And the same goes for omega-3. You know, omega-3 is probably, I think, one of the most important nutrients that is really overlooked. People just don't even really think about it. So, there are three types of these omega-3 fatty acids. There's the type that you can find in plant sources, alpha-linolenic acid, or ALA. Then there's EPA, which is eicosapentaenoic acid, and then DHA. Those are the two marine sources that you'll find in fish, but you can also find them in microalgae, which is more of a plant-based source.

There was a study that came out of Harvard, I think it was in 2009, which identified low intake of marine sources of omega-3 as basically one of the top six preventable causes of death. In other words, people are not eating enough seafood and fish. Because of that, it was calculated that something like 84,000 deaths per year were attributable to not getting enough EPA and DHA from the diet. This was really comparable to people eating trans fats. Everybody knows trans fats are bad. You walk into any grocery store and you see zero trans fats on every package. It's very much in the public awareness that trans fats are bad. Well, trans fats were responsible for about the same number of deaths as not getting EPA and DHA, about 82,000 deaths per year.

Before I go deeper into that, it makes you think: the same number of deaths were attributable to eating trans fats as to not eating enough EPA and DHA from marine sources, fish for example. You don't walk into a supermarket and see something saying, oh, this isn't seafood, this isn't getting your EPA and DHA, this is processed. But everything tells you about trans fats. It was just as important to get those omega-3 fatty acids from marine sources.

Now, I say marine sources because ALA, which is the common source of omega-3 found in plants like flaxseeds and walnuts, is actually considered the essential fatty acid because we can convert ALA into EPA and DHA. So, you know, all the government agencies that come up with these RDAs and all those standards that are set basically say, well, because we can make EPA and DHA from ALA, that's going to be the one that we focus on. The problem with that is that the conversion of ALA into EPA and then subsequently DHA is very inefficient, and there are widespread genetic differences with respect to that conversion.

Some people have an alteration in the desaturase gene that does the conversion of ALA into EPA, and they do it quite well. I would say the majority of people have another version and are not so great at it. To add fuel to the fire, having too much vegetable oil and omega-6 fatty acids can also matter. I don't want to demonize them so much, because you need linoleic acid and you need arachidonic acid. They're part of your cell membranes and have important functions. Getting them from whole-food sources like nuts is great. But vegetable oils are very concentrated, and a lot of cooking, restaurant food, and processed foods use vegetable oils. When omega-6 is too high, it can compete for the enzyme that's required to convert ALA into EPA.

You may be getting enough ALA, but that's the other problem: people aren't even eating flaxseeds and walnuts. They're not even getting enough ALA. So there are so many layers to this. That conversion is very inefficient when there's a lot of omega-6. On top of that, I would say the one saving grace is that estrogen does dramatically increase that conversion. It makes it up to 20% better. This is probably because DHA is so important for brain development. When a woman becomes pregnant, estrogen skyrockets. It's like 100 times higher than what it normally is. It's pretty apparent that nature has figured out a way to at least convert as much ALA as possible into EPA and DHA.

Anyway, that's where the genetics comes in. There's definitely regulation there. But I think the best way to get EPA and DHA is from eating a dietary source and measuring what's called the Omega-3 Index. The Omega-3 Index measures omega-3 fatty acid levels, including EPA and DHA, in red-blood-cell membranes. It's really important because most of the time when you go and get an omega-3 blood test, the plasma phospholipids are measured. That's better than nothing, but you're really looking more at your dietary intake in the last week or two. Red blood cells take about 120 days before they turn over, so that's a longer-term measure of your omega-3 status.

It's kind of like the difference between looking at fasting blood glucose and your HbA1c. You could have been intermittent fasting that day and your fasting blood glucose looks great, but is that a snapshot of what your daily blood glucose levels always look like? It might not be. So the Omega-3 Index is a long-term measure. There have been a variety of studies from Bill Harris. Bill Harris is the co-inventor of the Omega-3 Index test. I had him on my podcast about a year ago. I've actually joined the Fatty Acid Research Institute, which is a nonprofit institute studying the roles of fatty acids in human health. I've joined as an associate researcher, and so I'm doing some studies on omega-3 and brain health.

Bill has published a variety of studies looking at the Omega-3 Index and all-cause mortality and cardiovascular-related mortality. When you get the Omega-3 Index measured, most people in the United States have an Omega-3 Index of less than 5%. What Bill has shown from multiple studies is that people who have an Omega-3 Index of 8% have a five-year increase in life expectancy compared with those who have an Omega-3 Index of 4%. So that's 4% versus 8%. There's also evidence that it's related to cardiovascular mortality as well.

