#248

Atherosclerotic cardiovascular disease is already solved. We have the answer.

This is no joke. It is totally true and correct. I swear to god. :smiley:

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#249

Don’t tell me…let the suspense build…Omega 3s? I always thought Rhonda Patrick was GOD.

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#250

I think having a real heart attack might be less painful than the constant rehash of the same information by just reordering the sequence of words. Why am I here then? Because I thought that talking about salads was more interesting than going over and over how low your ApoB or LDL should be. Heart Disease is important so please wake me when there’s something NEW to talk about. For now, I’m going to start my own Salad Thread.

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#251

If people stop resisting the truth, then we can talk about salads.
Much more interesting things to discuss once the basics are out of the way.

#252

ngOrge,

The pontificating is Non-Stop!

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#253

Berberine: A Multi-Target Natural PCSK9 Inhibitor with the Potential to Treat Diabetes, Alzheimer’s, Cancer and Cardiovascular Disease

Caroline Coppinger et al. Curr Rev Clin Exp Pharmacol. 2024. PMID: 38361373.

Abstract

Berberine is a natural product with a wide range of pharmacological effects. It has antimicrobial, anti-cancer, anti-inflammatory, anti-hyperlipidemic, neuroprotective, and cholesterol-lowering properties, among others. It has been used in traditional Chinese and Ayurvedic medicine for 3000 years and is generally well-tolerated with few side effects. Its main drawback is low oral bioavailability, which has hindered widespread clinical use. However, recent interest has surged with the emergence of evidence that berberine is effective in treating cancer, diabetes, Alzheimer’s disease, and cardiovascular disease via multiple mechanisms. It enhances insulin sensitivity and secretion by pancreatic β-cells in Type 2 Diabetes Mellitus in addition to reducing pro-inflammatory cytokines such as IL-6, IL-1β, TLR4 and TNF-α. These cytokines are elevated in Alzheimer’s disease, cardiovascular disease, and diabetes. Reductions in pro-inflammatory cytokine levels are associated with positive outcomes such as improved cognition, reduced cardiovascular events, and improved glucose metabolism and insulin sensitivity. Berberine is a natural PCSK9 inhibitor, which contributes to its hypolipidemic effects. It also increases low-density lipoprotein receptor expression, reduces intestinal cholesterol absorption, and promotes cholesterol excretion from the liver to the bile. This translates into a notable decrease in LDL cholesterol levels. High LDL cholesterol levels are associated with increased cardiovascular disease risk. Novel synthetic berberine derivatives are currently being developed that optimize LDL reduction, bioavailability, and other pharmacokinetic properties.

PubMed Abstract

Full Text (Paywall)

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#254

Hi Vlasko, Just looking back at a number of your recent posts, it appears that you are just posting a number of studies without making any comments at all. I read your early explanations - here:

And here:
https://spotify.localizer.co/t/higher-ldl-cholesterol-is-associated-with-greater-longevity/12338/26?u=ng0rge
But I think it would be helpful to include some human comment to make it clear that they aren’t just being posted by a bot…especially since your public profile is hidden.

5 Likes
#255

Perhaps show him this short :thread: and then discuss

https://twitter.com/paddy_barrett/status/1762750170247111097?s=46&t=zJMJ1xVdRJYEDYz-DHipTw

#256

:rofl:
I’m awaiting for your show of your “Greater Knowledge”, which debunks the Mendelian Randomization studies and Randomized Controlled Trials. Or your reasoning why those methodologies are flawed.

There will just be crickets or no addressing of these things. And others can think about that.

1 Like
#257

I hope you are aware of their flaws, biases and limitations. All that glitters is not gold.

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#258

That doesn’t address my comment. I forgot the third option between crickets and not addressing these things. It is that someone else takes his place and misunderstands my position or straw mans it. And so it continues because there was no show of “Greater Knowledge”.

#259

As in my view you are not worthy of a conversation.

Any part of this you do not understand?

1 Like
#260

Let’s see what I said:

There we go. As expected.

