after our video on seed oils and inflammation, a lot of viewers have asked about cardiovascular
disease. do seed oils and omega-6s affect heart disease and cardiovascular disease?
so I recently sat down with Dr Kevin Maki. Kevin is the current president of the American
national lipid Association and the founder of MB clinical research and Consulting. he's
published hundreds of studies and book chapters on lipid biology, including work on omega-6's,
saturated fat and cardiovascular disease, so I figured no better person to address these
questions with. my goal is always to bring the top science and the top scientists on the planet
straight to your electronic device, so I'm really excited to release this series of videos with Dr
Maki. it's not just the nuggets of knowledge he shares with us, it's also getting to see
how professional scientist thinks and talks. as he answers my questions, try to notice how
every statement is rooted in evidence, how cautious he is, how he qualifies everything,
how he acknowledges areas of uncertainty. we live in an age of influencers yelling at
you about poison and toxins and superfoods with absolute unshakable confidence and no evidence,
so I think platforming more scientists is exactly what we need. enjoy. as you might know, there's a
lot of questions, a lot of curiosity by the public on the internet about omega-6s and omega-6-rich
oils and all these things, and people are getting all kinds of different messages from different
sources on the internet so it'd be great if you could give a slightly summarized version of that,
kind of the overview of the field, what is the evidence, and specifically with regards to
cardiovascular disease, what do we know in terms of the effect of omega-6s or omega-6-rich oils on
cardiovascular disease and kind of the main lines of evidence. sure thing, well there are two main
lines of evidence, observational evidence and then randomized controlled trials, and for randomized
controlled trials, unfortunately we don't have modern large-scale outcomes trials. for the most
part, we do for a few things like a Mediterranean dietary pattern, but most of the randomized
controlled trials that looked at actual outcomes like heart attacks and strokes and death were
completed decades ago and so they're difficult to interpret. so from the observational evidence,
what we generally see is that a diet higher in unsaturated fatty acids, and that would be either
omega-6 polyunsaturated fatty acids or omega-9 monounsaturated fatty acids, is associated with
lower risk for cardiovascular disease events, and saturated fatty acid intake is associated
with higher risk, but you always have to ask the question in nutrition, compared to what? and so
it does depend on what you compare it to. when you compare saturated fatty acid intake to trans fats,
trans fats are worse. when you compare saturated fatty acid intake to unsaturated fats, saturated
fats are worse. when you compare saturated fats to carbohydrates from starches, refined starches
and added sugars, they're roughly neutral. and when you compare saturated fatty acid intake to
intake of carbohydrates from whole grains, the saturated fatty acids look worse. so you know,
the question is always compared to what, and then we also have randomized controlled trials
to look at the effects of different fatty acids on biomarkers of disease risk, and so one of the main
biomarkers that we look at is LDL cholesterol. LDL-cholesterol is a surrogate marker, really,
for atherogenic lipoproteins, and a better marker is apolipoprotein B, because every potentially
atherogenic lipoprotein particle has one molecule of apob, so that's LDL particles, vldl particles,
chylomicron remnant particles and then IDL or intermediate density lipoprotein particles and
Lp(a) particles. so all the bad guys have of one molecule of apob. so I like to look at that but we
don't really measure that clinically in the U.S and so we use LDL cholesterol as an imperfect
indicator, and so what we see is if you feed people saturated fatty acids, LDL cholesterol
goes up, if you feed them monounsaturated fatty acids, LDL cholesterol goes down a little bit
compared to carbohydrates or saturated fats, and if you feed them polyunsaturated fatty acids,
omega-6, LDL cholesterol goes down more, so just to put that into perspective, compared to usual
diet, in a controlled feeding study that we did where we gave everybody all of their food during
the study period, we found that extra virgin olive oil, which is rich in mufas, monounsaturated fatty
acids, lowered LDL cholesterol by about three and a half percent. corn oil, which is rich in
omega-6 linoleic acid, lowered LDL cholesterol by about 11%, so LDL cholesterol is a biomarker that
we use to estimate risk, it's only one factor, but as far as lipoprotein levels go, as far as
the observational evidence goes and as far as the limited evidence we have from large-scale
randomized controlled outcomes trials go, the real winners are unsaturated fatty acids, and
that's both mono and polyunsaturated fatty acids. in our study that I mentioned where we fed people,
the lipid levels looked better with corn oil but blood pressure and heart rate went down with extra
