This is the main reason why I did not want to take much Berberine . People anecdotally report a lowering of heart rate with it. That was kind of freaky to me
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Anyone know the answer to how much of a CYP 3A4 inhibitor green tea is?
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Last night my resting heart rate was 52 according to fitbit. I take about 1.5g of Berberine a day. I don’t know if the two things are related, but I don’t think they are dose dependent as I was about 6 weeks ago only taking 0.5g of Berberine a day.
The main thing that affects my heart rate (beyond temporary things) is alcohol which increases my heart rate by 10-15 bpm. However, if I don’t drink alcohol for 3-4 days my rhr drops to just above 50. I last drank alcohol on Sunday.
Another thing that puts my heart rate up is being infected by a virus. That can cause an increase of about 5 bpm even if I am not really showing any symptoms. Covid is a good example of this.
My own view is that a low heart rate is something to be welcomed. I have tracked my blood pressure going to bed and waking up since 2016. Then my heart rate was in the upper 60s.
However, I have now been taking Berberine for quite some time (and 1.5g per day for the last 5-6 weeks).
My perception is that the lower heart rate did not coincide with starting on Berberine, but I am happy to check my records if you wish. I can be certain about this.
Incidentally my chronological age is almost 63 (14 more days to go)
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I take 4g of dry Parsley with my One meal I have before i take my 8mg of Rapa weekly.
Alternative to GF Juice i guess 
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Great job on getting your heart rate down John! What did you do specifically to get it down? I noticed you lost quite a bit of weight. Have you been doing cardio as well? It seems like you said you had been mainly walking briskly on your website. I watched a cpl of your videos, Great stuff! Will watch more when I have the chance
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I’m not sure about the effectiveness of dry parsley on the CYP3A4 inhibition… the references I’ve seen are using the fresh parsley juice…
Here: Using Parsley to increase Rapamycin Blood Levels
No new drug that could influence the sirolimus levels had been administered. The next day testing of the blood sirolimus level (14.6 ng/ml) confirmed that there was no laboratory mistake. A more detailed history was taken from the patient. It was learned that she regularly made a juice of parsley and consumed the parsley juice daily to lose weight and promote her health. The juice, which contained about 30 g of parsley, was consumed by the patient for 7 days.
Source: Petroselinum crispum, a commonly consumed food, affects sirolimus level in a renal transplant recipient: a case report - PMC
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I use dry parsley to Inhibit CD38 with Apigenin, I read somewhere it inhibits CyP3A4 as well, cant find the reference now.
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I do a small amount of resistance training eg pull ups and chin ups etc (but not without an initial jump). I also walk quickly particularly when i am walking alone. I rarely run. I dont go to the gym.
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I have started taking Citrus Bergamot 500mg 2x day but then I found that it apparently inhibits CYP3A4 in the same way as Grapefruit juice :
Grapefruit juice, fresh grapefruit, and citrus bergamot contain natural compounds that inactivate the CYP3A4 enzymes in your small intestine for up to 3 days at a time. Without these enzymes working to neutralize part of each dose, you can absorb more medicine, up to 50% more.
Similar to grapefruit, bergamot may also affect the absorption of some medicines.
I might hold back on Citrus Bergamot for the first couple of days after Rapa (6mg with Olive oil ) alternatively try 1-2 mg Rapa with Citrus Bergamot.
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This is just the opposite : Study progress of berberine for treating cardiovascular disease - PMC
and protect against cardiac senescence : Berberine exerts protective effects on cardiac senescence by regulating the Klotho/SIRT1 signaling pathway - ScienceDirect
Berberine is not only safer than metformin, but also seems to increase lifespan A LOT :
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This is very interesting. I have been drinking approx. 32oz of green tea (4 bags), which I do every morning, when I take my weekly dose (with a fatty meal: eggs, fish oil, full fat greek yogurt). At 6mg per 1x/wk, I haven’t noticed any side effects besides 2 canker sores (1 at a time) that healed in 3 days. I weigh 195 lbs; low body fat. I doubt the tea is giving me a multiplier effect unless I am under dosing.
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Can you provide your sources on that? Here’s what I found from a quick read through the literature:
Furocoumarins are the primary CYP3A4 inhibitors found in grapefruit (Schmiedlin-Ren et al. 1997). The Bergamonte standardized extract of citrus bergamot contains naringin, neohesperidin, neoeriocitrin, melitidin, and brutieridin.
Naringenin inhibited human CYP3A4, while naringin had minimal effect (Burkina et al. 2016).
