November 21, 2020

From podcast: https://bengreenfieldfitness.com/podcast/supplements-podcasts/epa-dha/

[00:00:00] Introduction

[00:01:29] Podcast Sponsors

[00:04:01] Guests Introduction

[00:08:34] The 2 Sources of Omega-3 Fatty Acids

[00:15:43] What Makes Essential Fatty Acids So Essential

[00:19:31] Omega-3 Fatty Acids Being Oxidized Once It Enters the Body Is a Misconception

[00:25:28] Ratio of Omega Fatty-Acids in The Body and What the Ratios Should Be

[00:33:03] Ethyl Ester and Triglyceride Forms of Omega-3 Fatty Acids

[00:35:59] Podcast Sponsors

[00:39:03] cont. Ethyl Ester and Triglyceride Forms of Omega-3 Fatty Acids

[00:45:06] What Genes Convert ALA or Plant-Based Oil into EPA/DHA

[00:52:15] Ratio of Omega-6 to Omega-3 Fatty Acids

[00:59:50] Link Between Omega-6 and Inflammation and Chronic Disease

[01:05:47] Contaminants in Fish Oil, Cleanliness, Sourcing, Concerns About Packaging, Shelf Life, Heat Exposure During the Manufacturing Process

[01:14:59] Final Comments

[01:16:50] End of Podcast

Ben:  On this episode of the Ben Greenfield Fitness Podcast.

William:  I think everybody's pretty happy with the omega-3s being good. What's questionable is the goodness or badness of the omega-6.

Kristina:  And the same goes for omega-6s, the essential polyunsaturated fatty acids, omega-6s also have huge roles to play in these pathways.

William:  It gets the news is when we're being screwed because these fish oils are all crap, what doesn't get the news is when those things are re-examined and shown to be untrue, you don't hear about.

Ben:  Health, performance, nutrition, longevity, ancestral living, biohacking, and much more. My name is Ben Greenfield. Welcome to the show.

Well, well, well, what do I have for you today? A podcast. That's what you expected, right? I've been getting a lot of questions about omega-3 fatty acids in fish oil, like, why should you take them? What kind of dosages and types are using these studies? What about all the people who say it's a waste of time? You're going to kill yourself by popping fish oil. What EPA and DHA do you look for? Are there people who shouldn't take fish oil? Are there things you can stack with fish oil that make it better? How can you test your omega-3 fatty acid status to see if you need fish oil? Well, I decided to get the experts on the show today to delve into all of this. So, it's going to be a doozy.

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Alright, let's go talk fish oil.

Well, folks, I'm going to do something I've never done before. I don't think I've ever dedicated an entire episode to fish oil and omega-3 fatty acids. But considering that I actually think that these compounds are probably one of the most well-researched and important compounds, specifically omega-3 fatty acids and fish oil, above nearly every supplement that exists, it's high time. I actually did some kind of a podcast on all the ins and outs of fish oil and omegas, everything from, what are the actual benefits and what kind of dosages and types of fish oil or omegas were used, and studies that show benefits? What EPA and DHA ratio should you look for? Are there certain things you can take with fish oil to amp up the benefits? How can you test your own fatty acid status within your body? A whole lot more. And of course, there are even a lot of people out there who say fish oil is bad for you and it's going to be rancid and oxidized in the body.

And so, I of course want to address that a little bit, too. So, I decided to get a couple of really good, true, unbiased fish oil experts on my show. And my first guest is Dr. William Harris. He is an internationally recognized expert on omega-3 fatty acids, particularly relevant to heart disease. He has a Ph.D. in human nutrition from University of Minnesota, and he's done a lot of post-doctoral work on the effects of fish oil on lipids, and he's been granted a bunch of NIH grants for studies on the effects of omega-3 fatty acids on human health. He has more than 300 publications related to fatty acids, and a couple of them relatively recent related specifically to cardiovascular disease.

And as if that weren't cool enough, his daughter is also steeped in omega-3 fatty acid or omega fatty acid and fish oil, studies herself, Kristina Harris Jackson, who is a Ph.D., and also a registered dietitian. And so, she also has done quite a bit of studying up on fish oil and researches it pretty heavily herself. And both Kristina and William have contributed to the field of omega fatty acid testing. You may be familiar with a test we'll probably talk about on today's show called OmegaQuant, which is one that you can test your omega fatty acid status. I've actually done that test myself. And so, they not only know a lot about the effects of fatty acids on the body, but also how to test for fatty acid status. And so, I guess my responsibility today aside from getting as much fish oil information out of Kristina and Bill as possible is to ensure I don't create any type of family feuds or father-daughter arguments on my show because I think this is the first one I've ever done with a father-daughter team. So, I hope you guys are up for this.

William:  I think we're good.

Kristina:  We're going to handle it.

Ben:  Okay. You guys get along okay?

William:  Oh, yeah.

Ben:  Yeah.

Kristina:  Mm-hmm.

Ben:  Now, do you actually work out of the same office, same lab?

William:  Yeah.

Kristina:  Yes.

William:  Same physical space, mm-hmm.

Ben:  Where is that at?

Kristina:  Sioux Falls, South Dakota.

Ben:  Okay. Cool. Out in the Dakotas. There's a lot of people out there, right? Super dense population.

Kristina:  Yeah. No, it's only the hearty Midwesterners can make it up here.

Ben:  Yup.

William:  See, we've got more cattle than we have people in South Dakota.

Ben:  Yup, exactly. That's been my impression of the Dakotas. I've driven across them before, but haven't spent a lot of time aside from–isn't the original like Walmart or Walgreens out in the Dakotas? Am I remembering properly?

William:  Wall Drug.

Ben:  Yeah, Wall Drug. That's out there, isn't it?

William:  Yeah. By the badlands and the black hills.

Ben:  Yeah. There you go.

Kristina:  It doesn't have anything to do with Walmart or Walgreens. It's just a funny little tourist place. You got to check it out.

Ben:  For some reason, that's like all I remember about the Dakotas when my family drove across the Dakotas in the camper when I was a teenager. I remember Wall Drugs. I think it's because they bought me like a giant Lego set or something there to keep me happy the rest of the trip.

Kristina:  Oh, yeah.

Ben:  That's my fond memory of the Dakotas. For everybody listening in, as we get going, I'll take some really good notes, and everything we talk about I'll put over at BenGreenfieldFitness.com/fishoilpodcast. That's BenGreenFitness.com/fishoilpodcast.

Now, the first question I want to ask you guys is a lot of people of course hear you're supposed to take fish oil, or that omega-3 fatty acids are actually good for you, and even arguably essential. What's that actually mean? Like, what from a cellular standpoint, if you were to consume fish oil or something rich in omega-3 fatty acids like salmon, or herring, or anchovies, or something like that, what's actually going on that makes these fatty acids so special, and what does it mean for them to be called essential?

William:  I'll start. I'll take even one step back and define what omega-3 fatty acids are because there's some confusion about that as well because there are fundamentally two sources of omega-3 in our diet. One is a plant-derived omega-3 called alpha-linolenic acid, which is an 18-carbon acid that's in the omega-3 family, but it's not the same thing as the fish-derived, fish oil derived omega-3s, which are EPA and DHA, which are 20 carbons and 22 carbons long. They're much bigger molecules. They are related, again being in the same family, but the ALA, the plant omega-3s doesn't really have the benefits of the EPA and DHA. So, I think when Kristina and I talk about omega-3, we're talking about EPA and DHA by and large, unless we need to talk about ALA.

Ben:  Now, the ALA issue is primarily the actual conversion of the plant-based ALA into EPA and DHA is remarkably low, from what I understand.

William:  Correct. Right. Then that's the problem because you can't get very much of the good stuff from eating ALA.

Ben:  Okay. And forgive me because I tend to rabbit hole sometimes when I ask a question, and here we go into the first rabbit hole because many people who are eating a vegan or plant-based diet, they get a little down about this idea that they can't get a lot of appreciable amounts of EPA or DHA from, say, seeds and nuts, but then they'll come back and bring up something like algal oil from algae as a potential bioavailable source of EPA and DHA. What do you think about that as far as a solution goes?

