Demystifying the Omega-6 Controversy
OmegaMatters: Episode 23
Hosts: Drs. Bill Harris & Kristina Harris Jackson
Guest: Dr. Martha Belury
Background and Key Takeaways:
In this episode, Drs. Harris and Jackson interview Dr. Martha Belury. Dr. Belury is the Carol S. Kennedy professor in the Department of Human Sciences of the Ohio State University. She received her PhD in biological sciences from the University of Texas, Austin, and her current focus is on the mechanisms by which bioactive lipids regulate insulin sensitivity and liver adipose tissue and muscle. She’s also interested in the role of energy balance and cancer prevention. And one of the bioactive lipids that she studied extensively is linoleic acid, an essential omega-6 fatty acid that today finds itself in the crosshairs of controversy. For more information on OmegaMatters, visit: https://omegaquant.com/omegamatters-broadcasts/
Dr. Kristina Harris Jackson: Welcome to OmegaMatters, where we talk all things omegas. I’m Kristina Jackson, this is Bill Harris. And today we will talk about omega-6 fatty acids and health with Dr. Martha Belury. Dr. Belury is the Carol S. Kennedy professor in the Department of Human Sciences of the Ohio State University. She received her PhD in biological sciences from the University of Texas, Austin, and her current focus is on the mechanisms by which bioactive lipids regulate insulin sensitivity and liver adipose tissue and muscle.
And she’s also interested in the role of energy balance and cancer prevention. And one of the bioactive lipids that she studied extensively is linoleic acid, an essential omega-6 fatty acid that today finds itself in the crosshairs of controversy. Some think linoleic is the best thing since sliced bread, while others see it as a dietary contaminant. So we’re hoping to bring some sanity and data to this discussion, so thank you for coming on, Martha.
Dr. Martha Belury: Thank you, Kristina, for having me.
Dr. Bill Harris: I’ll tell you, it’s only somebody who went to the Pennsylvania State University would say the Ohio State University.
Dr. Kristina Harris Jackson: Yes.
Dr. Bill Harris: Yes. I mean, it’s very important.
Dr. Kristina Harris Jackson: Isn’t it? I think it’s very marked.
Dr. Martha Belury: I just have to say, driving around Columbus, I saw a flag that said, “The.”
Dr. Kristina Harris Jackson: Yeah. Yep.
Dr. Martha Belury: Is that presumptuous? Maybe.
Dr. Kristina Harris Jackson: I like it.
Dr. Bill Harris: Well, here in Sioux Falls, we have a country club that’s called The Country Club of Sioux Falls.
Dr. Kristina Harris Jackson: Yes. It’s powerful, it’s powerful wording.
Dr. Bill Harris: Anyway, I digress.
Dr. Kristina Harris Jackson: But anyway, back to what we want to talk about today, omega-6 fatty acids, and actually, really, linoleic acid. We’re not really going to talk about all of them, just the one. Since you’re the expert. How did you get interested in looking at omega-6s and linoleic acid as a research topic?
Dr. Martha Belury: I am very interested in all polyunsaturated fatty acids. And when I first started my doctoral work at the University of Texas, I was working with Dr. Susan Fisher, who was one of experts in the whole prostaglandin field. And our goal was to understand how fish oils, rich in long-chain omega-3 fatty acids could inhibit skin cancer in a mouse model for skin cancer. And when we were doing this work, we found through various different tweaks to the mouse model that omega-3 fatty acids did nothing to inhibit skin carcinogenesis.
And then, we tested omega-6 fatty acids and found that, again, in opposition to our hypothesis, that they did inhibit skin carcinogenesis and the progression. And so, as a doctoral student a while ago, this was a great lesson in how science is almost always not what you expect, and yet when you design a good experiment, you know the findings are real, so then you have to dig a little deeper. And I’ve been digging a little deeper ever since, and it’s been quite a few years that I’ve been digging deeper.
Dr. Bill Harris: Wow.
Dr. Kristina Harris Jackson: That’s amazing. I didn’t know that was how it all began. So [as you kind of alluded to, it was against your hypothesis that the omega-6s would be protective in the skin cancer model. And so, I guess where did that hypothesis come from? Why are omega-6s thought to be detrimental to health from the get-go?
Dr. Martha Belury: Well, to dig a little deeper into what we found, we learned that omega-6 linoleic acid is an essential component of the waxy layer of your skin to maintain hydration, which again, if we all go back to our basic Nutrition 101 class, one of the key clinical manifestations of essential fatty acid deficiency is scaly skin, dehydration, et cetera. And so we, realized that when we assumed linoleic acid could be an up-the-pathway precursor to arachidonic acid, which then itself can become metabolized through enzymes to make prostaglandins and leukotrienes, we realized that there’s a lot of steps that we were assuming would just happen automatically that don’t happen automatically in the skin.
