#305

@RapAdmin

Any idea if taking Artichoke extract and Milk Thistle to prevent raised ALT and AST levels from all the medications I take, can interact with Rapamycin absorption?

Also just to be safe I do not take Citrus Bergamot 24hrs before or after my Rapa dosage as it has grapefruit like qualities which can inhibit some CYP enzymes, albeit pretty weakly.

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#306

No - Sorry, I’ve not looked into this issue at all.

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#307

If anyone is on a liver cleanse with Milk thistle, please keep in mind that :

" Taking milk thistle might decrease how well the liver breaks down sirolimus. This might increase the effects and side effects of sirolimus."

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#308

I don’t have time to look into this in any detail, but this quote suggests that milk thistle won’t reach high enough concentrations to influence rapamycin metabolism in humans unless perhaps in those that suffer from liver damage:

" Both SLM and GLZ formulations, taken by a relatively large number of patients (15 and 19, respectively), were shown to reduce sirolimus CL/F significantly by about 34%. Silymarin, a flavonolignan from the ‘milk thistle’ plant, has been used almost exclusively for hepatoprotection for hundreds of years all over the world [56]. It is a complex mixture of four flavonolignan isomers, namely silybin, isosilybin, silydianin and silychristin [56]. In vitro studies have shown that silymarin, in higher concentrations, has a strong inhibitory effect on both P450 3A4 [56–58] and P-gp [59–61]. The concentration tested in vitro exceeded physiologically attainable levels [56–58, 60, 61] and hence previous studies in vivo have shown no to mild inhibition effects when co-administered with ranitidine [62], nifedipine [63], midazolam [64] and indinavir [65, 66] in healthy volunteers. Recently, Schrieber et al. reported that AUC0–24 h for the sum of total silymarin flavonolignans was 2.4-, 3.3- and 4.7-fold higher for hepatitis C virus (HCV) noncirrhosis, non-alcoholic fatty liver disease, and HCV cirrhosis cohorts, respectively, compared with healthy volunteers [67]. It is a common practice in China as well as in the current study that SLM or GLZ is added by clinicians when patients have abnormal liver function indices. Therefore, the remarkable inhibition effect of SLM on sirolimus CL/F could be explained by accumulated high concentrations of SLM in these patients with hepatic impairment."

Quote is from here: Population pharmacokinetics of sirolimus in de novo Chinese adult renal transplant patients - PubMed

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#309

Hi

I get my testing done in the UK at the Nuffield ( Labs) with my blood draw at the Chandlers Ford Hospital - all very relaxed - results by email with 48hrs - £50 last time around - do it once a year - get confused by units - State side are different to here but can convert between

I arrange it direct with the labs and am happy to share a prior email to give contact details

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#310

Hi

How do you reply to a specific individual posing a question?

Thanks

#311

hit the reply button in the lower right hand part of their post. It’s not blue.

#312

A 200 ml glass of grapefruit juice increases the effect of 2 mg of rapamycin on average by how many times?

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#313

I think it’s 3 or 4 times.

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#314

It is difficult to say because it also depends upon when you take the grapefruit juice. 200ml is not that much grapefruit juice and may fall into the territory of not enough to fully inhibit the enzymes.

My own approach on this and I have used Pomelos, Pomegranates and Grapefruits is that I look at the outcome in terms of biomarker changes (and sleep disruption) and I make a simplistic assumption of a single compartment half life of 60 hours.

My last dosage assuming 16x3 (and maybe a bit)=50mg does fit with this. I have also worn a GCM whilst taking Rapamycin and that did show a shift in glucose processing.

However, in terms of Rapamycin users I am in the minority as I take it far less frequently than others. I think the peak serum level (or interstitial fluid level) is the most important thing for the positive effects, but I wish it to be out of my system most of the time to minimise negative effects.

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#315

Yeah, sorry I didn’t see the 200 ml part because I drink a pint and start an hour before I swallow the pills. I had to google how much is 200 ml in pints.