Another very interesting piece of data that Bill published was looking at smokers. Everybody knows smoking is terrible for your health. What can you do to accelerate the aging process? Smoking cigarettes and tobacco is terrible. This was so interesting: smokers who had a high Omega-3 Index, so they were smoking but they were also eating a lot of fish or supplementing with fish oil, had an 8% Omega-3 Index. They had the same life expectancy as nonsmokers with a low Omega-3 Index. In other words, smoking was like being deficient in omega-3. I was blown away by that. There's a beautiful graph in the paper. I forgot what journal it was published in. It was a couple of years ago, but it's just kind of mind-blowing.

Omega-3 plays so many different roles in the body. It accumulates in cell membranes and plays an important role in the way transporters and receptors function, because all those things are embedded in the cell membrane. For example, glucose transporters at the blood-brain barrier are altered and don't function well when DHA is deficient. That can cause less glucose to get into the brain, which obviously leads to many problems.

The metabolites of EPA and DHA also resolve inflammation in a very efficient and timely manner. These are the maresins, protectins, and resolvins. These specialized pro-resolving mediators play a very important role in inflammation. I think there's now enough evidence that chronic low-level inflammation is a driver of the aging process itself. In other words, it's not just increasing the risk of cardiovascular disease, dementia, and cancer, which it does, but it's involved in the process of aging. Inflammaging is a term that's used for the activation of the immune system accelerating the aging process. There's neuroinflammation, and there are these seven pillars of aging where you look at physiological processes that are happening. Genomic instability is one; protein misfolding is another. Inflammation was the thing that overlapped between brain aging and aging itself. It was the most important thing accelerating everything in the brain and also aging in the body.

Having omega-3 is, I think, one of the easiest things someone can do to improve their inflammatory processes and the structure and function of their transporters and receptors. I know you're going to ask me about research I'm most excited about, so I'll give you a preview of that. I'm also excited about a new role for omega-3 in muscle mass and sensitizing skeletal muscle to amino acids. There's been some work from Chris McGlory, who I had on my podcast just yesterday. He's shown that omega-3 is playing a role in disuse atrophy through a mechanism where it's not the anti-inflammatory effect of omega-3. It's doing something anabolic and somehow affecting muscle protein synthesis. He thinks it's sensitizing muscle to amino acids through some unknown mechanism they're trying to figure out. I'm pretty excited about that new research coming out. Muscle mass obviously is an important factor in aging as well.

So when it comes to omega-3, what do you do? Obviously, if you can eat fatty fish that's high in omega-3, salmon, mackerel, and sardines are all pretty good sources that are also low in contaminants like mercury and PCBs. By the way, there have now been studies showing that even though fish have these contaminants, the omega-3 fatty acids protect against them, even during pregnancy. Decades ago there was this big push that pregnant women should avoid eating fish because of mercury. I think that was a huge mistake. I'm actually involved in a study looking at the Omega-3 Index in cord blood and neurodevelopmental outcomes.

There have been a couple of studies. One big one, I think, was published in 2015. It basically showed that, among women eating fish, the omega-3 fatty acids protected against neurotoxicity. In fact, those children had better neural outcomes than children of women who avoided fish. There have also been studies looking at fish intake during pregnancy and intelligence at one year and seven years of life. I forget all the follow-up times, but omega-3 was correlated with improved intelligence if the mothers were eating fish. They were actually using mercury as a biomarker to validate their dietary recall, because the women who were taking in more omega-3 had higher mercury. The higher mercury was correlated with higher intelligence in the children, not because mercury is improving intelligence, but because the omega-3 is. The mercury did not seem to matter when omega-3 was present, because the omega-3 was protecting against potential toxic effects of mercury.

I know that was a bit of a tangent, but it's important because people are kind of scared of eating fish. There are some fish that you should be scared of, like swordfish, which is terribly high in mercury and not so high in omega-3. But things like wild-caught salmon are low in mercury and high in omega-3. Supplementing is also, I think, a really important option.

Looking at a 4% Omega-3 Index compared with 8%, I mentioned the five-year increase in life expectancy. There have been some studies showing that 1.5 to 2 grams a day of supplemental omega-3 can bring people from a 4% Omega-3 Index to an 8% Omega-3 Index. Now, keep in mind, people are prescribed 4 grams a day of either Lovaza or Vascepa, with Vascepa being purified EPA, and that's very safe. The way I like to think of omega-3 is that it's got the safety profile of a nutrient, but it is pharmacologically active.

So many people are not getting enough of it. I think something like 80% globally do not get enough EPA and DHA, and about 95% of people in the United States do not get enough. It's very important with respect to the way we're aging. I think it's important for cardiovascular health. I think it's important for brain health throughout the lifespan, from infancy to old age. So that's sort of my spiel on omega-3. I think it's very low-hanging fruit and an important thing that people can take in.