43 replies to this topic

[Daniel Cooper]

Guys,

 

Does anyone know of any downsides to taking berberine?  As I age I am sliding towards "pre pre-diabetes".  Fasting glucose is getting into the 90s.  

 

Looking at berberine my impression is that mg for mg it's about as effective as metformin, however I have this vague memory of someone alleging some downside to this supplement some time back, however I can't really find anything.

 

Anyone know of a reason not to supplement with berberine?

 

 

 

[Benko]

Examine.com has a lot of good info on it.

 

It inhibits CYP 26D, CYP 2C9, cyp 3a4 so it might not be a good idea to take it with a number of drugs including rapamycin. Some people get GI symptoms e.g. diarrhea (I didn't have any problems). It did make me hungry after taking it which I never had with gynostemma (another AMPK activator) though this lessened with time.

 

If you haven't tried it, various fasting protocols e.g. intermittent, Longo's, etc can lower fasting blood sugar.

 

 

 

 

Edited by Benko, 17 June 2019 - 10:28 PM.

[OP2040]

Metformin has the B12-blocking downside which is connected to various risks associated with Metformin users.  Since Berberine is so similar, but with somewhat different pathways, I searched and searched and searched for a B12 connection.  I can say confidently, there is no study out there that shows Berberine to have this effect.  But we know, absence of evidence isn't evidence of absence, so I plan to supplement my Berberine with B12.

 

For the record, Berbrine is one of the few supplements I've taken over the years where I can feel an actual tangible difference in the daily parameters I notice the most.

[Werper]

There was a post on here about potential cancer concerns with it.

[Oakman]

If there are any, they seem to be limited to gastrointestinal upset from my research on it. Moreover...

 

"Compared with metformin, berberine exhibited an identical effect in the regulation of glucose metabolism, such as HbA1c, FBG, PBG, fasting insulin and postprandial insulin. In the regulation of lipid metabolism, berberine activity is better than metformin. By week 13, triglycerides and total cholesterol in the berberine group had decreased and were significantly lower than in the metformin group (P<0.05)."

 

https://www.ncbi.nlm...les/PMC2410097/

 

As I don't have a Metformin prescription, I use it in replace of Dr. Sinclairs "Metformin, Resveratrol, NMN" protocol. I do cycle it month on, month off, roughly, for no particular reason, however I do use a 500 mg Berberine / 125 mg Silymarin combo rather than Berberine alone because this...

 

https://www.nutraing...etabolic-health

[aribadabar]

I think the concerns are regarding potential genotoxicity (<< Credit: Darryl) 

 

Good toxicity overview here: https://www.ncbi.nlm...les/PMC5478780/

[Oakman]

... I do cycle it month on, month off, roughly, for no particular reason, however I do use a 500 mg Berberine / 125 mg Silymarin combo ...

 

I think the concerns are regarding potential genotoxicity (<< Credit: Darryl) 

 

Good toxicity overview here: https://www.ncbi.nlm...les/PMC5478780/

Thanks, now I have some good reasons!

Edited by Oakman, 01 October 2019 - 11:46 PM.

[TheFountain]

 

For the record, Berbrine is one of the few supplements I've taken over the years where I can feel an actual tangible difference in the daily parameters I notice the most.

Such as?

Any info on Berberine supplemented with Citrus Bergamot?

[tintinet]

Took for a while. Associated with severe constipation for me.  Discontinued.

[DaveX]

Question to anyone who notices something either one way or the other: Does longterm Berberine supplementation either improve libido or sexual experience or decrease it? Due to its two-fold effect on 5HT1a receptors it should have some effect, however clarity usually ends on the postsynaptic receptors. And I also notice that it has an effect, however I'm never quite sure if acute or afterwards is better, which based on antagonism or agonism could give the opposite indications in either case. I know it does have some reported erection quality effect, however I'm not actually talking about that.

Edited by DaveX, 28 November 2019 - 04:11 AM.

[able]

New study on berberine shows impressive benefits for health and lifespan.

