#759

I guess you have a certain definition of big pharma that doesn’t include anybody that makes generics. As you said, generics aren’t zero profit.

Well, no, not exactly…but I do see the profit motive slowly creeping into all aspects of life as a corrupting force. Nobody should be happy about that - except those who reap the windfall…and a pox on them. If we don’t take steps to keep money, mostly from big corporations, like big pharma, out of politics, it will be us that pays the price.

#760

Typically, “big pharma” does not include generic manufacturers. They have different goals and are represented by different lobbying groups (for instance, in Europe, EFPIA for big pharma vs Medicines for Europe for generics). And they fight each other.

“Nobody should be happy about that”: I’m extremely happy about that. Only profit motive can help humanity find what is needed and fund innovation. Hopefully, one day, communism will be eradicated from the surface of the Earth. The only way to keep prices down is to increase competition by lowering barriers to entry. You can try to keep money out of politics, but keeping politics out of business is more efficient: “When buying and selling are controlled by legislation, the first things to be bought and sold are legislators.”

7 Likes
#761

Certainly we (or I) have derailed the thread. But at 743 posts, I expect @RapAdmin to step in and close it at any minute.
As in most things, my social/economic philosophy is neither pure communist/socialist or pure capitalist. I think unfettered/unregulated capitalism had it’s day (Milton Friedman et al) when people were more moral/ethical and the economy was growing with less stress. As competition became global with less domestic protections, it became more cutthroat with everyone pushing the boundaries in looking for an edge. This is exactly the point that you need incorruptible governments to step in and enforce rules that protect the environment, the workers, prevent monopolies and keep big business from running roughshod over small business (as we’re definitely seeing now). Should Facebook, Google, Amazon be able to buy up any competitor that might threaten them years in the future? How does that help society? That’s unfettered capitalism.
The warnings are all around us…the 2008 recession, the “Wolf of Wall Street” movie. Did it make you happy when he shouted out “I just stole grandma’s pension”. No regulation is a good thing?

1 Like
#762

This info on ion mobility analysis and descriptive cholesterol factors might be of interest:

1 Like
#763

In any case, pharmaceuticals are our best bet at the moment. People have tried the natural route for tens of thousends of years and it hasn’t helped them at all. None of the liquid metals, herbs or virgin blood helped at all.

3 Likes
#764

Well… the virgin blood might have been a little helpful, but perhaps better if Type-matched and supplied by IV (vs. oral use). :wink:

7 Likes
#765

Since when are diet, exercise and sleep not natural? And maybe it’s the not-natural pollution, forever chemicals, micro-plastics, stress levels, etc that are causing a lot of the problems.

But back on topic…the page from Quest Diagnostics posted by @Phillipe is a pretty good summary of things to track. The Lp-PLA 2 test is relatively new and looks promising (although expensive). It’s a measure of the specific inflammation of the arterial wall.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360470/

Metabolic diseases are chronic disorders correlated to a greater risk of cardiovascular event and death. Recently, many data have sustained the biological link between microvascular dysfunction, oxidative stress, vascular inflammation, and metabolic diseases. The determination of new and specific blood biomarkers of vascular inflammation associated with obesity-related metabolic syndrome (MetS) and diabetes such as lipoprotein-associated phospholipase A2 (Lp-PLA2) could be useful to identify subject with high risk of cardiovascular events. Lp-PLA2 participates by a crucial role in microvascular dysfunction and oxidative stress showing positive association with metabolic disorders. In this review, we will argue the evolving role of Lp-PLA2 in predicting cardiovascular events in metabolic disease patients.

It has been estimated that up to 80% of premature heart attacks and strokes are preventable. In recent years, atherosclerosis has become recognized as an inflammatory disease whose activity can be assessed by circulating biomarkers. Along with C-reactive protein (CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2) may now be considered as a biomarker with sufficient accumulated evidence to support its application in clinical practice. CRP is a well-known marker for inflammation. Patients with elevated levels of CRP have an increased risk for heart attack stroke, sudden death and vascular disease. Studies have shown a strong correlation between this enzyme and an increased risk for coronary and stroke events, independent of the traditional cardiovascular risk factors. Furthermore, Lp-PLA2 as a risk predictor has been shown to be independent of and complementary to high-sensitivity CRP (1-3).

