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Cardiometabolic Syndrome: Part 2 with Dr Bradley McEwen

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Cardiometabolic Syndrome: Part 2 with Dr Bradley McEwen

Cardiovascular and metabolic disease account for a large number of deaths in Australians, and we're not getting any healthier. As clinicians we're tasked everyday with making therapeutic decisions based on the best available science for a patient's individual health circumstances. There is an art to interpreting scientific conclusions drawn from nutritional and lifestyle modifications, which can often be ambiguous and leaving us with more questions than answers. This is where Dr Bradley McEwen's expertise is invaluable.

In today's part two podcast, Andrew and Brad expertly navigate the many evidence-based interventions for cardiometabolic syndrome(s) and how to draw out relevant conclusions to make rational clinical decisions. 

Covered in this episode

[00:49] Welcoming back Dr Bradley McEwen
[01:53] Media attention on fish oil science - what's the truth?
[10:25] The Opera and JELIS studies
[17:46] The Omega 3 Index 
[21:46] Omega-3 vs. Omega-6
[26:46] Nutrients for managing cardiovascular health
[29:34] Magnesium: they're not all created equal
[32:57] Red Yeast Rice and Policosanol
[38:48] Plant sterols and margarine
[41:38] Polyphenols and antioxidants

Andrew: This is FX Medicine, I'm Andrew Whitfield-Cook. Joining us on the line again today is Dr. Bradley McEwen. Brad’s a nutrition expert, naturopath, herbalist, educator and lecturer, researcher and mentor with over 19 years clinical experience. 

He received his Doctorate of Philosophy in Medicine from the University of Sydney, a Master of Health Science and Human Nutrition from Deakin University amongst other qualifications. Brad has numerous original research and review articles published in peer review journals, and he is also a peer reviewer of the international journals. His research interests include the effects of diet and nutrition on cardiovascular disease, diabetes, cardio metabolic syndrome, depression, anxiety, polycystic ovarian syndrome, cognition, and chronic disease. 

Brad has a strong passion for seeing people succeed and achieve their goals. And he also enjoys chocolate. Welcome back to FX Medicine, Brad. How are you? 

Brad: Thanks, Andrew. I'm very well and how is yourself? 

Andrew: Good. Thank you. Brad, in our last podcast we discussed the cardiometabolic syndrome and various lifestyle and dietary changes. Today we're going to be delving a little bit deeper into what exactly you can use, what has evidence, what's positive, what's negative, and where you might use it in some conditions and not in others. 

So, I think to start off, let's start with a negative; fish oil. About five or six years ago it was all glowing, it was all glossy. Fish oil was the latest basically, it was the latest cardiovascular medicine. But then some questions were raised. There was two papers published in early 2018, one just recently in May, a review article in May. But the one that concerns me most is the one that was published earlier in 2018 where it was a meta-analysis of various trials and it raised some real questions as to its benefits. Can we go through this one? 

Brad: Definitely. What I'd like to first start off with is, anytime we read a clinical trial or a meta-analysis systematic review, there are a number of things we have to look at particularly if it shows negative results. 

We need to think about who did the research, where the research was done, where was it published? Is it a peer review journal of high quality, or is it a blog kind of internet, whispers? How big was the study? Were there a number of participants that were too large to show a result, or too little to show a result? What was the study duration? And that's a very big one that I find interesting is, let's just say we're looking at cardiovascular endpoints, and they do a clinical trial for several months. But, cardiovascular disease develops over a period of time. So, therefore, the time points might not be long enough. 

Another example might be PCOS or premenstrual syndrome where they might only use a nutrient or herbal medicine for one menstrual cycle. That's not going to have enough effect on the person or the individuality of people to show a positive result. Was there an active treatment? What was the dosage? Also, what was the placebo? Because one of these studies that you're mentioning there, used olive oil as a comparison. And olive oil, of course, has omega three, six and nine in it. So it's comparing an omega three, was it three, six, nine. So the placebo effect is not exactly a true placebo. 

And, again, is it investigated on the right population? Is it in the right age? Gender? So I always advise people, you know, read the methodology and detail of a journal article because you need to know exactly how they did it, and what they're looking for at the time. And Omega-3, like you're saying, it's am fascinated by Omega-3, how great it is for people's health. Because there's a wide range of different health conditions and actions and functions within the body. So whenever I read a bit of a negative study, I'm always interested to find out more. 

Andrew: Well, let's look at this meta-analyses. What was the title of it and where was it published? 

Brad: So the title of this meta-analysis was the associations of omega-3 fatty acid supplement use of cardiovascular disease risk. It was published in JAMA in March 2018 this year. And it involves 10 major trials involving 77,917 individuals. So, it sort of fits the criteria of what I was looking at earlier with the number of people. 