virgin olive oil so I'm a fan of saying that in general in the U.S we eat more saturated fat than
is optimal and we should be striving to replace some of that saturated fat with unsaturated fats,
and that would be both linoleic acid or omega-6 and things like canola oil, avocado oil,
olive oil, that are rich in monounsaturated fatty acids. one thing that people ask when it comes to
observational data, there's a couple of caveats, and one of them is the Reliance on self-report,
there can be error, there can be... people may not be completely forthright or they may not remember,
things of this nature, but to some extent with omega-6s and with linoleic acid in particular
there is, I understand, a sort of a way around it by measuring serum markers, so to what extent
is that a reliable measure of intake and to what extent is... what has that taught us
in terms of also cardiovascular outcomes? when it comes to biomarkers there are certain
fatty acids for which biomarkers can be very valuable, so like omega-3 fatty acid intake,
when you look at things like red blood cell membranes, when you look at plasma phospholipids,
even total plasma levels, they really vary a lot, specifically EPA, icosa pentanoic acid and DHA,
docosahexanoic acid, dietary variation produces variation in these biomarkers,
so it works really well for that. works pretty well for linoleic acid as well, again, an omega-6
pufa. for other fatty acids not as well because, as an example, when humans convert carbohydrate
into fat they mainly produce palmitic acid, so the palmitic acid level in the blood reflects partly
what's in the diet and partly how much de novo lipogenesis is going on. so you have some similar
problems with the monounsaturated fatty acids, so again it depends on what you're looking at,
but you do get around this issue specifically with linoleic acid and EPA and DHA of uncertainty
because dietary measurements are very crude, if I ask you, over the last three months how many times
did you eat this? you're going to give an estimate but who knows how accurate it is. and so for huge
groups of people it works reasonably well, for smaller groups there's a lot of imprecision,
and so biomarkers are very helpful because they can help us quantify the exposure to these levels
of fatty acids. and then there are genetic variants that also influence the biomarker
levels and so forth, so they're not perfect tools but they are very helpful, and for the most part
when it comes to the omega-6 polyunsaturated fatty acids, the biomarker results really align very
well with the results from dietary estimation, and so they tell a pretty consistent story,
lower risk of cardiovascular disease associated with higher intake of omega-6 and omega-3
polyunsaturated fatty acids. my conclusion is that the bulk of the evidence, which has limitations,
supports the idea that we should be consuming more unsaturated fatty acids and try and replace
saturated fatty acids with unsaturated fatty acids from both omega-6 pufas and omega-9 mufas. what
about Omega-3s, are you leaving those out for a reason? not leaving them out for a reason,
I think that we have some pretty good evidence now and it comes from a number of sources,
that EPA in particular is helpful when it comes to cardiovascular disease risk, we have three
studies, none of them are perfect, but we have the reduce-it trial, we have the JELIS trial and then
we recently just saw results from respect-EPA, another study done in Japan like JELIS,
and all three of them have essentially shown the same thing, reduced cardiovascular disease event
risk when EPA is given, and it has to be at a decent dose, 2 of the trials use 1.8 grams a day,
one used four grams a day, and all three of them showed basically concordant results, sort of 20
to 25 percent reduction in cardiovascular disease events. respect-EPA for the primary outcome had
a p-value of 0.055, so taken in conjunction with JELIS I think two trials in Japan with essentially
the same intervention have shown benefit, and then in the reduce-it trial, which was four grams a day
of EPA or very close to four grams a day, about 3.8 grams, that trial showed about a 25% reduction
in the primary outcome which was cardiovascular disease events. the one fly in the ointment there
is that the placebo that was used was mineral oil and we have some evidence that mineral oil
makes some cardiovascular risk factors worse, and so what I would say is, it is possible that
some portion of that 25 percent was due to the adverse effects of the mineral oil on outcomes,
but when you... let's attribute five percent to that, that means we have three trials that
have all shown roughly 20 percent risk reduction with an EPA intervention. one of the things that
taking EPA does is it suppresses blood levels of arachidonic acid, so one possible contributing
mechanism is not only the benefits of EPA but the benefit that may result from reducing blood
levels of arachidonic acid. there are a couple of common questions in this area that people ask
when they hear this idea that unsaturated fats are more Health promoting or more cardio protective.