 

 

 

Berberine ameliorates cellular senescence and extends the lifespan of mice

 

https://onlinelibrar...1111/acel.13060

 

 

Based on these results, we expected BBR to extend the lifespan in naturally aged mice. The procedures we followed are shown in Figure 5a. Two independent experiments were conducted, one using 18‐month‐old mice (18M) and the other using 22‐month‐old mice (22M). We further reduced the dose to 50 mg/kg because of even longer treatment period. For the 18M and 22M groups, BBR was administered for four months and one month, respectively. The survival curves were recorded, and coordination was tested for all control and treated mice. Additionally, photographs of the 18M group mice were taken before sacrifice (˃20 months) to record the difference in fur density, a characteristic feature of aging in mice (Figure 5b and Figure S3 b). We observed that the mice from the control group (on the right) had sparse furs, especially on the back of the body and had less glossy hair as compared to BBR group. Administration of BBR extended the median residual lifespan from 85.5 days to 154 days (68.5 days, ~80% extension) as shown in Figure 5c. The entire lifespan was extended by ~ 16.49% as shown in Figure 5d. The coordination in the treatment group was also well maintained (Figure 5e). Furthermore, there was no significant difference in weekly average body weight between control and treatment groups indicating the safety of regular administration of relatively low doses of BBR (Figure S3 c). The mice from the 22M group were too old for the coordination test. Therefore, only survival curves of mice from the 22M group were recorded from the day when BBR was administered. BBR extended the median residual lifespan by ~ 12.5% (Figure 5f). Thus, we found that BBR has anti‐aging effect in naturally aged mice.

 

 

[OP2040]

This was a good study, but just wanted to mention that they used naturally aged mice but it was a relatively short-lived strain.  The authors didn't seem to think it mattered based on the mechanism of life extension but worth noting. 

 

Nothing in this thread so far that would scare me from it.  We already know that all rejuvenation strategies will correlate with cancer somehow because they use largely the same pathways.  since mice are more cancer prone to begin with, this is one area where mice studies can give us a good idea that something will or won't cause cancer in vivo. 

[tintinet]

Took for a while. Associated with severe constipation for me.  Discontinued.

“Constipation was one of the most common gastrointestinal complaints among diabetic patients after berberine intake.”

 

 

 

https://www.ncbi.nlm...les/PMC3478874/

[hamishm00]

The main ones for me are that it might inhibit b12 absorption in the same fashion as Metformin and that it has been associated with prolonged QT syndrome and other arrhythmia of the heart, although there are studies where this has happened I don't see many anecdotal complaints of this online, so it might be a rare side effect. Gastro issues (both constipation and also the opposite) seem to be a common side effect. It is an antiobiotic and it will affect the composition of your gut microbiota, but it's unclear whether this will be positive or negative in the long term, but it seems net/net to be positive.

Edited by hamishm00, 05 December 2019 - 11:51 AM.

[OP2040]

The B12 thing is at least easily addressed.  That recent study that showed that multivitamins are worthless had one exception and that was B vitamins.  It would be nice to get a definitive answer and there may even be one out there already, just need to find out by what mechanism Metformin causes such a deficiency and see if Berberine affects that same pathway.  But still, easily remedied with a B vitamin supplement.  I also like to take significant breaks from almost any supplement except ones that are meant to address acute illness.  It's just good practice due to tolerance, hormesis and for many other reasons.

 

I haven't read about the prolonged QT syndrome so I'll take your word on it.  I noticed that a lot of drugs/supplements that are specifically good for cardio have this warning.  I wonder if it's similar to the cancer thing whereby a regenerative program can either go too far and cause cancer, or cause cancer within a highly damaged environment.  Similarly prolonged QT might be one of those things where a drug is working too well.  If that is the case, then young healthy people with athletic levels of low heart rate and blood pressure should not take it, nor should people with heart failure.  Again, this is just speculation so go easy on me lol.

 

I tend to ignore gastro warnings.  Even the most screwed up people have some strengths, and for me it is my digestive system.  It works like I wish the rest of my body did, no problems to the point where I forget I even have a digestive system sometimes.