#316

Its hard to say even with a pint. It is likely to vary. However, I agree that if you take enough and get the timing right you can get an increase beyond 3 times.

In the end, however, dosing remains an inexact science where we don’t yet know what the best thing to do is.

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#317

One grapefruit provides about 177 ml of juice, so 200 ml is a little over 1 grapefruit.

Grapefruit juice typically provides a 3X multiple if taken 1-4 hours before Rapamycin.

I usually eat 2 grapefruits an hour before Rapa. I notice the difference between 1 and 2 grapefruits. 2 is more effective for me.

I have settled on a weekly dose of 5-6 mg + GFJ. It has the most benefits and fewest side effects for me.

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#318

I do 750ml of GFJ and a meal. Wait 3 hours. Have my rapamycin. I take 20mg and after 36 hours I still have 16.9ng/mL. From memory after 12 hours my blood work came back at 39 something. I hate to think what the peak is.

So I took a break this week. Next week I will do 10mg instead. And I put the pills in a table spoon of hemp oil. You can use extra virgin olive oil. If I can get around 8ng/mL after 36 hours it is probably still a bit high. On second thoughts I might take 8mg instead. I take my rapamycin around 10pm on Monday night.

I have a feeling that having food first reduce the acid problem so even though I used cheap Siroboon it is surprising. When my Biocon arrives I will repeat and see what happens. I will probably start with 8mg just to see if there is any difference.

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#319

Your lipids are very concerning.

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#320

That was 2 years ago. @Agetron how are your lipids today?

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#321

Rap what I found alarming was agetrons Triglycerides to HDL ratio. Divide the triglycerides by the HDL and that number should be 2 or less. Also his remnant
cholesterol was > than 24. Just a courtesy call. Hopefully he is aware and on top of this.

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#322

Hey Gregg - thanks for the sincere concern - and under normal circumstances I would agree. But not normal… second year in a row - at age 64 and now at age 66.5 years my coronnary calcium scan is zero - a normal great is a score of 6 - got that beat 2 years running.

Do I need statins if my calcium score is zero?

The American Heart Association (AHA) and several studies have concluded that a CAC score of zero means a person can typically avoid taking statins for cholesterol. People with a score of zero have a low risk of developing heart disease.Jan 31, 2022

My higher LDL- C and lipid profile seems to be from Familial Hypercholesterolemia (FH) that stated my family’s hsitory 3 gernerations back has never had issues of atherosclerosis or heart problems - living to 90’s in great health is the norm - strong Czech and Scottish genetics.

Imagine what I night achieve on rapamycin and acarbose. :wink:

Most recent coronary calcium scan.

20240628_000757
20240628_0007571920×2296 281 KB

Heart of a person under 35 years. Also as we age with no issues I think almost 67 is getting to that ages catagory - lol.
Higher total cholesterol levels may be associated with a lower risk of all-cause mortality, especially non-cardiovascular mortality.

Lower risk of cognitive decline
Higher non-HDL cholesterol levels may be associated with a lower risk of cognitive decline, especially in participants without baseline cardiovascular disease.

Longevity
High total cholesterol may be associated with longevity in the very elderly.

However, other research suggests that the associations of total cholesterol with mortality may vary with age, cause of death, and medical treatment. For example, some studies have shown that lowering cholesterol with drugs reduces the risk of heart disease in the elderly.

There is not enough evidence to make clinical recommendations about cholesterol treatment for the very elderly. Clinical judgment should guide decision-making until more research is available.

Is it advantageous to lower cholesterol in the elderly hypertensive?

Indeed, in the very elderly, there is evidence to suggest that high total cholesterol is associated with longevity.
考研

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#323

What is your CRP? That is a factor I think worth taking into account.

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#324

What is your ApoB?
How would you categorize your diet? Does it fit into one of the categories of keto, Mediterranean, paleo, carnivore?

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