Looking at the research here, we're sort of... The mean follow-up was 4.4 years and what they found was no significant association with reductions in fatal or non-fatal coronary heart disease or any other major cardiovascular events. 

Andrew: One of the...like, I've looked at that study myself and there was a few issues that I found. Not the least of which was one of the studies that I looked at used a massive dose of n-3 fatty acids. We're talking fish oils, 10 grams for two to five days prior cardiac surgery. Now, can you comment on this or like, do we just saw it together? 

Brad: Well, the interesting thing is we can comment. And I find it interesting that when you delve into the methodology, it was 10 grams loaded dose divided over three to five days, or eight grams divided over two days. Like the methodology was different from every participant. And that's what I found interesting. The leading point was different for each person. 

So it is actually very hard to compare. And one of the comments, in the article itself, is the variability of dosage was ‘whichever came first.’ So they either had the 10 grams divided over three to five days, or eight grams divided over two days. And just general mathematics shows that the different doses and each gram of fish oil, Omega-3, was equivalent to around about 465 milligrams of EPA, or eicosapentaenoic acid. And 375 milligrams of DHA or docosahexaenoic acid. 

So that's quite a good dose that we look at, as a practitioner, I would use that dosage several times a day. I really wouldn't use it in the morning as 10 grams of that, 10 times that. Because that's quite a high dose. That's equivalent to nearly eight and a half thousand milligrams of omega-3, active omega-3, so-to-say. 

Andrew: Yeah. 

Brad: And to me, that's just a big whopping dose in one go. I'd be spreading it out throughout the day. 

Andrew: But also, when you look at two to five days and you think about, like A) the requirement for a fatty acid to be taken in by the mouth, be up-taken by the gut, taken around the body, up-taken by the cells, placed in its correct positions and start working, is not two to five days, no way. Like, and I really question this, the setup of the trial. 

Brad: I do too, yeah. And I know what they're trying to do. They're trying to see whether or not omega-3 has a greater outcome at the end of the study. And it's nice that they're trying to do this kind of research, but platelets have a 7 to 10-day lifespan, and platelets carry omega-3. So to actually saturate the platelet content in the body, takes longer than three to five days. Let's just say 10 as a general mathematic. Red blood cells readily accepts the Omega-3 at a time. They have a lifespan of 120 days too. So to saturate all the red cells to be able to, like what you're saying, deliver the omega three to where it needs to be, in this case, the heart, because there's measuring actual fibrillation. So it's measuring heart rate and the variability of heart rate. It takes longer than three to five days to do that. 

So, even if you did do a very high dosage, to me, the idea of the study makes sense that they wanted to test whether or not omega-3 improved the outcome of the surgery, particularly actual fibrillation, but the time points are not long enough to see a great effect. 

If I had the opportunity to do this research myself, I would have done at least a 30-day lead-in. And, of course, you don't always know and people are going to have surgery. That's a tricky thing. But if people are booked in to have heart surgery and it's based on whatever health condition they have, the longer the time point, the better. And if you can do 30 days or even longer of omega-3 supplementation, not just in the morning as a big, you know, 10 gram dose, but let's just say several grams or like two grams, three times a day or three grams three times a day. That kind of dosage, the body actually absorbs and accepts more nutrients given over time. Think of it as like a safety mechanism in the body. 

Andrew: Yeah, that's right. Well, this is reflected in the great work by a professor Frank Rosenfeldt at the Alfred Hospital in Melbourne where they had a, I think it was a two week lead in product cardiac surgery. 

Let's move on though. Another study that in this meta-analysis in 2018. So this was The Opera Study. Now, this one, this was 400 milligrams EPA, DHA. And in the study, is it right? They failed in achieving 400 milligrams a day in a significant percentage of patients. Is that right? 

Brad: That's right. And that's the other interesting thing I look at. Again, with methodology is what is the actual dosage? So we've just talked about time frame, as in the lead into a study points or the endpoint of the study. It’s also, the therapeutic dosage. I want you to imagine now you've just had some fish, you just consumed a fish meal, that has X amount of EPA, DHA, the active ingredients of omega three so-to-say, some of the people in that study didn't even reach the equivalent of, you know, the dosage of a fish meal. And although it's very handy checking from minor doses like I did my research. Like, looking at low dose changes, if you're looking at larger endpoints like atrial fibrillation, heart attack, stroke, vascular, you know, endothelium changes, you need to have longer time points, but also appropriate dosage. 

Maybe what they could do is look at a dosage regime of one group of patients with, let's just say, 500 milligrams of omega-3 per day. Another group with 1000 milligrams of Omega-3 a day, another group 2000, do you know what I mean? Like doubling the dosage in each group. And if you do a randomised controlled trial, that will actually balance out the ages and health conditions, etc. Because that's why we use double-blind RCT’s is to make sure that each group has randomly selected to be very similar. 

