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Yes, for that reason I've cut back, but although I'm not prediabetic my glucose is consistently high. I've ordered some empagliflozin in hopes that will bring it into normal range so I can reduce it further but I doubt I will eliminate it altogether. As a side note, since cutting back the metformin I've been able to gain some wanted weight.
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I was about to start metformin, but decided that berberine (along with milk thistle extract) was a better alternative. I agree with you that the evidence thus far does not justify use of metformin by most non-diabetics. Many pre-diabetics, however, may indeed benefit, and should certainly discuss the issue with their doctor.
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Brian Valerie interesting. I’ve thought of Berberine as similar to Metformin enough that I’m stopping Berberine.
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Karl I haven't read any endocrinologists (not that I've read them all by any means!) who would be opposed to your decision, assuming you obtained the metformin by prescription.
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Brian Valerie I too stopped berberine, given that it in theory should inhibit positive adaptations to exercise just as metformin appears to do. It also has quite a few potential drug interactions, including with rapamycin (cyp 450 3A4 inhibition)
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David Here is one reference to Berberine and Exercise by Rhonda Patrick
https://www.foundmyfitness.com/topics/berberine
And another reference
https://www.ironmagazine.com/2015/metformin-and-muscle-growth/
They both do not "appear" to suggest the potential same negative exercise effects of BBR vs Metformin.
I added di-hydroberberine dhBBR (https://www.endur.com/products/dihydroberberine-sr-150-mg-sustained-release ) to my supplement stack, as it has far higher bioavailability compared to regular berberine.
https://www.mdpi.com/2072-6643/14/1/124/html
I added dhBBR as a mild AMPK/mTOR agent to possibly help lower my glucose area under the curve, and improve my lipids (longevity and cancer hack). There are dozens of studies showing the benefits of systemic BBR, in many different pathways. However, there are some gastro concerns to long term supplementation.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7697704/pdf/toxins-12-00713.pdf
I am strict ketogenic (one meal a day) dietary regiment, so I run very low glucose AUC normally and slightly elevated LDL/TC (although my TG/HDL and remnant cholesterol are excellent re CVD risk). I cannot say I've been able to discern any "biomarker" benefit uniquely attributed to dhBBR as of yet. It does appear to generate a bump in my normal peak hunger signal before my single daily meal dinner.
I wasn't aware that Berberine inhibited CYPA34, but as I take Rapamycin, this is positive beneficial pathway to boost bioavailability (like grapefruit juice).
https://pubmed.ncbi.nlm.nih.gov/21870106/
As n=1, I am also high daily resistance/aerobic exerciser, and have not noticed any negative impact of dhBBR, nor Rapamycin. Muscle protein synthesis (MPS) is a very complex mechanism, and it has now been shown that there are mTOR independent and Rapamycin independent pathways to MPS (https://www.mikhailblagosklonny.com/blog/how-rapamycin-prevents-muscle-loss-and-sarcopenia-first-draft/), and I have several PM's from muscle/mTOR researchers confirming same.
My muscle build and Vo2max improvement on these supplements is a testament to the complexity of these apparent black/white pathways.
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MAC. I'm very familiar with the research on berberine and its multitude of potential health benefits, but it does inhibit mitochondrial complex 1, and therefore could inhibit adaptations to exercise (compared to not taking it).
Taking berberine or DHB daily is quite different than taking grapefruit once weekly with rapa dose. You'd be increasing the entire area of the curve and extending elimination half life with daily berberine via inhibition of liver CYP 450 3A4. Grapefruit once weekly with your rapa dose only inhibits intestinal 3A4 and only affect absorption of that dose, not elimination.
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Reference for berberine/metformin inhibition of mitochondrial complex I:
https://pubmed.ncbi.nlm.nih.gov/29106036/
Berberine and cytochrome p450 inhibition:
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David Thanks David. I want to make sure I understand your comment. Are you suggesting that taking DHB daily will increase my Rapamycin AUC and reduce elimination of the weekly Rapamycin dosing? If I am trying to increase Rapamycin bioavailability and dampen mTOR (possible side effects notwithstanding), is daily BHB moving towards this goal? By extension, would any other daily food/supplement that inhibits CYP3A4 (I have confirmed my daily Curcumin inhibits CYP3A4), also produce similar amplification?
