How Omega-3s and Diet Can Affect ApoB

So this question was submitted by JQ, and I also saw this question in one form or another in this Q&A, and it has to do with ApoB and lipoproteins. So I've definitely covered this topic in detail in previous Q&As. I probably cover it once every year and a half or so or something like that. So the question has to do with ApoB and LDL cholesterol and those numbers being quite high, eating a fairly healthy diet or, you know, being relatively healthy, eating mostly low carb, exercising, being at a healthy weight, but still having high ApoB and LDL. And basically, is there anything to address? And I think first of all, understanding, look, ApoB is a protein that's produced in the liver. It provides structural support for lipoproteins, particularly VLDL.

So that's the precursor to LDL. ApoB is a marker of cardiovascular health for a couple of reasons. First, it's a more direct way to measure LDL particle number, which may be more relevant for cardiovascular health than total LDL cholesterol. Second, ApoB is what is likely to insert into arterial walls, which then basically allows the LDL lipoprotein to not be recycled. They sort of start that cascade of inflammation and foam cell formation. So ApoB is relevant, and there's a lot of interest in the regulation of ApoB. It's mostly regulated through degradation and not synthesis. So it's regulated mostly in getting rid of it and not the production of it. Your liver is really constantly making ApoB to some degree.

And we do know that there is one factor that regulates the synthesis or production of it, and that is inflammation, and particularly cytokines like TNF-alpha and interferon. TNF-alpha can be dramatically increased again under like conditions of intestinal permeability. And I talked a lot about this in a presentation I gave a couple of months ago and there are a variety of factors that can regulate intestinal permeability, stress, alcohol, diet, particularly a very, very high-fat refined carbohydrate diet but even a high-fat low-fiber diet in some cases can increase intestinal permeability.

Interestingly, we know that omega-3, particularly the marine omega-3s, DHA and EPA, so fish oil, supplementation has been shown to decrease ApoB levels in people with dyslipidemia and also in people with normal lipids. So the dose was about 1,500 milligrams of EPA and 1,000 milligrams of DHA. That was shown to decrease ApoB, possibly through this inflammation, you know, related mechanism or maybe other mechanisms as well. We know that that omega-3 has been shown to reduce TNF-alpha, for example. And in fact, omega-3 has been shown to reduce lipopolysaccharide induced from a meal. And again, lipopolysaccharide— when lipopolysaccharide makes its way into circulation from the gut, it increases TNF-alpha.

I think there's a lot of potential synergistic effects going on there with omega-3 where it's stopping the LPS release. And so that's one way it's reducing inflammatory markers like TNF-alpha. And it's also just resolving the inflammation quicker and lowering the inflammation. So I think that the omega-3 is probably one sort of low-hanging fruit avenue to explore with respect to ApoB reduction. Fish has also been shown to lower ApoB synthesis. So another study found that even higher dose of fish oil, so 1.8 grams of EPA and 1.2 grams of DHA, was able to lower ApoB production by 29% in people with normal blood lipids. So that's pretty cool. There was also a decrease in the VLDL pool size by 43%. So that's the sort of supplemental side of the story.

And again, you guys already know And you'll hear more about my supplementation routine in a minute, but you already know I'm a huge, huge fan of omega-3 supplementation. And I've also seen a variety of questions submitted in this Q&A about fish intake and concerns about heavy metals from fish intake and if there's a trade-off or not. So I will say this. Yes, to some degree, you're going to get some contamination from fish. The best thing you could do is go for the fish that are known to be lower in heavy metals and contaminants, right? Those are the wild Alaskan salmon, sardines. You got to find— obviously, there could be some contamination with arsenic with some of the sardines. But finding the smaller fish that are not accumulating these heavy metals as much.

But also keep in mind that there have been studies done, particularly in pregnant women, where pregnant women eating fish— in fact, the biomarker for fish intake was mercury. So they knew the women were eating more fish because their mercury levels were much higher. Than women that were not. And the omega-3 fatty acid content in the fish protected the developing fetus and not only protected the developing fetus, there was benefits from it. In other words, not getting the fish, even though there was lower mercury, was worse for the fetus, which is more sensitive, by the way, to heavy metals than an adult is. So they were more sensitive. So they're more sensitive to the heavy metals. And yet having the higher heavy metals was better because of the omega-3.