So, that'd be something I'll be doing is matching up the groups but with different dosage and comparing those dosages and then finding either a standard treatment as the, let's just say, the placebo group is an active treatment, or a proper placebo which doesn't have Omega-3 content in it. 

Andrew: What about a possible confounder in that trial of the, what is it? 18.8 grams of margarine per day? 

Brad: Yeah. I was laughing at that. There's a number of research articles out there now showing margarine as a substrate for the, you know, the plants sterols that we'll talk a little bit about later. So they're using that as a vehicle, so-to-say. But to me, it's margarine. 

Andrew: Yeah. 

Brad: You're adding in oils and fats, so-to-say, when you're trying to actually improve the balance of, let's just say cholesterol, triglycerides, platelets, but also at the endpoints. So to me, I just find that confounding factor, confounding, it’s just a weird thing to be looking at. 

Andrew: I think it's also worthy to point out though that what I've noticed from the major facial trials with major benefit, these trials were conducted in cultures that eat fish as a background dietary habit. And so, it's one of the things that I'm really keen on pushing, if you like, is if you're thinking that a supplement plus pizza, plus fast food, plus high sugar diet is going to have the same effect as a Mediterranean style, or a traditional Japanese style diet, which is high in seafood and minerals and things like that. I think we're asking a lot from a supplement. 

Brad: I agree. I think we're asking too much of a supplement to change. And think about it as the JELIS study that went for 4.6 years on average, so it was a five year follow up. And they took, you know, 1,800 milligrams of EPA per day, which is a very good dosage for this. And they compared it to a statin as well. So they actually had a very good model for their comparator. 

Andrew: Comparator, yeah. 

Brad: And it had around about 18,500 patients, so it was quite a large study. And what I found interesting with this, is they found a 19% relative reduction in major coronary events, like, heart attack, for example. And in patients with no history of heart disease, they actually found a reduction of 18% in those people that had that amount of Omega-3 or EPA in this case. 

So if you think about it, 18% to 19% reduction of risk, that's actually pretty good. You know, and like you said, a lot of these patients in the study were actually consuming fish and a relatively standardised Japanese diet, so to say. And these kind of things need to be taken into account that if you have a higher quality, let's just say Mediterranean Diet, low glycemic index foods, plenty of fruit and vegetables, nuts and seeds, plenty of water, physical activity, all the classic ‘good stuff’ that we promote. And then on top of that, take an omega-3 supplement or magnesium orotate, or coenzyme Q10, etc., all these other supplements on top, you're going see a greater response rate in that person because they're doing better things for themselves. 

But if you're consuming a westernised diet with lots of, what I say to people; “chippy chips and carby carbs, and high fat.” So a lot of people have heard that from me before. Chippy chips and carby carbs, and lots of fat. You're not helping yourself. I want you to think that the blood is flowing through you as a beautiful river. You know, it's flowing through it's got good nutrient content, you're detoxifying properly, you're clearing out all the excess, let's just say toxins and fats and metabolites that the body produces all the time and it clears it out. 

Now, if you have more of a westernised diet, high carbohydrate, high fat, low nutrient value, high energy density. The blood gets sluggish. And we're seeing that in a lot of research studies. The blood can actually gets sluggish. It's more coagulable, and I relate it to like being a sewage. It's slow, it's sluggish, it allows for more, you know, toxicants to, you know, bind up nutrients. It slows down altering the blood flow to the periphery, for example, leading to other health conditions. So if your blood's not moving and flowing correctly, you can't expect, you know, things to be absorbed properly into the cells. Like what you were saying earlier. You need to be able to digest and assimilate and absorb into platelets, red cells, the brain, the heart, the muscle tissue. You need to absorb all the nutrients into the body effectively. And if you're not helping it, it's going to be very hard. And taking, you know, wherever it's one gram or 10 grams a day of omega-3, it's going to be very hard to see a significant difference in one person or a thousand people. 

Andrew: So should we, therefore, be relying more on an index of our omega-3 intake? Or it's incorporation. So something like the omega-3 index developed by Dr. Bill Harris, William Harris? 

Brad: I totally agree. Because this is a good marker that has a lot of research behind it in the past. Some people think it's a new marker, but it's just come about more readily in Australia the last 10, 15 years because it's becoming more easily tested, I'd say. 

Bill Harris has done a lot of research with omega-3 index and I believe we can actually utilise markers. We could see the absorption of omega-3 and other nutrients like with different tests. One of the research studies recently was from the Framingham Heart Study, and as people know that study has been going since the 1940s, so it’s a very long-term study. The thing I love about the study is they're now looking at the offspring of the offspring of those original people. So we've got several generations. So every now and then we'll hear, '"Oh, such and such is good for us. Oh, no, it's not." And it's like, this can sound confusing, but they're looking at this Framingham Heart study, for example, and they've collected blood, lets just say every 5, 10 years depending on what cohort they're in since the 1940. 