And now, we’ve learned probably that is true all over the body, that linoleic acid is a precursor for arachidonic acid. And through a lot of new technology instrumentation, et cetera, we now know linoleic acid itself is a precursor to oxylipins, lipoxygenase products that are also often anti-inflammatory. And to add a little more to the complexity and what has evolved I think in the science overall is we now understand even that pro-inflammation prostaglandins and leukotrienes are needed so that you can then reach resolution of that inflammation.
So all of these compounds that we’re talking about, whether they’re from linoleic acid or arachidonic acid or long-chain omega-3 fatty acids are short-lived molecules that give a punch to inflammation and perhaps other events, but then that are resolved through some of these other oxylipins that are produced from the same fatty acids. So it’s very complicated. And the simple idea that we had in 1990 is now, I think, evolved to something a little more complex, and typically so in biology.
Dr. Kristina Harris Jackson: Yeah. We look at blood levels all the time and that the linoleic or arachidonic connection just isn’t there on a big scale. It’s the higher linoleic, the arachidonic just kind of stays where it’s going to stay.
Dr. Martha Belury: That’s exactly what we found in our mouse models, we can feed, we fed doses of linoleic acid, seven different doses, and arachidonic acid didn’t budge in the skin and in the phospholipids of the skin that we were looking at. And then, prostaglandins actually were lower with higher levels of linoleic acid.
Dr. Bill Harris: Arachidonic-derived?
Dr. Martha Belury: Arachidonic-derived, yeah. We were looking at arachidonic-derived.
Dr. Bill Harris: How much linoleic is converted to arachidonic? Do you know? What’s the percent?
Dr. Martha Belury: Well, and I think that’s partially dependent on how much arachidonic is mobilized to become prostaglandins, leukotrienes again, and resolvins. So, part of that is driven by that, part of it is driven by some of these genetic polymorphisms that some people carry where they’re more prone to change linoleic acid to arachidonic acid, which is basically a one, two, three-step pathway involving three different enzymes, so it’s not like our linoleic acid just gets converted to arachidonic acid.
But what I think has been shown time and again, and Kristina, you were just saying this in the samples you all analyze, is that higher levels of linoleic acid in the diet do not predict for higher levels of arachidonic acid almost universally. The studies where we do see changes are usually cell culture studies where yes, when you feed more linoleic acid, you might see more arachidonic acid, or sometimes you see it in tissues when there’s a super physiological dose of linoleic given. But I just haven’t seen it in vivo, both in our mouse models or clinical studies, and yet I’m still looking for the evidence for that.
Dr. Bill Harris: It’s one of the pillars of the omega-6s are bad story, right?
Dr. Martha Belury: Yes. It is, and I think it’s very controlled. Arachidonic acid levels are very highly controlled, I think, from multiple angles in the enzymatic pathways.
Dr. Bill Harris: Right.
Dr. Kristina Harris Jackson: Yeah. I think the only thing I’ve seen that consistently affects arachidonic levels is like EPA and DHA.
Dr. Bill Harris: Yes.
Dr. Kristina Harris Jackson: Making those go much higher reduces arachidonic.
Dr. Bill Harris: Yeah.
Dr. Kristina Harris Jackson: We’re of course getting into the weeds on arachidonic and linoleic, but we kind of look more at the dietary side of things and omega-6 linoleic being a part of soybean oil. Can you talk a little bit about how much omega-6 is in the diet, where it’s coming from, what’s changed over the last few years, kind of that whole story?
Dr. Martha Belury: Yeah. One of the things I often will see is this assumption that because vegetable oils have increased in prominence in the diets of many people in the United States, that that increase in vegetable oils, which can be rich in linoleic acid, correlates to an increase in obesity and diseases. But what’s often forgotten is there’s a lot of other things that have changed in our food supply over the last 50 to 100 years.
In fact, what we now are seeing is many vegetable oils that were rich in linoleic acid, like soybean, canola, sunflower seed oils, those are changing to be high, well, I’ll say high oleic acid and low linoleic acid. So again, we’re really interested in that linoleic acid. And these oils are changing due to plant breeding, which is old-fashioned genetic modification, for different reasons, not to get rid of linoleic acid, but really to increase this monounsaturated fat that doesn’t oxidize as quickly when the oil is stored or when it’s processed to make things like trans… I’m sorry, hydrogenated fats, which can produce trans fats.
