NIACIN Biomarkers pt2: Clusters & Macroctyes

NIACIN Biomarkers pt2: Clusters & Macroctyes

August 14, 2019 18 By Bertrand Dibbert


Niacin is one of those supplements
that everybody – a lot of people love to hate and why is that? why the debate?
Again, because you see some conflicts in the (scientific) literature. We’ll go into some
of those conflicts and some of the results in the second half of this video
this video’s on a – on an article that was suggested by Dr.
Angie Stones – Thank you again Dr. Stones. One of our viewers and, again, it’s
incredible what you learn from others if you just stop and listen. I’m
glad I stopped and took a look at that article. Without further ado, let’s go
ahead with part two of the article. Part one actually went into
this huge list of – of biomarkers that they were looking at, and it started to
talk a little bit about correlations. I bogged down a little bit there,
because, again, you can go back and look at the last half of that last video, you
see it gets somewhat tedious. Now, this part of the video talks about the actual
results and then it talks about – a very interesting part – clusters; clusters
of different components of the biomarkers and one of my favorite
clusters here has to do with macrocyte function and you’ll see why in this
video. Again, pardon me – may be spending too much time on that, let’s go into some
of the conclusions and discussions. So all subjects, again, the nineteen of them
had an atherogenic mix of dys – lipedema and insulin resistance. Their
ages – the mean was 47 with a standard deviation of 13 years; body mass index was 32 so, as I
said, these were obese middle-aged men; plasma triglycerides coming into it were
two seventeen cholesterol LDL or bad cholesterol was
125 so they had bad numbers coming into it as well HDL was very low. HOMA IR, as I mentioned before, was 3 times normal. Now, this was only an 8
week study and the – the folks that are major proponents of insulin
(I mean niacin) and I’m a proponent of niacin like everything – I don’t see
anything as black or white – I do think there – there’s more than just a signal in
the literature which would indicate benefit.. There’s a mixed bag of things going on
in this study. Actually, that’s what the – this study does. It goes into the
molecular reactions and says there’s clearly a mixed bag: you do get
some increase in insulin resistance and you get some improvement. A lot of other
areas and, again, I think some of those other areas are very, very interesting
and very helpful. I would say this – I get a lot of focus from viewers on the
increase in insulin resistance. I think John and I are both good examples. We’re both managing our insulin
resistance very well at this point and it’s a pattern that I see typically –
not within 8 weeks but within 6 months assuming you do the things you’re
supposed to do. The impact on insulin resistance does not appear to be
permanent. That’s one of the questions raised by this study, so yes it – it shows
that you do have an increase in insulin resistance but over the two months, well,
we already knew all that. What it doesn’t show is the impact over at 6-month
period. A couple of other things that it does show that are very interesting –
there are no changes on – on body mass index, things like that. It improved the
diyslipidemic profile. Here’s a couple of things that I thought were
very interesting – adhesion molecules and macrophage activation. Now why would they even look at that? Well, remember – let’s go back and think about
the mechanism for inflammation. First of all, it’s not so much having high LDL
that causes the problem, it’s having injury to the endothelium or intima so
once you get those cuts, nicks, injury to the endothelium, the lining of the artery –
that’s when LDL can get slipped through there and lodge in the wall of the
artery – the intima media space adhesion model molecules; then it stands
to reason and, again that’s just one of the theories that this hypotheses that that creates – does increase in adhesion molecules cause some of this problem? – In other words, things sticking to that slick endothelial lining of the wall due
to cuts and things like that – macrophage activation; why is that
interesting? Well, again, let’s think about inflammation. Once you get this plaque in
your artery walls, your immune system does want to come in,
absorb that LDL that’s parked in that artery wall, digest it and get it out of
there. Well, how does it digest it? Macrophages come in; they (I’m using a
little non verbals here) – they grasp the LDL, they bring it in there; Lysozymes
release enzymes within that macrophage to digest that LDL. Now, what happens with
significant inflammation – you get so much of this lysosomal activity – these
digestive enzymes in the lysozymes being released that it damages and even kills
the macrophage. So, again, you – there appears to be, at least in terms of
hypothesis generation, a major component of macrophage activation; to the extent
that you have death of the macrophage and spilling of those lysosomal
contents. That’s where you get the liquid – hot liquid plaque and that – that
again is what’s dangerous. That’s what causes the climb and the clot causes the
heart – the heart attack, the stroke, the dementia and all those other bad things.
So let’s just go through here – like I said, this article was gonna get geeky
enough and detailed and long enough without me going over a lot of the intro
stuff so I’ve been very geeky. Those of you who are starting to get bored, this
is going to go get even more so. So you may not want to watch the rest of it but
for those of you who are interested in again, deeper details around the
biomarkers, I couldn’t help but underline some of these issues as you see on this
page. I couldn’t help but underline a lot of them and why is that? Because this
page is talking about clusters. Clusters of those biomarkers and wanted to spend
some time going over that. So at a significance level of probability of
.001 – what that means is with – they found a lot of clusters of these