So they're able to actually now test for old markers and new markers. So there's a new research test available now to measure, let's just say, inflammatory mediators. You can measure that now and compare it backwards, so retroactively, look at the health conditions in the person and see whether or not those markers played a role. And omega-3 index is one of these markers. 

Andrew: Interesting. 

Brad: It's is, it’s very interesting. I like this kind of stuff. I get quite excited because it gives us something that we can look at. In this research study, Bill Harris had 2500 participants, so it's quite a good size study. And, you know, he was looking at...his group was looking at whether or not the omega-3 index was relating to, you know, coronary heart disease, cardiovascular disease, total stroke, etc. 

Andrew: What I'd love to see is, let's say, a culturally high intake of omega-3. So, you know, a Japanese or Mediterranean style culture, measuring omega-3 index, and then taking also a sample of a very westernised diet. So the American or Australian-type diet or even UK, and seeing if you get the same sorts of benefits from the same sorts of levels of omega-3, regardless of the intake of where you get that intake, but also taking into account the other dietary factors. So, you know, poor trans fat, high sat fat, all that sort of thing. 

Brad: I would love to see too. And the other thing I would love to see is, when those people move from let's just say, Japan, UK to Australia and US to Australia and they change to the standard Australian diet sometimes referred to as SAD, does it change? 

Andrew: Yeah. 

Brad: So you can look at it in their own population group and then the standard diet that they consume, and then when they moved to Australia. 

One of the main concerns people have had, let's just say you're living in the Mediterranean for half your life, you moved to Australia. Can you continue that Mediterranean style diet in Australia? With the foods that we have here, the different quality and quantity, etc, and research is indicating yes, but it's not exactly the same as living in that area. 

So I'd very much love to, you know, research what you just said, as in the population groups in their initial country. But then test and assess people who have moved to a different country to see if that changes.

Andrew: Yeah. 

Brad: Because sometimes the research shows as you take on the country that you moved to. 

Andrew: Yeah. That's right. 

Brad: With breast cancer studies, etc. 

Andrew: What about moving on from just omega-3 as an index, what about a comparison between omega 6 and omega-3? 

Brad: That's always an exciting thing because people always think omega-3 is anti-inflammatory and omega 6 is proinflammatory. It's not as simple as that. 

Omega-3, yes, it is primarily anti-inflammatory. Omega 6 does have some anti-inflammatory components to it. But it mainly stimulates arachidonic acid in the pro inflammatory pathways. So that's where the...it's the old picking the words, kind of thing. 

Andrew: It's also not necessarily anti as a static sort of thing, but relatively anti-inflammatory compared to arachidonic acid and the thromboxanes and things like that. So, it's not like a... Yeah. It's not like a blocker of inflammation per se. I think we've got to realise this, the physiological responses of the prostaglandins and the prostanoids 

Brad: That's correct. And also the level that you're consuming. 

Andrew: Yes. 

Brad: So typically, in westernised diets, we consume a more larger amounts of omega 6 compared to omega-3. And what I find interesting is, when they’ve looked at a lot of research into diets, high intake of omega 6 has led to oxidation of low-density lipoproteins or LDLs. It's led to increased platelet aggregation. And funnily enough, thinking of the omega-3 index that we're just talking about. Omega 6 interferes with the incorporation of the EPA and DHA into the cell membrane, into the phospholipids. So if you have a higher consumption of omega 6 foods, which is more the western diet, you may have a lower consumption of omega-3, but you can nearly block that incorporation of the healthier omega-3 into the cells. And that can lead to inflammatory effects, atherogenesis, a general inflammation in total. 

So I find it very interesting that, you know, again, we use block terms. We need to re-balance the diet. 

Andrew: Yes. 

Brad: So when we look at diets of better ratio, this is a ratio of omega 6 4 to1 of omega-3, it's been associated with a decrease in total mortality. A smaller ratio of around about 3 to 1 was seen to have a reduction of inflammation in rheumatoid arthritis. But a higher ratio didn't have that same effect. 

Andrew: Right. 

Brad: Patients with asthma had a reduction in their asthma symptoms, but a higher level of omega 6 had an adverse effect. 

So, it's very interesting. It comes back down to the old saying that we have this balance. If you balance out the ratios of around about, let's just say, I try and say to patients three to one to around about 5 to 1 is where we should be looking at as an omega 6, omega-3 food content. Because it was very hard to slip it the other way around some...I'm just looking at some diet, like the Paleolithic diet, had a better balance of omega 6 to omega-3. Particularly the vegetarian foods that they ate. 

If we think about the Greenland Inuit valued a lot of omega-3 foods. But funny enough, they also eat a lot of whale blubber and fat and seal and all these animal sources of fats. But then, again, they have a lower rate of, you know, cardiovascular events. And that was found early in 1970s.