Dr. Bill Harris: So it’s not being changed… I mean, obviously, the scientists are who are doing these genetic breeding experiments are not doing it for the health reasons, they’re doing it for stability of the oil?
Dr. Martha Belury: Mostly for stability. Yeah, I know too much about oil and nobody really cares. But when you hydrogenate these oils, so you hydrogenate a high oleic acid oil, you have half the amount of double bonds that you have to saturate to make that oil into a solid at room temperature. So with half the amount of double bonds, you basically have half the amount of chances of trans fats forming. And these synthetically-produced trans fats are not good for us, we know that. And those are fatty acids that are not, we don’t need them, we don’t want them. And in fact, at low levels, they’re very harmful for heart health.
And Dr. Harris, you know that more than anybody, because of all of the work you’ve done with heart disease over the years, which is your work, is some of the seminal work in this area and in fatty acid area. So that’s really, I think, why the oils have changed, is to address the need that the many food companies have to make a saturated fat product that they can put in a lot of their foods that’s very stable. It forms a matrix for their food products that they desire, it’s got great mouth quality, and yes, it doesn’t oxidize as quickly.
Dr. Bill Harris: And it doesn’t finish low in trans fats. It’s below one gram per serving or something like that.
Dr. Martha Belury: Exactly. So it’s getting a lot of goals in one product.
Dr. Bill Harris: What’s interesting to me is that there’s a fair amount of evidence that higher blood levels of monounsaturates are not associated with good outcomes.
Dr. Martha Belury: No. In fact, over a third of our fat calories is monounsaturated fat and it’s mostly oleic acid, which is probably not harmful. And I think there’s more, not a lot of data to show it’s protective, but I don’t see a lot of data that show high oleic acid in your blood is harmful, it’s just kind of a neutral fatty acid. Whereas as many, many studies have shown from around the world, not just in the United States, that higher linoleic acid and of course higher long-chain omega-3 fatty acids, like the omega-3 index, are very much associated with protection against heart disease. We know with linoleic acid, it’s highly associated with reduced risk for type two diabetes. A lot of studies are now showing reduced risk for weight gain in the trunk region, which we call central obesity.
Dr. Bill Harris: Elaborate on that, because we hear, again, one of the urban myths is that omega-6 causes body weight gain.
Dr. Martha Belury: So both correlative studies and actually some causal studies have shown now that higher levels of linoleic acid or linoleic acid oil supplementation reduce fat in the trunk region of a person and reduce visceral fat. And these are very rigorous randomized-controlled trials, almost always blind, and some are even crossover studies that have shown this. Our lab was one that showed the trunk fat reduction. But a few groups out of the Scandinavian countries have shown the reduction of adipose from the visceral measurement using magnetic resonance imaging.
Dr. Bill Harris: Is it just redistributed or is there just less, is body weight down, total fat?
Dr. Martha Belury: It’s not clear. Visceral fat, it is reduced. So it’s absolutely adipose tissue, it’s not just maybe fat in the liver, but some of those same groups have also shown reduced non-alcoholic fatty liver disease risk and reduction of fat in the liver when you measure it in people who have non-alcoholic fatty liver disease.
So all of these effects of linoleic acid could be related to some of its oxidized products that are from, enzymatic oxidized products, which you call oxylipins. They also could be associated with some of the very specific effects of linoleic acid and mitochondria because it’s an important fatty acid as part of the cardiolipin, phospholipid and mitochondria that produces more ATP energy. So it could be that it helps your body metabolize energy better.
Dr. Bill Harris: So you mentioned the word oxidation, and I think we three know what you’re talking about, but the public hears oxidation, they hear seed oils, they hear awful, oxidized oils is kind of bad. Can you take that apart a little bit?
Dr. Martha Belury: Yes, thank you for asking. So oxidized oils can be enzymatically driven, which is very controlled and it’s an important process in processing oil so that they become less lipid-like and more water-like so that you can get rid of those metabolites eventually. And then there’s non-enzymatic oxidation, which is what we think of as free-radical generating. And that non-enzymatic oxidation is what we consider to be kind of a wild hare kind of thing where you can’t control it and it propels into more free radical generation. And that non-enzymatic oxidation is what we associate with disease risk for things like heart disease, diabetes, tissue damage.
Dr. Bill Harris: So do vegetable oils have a lot of oxidized fatty acids in them?