William:  That's true. There are specific, what they call micro-algae on this planet that are single-celled organisms, kind of like parameciums, or we're trying to think of something that's small and people would remember. It's a single-celled algae. It's not kelp. I mean, we're not talking about seaweed here when you think about algae. Sometimes people think about–that's what comes into their mind when they think about algae, and it's not that. This is a particular species, two or three particular species that happen to make EPA or DHA naturally, and these are actually at the base of the marine food chain. This is where the omega-3s are originally made that finally rise up as smaller animals eat the algae, then bigger fish eat the little fish, et cetera. So, the omega-3s are not made by fish, they're made by plants originally. Plants, meaning, the algae. And so, there's some companies that have decided to go to the base of the food chain and they now grow these algaes in big ponds and harvest the omega-3s out of them and put them in capsules. And see, there are vegan-derived EPA and DHA products. It's exactly the same molecule as you get as you're eating fish, but it doesn't come from fish, it comes from algae. So, that's available.

Ben:  Yeah, yeah.

William:  But you can't eat it. There's not a food per se.

Ben:  Right. It would be in supplemental form. And I've looked into it. It seems to find a source of algal oil that is appreciably high in EPA and DHA. It tends to be prohibitively expensive from everything that I've found in terms of getting an algae that actually is going to provide higher amounts of DHA and EPA because apparently, it varies from algae to algae. Is that true in terms of the actual expense? Is that why it's not more popular?

William:  I think that's part of it. Part of the process is expensive to do, but as more and more companies–it'll be as demand grows, the price will go down. Look at computers, you know. Partly, what's really driving the demand for algal oils is the aquaculture industry because about 70% or 80% of the fish oil that's produced on this planet is actually fed back to fish in aquaculture. So, that's where most of it goes, and we can't just keep harvesting small fish to get their oil and feed it back to big fish. So, the long-term solution is to get the omega-3s for the aquaculture industry from growing algae.

Ben:  Right.

William:  And so, as that market grows, that industry grows, they'll be more available in the human market and it should come down in price.

Ben:  Yeah. Just an economies of scale issue because I think the algal oil I've looked into comes out to like 4.50 an ounce or so. Whereas if you look at like a really good fish oil, I think it's around like 2.50 an ounce, like $2.50 an ounce. So, yeah. You're still paying more for the algae from everything that I've seen. But you know what, just to close the loop on this whole idea of plant-based or vegan-friendly sources of omega-3 fatty acids, is there anything aside from algae that exists that you're aware of?

William:  Not really commercially available, but what is also being developed are some genetically modified land plants. I mean, like even soybean oil, but there's a thing called Camellia seed oil in Australia. Australia is working hard on this to put the genes into land-based plants that are already oil-producing plants, kind of like soybean oil, soybeans, and be able to grow essentially unlimited amounts of these plants, depending how much land you've got, and harvest the omega-3s out of that, and that would also be a source in the future. That's not available right now for human consumption, but I think that's going to be a huge game-changer.

Ben:  Okay. Cool.

William:  If people can put up with GMO.

Ben:  Yeah, yeah. I know that. That's something that a lot of people are a little bit concerned about. I'm not really against selective breeding or genetic modification if it can be shown to be healthy. I just always proceed with caution. The same way I'll approach the upcoming COVID vaccine is I won't be the first to take it, I can tell you that. I'll sit back and observe what's going on preferably from a long-term human standpoint before I make any decisions regarding that.

So, back to omega fatty acids though. So, we got into the weeds there for a second about algal oil and vegan sources, but regarding my initial question, why are they essential and what exactly are they doing for the human body that is so special? Kind of a big question to unpack, but can we return back to that and kind of delve into that a little bit?

Kristina:  So, I guess when we talk about what omega-3s are doing in our bodies, the main thing that we focus on is what role they're playing in cell membranes. And cell membranes are made up of fatty acids. They surround every cell in our body and they're not only important as like structural and a structural aspect of the cell, but they also provide starting products for different signaling pathways and they affect how the cells communicate internally and externally, and omega-3s appear to affect both of those arenas. So, when it comes to membrane fluidity, omega-3s having a lot of carbons, and also a lot of double bonds, it makes them take up more space kind of in the cell membrane and makes the cell membrane more flexible and more fluid, and that can be important for red blood cells specifically as they're trying to flow through the body, get through small capillaries, things like that. So, it does have this physical component that's important.

As far as signaling goes, omega-3s are really important in some pretty major inflammatory pathways, and they also are starting products for specialized pro-resolving mediators, which are another aspect of inflammation. It's kind of the healing after the inflammation that the body does. So, the starting products for those different molecules that the body takes from the membranes and uses to create different molecules that have huge effects on the body. And the same goes for omega-6s, the other side of the essential polyunsaturated fatty acids that make omega-6s also have huge roles to play in these pathways. They both work together, they're both very important. And so, those are two of the main roles I see as far as their membrane functionality.

Ben:  And by the way, regarding membrane functionality, is it true that your cell membranes are going to be comprised of the type of fats that you consume from a dietary standpoint? Meaning, if you consume, say, rancid or oxidized fats, or excess amounts of linoleic acid, et cetera, those are going to be incorporated into cell membranes more readily or more heavily than, say, like an omega-3 fatty acid?

Kristina:  I would say for the essential fatty acids, the essential omega-6, linoleic acid, and the essential omega-3, ALA, and then EPA and DHA, those are fatty acids that the body can't make. And so, those are incorporated more directly into your cells and more directly related to your diet. And the other fatty acids that only come from diet for humans are trans fats. So, those really are the main ones that we can see will go up and down pretty regularly with diet. Everything else, all saturated fats, monounsaturated fats, those are more affected by metabolism. And the body is also creating the cell membrane structure needed specific to each cell type. So, it's not just like exactly what you eat goes into every cell membrane equally distributed throughout the body. Liver cells might need a different type of pattern than a red blood cell, then lipoprotein. They just all have their own patterns. And so, we do see differences between plasma phospholipid patterns versus a red blood cell. They're slightly different, but we do see with the omega-3s because they do just come from the diet and EPA and DHA are so unique in the diet, that they're pretty well-tracked with what you eat compared to other fatty acids.

Ben:  Right, right. And something important that you brought up, and this was the second thing I wanted to highlight, was you talked about the signaling mechanisms of something like DHA and EPA. We know EPA is like a precursor to eicosanoids, which are signaling and inhibiting molecules, part of the inflammatory reaction as one example. I think what's interesting is that if you look at, at least this is what I've seen, a lot of the studies that investigate how omega-3 fatty acids are actually working, especially from a signaling standpoint to be able to modulate a normal inflammatory process or to be able to fight inflammation, it's actually their oxidation that appears to allow them to act on things like these inflammatory NF kappa-B pathways or other pathways responsible for inflammation. Meaning, they're actually oxidized upon consumption.

And this is interesting because I think it confuses a lot of people. And I've seen folks in the health and nutrition industry, say, you shouldn't eat fish oil because it's going to be oxidized or rancidized, or become rancid within the human body because of the 98.6 degrees of the bloodstream. But when I look at all these studies that actually show omega-3 fatty acids to have some pretty potent signaling mechanisms, it appears their oxidation within the human body is how that actually occurs. So, is that true? I mean, or is it a matter of us consuming omega-3 fatty acids, them getting into our bloodstream actually becoming damaging due to the temperature within our body? I think this confuses a lot of people.

William:  Yeah. Let me jump on that because I think there's a different–when we talk about the term oxidation, it has two different meanings. A biochemist would have one meaning and a food scientist would have another meaning.

Ben:  Okay.

William:  Because like you correctly point out, in order to become activated and used in the prostaglandin pathways, or leukotriene pathways, or these resolving mediators Kristina was talking about, oxygen molecules are added to the fatty acid very specifically by specific enzymes intended to do that. I mean, there's a purpose for them. And they add oxygen, and that is a, strictly speaking, an oxidation product. But when a food chemist or somebody who's smelling rancid fish oil is thinking about oxidation, they're thinking about what we call peroxidation, P-E-R, peroxidized, which really needs destroyed producing unwanted byproducts. And that kind of thing doesn't really happen in the body because you've got lots of different antioxidant systems that protect against that type of oxidation.

Ben:  Right, right. So, you're talking about lipid peroxidation, the actual oxidative degradation of the lipids themselves. That's actually a cell-damaging scenario. What you're saying is oxidation can occur to these omega-3 fatty acids resulting in free radicals that act as signaling molecules to enhance our ability to be able to modulate inflammation. Whereas lipid peroxidation would be the actual oxidative degradation of lipids that would cause cell damage, and there are two different scenarios.

William:  You got it.

Ben:  Okay. So, lipid peroxidation is not something that occurs if one were to consume, say, like a good fish oil that wasn't like a rancid or oxidized fish oil?

