#262

But isn’t pantethine molecularly much closer to coenzyme A and thus probably preferred?
And I haven’t seen many trials for LDL-C lowering done with pantothenic acid, most are done with pantethine. I haven’t really research it in any depth though.

#263

Yes, it is a link to a section on pantenthine:

Early studies suggested that pharmacological doses of pantethine, a pantothenic acid derivative, might have a cholesterol-lowering effect (30, 31). Pantethine is made of two molecules of pantetheine joined by a disulfide bond (chemical bond between two molecules of sulfur) (Figure 5). Pantethine is structurally related to coenzyme A and is found in the prosthetic group that is required for the biological function of acyl-carrier protein, formyltetrahydrofolate dehydrogenase, and α-aminoadipate semialdehyde synthase (see Function)

In a 16-week, randomized, double-blind, placebo-controlled study, daily pantethine supplementation (600 mg/day for 8 weeks, followed by 900 mg/day for another 8 weeks) significantly improved the profile of lipid parameters in 120 individuals at low-to-moderate risk of cardiovascular disease. After adjusting to baseline, pantethine was found to be significantly more effective than placebo in lowering the concentrations of low-density lipoprotein (LDL) cholesterol and apolipoprotein B (apoB), as well as reducing the ratio of triglycerides to high-density lipoprotein-cholesterol (TG:HDL-C) (32). In a randomized controlled trial of 24 individuals at low-to-moderate cardiovascular risk, pantethine supplementation (600 mg/day of pantethine for 8 weeks, followed by 900 mg for 8 weeks) decreased concentrations of total cholesterol, LDL cholesterol, and non-HDL cholesterol at 16 weeks compared to placebo (33). Although it appears to be well tolerated and potentially beneficial in improving cholesterol metabolism, pantethine is not a vitamin, and the decision to use pharmacological doses of pantethine to treat elevated blood cholesterol or triglycerides should only be made in collaboration with a qualified healthcare provider who provides appropriate follow up.

It seems to reduce apoB by 5%, perhaps I will look at something else.

#264

Yes. From memory it is after a rate limiting step, but a quick search didnt find a reference.

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#265

I have been thinking, that perhaps cycling BP medication may also be a good idea as medications like Losartan, candesartan, Telmisartan, Amlodipine, and Ramipril are all being studied as potential repurpose agents and are generally cardio and neuroprotective via different pathways and mechanisms.

@RapAdmin is there a reason Telmisartan is on your purchase list?

#266

Only because I have not seen it come up very often in my tracking of drugs that show life extension. I do know it’s being researched but I haven’t seen good results in multiple studies yet. If I have missed something please let me know.

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#267

I think what I am going to try next is pitavastatin 2 mg with berberine as it seems the effect is additive on LDL cholesterol:

2 months of oral treatment, 1 g/d of BBR or 20 mg/d of SIMVA monotherapy reduced serum LDL-c by 23.8% and 14.3% (P b .001 and P b .01 vs before treatment), respectively. As compared with the monotherapies, combination therapy showed an improved antilipid effect with 31.8% reduction of serum LDL-c at the end point (P b .001 vs before treatment, P b .05 vs BBR monotherapy, P b .01 vs SIMVA monotherapy)
kong2008.pdf (495.7 KB)

Using pitavastatin to avoid interactions.

I did look at some other supplements but there doesn’t seem to be any knowledge how they work, so they are much less studied. And they had small effects compared to berberine.

I did not know berberine has gone viral:

#268

Yes, i think there are at least two ways to go on this. A Bryan Johnson lite testing regimen would be interesting to put together. I don’t think there’s a thread on this yet? I’d love to see rap.news’ collective wisdom on this. Ideally the testing would cover all the hallmarks of aging (maybe they would be a good place to start?)

Alternatively… I’m interested in opinions on my approach of a minimal testing regimen coupled with cycling/pulsing of interventions which focusses solely on looking at blood glucose, apob and inflammation + functional tests and subjective wellbeing.

The logic would be that by cycling you can avoid chronic deficiency (induced by the pharma/supplement) and long term side effects. Side effects are usually a function of dose + duration. For example cycling on and off ezetimibe every few months is very unlikely to lead to deficiency in omega 3, whereas with long term use I would want to test for this. And it can easily be alternated with other apob lowering interventions (notwithstanding optimal target decisions!). This approach is also pragmatic because even BJohnson can’t testing for everything.

