I suffer from pretty significant atherosclerosis (just did a CLEERLY CTA scan…yikes!). In researching novel approaches to reduce plaque I came across an article about Trodusquemine (Drug shown to block artery fat takes a major step forward | News | The University of Aberdeen) and further research turned up this Pubmed article (Can Allostery Be a Key Strategy for Targeting PTP1B in Drug Discovery? A Lesson from Trodusquemine - PMC). According to Pubmed it not only reduces arterial plaque but has significant positive effects on diabetes, glucose control, obesity, neurological degeneration, and cancer!
So I thought I would reach out to our intellectual talent pool to see if anybody wants to Rapa their heads around this and give me your thoughts!
If it delivers, it’s just another statin. Helps increasing your median lifespan but won’t affect maximum lifespan, unlike rapamycin.
FWIW
“Squalamine and trodusquemine: two natural products for neurodegenerative diseases, from physical chemistry to the clinic”
https://pubs.rsc.org/en/content/articlehtml/2022/np/d1np00042j
I think you need both.
I’d try large doses of liposomal Vitamin C.
I appreciate that Linus Pauling has critics and detractors, but (i) Vitamin C has few in any serious contraindications and (ii) gets used in European clinics for both atherosclerosis and cancer treatment.
One can take liposomal C at home.
Liposomal C kind of recirculates through the body thereby producing higher serum levels of C (an order or more of magnitude) than IV C.
As memory serves, it can shuttle calcium from arteries to bone.
Cheap. Easy to do.
Added 31 Mar 2023
Vitamin C and Cardiovascular Disease: An Update
Vitamin C and Heart Health: A Review Based on Findings from Epidemiologic Studies
Jeezus there should be a group buy for THIS — I would make myself a Guinea pig:
Trodusquemine was discovered in a search for antimicrobial compounds supporting the innate immune system [4]. The search was motivated by the hypothesis that the surprising degree of immunity exhibited by certain animals could be due to the presence of endogenous antimicrobial compounds. The dogfish shark fell into that category. Sharks have an adaptive immune system that responds too slowly to defend against most bacterial or viral infections so one might imagine that these animals would be relatively short lived [5]. Surprisingly, the dogfish enjoys a healthy lifespan with an age limit of at least 100 years [6]. In fact, another member of the Squaliformes, the Greenland shark, is the longest living vertebrate with a male life span of at least 392 (+/- 120) years [7]. Trodusquemine has been shown to exert its effects by targeting specific centers in the brain [8].
The therapeutic effects of Trodusquemine demonstrated in animals include amelioration of the metabolic syndrome in mouse models of insulin resistance [9]; correction of hepatic steatosis in obese (ob/ob) mice [10]; reversal of atherosclerosis in LDLR knock-out mice [11]; inhibition of the growth of malignancy in rodents [12]; stimulation of the regeneration of tail-fin and heart muscle in zebrafish [13]; stimulation of regenerative repair of myocardial infarction and traumatic limb muscle injury in adult mice [14]; reversal of memory impairment, normalization of behavior, reduction of neuronal loss and increase in healthspan and lifespan in mouse models of Alzheimer’s disease [15]; reduction in alpha-synuclein aggregation and increase in healthspan and lifespan in a C.elegansParkinson’s model [16]; prevention of aortic valve calcification in a mouse atheroma model [17]; stimulation of T-cell anti-tumor immunity in a mouse model [18]; correction of systemic and hepatic inflammation, insulin resistance and hepatic dysfunction in horses suffering from equine metabolic syndrome [19].
Although the physiological basis for the healthy lifespan of certain shark species remains unknown, Trodusquemine targets well recognized aging associated processes at both the cellular level and in vivo across many species. These observations conducted in different laboratories suggest that Trodusquemine represents a novel, endogenous vertebrate geroprotector.
Actually since the price is stupid, group buy or no, the best way to go might be:
But apparently it’s high in mercury
development was discontinued because it could only be formulated for intravenous use
This is an issue thats hard to overcome; people like small molecule pills, not injections or IVs. This makes it much more difficult to administer (how many people do you know that take IV medications at home?), and therefore an extremely small potential market. And, even harder to utilize as a biohacker…
@Pestodude if I were you I’d get on all the lipid lowering medications that I could… bempedoic acid, rapatha, etc. quickly. Then contact Cyclarity and try to get on their clinical trial list: https://cyclaritytx.com
Oh I missed that it only works if administered by IV! Bummer.
I’ve been on 10mg Crestor for 10 years and my lipids are actually pretty good, including ApoB which is why it’s so frustrating and mystifying that my plaque load continues to go up.
Thanks for the info on Cyclarity, I’ll look into that!
Hysterical! Bravo!!!
If you don’t want any plaque build up its been argued that you need to have apoB around 20-30 mg/dl throughout life. Is your blood pressure optimal? I was reading some PCSK9i study long ago which showed regression of plaques IIRC. Statins can calcify plaques and increase CAC score I’ve heard, but it can stabilize them.
What is your Non-HDL-C in percentile? It is also atherogenic. What about Lp(a)? That is six times as atherogenic than LDL-apoB.
We’ve seen evidence of plaque regression at levels as high as 80mg/dL. The 20-40mg/dL limit should only apply to those who have every risk factor in existence like diabetes, morbid obesity…
Just becaues some people have regression of plaques lowering to 80 mg/dl doesn’t mean that atherosclerosis will not progress for you. If you lower it enough it becomes more certain. It might also increase for those people after study duration.
I hope this doesn’t turn into one of those threads that’s basically one or two people riding their hobby horses beyond the sunset.
There’s plenty of other threads re: APOB / LDL / statins etc. The new factor here is trodusquemine. According to the review I posted, it has MANY amazing applications beyond plaque clearing and for some of them — namely neuroprotection — it does seem to be orally bio available and cross the BBB.
The closer you get to the magic 20-40mg/dL range the more likely it is for you to regress plaque regardless of how many risk factors you got. But for most people the average rosuva/atorvastatin+zetia combo will put their LDL-C between 50-70mg/dL which is where plaque should, at the very least, no longer progress even assuming you have multiple existing risk factors. All other ways to further address LDL-C are either to expensive or require changing your entire diet. Hence I would rather focus on addressing other risk factors such as blood pressure or HbA1c where medication is cheap and stacks well.
Many substances purpotedly do that. Let it pass the ITP or some human trials first before we all start experimenting with it.
It might be worth it to lower costs and make room for a monthly injection of a PCSK9i on top of a statin at least. Praluent 150 mg one time a month.
For now it’s still way too expensive and inconvenient. Paying 150€ a month at the very least for a PCSK9i that you have to inject is not worth it. You can address blood pressure and HbA1c at the same time for just 10€ a month and will have done more to prevent cardiovascular disease.
I know that according to Attia the ApoB should be in that range. Mine is 44. The generally accepted range (I know, I know) is 50.0 - 155.0 mg/dL. Non HDL is 70. Lp(a) is <10. I’m on BP meds (Losartan) which keeps it around 120/80.
You don’t have to pay 150€ every month for your entire life. It might decrease in price over the years or CETPi might be available for cheaper later on. Since benefits compound it is more worth it to do it now than wait.