William:  No, no. And if you talk about rabbit holes, there was a study that was quite fascinating to me done a few years ago in Norway where they were very interested in what's the effect of truly oxidized, lipid peroxidized fish oils on human health because we always hear it's terrible and you stay away from these things if they have peroxidation. So, these scientists did what to me was an amazing experiment. They took a regular fish oil and they put it in a glass vial, and they bubbled oxygen, pure oxygen through it, which is extremely oxidizing, peroxidizing environment. They intentionally just whacked it with a big hammer of oxidation. And then, they encapsulated the stuff in pills, and then they did a randomized trial in humans giving them either the unoxidized fish oil and the oxidized fish oil, and they did that for like eight weeks.

And then, they went in and measured blood levels of these lipid peroxidation products, and inflammatory markers, and lipids, all kinds of stuff they measured, and they couldn't find any effect at all, which was–because the body has ways of cleaning up things that it doesn't want. I guess that's the way you'd interpret it. And I think maybe we get a little overly concerned about “oxidized fish oils.” When people actually do the experiment to ask the question, they can't find a problem with it, and especially when they oxidize fish oils far more than would ever happen in normal life where all manufacturers use nitrogen and try to protect them from–and most of that is to protect them from degrading, becoming so stinky, you can't eat them. But that stinkiness doesn't really come from EPA and DHA. It comes from other molecules in fish oils. Anyway, that's a rabbit hole you didn't maybe want to go down.

Ben:  Yeah. No, that makes sense. So, to clarify, these folks are simply confusing the difference between peroxidation and the oxidative degradation of lipids in which free radicals steal electrons from lipids and cell membranes resulting in cell damage and oxidation, this natural transfer of electrons that occurs all the time within normal human metabolism to create helpful signaling molecules.

William:  Exactly, exactly.

Ben:  Got it. That clears the air on that big time. Okay. So, back to the omega fatty acids, specifically the omega-3 fatty acids. One thing that's talked about quite a bit is the actual ratios of these omega fatty acids in the body. And I know that you guys, being steeped in the actual testing of ratios, and I don't mind if you want to include as your response to this question how this type of testing works, how have ideal ratios actually been studied, and what do we know about what the ratios should be?

Kristina:  I guess maybe you're talking about two different ratios. One, some people ask about the ratio of EPA to DHA, and sometimes people are talking about the ratio of omega-6s to omega-3s.

Ben:  Okay.

Kristina:  When we're talking about EPA to DHA, we don't have a strong opinion on that. We think both are generally good to have higher EPA products, and EPA has had a lot of success in recent research, and DHA also has shown benefits in research as well. But pure EPA, Vascepa is a pure EPA pharmaceutical drug, very high dose that had a very successful trial a year ago. And there's just been more research looking at EPA alone. That's been pretty positive. On the whole, I'm more of a proponent of have both of them, if you're eating it in fish, then you're getting nice ratios of both. It's present in nature. Both of them are together. And so, that's kind of where I default when it comes to the membranes, typically when we're looking at a red blood cell DHA is higher typically than EPA naturally in the membrane unless you take a high EPA product or a pure EPA product. And then, they can be about equal.

Ben:  And with EPA and DHA, it depends on the organ within the body, right? I mean, like in neuronal tissue in the brain, I know DHA levels are through the roof compared to EPA, like 300 times higher. Whereas EPA is important in other areas within the body, and it sounds like you see quite a bit of benefit if you were to say–just consume an EPA-based fatty acid, but you might be missing out on, say, like the effects of DHA on the brain.

Kristina:  Yeah. And we also see when people have tested taking just pure DHA versus pure EPA, when people took pure DHA, both EPA and DHA went up in red blood cells. So, there was some kind of biological happenings where both were increasing. When you took just EPA, it decreased DHA levels, increased EPA, but decreased DHA a little bit. We're not totally sure why, but we do see that you do get a little bit lower increases in the omega-3 index, the measure of EPA and DHA in red blood cells. That's what we focus on a pure EPA product.

Ben:  So, that all being said, before we talk about omega-3, omega-6 fatty acid ratios, is there like a studied exact ratio of EPA to DHA that is considered widely to be the ideal ratio?

William:  I'd say no.

Ben:  Okay.

William:  Like Tina kind of alluded to, or maybe she did, DHA really is the predominant omega-3 in membranes, not just the brain, everywhere. EPA is always much smaller. And in the red cell, it's roughly 85%–if you look at the two, 85% to 15%, something like that. I mean, way more DHA than EPA.

Ben:  Well, fish oil in general, if you look at the actual supplement industry, it tends to widely vary in the ratio of EPA to DHA. If you guys were going to take a fish oil, what would you look for in terms of actual ratios of DHA to EPA in a fish oil?

Kristina:  I don't look at the ratios. I just look at total dose. EPA plus DHA, what's that total dose that's getting me? That's the most important thing we've seen that affects–how much gets in your body is how much you're taking. And so, that's my main focus.

Ben:  What do you look for in dose?

Kristina:  That depends on your blood level, as it turns out. So, if you're very low, you would need a higher dose. So, we wrote a paper a couple years ago. We put together, I think it was 14 studies where we had done the blood work at OmegaQuant to measure fatty acid levels. These were studies done where it was controlled, individuals taking a known amount of omega-3s. We compiled all those studies together to see like how can we predict how much omega-3 it takes to increase the omega-3 index? And so, we were able to make an equation to say this dose should equal this increase in the omega-3 index, but the baseline omega-3 index is very important. So, where you're starting affects how much omega-3s you need to get to a desirable level. So, for the omega-3 index, which again is the EPA and DHA content of a red blood cell membrane, it's those two over the total number of fatty acids so we get a percentage. The desirable range that we've set is having an omega-3 index of 8% to about 12%.

Ben:  Okay.

Kristina:  And so, we have calculations to show how much EPA and DHA do you need to take in your diet, eat in your diet, take as a supplement to get to an omega-3 index of eight.

Ben:  Interesting. So, what one could do then is they could test. And from what I understand, the OmegaQuant test, the one that you just referred to for omega-3 index testing is just like that's an order to your home blood spot test. So, it's like a few drops of blood. You would send that off. And if your levels were below 8% on your index, that would indicate you would need to consume a higher amount of EPA and DHA for a certain number of days, and then retest?

Kristina:  Correct, yeah. So, I would recommend testing, and then you'd be able to use a–we have a calculator online. You could put in what level you were. So, you got your 4% omega-3 index. You wanted to get to eight. The calculator from the paper would say, if you're taking–oh, here comes another fun distinction about supplements. If you want to take an ethyl ester supplement, then you would need about 2.2 grams of that a day to get to 8%. If you're taking a triglyceride based supplement, it would be about 1.5 grams a day. There's a difference in bioavailability there.

Ben:  Okay. So, if I had an index of 4% and I want to get myself up to more ideal 8%, and I'll have you differentiate in just a second here, the difference between the ethyl ester and triglyceride. And we're taking like a fish oil that was in triglyceride form. I would just need to take like a thousand milligrams a day to get to that target index within how many or how many weeks.

Kristina:  This is like an HbA1c. It's like a three-month amount of time. So, I would say especially when you're just ramping up and trying to figure out what kind of supplement works for you, testing, trying a supplement, being really consistent with it for three months, and then retesting, we'll give you a really good idea if it's working for you, and if you need to increase your dose because that's kind of an average dose. So, half the people might need more and half might need less. Also, if you eat a lot of fish in your diet, you don't need to supplement as much. So, you might be fine just on your diet. If you are a pescatarian or you eat fish several times a week, you could be at 8% without supplementation, and that's great. Then you know it and you don't need to supplement beyond that if you don't want to.

Ben:  Okay. Got it. I have so many questions and what I want to ask is how genes or your particular type might influence that omega-3 index response to dietary changes. But before I ask you about if there's any kind of genetic variation here, you mentioned ethyl ester versus triglyceride referring to the fact that you would actually need more of a fish oil if you're taking the ethyl ester form versus the triglyceride form. So, what is the ethyl ester versus the triglyceride form, and why would that be the case?

Kristina:  This has really become clear to us as of late. So, there are just different ways that the omega-3s are processed and then concentrated into the fish oil capsules. And so, the ethyl ester omega-3 form was the first really highly concentrated capsule. That's how they're able to get so much EPA and DHA in that capsule. And then, the triglyceride form came later where the triglyceride form is what's a “more natural” form. That and phospholipids are how it would be present in a fish, not ethyl ester. But with triglycerides, there's three fatty acids on that. Typically, they're only one of those that would be EPA and DHA, and then they were able to make two of those EPA and DHA. So, they're able to more highly concentrate in a triglyceride formulation later on.