#261

Hi @scta123, i do like your approach in this area because you’re clearly aware of what we don’t yet know for certain. @Neo is someone else on the other side of the argument who is aware of the limits to our knowledge but is applying his best judgement to end at a different conclusion. That humility seems a little lacking in some quarters.:grimacing:

i do find this whole debate fascinating from a psychological perspective. It’s interesting when people become so wedded to an idea that they can’t hear contradictory evidence or argument. It seems that fear of statins on one side, and fear of heart disease on the other drives people into fixating on confirmatory evidence to the point that they’re incapable of rationally looking at all the evidence. That’s the only explanation i have as to why people can’t accept the strengths and weaknesses of each type of study. I’m curious what you think of this summary and whether I’ve missed anything.

The RCTs are limited because they focus on secondary prevention, are underpowered for all cause mortality, rely on subjective “cause of death” determination, are short term only and don’t provide clear evidence for extremely low targeted levels of apoB. So they can’t provide clear evidence of interventions in healthy individuals, for all cause mortality, for long term intervention, for long term side effects, or for targeting extremely low levels.

The cohort studies are limited because we cant be sure that there aren’t unidentified confounding diseases in the study populations that cause both low apob / ldl and mortality. Its impossible to ever know that you’ve identified all the confounders

The MR studies close some of the inference gap but they too can’t prove causality. They are inherently limited because they assume that there is no
confounding though pleiotropy (multiple phenotypic affects), no canalization (developmental compensation) and no coevolution of compensatory genes. They also don’t tell us about side effects and net benefit of pharmaceuticals which target just one known effect of the gene studied.

Given all these limitations its clearly rational to see that the science here hasn’t been settled. And that we’re all having to make educated guesses. Which is is why I’m continuingly surprised at how certain people are that they know “The Truth”. When it’s pretty obvious that no one does.

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#262

If he doesn’t want statins, why not bempedoic acid/ezetimibe instead? (same LDL lowering effect)

1 Like
#263

Well put. Still, the catalyst for agitation is the need to do something. (I suppose this is dependent upon each person situation; my situation is I need to act). So, how to decide what to do? It’s hard.

1 drug: benefits (probable, possible) vs negative effects (probable, possible). Timeline for benefits and negative effects showing up? Everyone is different: genetics, gut microbiome, etc. Every possible intervention is being put in best light by advocates/ put in worst light by detractors / spoke about honestly by a few scientists who also admit the limits of their knowledge.

Multiple drugs: above combined with polypharmacy effects.

Polypharmacy combined with aging effects. “No man ever steps in the same river twice, for it’s not the same river and he’s not the same man.”

Emotional complications: placebo, fear, need for hope, etc.

Very complicated. Too hard to know exactly what to do.

The only way through is personal data. Track biomarkers over time. Goals are important but improvement is the key. 80/20 prioritization for making the most of limited time. Make a plan. Start to implement. Gather new info. Reassess based on progress. New plan. Repeat forever.

This is where my mind has settled for now. I am here increasing my awareness of scientific research, anecdotal evidence, etc for ideas on what to try in my own path to getting better and toward goals of lower ACM. Buy time to benefit from emerging medicine and tech.

6 Likes
#264

I know, I was trying to cover my eyes but I couldn’t help peaking between my fingers to see what was happening (FOMO). But the case of @medaura 's husband seems like the perfect example of the debate. She says…
“p.s. for the record; even though his markers are terrible so far he has a CAC of zero and did extensive ultrasound checks of the main arteries when visiting the old country for just $150, zero signs of plaque or thickening. The cardiologist looked very carefully as she was concerned given his numbers for years now. He’s 45 — and his lipids have been different varieties of shit for at least 10-12 years. But has super low hsCRP levels so that’s that.”
Correct me if I’m wrong but - CAC of zero and zero signs of signs of plaque would indicate that his LDL, TG and ApoB numbers aren’t causing atherosclerosis. Why not? And does he really need to take action?

4 Likes
#265

If the MR posted by @Neo is correct regarding ApoB and AD then yes, that’s a reason to take action.

Otherwise yes, this example shows that LDL, TG and ApoB are not enough. But is that a reason not to lower them?

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#266

Well, If he’s really resistant to the idea, then the reason would be that you don’t want them to get divorced :wink:.

#267

That discussion becomes more surrealistic every day it seems. :slight_smile: