If I've heard it once, I've probably heard it a thousand times from
my wife that if I would just listen I'd learn a lot more. I have to admit she's
right; I've always learned more from patients, other docs I was working with
and now that I'm concentrating on the YouTube channel, I'm learning a lot from
the viewers. Angie Stones, thank you for
introducing this article. We'll talk about this article in just a minute. it's
a recent update that gets very, very deep into or maybe very molecular (in the
adjective sense of the word) into niacin. So Tom Deck reviewed it, said "It's a
great, a good article". He had some interesting comments about apo c3, apo e
VLDL, LDL, and small dense LDL. But let's go into the article itself. Now,
before we do, I will have to say this: According to the authors of the article,
you know, there were only 18 people; There were 18 obese middle-aged men;
40s, 50s, 60s - that had metabolic syndrome. What they said was this - was that
"hypothesis-generating study" whenever you see that term - it reminds me of
this quote somewhere, and I decided to look it up. Now, I've never heard of this
guy, David Levithan ever before, but here's the thing, the quote "Every answer creates new
questions" and that's the whole point with this article. That's what a
hypothesis-generating article is. So let's go back. We'll click
on, and you Dr. Angie Stones' link
and you get to journal of clinical epidemiology May - June 2018
"Niacin action in atherogenic mixed dyslipidemia of
metabolic syndrome: Insights from metabolic biomarker profiling and
network analysis". It sounds very deep and you noticed is - this niacin
study group. Before I go there, I'll just make a comment -
they really complicated the heck out of that article title. Basically,
what it's saying is - they're looking at Niacin. As we all know, there's a lot of
questions about: A. the biggest question is: Does niacin work or not? and B. If
so or if not - why?
and the reality is, they did raise a lot of questions. And, again,
we'll get there in just a couple of minutes but first, what is this niacin
study group? The link didn't take me anywhere so I actually tried looking up niacin study
group in Wikipedia and a couple of other places. I can't find it. If anybody knows
anything about the niacin study group, I'd be very interested in hearing about
that. There's a - there's. (these study groups..) - for example, the statin
Study Group. Rory (Collins) is very Pro statins so, most
of the time, if you see stuff coming out of - from the statin Study Group, you're
gonna see pro statin results. Niacin study group - I don't know. I've never
heard of it. I'd love to find out more about it. Now, before I go through the
details of this study, from here I put it on my usual Adobe so we could see a
little bit better and so I could mark it up and unfortunately, I really geeked out.
I ended up spending three hours on this article because it's very, very
interesting. I'm jumping to this image.
You can see this image is really talking about clusters. So, for example, hdl-c
increased, triglycerides decreased significantly; over here, tissue necrotic
necrotic factor - an inflammatory component decreased. Now, if you look at
this group up here, these are really more of the lipid profiles: apoE
apo B, Lp(a), LDL, apo, a1c, all of these - for the most part you get
improvements in the lipids (these green images) However, down in the bottom, this is all
glucose metabolism related stuff and, as you see, these greens are not always good because
you get increase in HOMA IR. Basically, HOMA IR very good and type
of analysis. It's a different, more technical type of analysis of insulin
resistance. So you got an increase in insulin resistance. Now, these guys came
in with a HOMA of what? 6 on average the normal HOMA IR should be less than 2;
certainly less than 3; so these guys, as I said they were obese middle-aged
man with - 19 middle-aged obese men with significant
insulin resistance coming into the study. Now, let's look over here. So here we are at
the top left; we have a cluster associated with lipids and, again, for the
most part significant improvements in the lipids. In the bottom left we have
the glucose metabolism area. Both of them have a little inflammatory marker IL-6.
Down here with the glucose and TNF alpha, up with the with the lipids and now here's
the major cluster of the inflammatory factors on the right.
CRP took a major dive, high sensitivity CRP c-reactive protein
and tissue necrotic factor (tnf). The other ones over here. All of those took
significant decreases so that is a great way to look at that picture in terms of
of what they showed. Let's go back to the title page; this is the place that I
looked it up - again, Journal of Clinical Epidemiology. Here it was in the Elsevier
- a group of journals. They tried to charge me for it but I was
able to get some get some of these images
either that or I've been through the paywall in the
past and forgot all about it. Now, I'm not gonna - they did have a good introduction.
This is going to be long enough and geeky enough but get out - without getting
into the introduction but I will tell you as you go through this. Basically,
this article shows time and time and time again, as you get deeper into the
molecular impacts of niacin, it's a mixed bag and that mixed bag could have
resulted in some of the mixed bag of impacts that we see. For example, the
studies like AIM HIGH and HPS 2 Thrive. Now, again this studies long enough; this
video is gonna be long enough; I'm not going to go through all the details on
the introduction in the background, I'm just gonna go to some of the
images. This is sort of like when I was a kid, I'd - you jump over all
the text because you get really bogged down. Unfortunately, I'm not that smart I
didn't jump over all the text, I read it. That's why I ended up spending a couple
of hours on it. But the images often show you the most important part of what's
going on. I had a mentor once, who would go in any article & he'd go straight to
the tables, the images. And, again, he was right; they show you
what you need to look at now. Unfortunately, you can't see all of the
things on - on this image but, basically, what they did - the vertical axis and
the horizontal axis are both the lists. The extensive list of the molecular
biomarkers that they looked at. Now, the - this green line that's totally green
right down the middle here is because you're looking at correlation. Top green
is a one-to-one perfect correlation bottom red is a negative. So, in other
words, it's significantly inversely related and then gray is zero where it's
maybe not so clear. So, again, this perfect green here is where the molecule is
perfectly correlated with itself. apoE, for example, is perfectly correlated with
apoE here. The third one - down the third one across. Now, let's look at something
that might be inversely related. I saw those a few minutes ago; apo B,
Homa, for example and well ... anyhow there were some interesting
correlations in here and, unfortunately, now that I've gone back and burned a
couple more hours of time, I can't find this but that's the way you look at this.
You basically look at something like - well, let's just go ahead and look at it.
HOMA - and it correlates perfectly with HOMA. it
correlates negatively (inversely) with TM and
with total cholesterol is fairly inverse to il-6. I guess that's interesting. Total
cholesterol is also negatively associated with HOMA. So, again, you're
getting some decrease in total cholesterol with niacin but an increase
in the HOMA, so that's what that means. You can see that right here in the
middle. Let's look at things like tissue necrotic factor, graphs - they don't have
them in alphabetical order and c-reactive protein - Actually, a fairly
grey type of correlation. Again, pardon me, maybe spending too much time on that.
Let's go into some of the conclusions and discussions. Actually, in editing this
video, I decided we really needed to break here and that's why you see the
different background. On second thought, what we're going to do is go back cut
this off now and as just a brief review we've talked about Etiel and this
group went way deep into studying the molecular biomarkers associated with
niacin. Again, thanks Dr. Stones for recommending this article. In the next
- the next video, it gets even geekier. It starts going into clusters. There
are 7 significant clusters of biomarkers and we'll get there next.