So, the ethyl ester is, I would say, most of the supplements in the U.S. that are fairly highly concentrated. And it doesn't say triglyceride based on there are probably ethyl esters. That's what I would assume. There are other supplements that will advertise the fact that they are triglyceride-based. And so, that's how you would know there really isn't a standardized way that it's reported if it's ethyl ester or triglyceride, which is unfortunate because it does make a difference. And the biggest difference that it makes as far as bioavailability goes is I think it's coming from an issue of whether or not people are taking their supplements with a meal. We see with ethyl esters, if you take it without a meal, they might not be absorbed at all. But if you take it with a meal, they're absorbed well. So, unless you're very consistent about that, that could be where some of this bioavailability difference comes from. Triglycerides don't seem to be as affected by that meal component as the ethyl esters.

Ben:  Interesting. I always really insist my fish oil is in triglyceride form, but then I also take it with a meal. But it sounds like what you're saying is if I'm getting my fish oil in triglyceride form, it's less important that it'd be taken with a meal. But if I am consuming the ethyl ester, just because perhaps that's just the brand that I happen to have, then I definitely, to increase bioavailability, need to take that with a meal preferably from what I understand a meal that contains fats.

Kristina:  Correct.

Ben:  Okay.

William:  All the pharmaceutical brand omega-3s like Lovaza, Vascepa, and some of the generics are all ethyl esters.

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Ben:  That's kind of odd. Why would the pharmaceutical companies not go with triglyceride if the bioavailability is higher?

William:  Well, because you can get more EPA and DHA molecules in a 1-gram capsule if they're ethyl ester forms than if they're triglyceride.

Ben:  But it's not as well-absorbed.

William:  Well, that wasn't the problem originally and nobody really realized that at the time.

Ben:  Alright, gotcha.

William:  And when they were first developed, people were told to take them with food and it really wasn't the problem. And the studies that were done in the '90s and early 2000s with like Lovaza, which was called Omacor at the time, were successful. They reduced risk for cardiovascular events. So, why question anything? And so, the whole distinction didn't really come up until maybe 10, 15 years ago when people started comparing ethyl ester forms to other forms of fatty acids. And seeing that taken on an empty stomach, the ethyl esters are not well-absorbed.

Ben:  Okay.

Kristina:  Yeah. For an individual, if you yourself are doing this and you're taking a supplement, and you test and re-test, and you've been taking an ethyl ester supplement not with food, you might see no change on your index. I have seen that.

Ben:  Wow!

Kristina:  Recently. So, that's why it's an expectation also for people that you could be taking something every day of your life, but not absorbing it. So, that's part of the reason to test is to know like, is this worth my money? Am I doing this right?

Ben:  Right. You don't want to create the so-called expensive P scenario. The other consideration here related to this calculator that you're referring to that if you're taking a fish oil and you want to see if your omega index is improving, and it's not might be influenced by your genetics. And that's something that I've looked into a little bit, these genes that can allow for–well, I know there's some genes that just simply based on someone coming from an ancestor that might have been more of a plant-based or seed and nut-consuming ancestry, they actually do appear to have some ALA converting genes that allow for slightly higher amounts of ALA to be converted into DHA and EPA. I think those are the FADS genes. It's still a pretty low amount of conversion that occurs, but some people can convert a little bit more to DHA and EPA based on those genes. But are there other genes that would influence your ability to be able to harness appreciable amounts of DHA or EPA from an animal-based oil or a fish oil?

William:  Let me jump in on that one because I think we have to think about two things. One is what genetic mutations shall we say, or conditions, affect your omega-3 levels? And that's where you're talking about the FADS genes, which means fatty acid desaturates. So, these are the enzymes in the body, or the genes that produce the enzymes that convert ALA to EPA and DHA. But they also convert linoleic acid to arachidonic acid, the longer chain. And yes, variations, natural variations by populations in the kinds of mutations that are present in the FADS genes can affect levels, particularly of arachidonic acid.

The omega-3s, EPA and DHA, are not much affected by mutations in the FADS genes, which we don't really understand why, but it explains very little of the difference between people. And we don't really know of any major genetic effect driving levels of omega-3 in a population, but the other question you've asked is, is there a genetic effect on the absorption of omega-3, or on the incorporation? Or might some people, when they take fish oil, get a big rise in their blood levels, and other people not get a big rise at all. And that's a different genetic question because now we're not talking about making the omega-3s like the FADS do, we're talking about what do you do with them coming pre-formed. You don't need to make them. You're eating them. Why is there a variability in response? And that's a completely unknown area at this point. Nobody has really studied carefully. You look at a population and find people that take 1-gram of omega-3 and their omega-3 index goes from 4 to 10. And other people take 1-gram omega-3 and their omega-3 index goes from four to five. What's different about those people? Nobody's really asked that question, what makes one guy have a huge response to it and the other hardly any? But there's something there and it's probably genetic. We don't know what it is at this point.

Ben:  Okay. But at this point, we do know that we have that OmegaQuant test, we've got a calculator, we've got access to things like fish oil or other forms of omega-3 fatty acids. So, pretty much anybody at a pretty low cost could just use themselves as a test case and see if what they're doing is working when it comes to increasing their omega-3 index, which is really what's most important here.

William:  Exactly.

Ben:  Okay. Alright, cool. So, we tackled DHA and EPA ratios. We established that this omega index, when it comes to omega-3 to omega-6 ratios, is essentially going to ideally be around 8% to 12%. And that is, correct me if I'm wrong, reflective of your omega-3, omega-6 balance?

William:  No.

Ben:  Okay. That's not. That's not testing your omega-3, omega-6 ratios?

William:  Right. So, we'll be talking about 8% to 12%. We're talking about EPA plus DHA.

Ben:  Okay. Gotcha.

William:  It's 8% of the total fatty acids.

Ben:  Okay. Now, what about the omega-3 to omega-6 ratios?

William:  That's a different question, right. Let me just back up for a second because I've run into people that don't understand why they're even called omega. Why aren't they called beta? Why aren't they called alpha? Where did omega come from? Do you know, Ben? Maybe you can tell your audience.

Ben:  I probably am not going to do as good a job describing it as you. I mean, I believe it's related to the fact that it's the location of the actual bond based on the–I think what's omega, like the 24^th letter of the Greek alphabet, something like that. So, it's the location on the actual carbon chain, correct?

William:  That's right. You got it. So, the first carbon in a fatty acid is called the alpha carbon, the first one. And that's the first letter of the Greek alphabet. And omega is the last letter of the Greek alphabet. So, the last carbon, whatever it is, whether it's a 10, or 12, or 15, or 18 carbons long, is called the omega carbon. And omega-3 fatty acid is a fatty acid where the first double bond counting from the omega carbon is in the third position. And omega-6 is simply a fatty acid where the first double bond counting from the omega is in the sixth position, and those are the two families of omega-3s. And we can't inter-convert those. Plants can actually take an omega-6 and put an omega-3, put a bond in to make it an omega-3 fatty acid, but animals can't do that. So, we have to eat both the omega-6 and omega-3 versions in order to have them.

Ben:  Right. So, in omega-3, if we were to count back three carbons in terms of the double bond location, if we were to count back three carbons from the end of a carbon chain and find the actual double bond located there, that would be an omega-3 fatty acid?

William:  Correct. Minus three. It's kind of what that dash means is minus three. So, it's three positions in. Exactly. That's right. And sometimes it's also called n−3 fatty acids, like the letter “n” because in chemistry, we always talk about a fatty acid being n carbons long, whether it's again 12, 15, 18. It's n carbons and you go to the nth carbon. You know the expression that's the nth?

Ben:  Mm-hmm.

William:  And count back three. So, that's the same thing as an omega. And some people don't understand that, and that's not critical. So, let's now jump into the omega-6. We can talk a long time about omega-6 and omega-3 ratios. I, for one, have not been a fan of that way of looking at the omega world, and for several reasons. Number one, when people talk about what's the omega-6 and omega-3 ratio, they don't explain which omega-3 and which omega-6 fatty acids are talking about.

Ben:  Right. And what you're saying is based on the nomenclature you've just established, we've got like alpha-linoleic acid, which would be like an 18:3 or EPA, I think that what's at, like a 25, and then DHA would be like a 22:6. So, there's all sorts of different locations of the actual double bond on this large variety of omega-3 fatty acids. And we're talking about omega-3 to omega-6 ratios. What you're saying is it's not clear which omega-3 is being referred to?