Andrew: And I think we're forgetting that original sort of research into omega-3s. You know, seems to be glossed over now. We've forgotten that. But, you know, it's a really interesting point. They had almost exclusively animal fat, I thought. And a very high intake of omega-3s. They did actually bleed, but it didn't cause issues with heart disease. 

Brad: That's right. And some of the early tests they did showed that from the 1970s that was Dyerberg and Bang, etc. They did a lot of research. So I find it interesting how once we get new research, we sometimes forget about the past. 

Andrew: Yes. 

Brad: And sometimes it's contradictory because this new research and new testing methods, but we should always remember the past, because it led us to where we are now with research. 

A lot of research was in the 1910s and the 1920s on Omega-3, which a lot of people didn't realise. Because they're using cod liver oil, they separated it out with the vitamin A, D, and omega-3. And they worked out that omega-3 in both animal and human studies, a deficiency led to dry skin, dry hair, hair falling out, general inflammation. So that was in the early days when they could test for a lot of these parameters, of course. But physically they noticed. And then that led onto further research. 

So we can't just discount old research. We should utilise it and then see what we can support it with today. Or, it may be the total opposite, but we still have to remember the research from the past. 

Andrew: Let's move on to other nutrients that might be of benefit in cardiovascular and other heart diseases. So probably the poster child of heart health, would be coenzyme Q10. 

Brad: Yes. 

Andrew: Let's talk a little bit about what does the research show us, and what about the new kid on the block versus the old salt? 

Brad: Well, I love coenzyme Q10 because it just does a lot of things in the body. So it has that anti-oxidant anti-inflammatory effect in the body itself. It has that cellular bio-energetics I like to call it, where it fires up the mitochondria and the cellular machinery. So it like gets everything up and running. And it's also protective of liquid membranes, plasma, you know, the LDLs, etc. And it modulates gene expression. 

So it's more and more research is showing that coenzyme Q10 does play a major role in general health, but particularly of course in cardiovascular disease. There's been a number of studies out there showing that coenzyme Q10 as being deficient in people with hypertension, heart failure, statin use, and that could be due to the pathways that coenzyme Q10’s made in the body as well. 

And there's been a number of, you know, clinical trials and meta analyses on coenzyme Q10 itself showing benefit in, you know, cardiovascular risk reduction, reduction of heart attacks, etc. So I find it very interesting that it is seen as the new kid on the block. When I first started in clinical practice, the highest level of coenzyme Q10 you can get was 12 milligrams. So not that easy to work with. 

Andrew: No. 

Brad: But these days we've got much higher doses and, of course, we've got the active form. 

Andrew: I'm very interested though. Again, I'll mention the work of professor Frank Rosenfeldt, like, it's really good work. I get that it wasn't necessarily a hard end-point, and it'd be wonderful to see, you know, some more solid endpoints used in other research. But he used what's called a ‘metabolic formula.’ Which included coenzyme Q10, the ubiquinone form, magnesium orotate and selenium and lipoic acid. That was the other thing. 

Brad: That’s right. 

Andrew: Plus a separate supplement of fish oil prior to cardiac surgery. And he looked at certain parameters after cardiac surgery, and they had, the big one was a cost saving, of course, the economics of medicine, which is a cracker. But, you know, they had reduces in drug therapy. They had reduces of hospital stay. They had reduces of atrial fib after surgery, which is a real bad thing to have after surgery. So, I think this sort of research really needs to be followed up with some other research championed around the world. It would just be really interesting to see. 

But can you comment on things like the combinations, or indeed, just alone? What about magnesium alone? What sort of magnesium do you prefer? You know, do you ever use different ligands? 

Brad: I do. And again, this is the interesting thing, following on from what we talked about with omega-3, it’s not just one thing. So we talked about omega-3 and diet lifestyle. 

In the case of this formula. It was a great all-rounder. It did have magnesium, orotate, ubiquinone in there, it did have like like lipoic acid and selenium. And these are great as a combination of anti-oxidants and anti-inflammatory all in different parts of the body. 

Generally speaking with magnesium, if I'm thinking of cardiovascular or cardiometabolic syndrome, I like to go from magnesium orotate. Because it's very specific for the heart muscle, the heart rhythm. It's very specific… well, general muscle function. But it's very specific in re-regulating heart rhythm, vascular tone, vasodilation. I sometimes add that up with a general magnesium like a glycinate or chelate form. Because these are well-tolerated and absorbed as well. And with some patients, depending on their health condition, I'll combine the two, so they'll have a magnesium orotate around about 50 milligrams one to two times a day, for example. And then I'll combine that at the same time with another magnesium form, such as the glycinate or chelate form. And that can be anywhere between 150 to 200 milligrams a dose and combined the two. And I've seen a greater effect clinically in patients that way. 