Dr. Martha Belury: Well, yeah, good question. So if they do, you shouldn’t eat them, but you would smell it and taste it. Just like with any fatty acid, and including long-chain omega-3 fatty acids, if they start oxidizing, you get that taste and that smell that we often associate with fishiness. It’s not the fish that are smelly, it’s the oxidation of those oils, which would be telling you that oils aren’t fresh, that they haven’t been stored well and you shouldn’t consume them. And that’s true for any oil, whether it’s an omega-3 fatty acid oil or omega-6 fatty-acid-rich oil or even monounsaturated oil.
Dr. Kristina Harris Jackson: Yeah, anything but good, stinky cheese. If it stinks, you want to stay away from it.
Dr. Bill Harris: Well, cheese, are you kidding?
Dr. Kristina Harris Jackson: Stinky cheese is good.
Dr. Bill Harris: Well, there’s certain cheeses that are stinky and they’re on purpose stinky.
Dr. Kristina Harris Jackson: I know, that’s what I’m saying.
Dr. Bill Harris: Oh, okay.
Dr. Kristina Harris Jackson: That’s great. I think that really helps clarify some of the confusion around oxidation, lipids, these oils, what’s going on in our food systems and why, which is very helpful. Kind of related to what we were talking about before with blood levels, how does dietary intake of linoleic correspond to blood levels of linoleic acid? What’s affecting the blood level?
Dr. Martha Belury: One would think that because linoleic acid is one of only two required fatty acids, your body can’t make it, that if you eat a certain level, you’d see a certain level in your blood because your body can’t make it, so the only level that’s in your blood is from your diet. But we also know that what’s in the blood turns over and becomes other things, it goes on to form all these enzymatic oxidized products, which are good. They act as signaling molecules, they can act to bind to receptors to cause different things to happen in cells.
And so, because of that, the blood level and the diet level are not that strongly correlated. They are significant, but when I talk to people who are used to high levels of correlation, they look at it and they go, “Really? You think that’s good?” And I say, “Yes, in the diet field, we think that’s pretty good.” So you can use blood levels as a marker for dietary intake. And we, in fact, do. We just know that there’s some variability with that blood level. And as I mentioned earlier, even genetic predisposition for some people, they metabolize linoleic acid a lot faster to downstream fatty acids, like arachidonic acid and other products, but also to then oxylipins. So there’s different things in each of us that affect our levels of linoleic acid beyond our diet.
Dr. Kristina Harris Jackson: So input’s diet, but output could be oxidation products or being elongated and desaturated to longer-chain fatty acids and any other things.
Dr. Bill Harris: Well, it’s then stored in the adipose tissue too…
Dr. Kristina Harris Jackson: Yeah.
Dr. Martha Belury: Yeah, maybe being picked up by different tissues and… That’s true. Thank you.
Dr. Bill Harris: So if you’re stuck in an elevator with a person who’s got an honest question about omega-6, they’ve heard that they’re bad for you and they really want to know before you get to the 10th floor, what do you think? I mean, you got an elevator speech for omega-6?
Dr. Martha Belury: My elevator speech is, the good news is I think we have to rethink that assumption that linoleic acid is bad for us, and we’re rethinking it because of the newest evidence within the past 20 years, but every year we see more and more accumulating evidence that linoleic acid could be actually good for us. And we think it is good for us, for not only fulfilling needs for requirements because it is an essential nutrient in our diet, but we think it has some of these other health benefits.
And in fact, for over 70 years, we’ve known it is associated with protection for heart disease. And the American Heart Association has published quite a few papers to remind practitioners and scientists that this has been pretty well documented time, and time, and time again.
Dr. Bill Harris: But our ancestors, with age, that one-to-one, omega-6, omega-3 and they were really, really healthy. They didn’t have heart disease or cancer.
Dr. Martha Belury: Right. So I never knew a dietician was taking their dietary intakes back a gazillion years ago. And of course, I do wonder how when you died at the age of 22 or maybe 35, how that could be affecting some of those data, but I try not to get into those weeds, Dr. Harris.
Dr. Bill Harris: Yeah, I wouldn’t follow me in.
Dr. Martha Belury: No, no.
Dr. Bill Harris: Don’t worry.
Dr. Kristina Harris Jackson: Yeah. I have two specific questions, and one is around, I guess I’ll start with this, linoleic acid and insulin resistance. And you’re seeing this correlation and I read somewhere that insulin increases the activity of the delta, the delta-6 desaturase and that could be one of the reasons why a higher linoleic acid level is associated with better insulin activity, essentially. Is that something you’ve heard, learned about, thought about?
Dr. Martha Belury: Actually, I would look at it almost in the opposite way, that if your linoleic acid is improving insulin sensitivity, your body doesn’t have to pump out as much insulin. So your insulin levels start to go down in your body, that’s what insulin resistance does. And so, a surrogate weighted measure insulin resistance, first of all, you could look at glucose disappearance after you give some insulin and that’s done with a clamp if you really want to measure it with really good sensitivity.