William:  Right, right. They're all mixed up. You can't tell. In omega-6, there's like seven omega-6 fatty acids in the blood. So, which ones do you mean when you say that ratio? And it also presumes that like ALA and EPA and DHA have the same biologic activity. They're the same value and they're not, and that's true in the omega-6 side, too. So, it's just a very imprecise way of talking, and you don't really know what people are talking about when they say, “I want omega-6, omega-3 ratio at 10.

Ben:  Well, it was always my impression that when we're talking about omega-6 to omega-3 fatty acid ratios–and a lot of people will say, “Well, a typical Western diet context, you're going to see like 10 to 1 all the way up to 50 to 1 omega 6 to omega 3.” I mean, dramatically higher levels of omega-6 sadly often derived from like industrial seed oils that it was just reflecting the total amount of omega-6s and the total amount of omega-3s regardless of the actual nomenclature from a numerical standpoint of what type of omega-6 and type of omega-3 it is. I just assumed they were throwing them all in the bucket and saying, “Here's how many omega-6s you have and here's how many omega-3s you have from a ratio standpoint.”

William:  And then, they do, and that's very confusing because it doesn't really tell you anything about the health status because some of those fatty acids are good for you and some of them are not, which ones are in your ratio. And the other problem with the ratio is you can have very high levels of omega-6 and omega-3 in your blood or in your diet, or you can have very low levels of omega-6 to omega-3, and you have the same ratio.

Ben:  Yeah. That's a good point. Or you could have like a really favorable ratio. Let's say your ratio is 1 to 1, but the omega-3s that were making that ratio favorable could be primarily, say, like alpha-linoleic acid or ALA rather than large amounts of EPA and DHA.

William:  You got it. Right.

Ben:  Interesting.

William:  Right. And I think a fourth point that I like to make about that ratio is it presumes that all the omega-6s are bad, and all the omega-3s are good. It's kind of a white hat, black hat thing. And that is just not true. It's just not been held up. We've seen several studies. We were part of some of them. I think everybody's pretty happy with the omega-3s being good. That's not questionable. What's questionable is the goodness or badness of the omega-6. And primarily, we're talking about linoleic acid, which is the fundamental one in our diet, the true essential omega-6 fatty acid. We can't make it.

We've seen some very big, large trials that have looked at blood levels of linoleic acid in tens of thousands of people, and then followed those people for several years to look for the development of cardiovascular disease or diabetes. And in both situations, higher levels of linoleic acid in the blood always predict lower incidence of heart disease and diabetes, which fundamentally means, and if you look at the other way, having a lower level of omega-6 linoleic in your blood is associated with increased risk for cardiovascular disease and diabetes going down. So, the omega-6s aren't necessarily bad. And so, to make a ratio of something that maybe is good versus something else that's good, why have a ratio of good to good? What's the point of that? So, to me, why we like the omega-3 index, which just focuses on EPA and DHA, is that those are the fatty acids that are missing in our diet. We've got plenty of omega-6. Don't worry about omega-6. Worry about getting enough EPA and DHA. So, that's why we focus on it.

Ben:  Yeah. From my understanding, and you're correct, the omega-6 to omega-3 ratio is a little foggy in terms of actually defining which omega-6s and which omega-3s, but I do know that we know based on research, and correct me if I'm wrong, that chronic excessive production of omega-6 eicosanoids that is correlated with arthritis and inflammation and cancer, the linoleic acid that you just referred to might be less problematic. But we know eicosanoids could be problematic, and I think we also know beyond a shadow of a doubt that a high consumption of oxidized PUFAs, which are going to primarily be found in vegetable oil, which are higher in omega-6s, is problematic for a variety of chronic disease conditions. And so, you could at least say, “Well, limit your intake of oxidized or rancid PUFAs in general and particularly limit your intake of industrial seed oils or vegetable oils and you're probably at least going to, no matter what the omega-6 to omega-3 ratio is, ensure that you have a lower level of the problematic omega-6s.”

William:  Yeah. So, the omega-6 that gives rise to the eicosanoids that you're talking about in the inflammatory pathway, that's primarily arachidonic acid, which is now a synthetic product of linoleic acid. The thing is when people have asked the question, “How much can I affect my tissue levels of arachidonic acid by changing my linoleic acid intake?” And you would think, “Oh, well, it ought to be 1 to 1.” Right? The more linoleic you eat, the higher your arachidonic ought to be. And if you eat less linoleic, then you should have less arachidonic. The trouble is that's just not what the science or what the experiments show because arachidonic acid is so important. The synthesis of it is very regulated so that tissue levels may remain pretty much the same regardless of how much linoleic you're eating. I mean, to a point, obviously stop eating it completely, you're going to run out eventually.

But within the range of most experimental studies when they've added more linoleic acid to the diet and then measured the effect on blood levels of arachidonic, or if they've taken a linoleic out of the diet and measured the effect on arachidonic, they find that there's neither one of those strategies changes the arachidonic acid level. It's just flat. And so, you really can't do much to change how much arachidonic is circulating in your blood presuming that arachidonic gives rise only to adverse molecules, bad pro-inflammatory–that's not true either, but that's the assumption. But changing your linoleic acid intake isn't going to change that very much. So, it's a different question you're talking about oxidized oils. Yeah. People shouldn't be eating oxidized oils. I think it's debatable whether the standard vegetable oil that's on the shelf is really an oxidized oil. I would probably take some exception to that, or I would say there are other things in life to worry about worse than that.

Ben:  Really? You don't think like processed or oxidized industrial seed oils are a major contributor to chronic disease risk factors?

William:  No.

Ben:  Really? That's interesting because a lot of people in the health sector believe that they are.

William:  I know. I'd like to see the evidence. That's all. And not just looking at a metabolic chart. I'd like to really see the clinical–

Ben:  So, you would be okay with like cooking with canola oil or potentially consuming a high amount of other vegetable-based oils?

William:  Generally speaking, yeah. I mean, again, what we're seeing is if you have higher levels of linoleic in your blood, that means you are eating more linoleic, which comes from vegetable oils. I mean, that's far and away the primary source. The only way to get higher levels of linoleic in your blood is to eat more. You can't make it. And if the data from these large worldwide epidemiologic studies looking at blood levels of linoleic and how they associate with important–not every disease has been studied. I'm just talking about cardiovascular disease and diabetes. So, some of the big ones, but it's not Alzheimer's disease, it's not arthritis. Those haven't really been looked at in the same context. What's the relationship between blood levels and incidents of rheumatoid arthritis? That's a good question. But for heart disease and diabetes, the evidence to me says higher levels of linoleic are good for your heart and good for your metabolism because less people develop diseases if they have higher omega-6 levels. So, that speaks to me, yeah.

Ben:  I guess what we might be leaving out of the equation here though is, let's say canola oil, for example, we know that that's one of the crops that has been developed to be roundup ready or bioengineered to survive glyphosate. And so, there's extremely high levels of glyphosate in some of these oils. The hexane solvent extraction required to make them results in even more oxidation. We know they have a certain amount of trans fat content, specifically like the canola and the soybean oil. So, maybe linoleic acid considerations aside, there are other potential toxins being consumed with canola oil that I would think would still make it problematic.

William:  Could be. And we're getting out of my area of expertise.

Ben:  I mean, I'm personally very careful with my consumption of industrial seed and nut-based oils and vegetable oils.

William:  Yeah, yeah. And that's cool. I don't have a problem with it. It's the across the board vilification of omega-6 that bothers me.

Ben:  I got you. Okay.

Kristina:  And one other thing on ratios is the best way to decrease your ratio is to increase the omega-3 side. It just moves a lot faster, and it's a lot easier, and that's the one we know is a good thing to have higher levels. And another thing is when you do increase your blood levels of EPA and DHA, to some extent, arachidonic acid is replaced by EPA.

Ben:  Yeah. That's a good point.

Kristina:  So, that actually not only get more of the omega-3s, but it does replace arachidonic and the membrane. We almost always see when you shift and you have more long-chain omega-3s in your membrane, the long-chain omega-6s go down a little bit. That's where the proportion is corrected.

Ben:  Yeah. Suggesting that in a Western diet context, the consumption of omega-3 fatty acids becomes even more important, arguably, just based on the amount of linoleic acid that we might be consuming, or industrial seed oils. Now, I had mentioned briefly about some of the potential issues with contaminants in something like canola oil, but I believe there are also concerns regarding fish oil that are similar, cleanliness, sourcing, et cetera. Do you guys look into that at all in terms of fish oil manufacturers and the type of fish, the waters from which the fish are being harvested, the cleanliness, the packaging, the shipping? What kind of things do people need to be taking into consideration when it comes to not all fish oil being created equal?