Magnesium's also involved with glutathione production. So the body's natural antioxidant. Metabolism of the pathways for anti-inflammatory, you know, the delta five and delta six desaturase pathways. Cell membrane integrity, stabilisation, cell signaling. Again, this is what omega-3 does. Conduction of nerve impulses, omega-3 also does that as well as magnesium. So, a lot of these nutrients together, are the old synergism that we talk about, the one plus one equals three. 

So when you use one, you'll get some results when you combine it with another, you can get an additional synergistic result. And selenium also has the benefits of, you now, thyroid function, metabolic rate, blood glucose regulation, and again, anti-inflammatory, antioxidant. So it's a combination. Lipoic acid, water and fat soluble antioxidant. So it's in and outside the cell protecting the membrane from damage. 

So this is a great formula. I'd love to see it utilized… that kind of formula itself, utilised a lot more in clinical trials, of all different health conditions, not just cardiovascular. But maybe thinking about other, let's just say chronic diseases.

Andrew: Yeah. 

Brad: Like the arthritis’; osteoarthritis, rheumatoid arthritis, asthmas, etc. Like, the other chronic long-term diseases. Because this is like a power-pack of the nutritional formula combination. And, you know, Frank's work is game-breaking. It's world-leading research that can really open up the door to more health benefits for a greater range of people. I think it's fantastic work. 

Andrew: What about some of the different types of nutritional interventions available on the market. That, let's say are a little bit more controversial. Things like red yeast rice and policosanol. Can you comment on those? What's your use been? 

Brad: Yeah, yes, I can. Red yeast rice has been, you know, been around for a long time. And what they’ve found, just to explain a bit further, it's fermentation of red rice by a fungus. So there’s your like, your yeast effect in there. And it produces a substance called monacolin K. And that's been seen to be a, HMG CoA reductase inhibitor. So it actually works down the same pathway as a statin. And funny enough, one of the statins is actually formed from this monacolin K. So it does have that statin effect. They 've done a number of studies where they found that the red yeast rice was very similar to Pravastatin, for example. Where they found a reduction of 27% of LDL cholesterol versus 30, that's pretty significant. It was very similar. It had greater effects in lowering total cholesterol levels. And it's funny enough, it doesn't give you the muscle aches and pains that the statins can do in some people. So I find that interesting. 

Andrew: Is that because I have this very vague memory of red yeast rice was working, yes, as a statin, but there was also some other actions. Is that how it's sort of protecting against this, myositis issue? 

Brad: That's correct. When you think about it, a statin is very specific for a pathway. It's looking at inhibiting or reducing one pathway which is HMG CoA reductase. When we use more nutritional / herbal formulas, they have this multifunctional roles, so yes it is working on the same pathway as a statin, but it's also working with other fatty acid metabolism pathways and slightly down an anti-inflammatory route. There's not a lot of research done on this molecule because it's sort of, it has its ebbs and flows. Like, every now and then I'll have people ask me about it and then a year or two go by.

Andrew: Yeah. 

Brad: And then I won’t get asked again. But there is enough research for me to be happy for people to use it. Like, a reduction of 1 millimole of LDL cholesterol, that's actually a very good result. It doesn't sound like much to people, but when you only have, you know, 3 to 5 millimoles depending on the person of LDL cholesterol in a general person, that's actually quite a significant drop. 

Andrew: So it's a reduction in LDL not total cholesterol? 

Brad: Funny enough, both. Total cholesterol and LDL cholesterol. But what they found was it didn't have any major impact on triglycerides or increasing HDL. So it may be working on the very low dense lipoproteins, and other factors as well. 

So it's very interesting. And the other thing is, I quite like using this in some people when they’ve used statins and they've had that really severe aches and pains, is this formula doesn't seem to reduce ubiquinone in body. So it doesn't have an effect on the coenzyme Q10 levels. 

So for me, there's enough evidence for me to start using red yeast rice and clinic. It's not a supplement that's had a lot of research on it, but there is enough for me as a practitioner to utilise it, and do some clinical research myself. But, again, I'd like to see larger studies. 

Andrew: Yeah. What about policosanol? 

Brad: Oh, there we go snap. Policosanol is another one that has its ebbs and flows as well. And an interesting thing about this, this is...it's a mixture of long chain, you know, aliphatic alcohols and it's available in a number of plants and some time ago in the 1990s was put into a supplement. And, again, it has this mild inhibition of HMG CoA reductase. So, again, a very mild statin effect. 