Lipoprotein-associated phospholipase A2 is among the multiple cardiovascular biomarkers that have been associated with increased cardiovascular disease (CVD) risk. Lp-PLA2 appears, however, to be relatively unique in its high specificity for vascular inflammation as opposed to systemic inflammation, its low biologic variability, and its direct role in the causal pathway of plaque inflammation.

It is now well established that Lipoprotein-associated phospholipase A2 (Lp-PLA2) is intimately associated with Lp(a). Lp-PLA2 can be used to determine cardiovascular risk, both of coronary heart disease and cerebrovascular disease. Lp-PLA2 is an enzyme that has been identified as a novel risk factor for coronary events and stroke. Lp-PLA2 activity is an independent predictor of coronary heart disease and ischemic stroke in the general population.

https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=lipoprotein_phospholipase_a2

This test looks for a specific lipoprotein, Lp-PLA2, in your blood. The test is used to help predict your risk for cardiovascular disease and stroke.

Lipids are fats in your blood. Lipoproteins are combinations of fats and proteins that carry the fats in your bloodstream. If you have Lp-PLA2 in your blood, you may have fatty deposits in your arteries that are at risk of rupturing and causing heart disease or stroke.

This test may help your healthcare provider figure out what treatments would be best for you to prevent a stroke. Things that can be done to prevent problems include taking medicines that lower lipid levels and making lifestyle changes.

New research suggests that Lp-PLA2 may better show who is at risk for heart disease and stroke than HDL (“good”) cholesterol, LDL (“bad”) cholesterol, and VLDL cholesterol.

3 Likes
#766

@Virilius Here’s a question for you. Globally, how many centenarian men, alive today, don’t take statins? Or, let’s go even further…don’t take any pharmaceuticals at all?

3 Likes
#767

There are mice in the ITP control group who live even longer than the mice in the treatment groups. Does this mean rapamycin/acarbose/etc. are useless?
Imo it is pointless to look at outliers. I don’t have relatives who lived beyond 85 and don’t live in a blue zone so chances are that without medication, I will die in my 80s aswell.
Also, there are examples like Kissinger who got to 100 just by taking high dose statins.

3 Likes
#768

Since many of these medications are fairly recent developments, we have no way to gauge how they affect longevity. Even Rapamycin which has been around a long time has not been taken by healthy individuals for very long for life extension.

I’ll believe the scientific studies that show these meds extend lifespan and healthspan.

And I’ll use my common sense to extrapolate their effects to humans (for those done on animals). :wink: I may be wrong on some, but I’m sure there are some winners in the pharmaceutical bunch I’ve picked.

3 Likes
#769

Gonadal status modulates large elastic artery stiffness in healthy middle-aged and older men | GeroScience

Hypogonadism is a risk factor for cardiovascular disease (CVD) in men related, in part, to increased oxidative stress. Elevated large artery stiffness and central pulsatile hemodynamics (e.g., pulse pressure and wave reflection magnitude) are independent risk factors for CVD. However, whether large artery stiffness and central pulsatile hemodynamics are (1) elevated in hypogonadal men independent of traditional CVD risk factors and (2) related to increased oxidative stress is unknown

GUy6k-6WgAEqg_M
GUy6k-6WgAEqg_M919×600 109 KB

Paywalled paper:

4 Likes
#770

Finally something new, two new drug targets APOC3 (triglycerides), ANGPTL3 (triglycerides, cholesterol) being studied. Found via mendelian randomization studies to lower coronary artery disease.

