scores on tests of cognition. Meanwhile, individuals with higher plasma DHA levels have been shown to be 47% less likely to be diagnosed with dementia over a nine year period.
The key takeaway here is that EPA and DHA are essential fatty acids, meaning that your body cannot efficiently manufacture them and you need to acquire them from the diet. It makes sense, accordingly, that an inadequate level of EPA and DHA would be linked to poorer health and performance. And it is all too common, with most Americans failing to acquire enough. But luckily, it is now super easy to find out your own EPA+DHA status.
Random Trivia & Weird News
The original snake oil may have had actual health benefits — via omega-3 fatty acids.
The term “snake oil,” dating back to the 1800s, is now used to refer to false or fraudulent medical products.
But ironically, snake oil in its original form may not have been fake at all.
Back in the nineteenth century, Chinese laborers used oil extracted from Chinese water snakes as a traditional remedy to alleviate inflammation and joint pain. A lab analysis published in 1989 revealed that this oil was an extremely rich source of EPA, greater even than salmon, and thus could plausibly have played a role in resolving inflammatory processes.
Later, American salesmen started selling their own versions of "snake oil.” These products, in contrast, likely didn’t even contain snake oil, and almost certainly were devoid of medicinal value.
As a result, snake oil became synonymous with fake cures and medical deception.
Podcasts We Loved This Week
- Danny Lennon & Alan Flanagan: Can fish oil supplementation increase risk of irregular heart rhythms? Via Sigma Nutrition Radio.
- David Grimm & Ted Schultz: Scientific evidence that cats are liquids, and when ants started their fungus farms. Via Science Podcast.
Products We Like
OmegaQuant Omega-3 Index Test
Currently, the best way to measure omega-3 status is by analyzing the proportion of EPA and DHA in red blood cell membranes, which has come to be known as the omega-3 index. The omega-3 index has the advantage of being highly stable, since red blood cells only turn over every few months, as well as a reliable indicator of whole body status since levels of omega-3s in red blood cells are known to reflect other tissues.
Here is an illustration of how powerful the omega-3 index is, as a predictor of mortality. Members of the Framingham Offspring Cohort had their blood analyzed for fatty acid patterns and were evaluated over 11 years. During that time, the omega-3 index was compared with standard risk factors, including smoking.
Over that period, the survival percentage was as follows:
- 85% for non-smoker with high omega-3 index
- 71% for non-smoker with low omega-3 index
- 71% for smoker with high omega-3 index
- 47% for smoker with low omega-3 index
So, non-smokers with a low omega-3 index had the same risk of death as current smokers with a high omega-3 index!
If you want to know whether you have a healthy level of omega-3s, taking the test is super easy. You just send a single drop of blood in the mail, and the lab will analyze the sample for EPA and DHA. In about a week, they’ll let you know where you stand.
humanOS Catalog Feature of the Week
Body Timing and Health
In this course, Dan goes over the evolution and physiological purpose of biological rhythms, as well as how they are regulated in response to environmental stimuli. Then, he delves into how these biological clocks influence both acute performance and long-term health, and what happens when they get out of sync.
Finally, all of this juicy info is synthesized into practical applications — what you can do right now to align your circadian rhythms, to keep your mind and body working at their very best. Since we’re getting close to the end of Daylight Saving Time, it might be good to brush up on this topic!
Wishing you the best,