William:  First of all, in the actual processing of fish oils, there's like 10 different steps they use to clean stuff up, to remove this, to remove that, to stabilize this and that. The stuff is stinky. You got to work pretty hard to make it palatable for humans, like we're talking about PCBs, dioxins, things like that. Those are very much now had been removed by improved processing of oils. There's a famous study that came out of New Zealand saying though X number of–a big percentage of the fish oil brands are oxidized and don't contain the EPA and DHA content. Then, two or three other studies are done with many more samples using different laboratories and saying, “No, that's not true at all.” Most of them meeting the national or the GOED, Global Organization for EPA, DHA, meeting their standards for oxidation and for EPA and DHA content. And so, what gets the press, it gets the news, is when we're being screwed because these fish oils are all crap. What doesn't get the news is when those things are re-examined and shown to be untrue, you don't hear about it.

Ben:  Yeah. But, I mean, like I saw one study–I think I might have sent it over to you guys about children's daily exposure to these polychlorinated biphenyls, these problematic PCBs, these contaminants. I think they looked at like 13 different over-the-counter kids, dietary supplements had fish oils, and then they looked at PCB exposure and every single one had a concerningly high level of PCBs suggesting–and I think that was like a 2013, 2014 study. Maybe things have changed in the past five or six years, but at least gives me concern regarding that. And also, I'm not sure how many of the metals in some of these compounds are also present or removed in the processing, but I've seen enough to at least make me concerned.

William:  Yeah, yeah. Metals shouldn't be because fundamentally, metals go with the water and the oils don't dissolve metals. So, that's usually not a problem. I don't remember seeing a paper from you. I'd like to see that. I may dismiss it to see the–

Ben:  Yeah. Well, the title of the study was “Children's Daily Exposure to PCBs from Dietary Supplements Containing Fish Oil.” It was a 2013 study where they analyzed I think a little over a dozen different over-the-counter children supplements. And they did find it to be pretty high.

William:  So this is 2013 PCBs. Okay. Yeah. I need to look at that because I'm–you don't remember the first author by any chance, do you?

Ben:  It was Ashley, Jeffrey Ashley.

Kristina:  I have [01:02:49] _____ and it says the main daily exposure values range from 2.5 to 50.3 nanograms of PCBs per day, and I'm not sure what the recommended–what the toxicity level for PCBs is. With like mercury and fish, the levels set for toxicity are extremely conservative. And so, hitting those toxicity levels, there is–

Ben:  Well, that's why fish oil is actually safer than eating fish when it comes to mercury exposure just because you are removing a lot of the metals during the oil isolation process, but I think there is a–what is the International Fish Oil Standards rating? That's the one that looks at the actual amount of mercury in a fish oil.

William:  Yeah. IFOS, right.

Ben:  Yeah. I think IFOS certified is a good bet. And usually, if the fish is coming from like a so-called smash source like sardines or anchovies, mackerel, herring, some of the smaller down the chain fish versus like swordfish, or shark, or mackerel, or like a king mackerel, or something like that, there's less concern about mercury. But I think that the actual type of fish, the waters it was in, and how high up it is in the food chain can still affect slightly the mercury content and the fish oil, from what I understand.

William:  Right. Again, mercury and fish oil is not a problem in my view. What can be is as you said, these lipid-soluble products, like PCBs, dioxins, things like that. Now, those do travel with the lipids. So, that can be a problem. And there was a big hullabaloo 10, 15 years ago about farm salmon having very high levels. Mostly, these were from Scotland and the Baltic sea. But they got a tremendous amount of press, and then the industry has cleaned up a lot, cleaned up the food that they've been feeding these salmon, and now the levels are much, much lower.

Ben:  Right. But it does make a good point. I mean, if you are concerned, you're almost better off optimizing your omega fatty acid status and you're getting your DHA and EPA from fish oil versus fish if you really can't get clean fish.

William:  Well, true. Exactly. Right.

Ben:  Okay. So, we've covered a lot here so far and I want to be respectful of your guys' time, but I do have just a couple other questions I want to throw at you if you have just a bit of time left.

William:  No. Take it.

Ben:  The first is you'll find this concern about the packaging shelf life heat exposed to the fish oil during the supplementation or manufacturing process. And so, as a result of that, you'll see antioxidants added to a lot of fish oil supplements. What's your guys' take on that in terms of like preserving the fish oil somehow from rancidity or oxidation using certain additions like–vitamin E is one popular one, astaxanthin is another. I mean, do you guys look into that at all?

William:  We don't really spend a lot of time looking at fish oils per se. We're more looking at blood of humans, but yeah. That makes a lot of sense to add an antioxidant. I know the processing is they try to be very careful and always to exclude oxygen from contacting the oil. So, they use either argon or nitrogen, a neutral inert gas always to cover the omega-3, the fish oils. And when they encapsulate them, they also do it in a nitrogen blanketed environment. And once they're in the capsule, they're really impervious to oxygen. It just can't get there. We used to look at supplements many years ago that we had received for a study, and that we did in 1990, and we found the box when we cleaned the lab out in 2000, and we said, “Well, I wonder how the fish oil looks.” And we'd analyze the capsule again. It was exactly the same omega-3 content as it was before. So, I felt pretty good about that.

Ben:  I wonder if that would indicate that if–and I don't know if you have any thoughts on this. A lot of companies would like bottled or liquid fish oils versus encapsulated fish oils. It sounds to me like what you're saying, like an encapsulation would possibly be a little bit more protective versus shipping the fish oil in like a liquid bottle.

Kristina:  I've been using a liquid and I love it. I don't know if there's a real difference oxidation-wise between liquid and capsule. Again, we don't really think that's that big of an issue. It doesn't appear to be in the literature we've seen. So, for me, I mean, I've personally been taking a liquid fish oil for three months now and it's raised my levels more than anything else has. So, it's working.

Ben:  Yeah.

Kristina:  I mean, it's a high quality supplement.

William:  Well, the industry has food scientists who've been working on different ways to protect the integrity of fish oils now for 30, 40 years, and they're getting better all the time at it. And so, you can have these liquid oils that don't go rancid. If you keep them in the fridge, they don't go rancid. But the thing I think people need to realize is you can have an oil that smells pretty bad, that's “gone rancid.” And the omega-3 content is not going to have changed at all, the actual measurable amount of EPA and DHA because it's not really so much those fatty acids that are being broken down. Maybe a few of them are, but the molecules that get made from some of the other components that do break down are extremely potent in odor, and it takes six molecules. It's all you got to have to be able to smell crappy fish.

Ben:  Yeah.

William:  A very little amount can make a big difference in the smell, but the actual amount of EPA and DHA per capsule really hasn't changed, but you wouldn't want to take it because it tastes bad. Now, it smells bad, therefore, all the omega-3s are gone. It's just not. That's not the case.

Ben:  Right.

William:  It's a small point perhaps, but I think the liquid oils that people are coming out with, you certainly can get bigger doses of omega-3 very easily. And if you keep it in the fridge and you don't let it sit there for three months–

Ben:  Yeah. I was going to say if anything, it would be the peroxidation we were referring to earlier that you may want to be aware of with that heating, which could cause some amount of lipid damage. And when I look at the food science industry, there are certain things. Probably astaxanthin in terms of natural preservatives is the one I see most often studied right now as a way to limit rancidity or oxidation in fish oil. And you'll see a lot of manufacturers adding that now. Some are still using like tocopherols or synthetic vitamin E as another one. Others will use rosemary as another one.

William:  Rosemary, yeah. There's a rosemary extract that's–whoever fits that out, I don't know.

Ben:  I think of the two I've seen, I've been most impressed with astaxanthin and with rosemary extract as a potential way to at least ensure that should the fish oil get exposed to heat or light, et cetera. It's a little bit more safe. So, I think it is important consideration that I personally don't get much of a fishy smell or a fishy taste from those type of compounds.

Kristina:  It's hard to know what's in your supplement, unfortunately. I mean, you look at the back panel, you can see the dosage, you can see what's packaged with it, if it has rosemary extract. It's just the only way you really know if it's working is testing frequently so that you get to a product that you trust and you know it was working for you. And that's what's hard with the supplement industry is because it's not regulated that well, I mean it's not officially regulated, there are things that have to be reported. That is where testing allows you to figure out what works for you and what is actually getting into your body. And that can be different for different people, but there's not a whole lot else that an individual can do except for look for certifications, and look for information, and look for companies that do things the way you think that it should be done.