I find it interesting that these people are so clear, direct, simple, rooted in causality, like listening to a human equivalent raptor 3 engine, while the cholesterol deniers and other gurus are raptor 1 engines but that will blow up.

image

6 Likes
#771

Lol. Usually the controversies on this list are plant based vs carnivore or low mTor vs muscle protein synthesis, not so much on how much regulation is best or whether profit motives are evil. But keep at it guys, smart and entertaining arguments on both sides.

3 Likes
#772

Not sure what to think about this paper but sharing it FYI:

Benefits of intensive lipid-lowering therapies in patients with acute coronary syndrome: a systematic review and meta-analysis 2024

Nine trials involving 38,640 patients with ACS were identified. Pooled results suggested that intensive lipid-lowering therapies are associated with a reduction in the risk of three-point MACE (RR, 0.88; 95% CI, 0.83–0.94; p < 0.001), recurrent ACS (RR, 0.82; 95% CI, 0.71–0.96; p = 0.013), nonfatal myocardial infarction (MI) (RR, 0.87; 95% CI, 0.81–0.93; p < 0.001), stroke (RR, 0.83; 95% CI, 0.73–0.94; p = 0.003), and unstable angina-related hospitalization (RR, 0.57; 95% CI, 0.33–0.99; p = 0.046), but not all-cause mortality (RR, 0.94; 95% CI, 0.82–1.07; p = 0.329), cardiovascular disease-related mortality (RR, 0.96; 95% CI, 0.88–1.06; p = 0.457) or coronary revascularization (RR, 0.89; 95% CI, 0.79–1.00; p = 0.057).
In total, these trials enrolled 38,640 patients with ACS (9,894 female [25.6%]; mean age, 61.1 [10.1] years), and the average follow-up duration was 4.7 years (range: 8 weeks − 7 years).
All trials compared ezetimibe or PCSK9 inhibitors plus statin treatment with statin treatment alone, including five studies on ezetimibe and three on PCSK9 inhibitors, with the exception of one study that compared PCSK9 inhibitors plus ezetimibe and statins with ezetimibe plus statins.
However, in the present study, when the pooled analyses were restricted to studies in which high-intensity statins were administered to patients in the control group, a significant reduction in all-cause mortality risk was observed and the effect size was reduced. We considered that the initiation of intensive lipid-lowering treatment as soon as possible after ACS could benefit patients more than the use of a high-intensity statin without the consideration of costs.

7 Likes
#773

I also have Atorvastatin on order. If I remember correctly you drink grapefruit juice with your Rapamycin doses? I think there is a negative interaction between these two (Atorvastatin & GFJ). Might be worth reading up about.

Simple solution is to wait 24 hours after the GFJ and then take the statin. You probably know this but just thought I’d mention it as a reminder to anyone taking statins and using GFJ with Rapamycin.

2 Likes
#774

I take a 5 mg dose of Atorvastatin at night. I take my grapefruit juice and Rapamycin in the morning once a week. In the worst case, my Atorvastatin dose may be increased a bit.

Thank you for your concern and it is a valid point for those who take grapefruit juice and Atorvastatin at a similar time. :slight_smile:

2 Likes
#775

Are you taking higher doses once a week now and have you changed it up? I thought you were “megadosing” every fortnight.

#776

I still take 5-6 mg of Rapamycin + GFJ (17-21 mg equivalent) weekly. I take 5 mg of Atorvastatin daily.

1 Like
#777

Not all cause mortality. Not a surprise for me. Old people need the LDL as it is part of the immune system:

Beta cyclodextrin removes sLDL. You see why this is a modern miracle when you watch this video.

4 Likes
#778

But but but… 1/ it doesn’t increase all-cause mortality either (I would like to see the survival curves, the RR is 0.94 so it’s possible that with larger cohorts and longer followup periods, you’d see an ACM reduction) and 2/ “when the pooled analyses were restricted to studies in which high-intensity statins were administered to patients in the control group, a significant reduction in all-cause mortality risk was observed and the effect size was reduced”. So at least it confirms that “ezetimibe or PCSK9 inhibitors plus statin” is better in terms of ACM than high-intensity statins alone.

4 Likes