The interesting thing is, a lot of research is from the 1990s. They did find a lipid-lowering effect in healthy patients or volunteers, I should say, people who have high cholesterol, people with type II diabetes, even in postmenopausal women, they found a lipid lowering effect, particularly with LDLs. And some of that research was around about 25% reduction and a 10% increase in HDL cholesterol. But the interesting thing is, there's a very limited amount of research. A number of the research came from the 1990s often from Cuba. So the research was in Cuba, and a lot of other research may not have necessarily backed that up. 

Andrew: Yeah. So we have the issue of bias there. 

Brad: So a little bit of issue of bias. And why hasn't there been a lot of studies done since? Is my also view as well. So a lot of research is from the 1990’s. Sometimes we move on when we find a result, but I'd like to see a resurgence in policosonal because quite a number of people use it. They buy it. They read the packet, so to say, or they read a blog, or, you know, internet search on it, and they find that policosanol was quite good. But they're not understanding that this is the older research that needs to be reconfirmed today. Although we were saying earlier that we shouldn't discount on research, we need to think about a lot of this research was from the 1990s from the… most of it from the one country. So we should expand on that point. And, yeah, doing some clinical trials in Australia would be great. 

Andrew: What about plant sterols? They sort of hit a high point around about five, six years ago. Apart from, you know, this sort of flutter. Every now and again you'll see a margarine ad coming up, which just makes me shake my head. 

Brad: I find it interesting. I'm laughing at it like yourself that we're trying to do one good thing, and we're using a vehicle is what they call it, it's margarine. And I query the carrier of the vehicle of it that, 'Yes, we should have, you know, food sources, but a lot of the food sources are varied and not a higher dose. But we should think of something of it better than margarine.’ 

The interesting thing about plants, there are a number of research papers showing it does decrease intestinal absorption of cholesterol, you know, in the large intestine, for example, in the small intestine, I should say. It decreases the cholesterol pool in the liver. Which then increases the expression of LDL receptors resulting in a higher intake of plasma LDL. The body then metabolises it a lot better saying, you know, the LDL fractions are changed in the body. The body itself kicks into gear to metabolise it more effectively. 

So there is research showing reduction of LDL cholesterol, and a lot of the research has shown 1 to 3 grams of plant sterols. So that's quite a lot. One to three grams. Reduces LDL cholesterol by around about 5% to 15% because the studies are quite varied. But if you're thinking of that plant sterol dosage in a dose of margarine, and that margarine maybe five grams. I can't remember how much of those are plant sterols...and it's not going to be more than half of that in margarine because it’s not… It just doesn't make sense to me. 

So, for me, plant sterols, there is enough research again, for me to start thinking about using it. I’m going to look at the plant sources. I’m going to do more research into that myself. Later on today, I'm going to do more reading into it. But, to me, it's the vehicle that's depleting the researchers and should they have chosen a different vehicle, they may have actually had a better result in LDL reduction. Because the margarine itself has a negative impact on the body. 

So for me, the jury still out on plant sterols, mainly because of the margarine component. But there is enough there for me to say there is merit in plant sterols. The physiological effect where how it lowers the absorption of cholesterol in the intestines, it decreases the pool in the liver, and makes the body start to utilise the LDLs more effectively. There is enough physiological research for me to start thinking, "Yes, I'll prescribe plants sterols more, but no, not in the vehicle of margarine." 

Andrew: What about polyphenols and antioxidants, for instance? I hate that word ‘antioxidants.’ But, you know, let's term them antioxidants and just be done with it. You know, it's been very controversial. The national heart foundation of Australia has basically said there's no evidence. Ross Walker has countered that. And they said, "Why are you always asking something that takes decades to work, indeed, a pathology that takes decades to express?" And then you're asking this intervention of a few weeks, even a few months to have a beneficial reversal effect when, instead, what you should be doing is taking these things over at least five years, probably 10 years before you're seeing any benefit. What's your comment? And what's been your usage of these? 

Brad: Well, I totally agree with Ross here. Because it just makes sense that a condition that doesn't happen overnight, can't be treated by something overnight. 

So five to 10 years is, people saying...That's a long time. Well, it is. But it's also been a long time that you've been eating a poor diet…

Andrew: Yeah. 

Brad: And not exercising properly, so you're not helping yourself. That takes time to develop. 

Now, I'm a bit funny with the word antioxidant as well. Because half the things we prescribe are antioxidant in nature, and the other half form or metabolise antioxidants as a nutritionist, naturopath. So pretty much a lot of the things we do are antioxidant as a phrase. 

Now, the thing about polyphenols is… the Mediterranean diet full it, of course, the olive oil, the red wine, the fruit and vegetables. Red wine always gets people's interest, they think "I can drink a glass of red wine." I go, "Well, settle down there.” You know. Red wine's good. My favorite chocolate, as we talked about last time, does have a polyphenol component to it along with the cacao and other things as well. So there are a number of foods that we can utilise with polyphenols. So we don't always have to have a glass of red wine, although we do enjoy that particularly next to a fire, kicking back relaxing, but no... 