There's so much information and there's so much scary news out there about fish oil, what's potentially in it, and if it's oxidized, and it's almost paralyzing to me because it's hard to know like where do you go for information on this. And so, that's where for me, I really appreciate the testing is because I can see for myself, and also feel for myself what's happening if I get my levels up, what does it take for me on this product versus this product. And then, that to me is the ultimate point of taking the fish oil is to get it in your body.

Ben:  Yeah, yeah. And I think probably that was one of my biggest takeaways from our discussion today is that–and I wasn't aware that you can test that easily or frequently until I looked into this OmegaQuant deal. And so, really, I think this idea of testing, consuming a good fish oil, and then retesting on a regular basis until your index is good, and then maintaining levels once your index is 8% to 12% will at least give you the peace of mind that you're getting the most important thing, which is essentially, from what I understand based on our discussion today, elevated levels of DHA and EPA so that your omega index percentage is high. And if you're just going to do like one thing based on everything you've learned, it would be to do that and then to consume something like a fish oil or a clean fish on a regular basis to be able to get it up to that percentage. And after a series of tests, then you'd be able to pretty much know that you're at that 8% to 12%. By the way, what's the test cost? I'm just curious how prohibitively expensive this might be.

William:  It's outrageous.

Kristina:  It's wild. The omega-3 index kit, the basic kit where you get your omega-3 index is $50. We do an analysis of the omega-3 index. You can get omega-3, omega-6 ratios, trans fat index, that is 75, I think, the omega-3 index plus kit. And then, we have the complete kit where you get those, plus we just give you every fatty acid that we measure. We measure 24 fatty acids every time we assess omega-3 index status, and we'll give you the individual values of those as percentages. And then, you can nerd out on that because it's a lot of information, and you can see your linoleic acid level, and you can see your arachidonic level, and you can see your individual EPA and DHA levels, and you can really dig into it. But we think by far and away, the omega-3 index is the main number to look at, and that's the main one that's going to be changing.

And so, that test is great, and that's what if you are going to test frequently to ramp up your numbers, then you can do it more frequently with the cheaper test. And then, every once a year, do a complete, if you want to just check out your other fatty acids. But I would recommend as fast as your levels can go up, and you can get them up pretty quickly within three or four months. Depending on how much omega-3 you're taking, you can easily get it up into the 8 to 12 range from wherever you are in three or four months. You don't want to test really any more frequently than that, but you might want to test over your first year maybe, like every three months, and see, what is this dose doing? Do I need to increase my dose? Have I plateaued? Am I going too high? Do I want to bring it back down? Not that we think being above 12% omega-3 index, we don't have evidence that that is actually harmful, it just appears that most of the benefit that's achieved with high omega-3 levels are within 8% to 12%. It's kind of a goldilocks spot for us. So, you just don't need to push it up there, but if you want to be up there, go for it.

William:  How much that test costs?

Kristina:  A hundred. Sorry, the complete is 100. Basic, just the omega-3 index is 50.

Ben:  Okay.

Kristina:  And the middle one is like 75.

Ben:  Okay. Cool. And then, I notice you guys do a vitamin D test, too, which is actually kind of cool because I think we could say all the same things about vitamin D, best way to know vitamin D status. And I've recently had a really great discussion with Dr. Mercola about this, although I don't think that podcast comes out until after this one comes out basically rather than just taking vitamin D willy-nilly at 2,000 or 4,000 or 8,000 IU a day. Recommendations vary. It's pretty easy to just do a blood test supplement and then ensure that your levels are between about 40 to 80. And it looks like you guys do a vitamin D panel as well, which means if you want to kill two birds with one stone, you could just do the vitamin D and the omega. And from a self-quantification standpoint, two easy ways to know that you're not just making expensive P, as alluded to earlier.

So, what I'll do is I'll link to the OmegaQuants test in the shownotes. I'll link to resources, studies, everything else that we discussed along with your guys' research websites, if folks go to BenGreenfieldFitness.com/fishoilpodcast. That's BenGreenfieldFitness.com/fishoilpodcast. And in the meantime, you guys, thanks for coming on. This has been really fascinating, and I think we'll–well, it's going to answer a lot of questions, might generate a lot of questions. But again, you guys can go to the shownotes if you have your own questions, or comments, or feedback to add. But I really appreciate you coming on, Kristina and Bill, or I should say Tina, as your father calls you, and Bill.

Kristina:  Either way.

Ben:  Dr. Harris and Dr. Jackson.

William:  When she was a kid, yeah. Harris and Jackson, that works just fine.

Kristina:  Yes.

Ben:  Alright, cool. Well, thanks for joining me, guys. I really appreciate it.

William:  You have great questions, Ben. You're very well read on this, understandably so.

Ben:  Awesome.

William:  Thank you.

Ben:  Awesome. Thank you. Alright, folks. Well, until next time. I'm Ben Greenfield along with Dr. William S. Harris and Dr. Kristina Harris-Jackson signing out from BenGreenfieldFitness.com. Have an amazing week.

Well, thanks for listening to today's show. You can grab all the shownotes, the resources, pretty much everything that I mentioned over at BenGreenfieldFitness.com, along with plenty of other goodies from me, including the highly helpful “Ben Recommends” page, which is a list of pretty much everything that I've ever recommended for hormone, sleep, digestion, fat loss, performance, and plenty more. Please, also, know that all the links, all the promo codes, that I mentioned during this and every episode, helped to make this podcast happen and to generate income that enables me to keep bringing you this content every single week. When you listen in, be sure to use the links in the shownotes, use the promo codes that I generate, because that helps to float this thing and keep it coming to you each and every week.

 

 

After publishing my recent giant fish oil article, “A Deep “Dive” Into The Fascinating World Of Fish Oil, The Right Fat Ratios In Your Diet, Plant Vs. Animal Based Oils & The Exact Fish Oil Ben Greenfield Uses Every Day,” discussing fish oil and omega 3:omega 6 fatty acid balance in this recent podcast, and even launching a brand new fish oil called Kion Omega, I've been getting plenty of questions about fish oil, including:

• Based on human clinical research, what are the actual proven benefits of fish oil?
• What kind of dosages/types of fish oil were used in studies?
• Are there concerns about rancidity/oxidation when taking fish oil?
• What EPA/DHA ratio is ideal?
• Are there people who shouldn't take fish oil?
• Are there certain nutrients or supplements that should be taken with fish oil?
• How can one test their omega fatty acid status?
• And many more.

So, I finally decided to get a couple of true, unbiased fish oil experts on my show.

Dr. William S. Harris, an internationally recognized expert on omega-3 fatty acids and how they can benefit patients with heart disease is my first guest. He obtained his Ph.D. in human nutrition from the University of Minnesota and did post-doctoral fellowships in clinical nutrition and lipid metabolism at the Oregon Health Sciences University.

Dr. Harris' interest in omega-3 fatty acids began with his postdoctoral work when he published his first study on the effects of salmon oil on serum lipids in humans. Since that time, he has been the recipient of five NIH grants for studies on the effects of omega-3 fatty acids (EPA and DHA) on human health. He has more than 300 publications relating to fatty acids (including omega-3s) in medical literature and was an author on two American Heart Association scientific statements on fatty acids:

• Fish Consumption, Fish Oil, Omega-3 Fatty Acids and Cardiovascular Disease
• Omega-6 Fatty Acids and Risk for Cardiovascular Disease

Dr. Harris is a professor in the Department of Medicine in the Sanford School of Medicine at the University of South Dakota and the president and CEO of OmegaQuant.

Dr. Harris' daughter, Dr. Kristina Harris Jackson, Ph.D., RD is my second guest. Dr. Jackson received her Ph.D. in nutritional sciences from Pennsylvania State University in 2013 and completed her training to become a Registered Dietitian in 2014. As a graduate student, she studied under Dr. Penny Kris-Etherton, an internationally-recognized expert in fats and nutrition. She worked as a postdoctoral fellow at the University of Colorado, Denver under Dr. John Peters in the area of worksite wellness before returning to the omega-3 field.

Dr. Jackson joined the family business, OmegaQuant Analytics, as a research associate in 2014, with a particular focus on omega-3s in maternal health, helping create the Prenatal DHA test and the Mother’s Milk DHA test. In 2020, she became assistant professor in the Department of Internal Medicine at the University of South Dakota Sanford School of Medicine. She lives in Sioux Falls, South Dakota with her husband, two kids, one old dog, and four grandparents.