the main one is probably regarding a couple of specific randomized control trials from
the 60s and 70s, Minnesota and Sydney, this is probably question number one.
what do we know about these trials and are there caveats, how reliable are they, what do they teach
us? well, I think a lot of caveats, and kudos to Chris ramsden and Joe hiblin for going back and
unearthing more information about these trials so that they could really be considered but there's
only so much you can do when a trial was conducted decades ago and you're sort of forensically trying
to reconstruct what was done. also, the outcome that was really focused on was cardiovascular
mortality as well as total mortality, and that's a complicated outcome, so some of cardiovascular
mortality is due to events, heart attacks, and some is due to, heart attacks and strokes on the
one hand, some is due to arrhythmias. sometimes it's difficult to classify, so in modern trials
if you look at all of the myocardial infarctions that are submitted to adjudication committees,
very often 20 percent of them are rejected, and the conclusion of the committee that's reviewing
it is, we can't tell for sure that this is a myocardial infarction, so I think that looking
at trials from decades ago is problematic both in terms of assessing the outcomes and also because
people were very different then, a much higher prevalence of smoking, and years ago the diet
was very different, it was very common to have something like 16 percent of your calories from
saturated fatty acids back then as compared to about 11% today, so the people were different
in many respects, lifestyle-wise and in their characteristics, and the assessment of outcomes
was different than it would be in a modern trial, so I think they tell us some things but we have
to be very careful about over interpreting them, and so what I'll say is that for those studies
the conclusion was essentially that the studies did not support a benefit of replacing saturated
fatty acids with unsaturated fatty acids, with a couple of caveats, one issue that's been raised is
the possibility that the unsaturated fatty acids came along with some trans fatty acids, and we
can't tell, I mean you can't go back decades and say, well, we're gonna go to the storage unit and
take some of the intervention foods and test them, so all you can do is look at the records and try
and assess whether that was true. I think it's uncertain, and so I view those in the same way
I view a lot of observational evidence, they're reasonable for hypothesis generation and we really
need to test these ideas in large-scale randomized controlled outcomes trials, and I'm sad to say
that Spain is way ahead of us in funding those, it's kind of an embarrassment the United States
has not funded these trials even though every five years we update our dietary recommendations,
we don't follow that up with large-scale trials to test them. one specific argument or question I've
heard regarding Sydney is that this likelihood of the trans fats is not very believable because the
level of total cholesterol, serum cholesterol or LDL cholesterol, I forget which one they measured,
came down by 20 points or so, and so the argument is that if they were replacing... if
the comparator were trans fats you would expect an increase in total cholesterol. to what extent is
that a valid argument? yeah well you have these competing effects, so you have the influence of
the unsaturated fatty acids, and even if some trans fatty acids came along with it, you've got
unsaturated fatty acids lowering LDL cholesterol, trans fatty acids would tend to have the opposite
effect, and so the net would depend on the ratio of unsaturated to transunsaturated fatty acids,
and so that does bolster the argument that it was mainly unsaturated pufas that were being given,
but trans fats have a very strong and linear relationship to cardiovascular risk that's
probably partly mediated through effects on lipids but partly mediated through other effects,
so, again, it is just another one of the question marks we have about these trials, and why I am
hopeful that we'll see new trials undertaken, but one thing that I think may help with that is that
outcomes trials are very large and expensive and they take a long time to generate enough events
but we now have Imaging Technologies where you can have much smaller studies and look at a much
better surrogate marker than just lipid levels or blood pressure and what have you, and look at
the actual progression of atherosclerosis and you can do that non-invasively now,
and with new AI Technologies we're getting much much better at reading those and detecting small
changes, so I'm hopeful that we'll have dietary intervention trials where they
don't have to last for 10 years, they can last for a couple of years of follow-up and we´ll
have very reliable evidence about progression of atherosclerosis, which doesn't tell the full
story but it certainly tells a big portion of the story. so I'm optimistic we'll have that,
it's not going to be in the next couple of years but hopefully before I die of natural causes.
hopefully long before we're all gone. we also discussed the effect of seed oils on inflammation,
insulin resistance, body weight, the omega-3 to omega-6 ratio and a lot of
other topics so stay tuned for those videos dropping as soon as we can finalize them,
thanks for watching, take care, let me know your questions below, I'll catch you next week