(Miniscalco et al. 1992) appears to broadly agree, noting that “No inhibition of naringenin was found… until higher concentrations, 300 and 500 [μM], were added.” But the article is old enough that my institutional access can’t crack the paywall. Adding some evidence from a slightly different angle, (Edwards and Bernier 1996) argue that “naringin and naringenin are not the primary CYP3A inhibitors in grapefruit juice”.
(Ho et al. 2001) rounds out the picture: “the inhibition of [human CYP3A4 activity] by bergapten (67%), and quercetin (55%) was greater than naringenin (39%) and naringin (6%), at the same inhibitor concentration of 100 M.”
A quick pass through the literature didn’t yield anything substantial on CYP3A4 inhibition by neoeriocitrin, melitidin, or brutieridin.
I haven’t reviewed the literature on this extensively, but I think it’s important to distinguish the duration of any effect from the duration of a meaningful effect. For example, (Lilja et al. 2000) concludes:
When simvastatin is taken 24 hours after ingestion of “high-dose” grapefruit juice, the effect of grapefruit juice on the AUC of simvastatin is only about 10% of the effect observed during concomitant intake of grapefruit juice and simvastatin.
So, even in the case of a strong CYP3A4 inhibitor, the effect appears to drop off steeply after the first day. Taken together, this collection of data points leaves me with no-to-minimal concern about citrus bergamot and CYP3A4 inhibition. If you have sources that paint a different picture, please share.
Still—if blunted hyperlipidemia is the rationale for combining citrus bergamot with rapamycin, I suspect rosuvastatin would be a better option. We know much more about its mechanism of action. The best option, though, is probably a PCSK9 inhibitor. In C57BL/6 mice, rapamycin increases expression of PCSK9—decreasing hepatic LDLR protein and increasing circulating LDL (Ai et al. 2012). PCSK9-/- mice were unaffected.
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@McAlister Great thought-out reply. Thanks for your informative response and glad to have you here!
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Thanks for this. I did see some of those articles in my amateur digging. One thing I learned is there are two types of inhibition: there’s inhibition of the initial production of the enzyme (I forget the term) and this is what grapefruit juice does. One paper btw showed that the maximum inhibition effect peaked about ten hours later. Something to experiment with, drinking GFJ earlier in the day before taking Rapa in the afternoon (the curve was gradual, suggesting precision in timing wouldn’t be important)
The other inhibition effect was termed “mechanical” and this was an immediate inhibition or blocking of the enzyme already present. Ginko was one substance that did this for CYP3A4 - there were several. So taking one of these “mechanical” inhibitors WITH the Rapa dose might also amplify the effect. If that’s what’s wanted of course.
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Yes - I’ve seen people who take rapamycin and GFJ take the GFJ the night before, (or eat the fruit) then again an hour or two before taking the rapamycin. I’ve not seen any blood/sirolimus testes comparing these approaches though.
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Hello everyone,
I’ve been taking rapamycin at a dose of 6mg/week and wanted to inquire about any potential interactions or side effects when combining it with the following supplements:
Fish oil
Magnesium
Vitamin D
Creatine
Collagen
Acarbose
Betaine
Additionally, I occasionally take the following supplements but avoid them 1-2 days before and after taking rapamycin:
Spermidine
Quercetin (CYP3a4???)
Sulphoraphane
Bergamotte
Red rice monacoline-k
Metformin
Psyllium husk
For context, I typically consume all the supplements together in the morning, with the exception of acarbose and psyllium husk, which I take with meals.
Has anyone here experienced any side effects or interactions when combining rapamycin with any of the above supplements or drugs? I’d greatly appreciate any insights or experiences you can share.
I gather its better to take it with food than without.
Thank you in advance!
Thats a big list… the only obvious issue I see is this one.
You do have to watch Quercetin for sure:
Quercetin, a flavonoid present in various fruits, is a potent in vitro inhibitor of CYP3A .
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With regard to ginger, which I tend to partake in quite often, is there any scientific data to substantiate the intake of ginger and its associative effect on the efficacy of Rapamycin?
Thanks!
It seems that there is moderate inhibition of the CYP3A4 enzymes, so a moderate effect on increasing bioavailability of rapamycin (ie. increasing the effective dose). What exactly that translates to in terms of multiplier effect I don’t know.
You can just search on “Ginger CYP3A4 inhibition” to learn more.
All three gingerols potently inhibited CYP2C9 activity, exerted moderate inhibition on CYP2C19 and CYP3A4
Source: Pungent ginger components modulates human cytochrome P450 enzymes in vitro - PMC
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I appreciate the response and additional resource suggestions. I will dig a little deeper and see what I can glean. All in all, not a big deal as I can refrain a bit before and after taking my weekly Rapa dose.
Thank you!
Jeff
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