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MAC. If DHB also inhibits 3A4 like berberine (I haven't seen any studies, so maybe maybe not?), but if it does, then yes it would increase the AUC and delay clearance by the liver, thus serving to help defeat the purpose of the washout between doses. Occasional grapefruit only appears to affect 3A4 in the intestine, so just affects absorption when used at time of weekly or biweekly dosing (not elimination). We went through this in detail, with references, on the rapamycin.news site. If curcumin also inhibits 3A4 in the liver, in humans and in clinically relevant doses when given orally, then this could do the same thing.
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I am not sure about the analysis in the recent report on Metformin. I have been taking Berberine. I have not noticed any effect.
Recently I implanted a Continuous Glucose Monitor. That has confirmed that I am neither diabetic nor pre-diabetic. However, I don't know what it would have said had I not taken some Berberine. I would not be surprised if in fact it is insufficiently bioavailable to have any effect, but I am busy doing a lot of other experimentation and have not really got the time to try to check out the effects of Berberine.
Berberine may help with cholestorol.
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John Hemming have you compared on Berberine and off Berberine on your monitor?
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Karl That's a good idea. I have a few more days left on this session. I am going to try a hack to extend the session beyond 10 days, but otherwise I am intending to end the CGM at the end of this session. I have had some issues with the taping, but in fact at the moment I have resolved those and it is no longer irritating. Hence I have taken Berberine out of my stack. I have no objection to posting the charts if people are interested. The elimination half life is about 5 hours so it should be possible to see a difference over the next couple of days. If the hack does not work I have about 3 more days on this session. If it works I will probably take it until Sunday when I replace my stack anyway. I might even try alternating Berberine by day as the half life is probably short enough to see the effects of that. I would like to experiment with Metformin in the same way.
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Karl At the moment it appears my blood sugar is slightly lower having stopped Berberine, but I actually need to do a more rigorous test probably cycling it every 2-3 days. I will not take it today and might take it tomorrow and then see what happens.
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Well I have six days of data that is comparable. The first two days I took 1 capsule of Berberine at 8.30am, the second two days I took none and the third two days I took 2 capsules of Berberine at 8.30am.
I have not included the other days of the session because I only calibrated the CGM part way through and it was adjusted by about 2 mmol/l. That makes those readings not comparable. I did not calibrate the CGM during this period because I am not sure that calibration is that consistent and hence I preferred to have comparable relatively data rather than data that might have been more reliable on an absolute basis.
If anything the blood sugar was lower on days I didn't take Berberine, but I have not tried to control that many variables and I would say that the results were not conclusive. My breakfast is consistent and my lunch is also consistent. At times I walk rapidly to my office which takes the blood sugar temporarily down. I am drinking alcohol most nights, varying amounts. My dinner varies, but I avoid high GI foods and don't eat a lot of carbs. I often go to sleep between 9 and 10pm.
The precision of the CGM is 0.1 mmol/l and I do have a CSV file of the results. I am quite irritated by the difficulty of making Excel behave for charts so I am thinking of writing a java program to report on heart rate and blood sugar as well as other things. However, I know that will take me a few hours so I have not done it yet.
I have now ended this CGM session. I will do another session of 10 days in the future, but not immediately as I want to think carefully about how best to structure the session in terms of foods/supplements etc.
I must admit that I find the data quite interesting. All I have had previously is random blood sugar tests (the most recent of which was 3.5 mmol/l and an HbA1c which was 30 mmol/mol. Those were May last year, but are not inconsistent with these results.
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John Hemming I also noticed what seemed like significantly higher blood glucose readings on my CGM while I was still taking berberine (500mg three times daily). I was really shocked, and figured it had to be some kind of error or outlier. Now I'm not so sure.
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David That's why I think sharing information like this is important. We rely on research a lot of which is really good, but not all of it is right. My CGM reports for just 6 days might be quite helpful. If we can put a lot of this together we can get a better understanding of the impact of various substances.
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I have found this which looks at Berberine evidence
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2467395/
It appears that Berberine reduces blood sugar for people with diabetes. (type 2) I am not sure, however, what information there is about Berberine for people who are not diabetic.
The review I link to does give good reasons for continuing Berberine, however.