During this discussion, you'll discover:

-The 2 sources of omega-3 fatty acids…8:35

1. Plant-derived fatty acid alpha-linolenic acid (ALA), 18 carbons; an acid in the omega-3 family – not the same thing as the fish-derived omega-3
2. Fish derived eicosapentaenoic acid (EPA), 20 carbons and docosahexaenoic acid (DHA), 22 carbons

• Cannot get much of the good stuff from ALA (seeds and nuts)
• Algal oil from microalgae (single-cell organism, not kelp) that make EPA/DHA naturally; at the base of the marine food chain
  • Omega-3 fatty acids are made by plants, not fish
• Some companies grow these algae in big ponds, harvest the omega-3 fatty acids, and put in capsules
  • Vegan-derived EPA/DHA products have exactly the same molecules as EPA/DHA derived from fish, but does not come from fish, it comes from algae
  • Process is expensive
• Aquaculture industry is driving the demand for algal oil
  • 70-80% of fish oil produced is fed back to the fish
• Other sources of fish oil are genetically modified land plants
  • Canela seed oil; Australia is at the forefront of putting genes into oil-producing land plants, such as soybeans

-What makes essential fatty acids so essential…15:45

• Cell membranes, made up of fatty acids, surround every cell in the body
  • For structural aspect of the cell
  • Provides starting products for different signaling pathways, affects how cells communicate internally and externally
  • Membrane fluidity; more carbon and double bonds make cell membranes more flexible and fluid
• Cell membranes are comprised of dietary fats
  • The body can’t make the essential omega-6 fatty acids (linoleic) and omega-3 fatty acids (ALA, EPA, and DHA); these come from the diet
  • Trans-fats are also dietary fats
• Other fats, like saturated fats and monounsaturated fats, are affected by metabolism

-Omega-3 fatty acids being oxidized once they enter the body is a misconception…19:36

• Oxidation has different meanings to a biochemist and a food scientist
  • Oxygen molecules are added to the fatty acids by enzymes in order to be activated
  • Lipid peroxidation destroys, produces unwanted by-products; does not happen inside the body because of the different antioxidants that protect against this type of oxidation
• Article: Oxidized fish oil does not influence established markers of oxidative stress in healthy human subjects: a randomised controlled trial 
  • The body has ways of cleaning up things it doesn’t want

-Ratio of omega fatty acids in the body and what the ratios should be…25:32

• Ideal ratio of EPA to DHA is in fish
  • EPA taken alone increases EPA and decreases DHA a little bit; increased omega-3 index – the measure of EPA/DHA in red blood cells (RBC)
  • Pure DHA taken alone increases both EPA and DHA in RBC
  • DHA is the predominant omega-3 fatty acid in membranes
  • 85% DHA to 15% EPA in RBC
  • In fish oil, total dose (EPA+DHA) is the important thing
  • A study found the ideal optimum fatty acid levels (EPA+DHA) to be 8-12% index
• Ratio of omega-6 to omega-3

-Ethyl ester and triglyceride forms of omega-3 fatty acids…33:20

• Different ways omega-3 fatty acids are processed and concentrated
  • Ethyl ester is the first highly concentrated form; first to be concentrated into a capsule
  • Triglyceride form is the more natural form (how it would be present in fish)
• Most fish oil supplements in the U.S., if it does not indicate it is in triglyceride form, is an ethyl ester
• No standardized way to know if it is triglyceride or ethyl ester
• Biggest difference as far as bioavailability goes is if supplements are taken with meals
  • Ethyl esters, if taken without a meal might not be absorbed at all; absorbed well if taken with a meal, preferably a meal that contains fats
  • Triglycerides are not affected as much by that meal component as ethyl esters
• All pharmaceutical brands of fish oil are ethyl esters
  • More EPA and DHA molecules in a 1 gram capsule if in ethyl ester form
• Distinction only came up around 15 years ago when ethyl ester form of fatty acids was seen as not well-absorbed by the body when taken on an empty stomach
  • Taking ethyl ester form supplements without food might not get the desired omega-3 index result

-Which genes convert ALA or plant-based oil into EPA/DHA…45:15

• Genetic conditions that affect omega-3 fatty acid levels
  • FADS genes produce the enzymes that convert ALA to EPA and DHA
  • Enzymes also convert linoleic acid to arachidonic acid (polyunsaturated omega-6 fatty acid)
• Natural variations by populations in the kinds of mutations that are present in the FADS genes can affect levels, particularly of arachidonic acid
• Omega-3 EPA/DHA not much affected by the FADS genes
• Major genetic effect driving omega-3 levels in the population is not known
• Is there a genetic effect on the absorption of omega-3 in the population?
  • No study on why a certain population has a huge absorption response while in another population, there is hardly any response
• Nomenclature:
  • Omega-3 ­– a fatty acid where the 1ˢᵗ double bond counting from the omega carbon is in the third position
  • Omega-6 – a fatty acid where the 1ˢᵗ double bond counting from the omega carbon is in the sixth position
• Cannot be inter-converted
• Plants can convert omega-6s into omega-3s, animals cannot

-Ratio of omega-6 to omega-3 fatty acids…52:17

• “Ratio of omega-6 to omega-3” is imprecise – It’s not clear what type omega-6 or omega-3 is referred to; For example, there are 7 omega-6 fatty acids in the blood
  • It also presumes that ALA and EPA/DHA have the same biologic activity or they have the same value when they do not
  • The same is also true on the omega-6 side
• To say “total omega-6 to total omega-3 ratio” would also be confusing; it does not say what type fatty acids are there; it does not tell anything about their effect on health – some fatty acids are beneficial and some are not
• You can have very high levels of omega-6 and omega-3 in your blood, or you can have very low levels, and yet have the same ratio
• It also presumes that all omega-6s are bad and all omega-3s are good, which is not true
  • Omega-3 fatty acids being good is not questionable
  • What’s questionable is the goodness or badness of omega-6s; linoleic acid is not made in the body and has to be eaten
  • Studies have shown that high levels of linoleic acid in the blood always predict a lower incidence of heart disease and diabetes, and conversely
• Focus on the omega-3 index is that EPA and DHA are what is missing in our diets; there are plenty of omega-6s

-Link between Omega-6 and inflammation and chronic disease…1:00:18

• High consumption of oxidized PUFAs, primarily found in vegetable oils, which are high in omega-6 fatty acids
• Omega-6 fatty acid that gives rise to eicosanoids in the inflammatory pathway is arachidonic acid, a synthetic product of linoleic acid
• Eicosanoids are associated with an increased incidence of inflammation and chronic diseases like arthritis, cancer, etc.
• Synthesis of arachidonic acid is very regulated; tissue levels remain the same regardless of the amount of linoleic acid consumed… to a point (it eventually runs out if linoleic acid consumption is stopped)
• Higher levels of linoleic acid in the blood means you are eating more of it, which comes from vegetable oil; the only way to get high levels in your blood is to eat more
• For heart disease and diabetes, higher levels of linoleic acid are good for the heart and metabolism; fewer people develop these diseases if they have high levels of linoleic acid
• The best way to decrease the ratio is to increase your omega-3 side; by increasing EPA/DHA, EPA replaces, to some extent, the arachidonic acid
  • Having more long-chain omega-3 in the membranes lowers omega-6, correcting the proportion

-Contaminants in fish oil, cleanliness, sourcing; concerns about packaging, shelf life, heat exposure during the manufacturing process…1:06:13

• Article: Children's daily exposure to polychlorinated biphenyls from dietary supplements containing fish oils
• Adding antioxidants makes a lot of sense
• Nitrogen-blanketed environment during encapsulation
• Fish oil “gone rancid” does not necessarily mean the omega-3 fatty acids are gone, it just smells bad; the bad smell is caused by any number of 6 molecules
• The best way to know the fish oil supplements are working for you is by testing
• OmegaQuant Omega-3 Index Test

-And much more!

Resources from this episode:

–OmegaQuant Omega-3 Index Test

–Kion Omega (use code BEN10 to save 10%)

-Articles:

• Oxidised fish oil does not influence established markers of oxidative stress in healthy human subjects: a randomised controlled trial
• Children's daily exposure to polychlorinated biphenyls from dietary supplements containing fish oils
• Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease
• Omega-6 Fatty Acids and Risk for Cardiovascular Disease

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