 

All in all, for such a good metformin replacement, this looks like a good risk/reward balance for most people.  As I've said in other threads, I sometimes worry about model bias in some of the studies we read.  Since aging is almost never studied, much of it is based on disease models, and diabetes is particularly popular thing for people to waste time studying.  It's entirely possible that what is good for diabetics may not be particularly good for non-diabetics.  I have this issue when studying cardio issues.  I'd say a good 75% of studies in mice and men are on diabetic versions of various cardiovascular issues.  Since curing the diabetes often cures the cardiovascular disease, it always looks quite nice on paper.  But diabetes is one of perhaps thousands of types of damage that can cause cardio issues, and it's another example of whack-a-mole to try to address all of them.  I've come to the conclusion that in many cases these models bear no relation whatsoever to how a disease process manifests in non-diabetics.  I guess that's why we all focus on aging and not particular diseases, but the temptation is always there to cure a single aging disease within it's abstract bubble.

Edited by OP2040, 05 December 2019 - 12:49 PM.

[hamishm00]

The B12 thing is at least easily addressed.  That recent study that showed that multivitamins are worthless had one exception and that was B vitamins.  It would be nice to get a definitive answer and there may even be one out there already, just need to find out by what mechanism Metformin causes such a deficiency and see if Berberine affects that same pathway.  But still, easily remedied with a B vitamin supplement.  I also like to take significant breaks from almost any supplement except ones that are meant to address acute illness.  It's just good practice due to tolerance, hormesis and for many other reasons.

 

I am not aware of any science out there on the pathway or mechanism of action in which Metformin affects b12 levels. It would be fascinating to hear from anyone who may be able to shine a light on this.

 

 

I haven't read about the prolonged QT syndrome so I'll take your word on it.  I noticed that a lot of drugs/supplements that are specifically good for cardio have this warning.  I wonder if it's similar to the cancer thing whereby a regenerative program can either go too far and cause cancer, or cause cancer within a highly damaged environment.  Similarly prolonged QT might be one of those things where a drug is working too well.  If that is the case, then young healthy people with athletic levels of low heart rate and blood pressure should not take it, nor should people with heart failure.  Again, this is just speculation so go easy on me lol.

 

I think this is spot on. In fact one study I read where Berberine induced irregular heart beats in an individual was where they already had a bradycardia (slow heart beat). So you're right, this could apply to impaired individuals (or to athletes who have athletic bradycardia). In any event, the irregular heartbeat issue doesn't seem to be a big deal because the effects of the Berberine are not permanent and regular sinus rhythm will return following a Berberine washout period.

[OP2040]

Hamishm00, I'm glad that long QT theory makes sense to you as well, so I'm not crazy lol.  I think we all forget sometimes that a major hallmark of health is homeostasis.  It's easy to want to drive a seemingly bad thing down to 0, but processes don't work like that.  Both extremes can cause disease, even if one end of the spectrum is more often seen than the other 90% of the time,  for evolutionary (anti-cancer bias) or cultural reasons (abundant food).

 