Andrew: With some chocolate. 

Brad: ...no marshmallows. Yeah, chocolate is okay but no marshmallows. 

Andrew: No marshmallows, yeah. 

Brad: So, there's research coming through that, again, that some of the polyphenols may again inhibit HMG CoA reductase pathway. So similar to a statin. There's research showing, you know, reductions of LDL cholesterol in some cases, up to 30% reduction. That's a massive reduction in anyone's book. 

Andrew: Yeah. That's huge. 

Brad: Triglyceride levels, 30% to 40% reduction. And we think, "Wow, you know, that's a large amount," and some of these are products, so like Bergamot, for example. You know, from Bergamot itself.

Andrew: Yep. 

Brad: And others are just, you know, again, red wine studies and chocolate studies, etc. that have been found to improve the metabolic profiles. It's not just cholesterol, but platelet function, coagulation, anti-inflammatory pathways. 

So polyphenols need a lot more research. But the interesting thing is, since they are wide and varied in the diet, olive oil, red wine, fruit and vegetables like I was saying…

Andrew: Yes. 

Brad: It takes a long time for dietary studies to show a positive result in the reduction of, let's just say, you know, the bad side of cardiovascular disease, you know, the LDL cholesterols and platelet function coagulation, etc. 

But if you have a life long, Mediterranean style diet, low glycemic index, the classic stuff we're talking about earlier. This five to 10-year period, is actually more achievable. When you say to someone, have a healthy diet, a healthy lifestyle, yes, you can drink red wine, but watch the limit that you're having. Go for a walk every day. Do your hobbies. Have a timeout, you know, all the classic stuff that we talk about. This will have a greater impact on cardio and metabolic syndrome. But also on the wider health of the person, particularly mental health. Polyphenols play a major role in their health. And, again, I'm all for it. More research needs to be done on its individual components, but, again, when we eat nuts and seeds and vegetables, we're not eating selenium, or a certain nutrient. We’re combining the nutrients like, Frank's work and that formula we talked about earlier. We're combining more than one thing together to get that synergistic effect. And polyphenols are the way to go. 

Andrew: Salient point, Brad. I love the way that you've really tied that in because the evidence really reflects that. That you can't take a supplement and ask it to battle a poor diet. You've really got to look at your diet. Thank you, so much for taking us through these relevant issues, relevant interventions today, and, indeed, what to look out for and what to be cautious of when looking at formulating a lifestyle and, you know, a supplementation plan for somebody with a cardiometabolic issues. And I look forward to our next Podcast. It will be great. 

Brad: So do I. Thank you very much. 

Andrew: This is FX Medicine, I'm Andrew Whitfield-Cook.

Additional Resources

Dr Bradley McEwen

Research explored in this episode

Aung T, Halsey J, Kromhout D, et al. Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks. Meta-analysis of 10 Trials Involving 77 917 Individuals. JAMA Cardiol. 2018 Jan 31;3(3):225-233.

Mozaffarian D, Marchioli R, Macchia A, et al. Fish oil and postoperative atrial fibrillation: the Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial. JAMA. 2012 Nov 21;308(19):2001-11

Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007 Mar 31;369(9567):1090-1098.

Mahmood SS, Levy D, Vasan RS, et al. The Framingham Heart Study and the Epidemiology of Cardiovascular Diseases: A Historical Perspective. Lancet. 2014 Mar 15; 383(9921): 999–1008.

Drudi LM, Schaller MS, Hiramoto J, et al. Predictors of change in omega-3 index with fish oil supplementation in peripheral artery disease. J Surg Res. 2017 Apr;210:124-131.

Allaire J, Harris WS, Vors C, et al. Supplementation with high-dose docosahexaenoic acid increases the Omega-3 Index more than high-dose eicosapentaenoic acid. Prostaglandins Leukot Essent Fatty Acids. 2017 May;120:8-14. 

Bang HO, Dyerberg J, Sinclair HM. The composition of the Eskimo food in north western Greenland. Am J Clin Nutr. 1980 Dec;33(12):2657-61. 

Dyerberg, J, Bang HO, Soffersen E, et al. Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet. 1978 Jul 15;2(8081):117-9. 

Bang HO, Dyerberg J, Nielsen AB. Plasma lipid and lipoprotein pattern in Greenlandic West-coast Eskimos. Lancet. 1971 Jun 5;1(7710):1143-5. 

Leong JY, van der Merwe J, Pepe S, et al. Perioperative metabolic therapy improves redox status and outcomes in cardiac surgery patients: a randomised trial. Heart Lung Circ. 2010 Oct;19(10):584-91. 

Rosenfeldt FL. Editorial: Metabolic Supplementation with Orotic Acid and Magnesium Orotate. Cardiovasc Drugs Ther. 1998;12:147-152.

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