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Sep 20

Siobhan Debuts on 2 Keto Dudes

Our very own Siobhan Huggins was on 2 Keto Dudes for a really fantastic talk. They got into Full Geek with a lot of in-depth discussion on immune response, modified LDL, and the receptors that love them! This should be required listening for anyone interested in the process behind lipids and their role in the larger process of atherosclerosis.

Lipid Dysregulation with Siobhan Huggins

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14 Comments on "Siobhan Debuts on 2 Keto Dudes"

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C
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Great interview! Check out this page: https://profgrant.com/2017/09/19/a-short-guide-to-reverse-cholesterol-transport/

It has an interested video that animates some of this.

Question – how does this all get calcified into hard plaques in the arteries? And are soft plaques dangerous (i.e. those that haven’t yet been calcified and don’t show up on a CAC scan)?

Siobhan Huggins
Admin
Yes I have seen! I agree it is worth sharing/viewing 🙂 As for your question, the truth is I don’t quite know yet! I could make some guesses (a hard/stabilizing protective “bandage” to protect damaged areas where rupture has occurred for example) but it would be just that – a guess. It isn’t something I’ve reached in my studies yet, although I certainly would love to take a magnifying glass to it and figure out why it happens! It was mentioned in the podcast that Ivor Cummins does touch on plaque a bit, and lo and behold he does have… Read more »
C
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Hi Siobhan, I just found a reference to a recent study on hard vs soft plaques, which seems to confirm that we really only need to worry about the hard (calcified) plaques: https://www.medicalnewstoday.com/articles/316408.php and https://intermountainhealthcare.org/news/2017/03/major-study-of-atherosclerotic-plaque-deposits-shows-potential-breakthrough-in-determining-risk-for-heart-attacks/ Unfortunately I could not find the referenced study on PubMed. If that is the case, then what is the specific mechanism that causes the calcification? I found this paper referenced on Peter Dobromylskyj’s blog (Hyperlipid…. been following it for a while now, http://high-fat-nutrition.blogspot.com/): https://www.ncbi.nlm.nih.gov/pubmed/17606264?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum I think it provides some clues. And would confirm what Ivor said in his Ketofest talk (wish I could have been… Read more »
xtronics
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There is great debate if calcified plaque is more dangerous that soft plaque. Some believe that statins do their little bit of good by promoting calcification. I think the amount of plaque is a good indication of the amount of disease – but doing things that reduce the calcification may or may not do net good. I take K2 – it is a hunch – I know I don’t know if it does net good. But if we look at CAD as 2 things – what causes it – how to prevent the cause. And what to do once we… Read more »
C
Guest

Here is a new study (August 2017) that further expands on the association between MGP, insulin and arterial calcification here: https://www.ncbi.nlm.nih.gov/pubmed/28654853

Unfortunately, the actual paper is behind a paywall.

They used HOMA-IR to estimate insulin resistance (I don’t know why they didn’t use the Kraft assay, which measures actual insulin resistance and is not dependent on a glucose variable). FYI, here is a convenient calculator for the simple HOMA-IR metric: http://www.thebloodcode.com/homa-ir-calculator/

Siobhan Huggins
Admin

Thanks for the link! I took a look through the study and to be honest it’s not altogether surprising (with what I know about insulin resistance and heart disease, and severity of atherosclerosis and calcification), but it does provide a hint as to where to begin with looking deeper into it.

I agree about the kraft assay, as well. I wish people would use it more often (especially in studies like this), but I am betting it will catch on the more time goes on.

xtronics
Guest
Exactly why do you see the correlation of cholesterol with atherosclerosis seen as causation? How do we know that the arrow of causation isn’t the other-way-round? (CAD causes an immune reaction that causes LDL to go up? ) or many other possibilities. First, we need to know what we don’t know – anyway – correlations don’t show cause and effect. If we look at the long list of drugs that reduce LDL and yet don’t effect mortality – one has to assume that it isn’t causative. Only statins have an effect – a very small effect – (NNT 83 over… Read more »
C
Guest

I have also been following Dr. Kendrick’s blog…. his latest posts have been phenomenal! Great stuff…

Siobhan Huggins
Admin
Hi, and thanks for the comment! Actually – I completely agree with you. I don’t think LDL (or modified LDL) is a root cause for atherosclerosis. I don’t even think native LDL contributes much (if at all) to the pathogenesis of the process, just based off of what I have learned so far. I merely have observed, based off of the evidence I’ve seen (e.g. studies, textbooks, etc), that modified LDL has a mechanistic role in the development of atherosclerosis. I realize that the title of the podcast of the episode may be rather misleading, but I do address in… Read more »
xtronics
Guest
As far as “modified LDL” – what ever that is – first LDL is not a single thing – it is a class of lipoproteins – an interesting subclass is oxLDL. If we consider oxLDL an important type of modification – we can then ask what changes the level of oxLDL? Turns out eating PUFA increases it – probably because they have double carbon bonds that are less stable than the single bonds found in Sat-fats. We also know that dietary polyphenols seem to lower oxLDL (but too much polyphenols isn’t good for us – no definitive studies for optimal… Read more »
Siobhan Huggins
Admin
You are correct in that the term “LDL” is a class – “modified LDL” refers to detrimental modification that can occur to this class (VLDL, LDL [phase], etc), this modification can mean a change in apoB (such as what occurs during glycation), a change in the fatty acids (such as PUFA oxidation as you mention), a change in the cargo (such as oxidation of the cholesterol e.g. production of oxysterol), and quite a few other things. Generally when modified LDL is mentioned it refers to oxLDL – but not always. Modified LDL, including but not limited to oxLDL, is recognized… Read more »
xtronics
Guest
Actually foam cells do swell the intima of artery walls – constricting flow – not a ‘good-thing’. These bumps are likely locations of clots forming – blocking the artery ( if you don’t like the word “crimping”) oxLDL is actually several things – and there is what they call doubly oxidized LDL – once oxidized it appears to be able to change more. Glycation complicates the picture further. Lp(a) – LDL with APO(a) added – can also be oxidized. Understanding that the recommended consumption of PUFA increases the level of these products should give us pause – and good reason… Read more »
C
Guest
Hi xtronics, love your fatty acids page. One question I have regards the peroxidation of linoleic acid stored in adipose tissue when a person loses weight. Studies have shown the linoleic acid content of “fat cells” skyrocket over the last 50 years (see http://advances.nutrition.org/content/6/6/660.full.pdf). When linoleic acid is oxidized, because of its double bonds it releases all sorts of nasty stuff, like aldehydes, 4-HNE, etc (see list here: http://www.cyberlipid.org/perox/oxid0009.htm). Some of these compounds are known to cause serious inflammation resulting in cancer, probably heart disease, etc. If an obese person decides to lose weight and burns their fat, do they… Read more »
xtronics
Guest
PUFA – and particularly LA gets concentrated in adipose tissue – and when someone loses weight – it comes out and can yes – I suspect it might do harm. On the other hand – being overweight long term appears harmful at some level. I don’t think we have a clear picture on how the risks balance. That these fatty acids effect insulin sensitivity – and are thought to have a 600-day half life is sobering.. Yes – Pedro has hinted a bit – but there is a huge lack of definitive studies – he seems reluctant to speculate like… Read more »