The interesting case of cardiovascular disease is a case study in this.  As we know the very beginnings of cardio disease, sometimes quite early in life, it looks a lot like hyperfunction.   A very strong immune response, strong sympathetic activation and response, obesity/growth.  These and lots of other examples are processes that could easily be cast as "too much" of a good thing.  Too much growth, too much fat storage, too much immune reaction, and so on.    But then really late in the disease process, you get the opposite on every one of these counts.  Frailty is the opposite of growth, people often lose a lot of weight when they are in the later disease states, immunosenescence, slow reaction times.  All of this sounds like the "hyperfunction theory of aging".  The problem I have with that theory is that it describes something real, but I'm not convinced of the entire package that comes with it.  It's not clear that slowing down these functions will get you to radical life extension.  mTOR inhibition does exactly this for all of my examples, which is why it's a major example used by the hyperfunction theory.  And mTOR , as well as other nutrient-sensing pathways, are pretty amazing interventions, arguably still the best we have.  But are we to believe that tamping down these hyperactive systems will lead to a permanent homoestasis and youthful state?  I do not believe that for a minute.  The hyperfunction theory is really just an addition to other classic theories.  For example, if we had upregulated DNA repair mechanisms throughout life, would hyperfunction happen at all?  I doubt that it would, in which case hyperfunction is an artifact, and DNA damage (lack of repair) is a major theoretical cause of aging,  If the immune system were truly just hyperfunctioning, would it not continue to clear senescent cells at the same rate throughout life, thus benefiting the organism?  The selection shadow implies that we lack something functional later in life, not that we gain something.  If it were true that the unchecked continuation of the developmental plan caused all of these problems, then it would be true that we would continue to grow in a healthy state until it overwhelmed us, not in a disease state.  Lobsters are a great example of this.  Arguably, the hyperfunction theory works for them because they continue to grow, grow, grow and then die of some consequence of that growth.  They should also have a selection shadow because they certainly do not live forever.  But their growth is in no way detrimental to them except at the very end and for trivial reasons.  Their growth is a boon.  Our continued growth would also be a boon if our repair mechanisms did not decline with age.  For the lobster it's telomeres, and maybe some other things.  For Naked Mole rats it's upregulated redox pathways throught life.  In all cases like this, we can find something that has not declined with age.

 

Back to Berberine.  We are very much overcomplicating this as usual.  Take it if you have the beginnings of a metabolic condition.  And although there is absolutely no evidence that it causes B12 deficiency, take a B12 supplement if you feel it necessary.  B12 deficiency is something that is easily noticed and corrected if you know the signs, so it's not all that scary.  Berberine has an excellent safety profile.  Longecity is notorious for cynicism, negativity and digging out any and all possible negatives of a given supplement.  The fact that this all we can drum up probably makes it one of the safest supplements on the planet.  Finally, lets keep up with the times.  Calorie restriction mimetic (nutrient-sensing pathways) are almost ancient technologies.  At this point, we can just read the vast literature, make a decision but then please move on.  These pathways are not the answer, they are just very helpful in keeping us healthier until better technologies come along.  They won't keep you healthy if you engage in analysis paralysis.  Even senolytics is fast becoming an established biotechniology, at least for all of us on the cutting edge.  IF you are of a certain age or disease status and are serious about sticking around in a healthy state, then you should already be taking both of these categories.  But then you should move on.  They are like the smart phone.  We largely know what they do, we know we want them and even need them, but no one is all that excited anymore about the next iphone because it's an established technology of known value.  Now come join the cool kids on the epigenetics frontier.  Even David Sinclair has done so.  There's lots to do and learn, and y'all are too smart to waste your time tweaking smartphones to be .0000001% better.  Got it?

 

Edited by OP2040, 08 December 2019 - 02:56 PM.

[Groundhog Day]

Anyone know what mechanism berberine causes insomnia in some individuals (me)? Metformin does the same thing. I'm prediabetic and really want to take it as I have taken every other step to lower it. I'm slim and very fit, eat well, etc. 

[William Sterog]

Anyone know what mechanism berberine causes insomnia in some individuals (me)? Metformin does the same thing. I'm prediabetic and really want to take it as I have taken every other step to lower it. I'm slim and very fit, eat well, etc.

Hypoglycemia, maybe?

[Groundhog Day]

There's a diabetes blog that has a pretty harsh take on berberine:

 

Several mainstream studies claims to have found that berberine inhibits DPP-4 and raises the concentration of the incretin hormone GLP-1 which is the mechanism used by the incretin drugs Januvia,  Onglyza, and Trajenta. As discussed elsewhere, inhibiting DPP-4 can turn off a mechanism the immune system uses to kill cells that have become cancerous, which may make these a poor choice of drug. In addition, accumulating evidence is pointing to the possibility that artificially raising GLP-1 levels over a long period of time leads to the growth of abnormal cells in the pancreas which may grow into the ducts and cause pancreatitis or turn into precancerous tumors.  (Details HERE)

Mainstream research also finds that berberine has a significant impact on your liver. Repeated use downregulates several important enzymes (P450 cytochromes ) that the body uses to eliminate drugs. You can read about that here: http://www.ncbi.nlm....pubmed/21870106.

