Bad News for Berberine

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This is an older study, and it’s one I’ve looked at several times during my digging through the annals of scientific scrutiny. Honestly, if it was any other drug I’d really not care too much about it. I’d probably post it up and say stear clear of it, and then move on to the next topic. But Berberine has a host of some really awesome effects, from anti-depressant properties, to glucose lowering, to lipid altering, hell it even kicks the shit out of yeast and other microbial infections. It’s a really fantastic drug in a lot of ways. But when you see research like this, it’s an undeniable conclusion that this is a drug that should be shied away from if muscle preservation and accumulation is one of your goals in the gym.

 

Have you developed insulin resistance, metabolic syndrome, cholesterol problems, blood sugar problems, high blood pressure, depression, or systemic yeast/fungal infections? Then Berberine will sound like the first and last thing you will ever need to treat what ails you. It really is that ubiquitous, and I’m not saying that it’s useful for all of these things in a wishy washy way. I mean to say if you take a significant enough dose of it, you will find your BP drop within hours or days, you will find a more positive mood creeping over you. You will find the ups and downs of blood sugar to be a thing of the past. You will find all symptoms of a microbial infection begin to dissipate quickly. In short, Berberine kicks ass.

Harvested from goldenseal, oregon grape root, and barberry, Berberine is a unique alkaloid that affects many different systems in the body. It is nearly a miracle anti-diabetic drug, making metformin look like tictacs, and attacking the issue of diabetes from every possible angle – from inhibiting Foxo-1 (which integrates insulin signalling with mitochondrial functioning) to making beta cells within the pancreas more capable of responding to glucose loads, to increasing incretin, to increasing adip0nectin.

In cancer studies it not only inhibits the growth of certain types of cancers, but actually makes the outcome of radiation treatment more tolerable by limiting some of the negative effects that come from that type of treatment.

As for mood and cognition – it’s a very suitable drug for alzheimer’s disease treatment (not a cure mind you, but in alignment with some of the other preferred methods of treatment like acetylcholinesterase inhibitors). Berberine inhibits prolyl oligopeptidase (POP) in a dose-dependent manner. It acts as an herbal anti-depressant and has a wide range of beneficial effects on mood, increasing serotonin turnover and antagonizes orexin receptors. It may also function like tianeptine in that it increases serotonin transporters in the brain.

Hell, it’s even being investigated as  an HIV treatment, not to cure the disease but to treat the underlying ailments that this virus causes.

So why am I so bummed out? Berberine rocks, there is no doubt. There’s just one catch. That catch has a name, and it’s name is Atrogin-1.

Atrogin-1 is a unique modulator of muscle. It not only inhibits muscle protein synthesis, it actually encourages the degradation of muscle tissue.

“Atrogin-1 not only increased proteolysis but also reduced protein synthesis by mechanisms that were independent of decreased phosphorylation of Akt or forkhead transcription factors. Impaired protein synthesis was dependent on a reduction in eIF3-f, an essential regulator of protein synthesis. Berberine impaired energy metabolism, activating AMP-activated protein kinase and providing an alternative mechanism for the stimulation of atrogin-1 expression. “

So Berberine not only activated atrogin-1 directly, it also indirectly activated it by activating AMPk, which as you learned from my previous article will increase myostatin expression, which will ultimately decrease muscle protein synthesis.

There is some potential hope here though. In the same study, the authors went on to mention this:

When we increased mitochondrial biogenesis by expressing peroxisome proliferator-activated receptor gamma coactivator-1alpha, berberine-induced changes in muscle protein metabolism were prevented.

So it seems like a PPAR-gamma activator my actually prevent this muscle protein issue. The only issue with this is that ppar-gamma agonism can be a bit sneaky. Too much of it for chronic periods can cause adipogenesis. PPAR-gamma is a failsafe mechanism designed by mother nature to protect us from excessive glucose. The final step in preventing this problem, when all else fails, is to make new adipose tissue and store the sugar as triglycerides. So you guessed it, the one key we have here to prevent the debilitating effects of Berberine, is a mechanism designed to induce adipogenesis.  Not exactly a tradeoff in the right direction.

Also, be careful when taking Berberine if you are on losartan, midozolam or dextromethorphan. If for some reason, after reading my article you are still bent on using this drug, you need to be aware that it inhibits the enzymes necessary to break down the drugs I just mentioned.

So what do I do with this big tub of Yellow Gold? I’m not sure right now. Honestly, it was the first supplement I had used in a long time that not only made me very insulin sensitive, but made me feel tons better and lifted depression. It’s hard to walk away from. I will be looking into this further and hoping to learn more about this. The one good thing we have going for us here is that the study I am citing was done on rats. Perhaps there is some major difference between rat muscle and human muscle that will spare us of these negative effects. I am also opening this discussion up to people that are much smarter than I am on this field and I hope they will chime in if the research they have read, or the study I am pointing out, has some holes in it that need to be explored. As I have said before, sometimes I know just enough to be dangerous.

But in the meantime, if building and preserving muscle tissue is one of your sacred values, I would set the Berberine down, or at least use it sparingly, as a once a week or once a month run to help restore sensitivity to insulin, or to treat a microbial infection of some sort.

 

Diabetes. 2010 Aug;59(8):1879-89. Epub 2010 Jun 3.

Atrogin-1 affects muscle protein synthesis and degradation when energy metabolism is impaired by the antidiabetes drug berberine.

Source

Renal Division, Jimin Hospital, Shanghai, People’s Republic of China.

Abstract

OBJECTIVE:

Defects in insulin/IGF-1 signaling stimulate muscle protein loss by suppressing protein synthesis and increasing protein degradation. Since an herbal compound, berberine, lowers blood levels of glucose and lipids, we proposed that it would improve insulin/IGF-1 signaling, blocking muscle protein losses.

RESEARCH DESIGN AND METHODS:

We evaluated whether berberine ameliorates muscle atrophy in db/db mice, a model of type 2 diabetes, by measuring protein synthesis and degradation in muscles of normal and db/db mice treated with or without berberine. We also examined mechanisms for berberine-induced changes in muscle protein metabolism.

RESULTS:

Berberine administration decreased protein synthesis and increased degradation in muscles of normal and db/db mice. The protein catabolic mechanism depended on berberine-stimulated expression of the E3 ubiquitin ligase, atrogin-1. Atrogin-1 not only increased proteolysis but also reduced protein synthesis by mechanisms that were independent of decreased phosphorylation of Akt or forkhead transcription factors. Impaired protein synthesis was dependent on a reduction in eIF3-f, an essential regulator of protein synthesis. Berberine impaired energy metabolism, activating AMP-activated protein kinase and providing an alternative mechanism for the stimulation of atrogin-1 expression. When we increased mitochondrial biogenesis by expressing peroxisome proliferator-activated receptor gamma coactivator-1alpha, berberine-induced changes in muscle protein metabolism were prevented.

CONCLUSIONS:

Berberine impairs muscle metabolism by two novel mechanisms. It impairs mitochonidrial function stimulating the expression of atrogin-1 without affecting phosphorylation of forkhead transcription factors. The increase in atrogin-1 not only stimulated protein degradation but also suppressed protein synthesis, causing muscle atrophy.

 

 

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