So it's like the omega-3 is negating some of these potential adverse effects from these heavy metals. Not to mention again, excreting some of these heavy metals through sweat and also through things like beta-mercaptans from garlic, which helps excrete it through urine, also helps. So I personally choose to eat fish, but if you're super, super concerned about heavy metals and you Get your heavy metals measured. That's something to keep in mind is also having your Omega-3 Index measured and how high is your Omega-3 Index because that should really tell you something, not to mention the fact that you can also obviously supplement with a higher dose of omega-3 and maybe cut down some of your fish intake if that's also a really big concern.

For me, I— I personally like to eat the fish in addition. There's other micronutrients that are also present in the fish that are beneficial as well. So I think that that's kind of my take on that. And that was a big tangent. I'm going to get back to the ApoB here— I mean, to the ApoB story here because there's also a story to be told with respect to diet. And I know that a lot of people follow a low-carb diet, and JQ had mentioned it in his initial question. And there's been some really interesting research, a lot of it from my friend and former colleague, Dr. Ron Krauss, who's done a lot of work on this, looking at how different types of diets, low-carb versus low-fat, and how they affect ApoB and how they affect other risk factors like small dense LDL, for example.

And it's interesting because it really— the dietary effects on ApoB and small dense LDL really come down to where a person is at their baseline in terms of their phenotype. So there's a big genetic predisposition to whether or not a person is a phenotype A versus a phenotype B. In other words, whether or not they're making more of the small dense LDL products versus not. And so starting out on, you know, someone that's already genetically predisposed to making a lot of small dense LDL is something that's important to consider when making dietary changes. So for example, looking at a high-fat versus a low-fat diet and then switching, you know, doing a switchover. So men that did either a high-fat or low-fat and then they switched the diet.

After doing the diet, after the high-fat diet, the individuals were classified as either phenotype A or phenotype B. And then if they were following a low-fat diet, all the phenotype B individuals stayed phenotype B. But about 36% of those people shifted from a phenotype A to a phenotype B, whereas about half, like 51% of the people remained phenotype A. After the low-fat diet, phenotype B subjects had a greater decrease in their total cholesterol, and also they decreased their ApoB, whereas phenotype A— compared to phenotype A. Whereas phenotype A people had reductions in their Their total cholesterol, but they also had no change in their ApoB.

So it seems as though a low-fat diet may be more beneficial for people that already are phenotype B, already are people that are genetically predisposed to making small dense LDL. So phenotype B people are predisposed to higher small dense LDL, higher ApoB than phenotype A. So a low-fat diet may not necessarily benefit people that are phenotype A that already sort of are not genetically predisposed to that, but it may benefit some of the people that are phenotype B. And that would be something to sort of explore through some self-experimentation. There's another study that showed people again that are phenotype B that are put on a high saturated fat diet. had a significant increase in ApoB and also a significant increase in small and also total LDL particles.

So again, it might— this might mean that people that have a phenotype B type of lipid profile might not do well on a very low-carb, high-fat diet. And that is— I also think this is also something where looking at the conflicting data, this is— there's a genetic component in there. And I think that that's not usually considered. But if a phenotype is measured at the baseline, is this person phenotype A or phenotype B, then you can kind of maybe say, well, maybe I'm phenotype B. Maybe I should not be doing so much of a high-fat, low-carb diet. Maybe I should be eating more fiber and eating more mono and polyunsaturated fats and less of the high saturated fat.

And this was also asked by Bernardo, who asked if there was any recommendations for a low-carb diet with the problem, again, of elevating ApoB due to the consumption of high quantities of fat. And he was talking about doing keto for years and his LDL going just through the roof and his ApoB also going really high. So again, I would say many low-carb or keto eaters do eat a lot of saturated fat, and some of these people that are already ApoB to start with might consider doing a low saturated diet, sort of fat, like a low saturated fat diet, and to see how that affects lipids. So low dairy, low cheese, low butter, low red meat, low coconut oil, low palm oil, like basically very low, or if any of those.

Replace those things with avocado oil, with olive oil, with avocados and oils and nuts and fat from like salmon. And if you really, really, really want to do the keto version of it, again, like you can do a keto diet, but instead of doing all the saturated fat, you do mono and polyunsaturated fat. And that would be something to really check because there are, again, people that are already phenotype B that can increase their ApoB and do worse with a low-carb, high-fat diet, particularly when it's low-carb, high-saturated fat.