 

https://diabetesupda...ry-well-be.html

 

 

[Charles Thompson]

Read the article I posted in another thread about corona and you can see that it seems a very healthy ingredient in general with effects including exhibiting antiviral properties including against influenza. Could be useful in the current environment although the article mentions oxymatrine and Ecklonia as having the same (greater?) benefits.

One thing i can say is that if your goal is improving body composition, Berberine has a ton of real world feedback behind it.

[Dallasboy]

Read the article I posted in another thread about corona and you can see that it seems a very healthy ingredient in general with effects including exhibiting antiviral properties including against influenza. Could be useful in the current environment although the article mentions oxymatrine and Ecklonia as having the same (greater?) benefits.

One thing i can say is that if your goal is improving body composition, Berberine has a ton of real world feedback behind it.

 

BOOMER!!

[Charles Thompson]

Lol, no idea what boomer means but I’m assuming you mean post the article here so here is what I was referring to

https://www.predator...-immune-support

[RWhigham]

Berberine is a topoisomerase inhibitor or poison.  Mechanism study of goldenseal-associated DNA damage

• The toxic potencies of five goldenseal alkaloid constituents were compared.
• Berberine appeared to be the most potent DNA damage inducer.
• DNA damage was directly associated with the inhibitory effect of Topo II.
• The extent of DNA damage was positively correlated to the berberine content in goldenseal products

Here are the top topoisomerase inhibitors (or poisons) that are common in the supplement world

• Fisetin
• Quercetin
• Apigenin
• EGCG
• Berberine

Radiologists aren't held responsible for the DNA damage their equipment causes because the ill health effects (largely cancer) don't show up until years later. Perhaps the same could be true for some supplements.

Edited by RWhigham, 08 April 2020 - 08:10 PM.

[pamojja]

Here a functioning link: https://www.scienced...378427413008412. Therefore are we talking about in-vitro only, without all the enzymatic reactions and micronutrients present in multitudes for smooth functioning of what we call life?

 

And since time immorial life flourished very well even with strawberries, capers, parsley, greent tea and goldenseal.

[RWhigham]

And since time immorial life flourished very well even with strawberries, capers, parsley, greent tea and goldenseal.

Good point. But "the dose makes the poison"  Natural sources and supplements doses are often quite different.

 

The same can be said for supplement doses and "in vitro" doses, so many studies are ridiculous     But I try to protect my DNA zealously.

Edited by RWhigham, 08 April 2020 - 09:06 PM.

[TheFountain]

https://www.ncbi.nlm... cardiac damage.

Edited by TheFountain, 27 January 2022 - 10:44 AM.

[TheFountain]

Not to bring Metformin back into the discussion but I will anyway. There is research showing ceramide reduction in diabetics with Metformin usage. I wonder if the same is true for Berberine.

 

Also, any update on the downsides? 

 

I am considering going back to Berberine for a little bit since Metformin supposedly lowers Testosterone levels while Berberine has been shown to increase Testosterone levels. 

[syr_]

Does anyone know of any downsides to taking berberine?

Taste. it's bitter like a mofo.

[johnhemming]

I recently bought a Continuous Glucose Monitor.  (Dexcom G6).  It confirms I am not pre-diabetic, but I do take Berberine.  I would need to stop Berberine to get a base measurement and I am concentrating on other things at the moment so I don't want to change Berberine.

 

The way Dexcom work is that you buy "sessions".  The sessions last 10 days and require a new implant after 10 days.  I have not yet decided whether or not to continue after the first 10 days or whether to have a break.  I have bought three sessions.  I may have another session later in the year.  The implant which I am wearing in my belly is very mildly irritating.  I made a real hash of getting calibration measurement as well.  However, I now know how to do all of these things.

 

I do recommend this as an additional source of information, however.