biomarkers and if you looked at it from a probability perspective, the
probability was one in a thousand. So there’s probably significant correlation
in these clusters. Now, what were the clusters? There were 7 distinct
clusters. The first one is a decrease in triglycerides – was strongly
(excuse me – negatively) correlated with increments in those like hdl-c Duh! if you haven’t seen any of my videos
on the triglyceride / HDL ratio, you need to take a look at them. Those decreasing
triglycerides, increasing HDL both have an impact – very positive impact and – you
know a high ratio of triglycerides over HDL is my major tip-off. That’s the first
thing I look at when I look at a cholesterol test
because it shows the patient has metabolic syndrome or insulin resistance.
Insulin causes the body to shut down triglyceride (fat) burning and it also tends
to chew up HDL so that’s why you tend to see that with high insulin level levels.
Now, furthermore, theHDL-C cholesterol and apo a1 ratio is integral to that
cluster. Significant thoughts in terms of – okay what’s going on here?
reduction in total cholesterol and LDL were the main – main drivers (bad English) of a cluster integrating reductions in apoB & Lp(a); Apo a1 was significantly associated with this cluster. So, again,
John has told you a couple of times, he’s got what he considers to be significant
Lp(a) when I think it’s 120s, 130s, 150s, 180 is that kind of number like I’ve mentioned before, I take care of
several people that have 400 500. They – you know – they’re – they
have some of that French, Canadian gene pool creating significant Lp(a)
problems. Now, what does this mean? It’s just that Lp(a) is significantly
associated with apoA 1 and apo b 1 I think what it’s – again – more
hypothesis-generating given my experience, I think what that
means is Lp(a) and again given my experience with it, I think
this is supportive of the hypothesis that Lp(a) is
really more of a reaction to things that you’ll see with apoA1 and apoB. In
other words, getting insulin resistance and damage to the – that intima back under
control; we gets out of control and Lp(a) appears to be something that
increases to help patch that up. The third cluster – insulin resistance HOMA
IR insulin and il-6 levels. Now, what was interesting, however, fasting glucose
levels were independent of this cluster despite significant elevation on
treatment. So on treatment reduction in apo e levels did not correlate with
changes in any lipids and he was (Tom Decker, one of the viewers made a couple of comments about that) but rather clustered
with those circulating of mmp-9, it’s a matrix metalloprotease produced by – monocyte-derived macrophages. Again, we get back to the role of macrophages in this
inflammation process. Now, there’s a separate cluster elevation in
adiponectin on treatment correlated with non
significant increment in cystatin C. 2 distinct clusters of inflammatory
markers were identified, 1 with I cam 1 and 1 with TNF; TNF is tissue
necrotic factor. Now, remarkably, and despite a 20% decrease on treatment
concomitant with those with athero- genic lipoprotein lipids, changes in apo c3 levels were independent of all other biomarkers. What does that mean? I
have no clue. If – if you do, please comment please fill us in with respect to biomarkers associated with hepatic function and
metabolism glucose tolerance levels decreased independently while those of
homocysteine increase. So there’s a lot of folks out there that love to focus on
homocysteine and you’ll go “Aha! that’s the problem with niacin. It increases
homocysteine.” Maybe you’re right. Again, I’m not stopping my niacin. NSC
is a potential marker for macrophage activation. It was
independently reduced and, again, it goes on into further components of
inflammation. Here’s another way of looking at it. Here’s the actual tables; I’m gonna zip through these lipids and lipoproteins, bad cholesterol, LDL 17% decrease; apoB – B which is the protein part of bad LDL 21% decrease; HDL 13% increased; so a lot
of interesting things; Lp(a) 21% decreased; and apo A 25%
decreased; Again, we’ve had several people focus on that. I don’t think I’m smart
enough to understand fully the impact of apoE. Now, I’ve done several videos on
apoE and I’ve had – obviously, I know several facts about it but I think
there’s some more subtle theories going around that I’m not sure that’s
significant. Anyway, HOMA IR increased; insulin increased; and c-peptide
increased. C-peptide is a part of the original genetic structure of insulin
before it gets cleaved into functioning insulin – so what that basically means
that – I don’t think that’s that significant for this study, other
than to mean that – you know – this was endogenous or insulin made by the person
and these people weren’t getting insulin so that’s why I don’t – I don’t understand
their desire to get that, other than just to be complete but significant immediate
insulin resistance, as I’ve said I’m not surprised about that; My question is – Does
it last six months or longer? and I don’t think that’s the case. Look at some of
these inflammatory markers: tissue necrotic factors – three of them here;
12%, 12% and 14% decrease; CRP took a nosedive – 36 – 40% decrease; homocysteine 26% increase; adhesion molecules (I
haven’t heard of those before, I’ve heard obviously of the adhesion process)
but, again, significant decrease in adhesion. So, as we talked before, maybe
that’s helping; maybe that would help decrease this process of plaque getting
deposited because first the theory is that – first. it has to get stuck or
adhere to the lining of the artery before it gets there. Now, as I have said
many times, once I get going on the geeky parts of some of this, I can go forever.
As our friend, I don’t even remember his name now, said – there are always answers.
Be careful when you start getting there though because every answer creates a
whole new set of questions. If you’ve made it this far, thank you very much for
your interest.