V Curious which other tests people here think we should be doing.

#269

What interactions?

Btw the study you attached is a rat study, not human. Have you found any similar data for humans?
It seems too good that berberine would have that strong effect in humans at normal dosing.

#270

The study includes human trial, my quote is from that.

Berberine inhibits CYP3A4 which many statins are metabolized with. I think pitavastatin has some other metabolism.

The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins

https://www.sciencedirect.com/science/article/abs/pii/S0009279718304095

I don’t know about hERG channel though, do you know?

#271

I checked some other trials with berberine and I am not sure it reduces apoB in any significant capacity, you are looking at added affect of maybe few %. Berberine on it’s own has probably same capacity as larger dose omega3. I wouldn’t dismiss it, but probably it wont add much. Again it reduces LDL-C more than apoB.
I would still prefer Ezetimibe in 5 or even 2,5mg dose. Probably EOD. Probably safer and added effect is more predictable and combination that is much better studied.

Berberine alone reduced total cholesterol by 12.1 mg/dL and triglycerides by 17.4 mg/dL. Berberine alone also decreased LDL by 9.3 mg/dL, but this was finding was not statistically significant. Berberine had no clear effect on AST, ALT, CK, or CRP.

What about hERG? It is important in heart function (electrical activity). I will read the study you attached. If berberine in combination messes with that I would not take it.

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#272

That’s a much more decrease with Silybum maranium:

as did combination therapy with Silybum maranium for TC (MD -31.81 mg/dL [95%CI: -59.88 to -3.73]) and LDL (MD -30.82 mg/dL [95%CI: -56.48 to -5.16]).

What is the percent decrease though?

I don’t think it’s that relevant as the study showed simvastatin and atorvastatin also inhibit hERG, meaning I wonder if it’s even accurate.

Ezetimibe is weak I think but it’s more studied.

1 Like
#273

I’d say Bempedoic Acid and Ezetemibe combined are equal to or better than a statin based on effectiveness and side effects.

I just ordered over a year supply of both for about 170 USD.

4 Likes
#274

Yeah but a statin isn’t enough to me, and I don’t think statin + ezetimibe will be enough either.

#275

Pitavastatin seems safe for hERG though:

Pitavastatin did not affect the hERG current but the lactone metabolite had weak effects on both hERG and action potentials of guinea pig papillary muscle at 3 µM. The lactone suppressed hERG current by about 13% in hERG transfected HEK293 cells at 1 µM (>1000 times the estimated clinical free Cmax of lactone). The No Observable Effect Level (NOEL) of 0.3 μM is equivalent to circa 300 times the estimated clinical free Cmax of lactone.

No significant ECG abnormalities were noted in dogs in the PO and IV cardiovascular safety studies, nor in any of the repeat dose toxicity studies conducted in dogs or monkeys. Neither pitavastatin nor its lactone metabolite caused QT prolongation at 4 mg or at 16 mg in clinical studies.

https://www.tga.gov.au/sites/default/files/auspar-pitavastatin-130902.docx

#276

I don’t think there is any supplement that will be better.
Just add enough omega3, fibers and physical activity to your Mediterranean diet. These three are safest, most studied and probably with most benefits in healthspan and longevity.

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#277

You’re not so interested in berberine anymore, lol?
I don’t think this will decrease apoB to 20-30 mg/dl.

And I don’t eat a mediterranean diet although I have tried to eat more of those foods in my diet.

#278

This paper agreed with you

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#279

Berberine case report with long QT syndrome, together with hemp oil inhibitors:

We report the case of acquired long QT syndrome with torsades de pointes secondary to hemp oil and berberine supplements.

Yeah I’m probably skipping berberine.

When it comes to not falling over and dropping dead suddenly, pharma with all the safety data is much more preferable. Can’t trust a random supplement that doesn’t have a lot of research on safety.

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Berberine Supplement
#280

Possibly you have too much of something? Like a heavy metal or Iron. This just happened to me.

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#281

Could BA/EZE + the lowest rosuvastatin (5 mg?) do the job? (as rosuvastatin seems to be the “safest” one)

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