The other way is you could look at fasting insulin levels, and fasting insulin levels can tell us if someone’s insulin resistant, because as you become more insulin resistant, before you become a person with type two diabetes, your pancreas is working harder and harder to increase your insulin to get all that glucose out of your blood. So we kind of look at it as if, “Well, linoleic acid could be improving insulin sensitivity, that allows for your insulin levels to start to come down, which then might be the reason we see this lower visceral fat, lower lipogenesis in some of these tissues.”
So I kind of look at it that way. And then we don’t know which is which, but I’m thinking linoleic acid has something causative to do with improving insulin sensitivity.
Dr. Bill Harris: Is there a relationship between blood linoleic levels and fasting insulin?
Dr. Martha Belury: There is, and insulin sensitivity using a clamp. People who did that work, again, are mostly people out of Sweden, Ben Besbe’s group. Ben is now retired, I think you probably knew Ben doing his work. And then, some of his proteges are still in Stockholm doing some of that work. There are now other groups showing that with insulin resistance being reduced in people who supplemented with oils rich in linoleic acid, compared to other oils.
Dr. Kristina Harris Jackson: So the linoleic acid is acting on the exterior, like the muscle and the liver and adipose tissue, and making those more able to act on insulin or take glucose out of the bloodstream. Is that the idea?
Dr. Martha Belury: Yep, that’s right.
Dr. Kristina Harris Jackson: That’s very cool. I like that. The other question I had was kind of around some of the things that people are worried about with high linoleic and the diet, and worried that it will slow down the omega-3 pathway, so people could, maybe if they didn’t have ALA in the diet or linoleic in the diet, they could just eat plant-based ALA, walnuts, things like that, and transfer those to EPA and DHA more easily. Any thoughts around that argument, that process, data there that you have?
Dr. Martha Belury: A few things. In my view of the literature, and we’ve never done what we would call tracer studies where we pit a tracer amount of linoleic acid with a tracer amount of ALA, but I think some people have done that. They’ve shown that the downstream enzymes that convert ALA to EPA and DHA are actually regulated by those upstream fatty acids, ALA and LA. So if you have more LA, there’s more desaturase that is promoted to be elongating it. And the same is true with ALA.
So pitting one against the other is not necessarily, I think, going to actually hurt the other one being metabolized as much as people think. And that’s what we kind of see, is that there’s not a lot of conversion of either one, actually, to their longer-chain metabolites. It’s more of what we think is happening enzymatically with those changes downstream, so desaturases and elongases, but I know delta-6 desaturase is one of the more sensitive enzymes that’s responsive to their upstream linoleic acid and ALA. And that was work, I think, done actually quite a few years ago, and some of that work done was done at the Ohio State University.
Dr. Bill Harris: Wow, really?
Dr. Kristina Harris Jackson: Very good.
Dr. Martha Belury: Not by me.
Dr. Kristina Harris Jackson: Those are my burning questions that I have. Do you have any more to wrap up?
Dr. Bill Harris: Just to follow up on that last comment, I mean, the idea that even if it were true, that a really, really low linoleic acid, like a 1% energy linoleic diet would help you convert ALA to EPA more so than a six or 7%. Fine, I mean, that may be true, but that doesn’t necessarily mean it’s good for your health.
Dr. Martha Belury: Well, and that’s kind of like if you give anything in one, if you don’t have any linoleic acid to convert, of course, you’ll convert more ALA because you’ve got that parent compound that’s turning on delta-6 desaturase and forming that whole cascade. So yes, I agree with you, and I think that’s where that omega-6- omega-3 ratio is not really where we want to be going with our messaging for both scientists and clinicians.
And of course, I guess then a third thing is for the public, I think that’s very misleading, that we want to increase or decrease our linoleic acid to form a better amount of long-chain omega-3s. I think we want both in our diets, and I certainly think with our food supply, we can get both in good, healthy levels.
Dr. Bill Harris: That sounds like a nice concluding statement, I like that.
Dr. Kristina Harris Jackson: Yeah. Very good. All right, well, that is all we have for today. Thank you so much, Martha. These were really helpful, answered a lot of my own personal questions, so thank you for that. And if we have any more questions, we will have you back on.
Dr. Martha Belury: I am so glad to see both of you today. Have a great holiday, great weekend.
Dr. Bill Harris: You too, you too. Thank you very much, Martha. Bye-bye.
Dr. Martha Belury: Bye.
Dr. Kristina Harris Jackson: All right. That was great.