Berberine -- Supplement or Pharmaceutical? Does it matter?

I have commented a few times before on supplement usage in "The Community".  For example, here. It always amazes me the litany of pronouncements on the macro/micro nutrient superiority of one's chosen diet that are side-by-side accompanied by an even longer litany of supplements.  It is pervasive, and dare I use the "a" word, addictive.  When I first found the LC web in 2009 I was rather astounded by the amount of supplements some were taking.  At some point, if one is supplementing their diet with a handful of pills, one needs to take a step back and recognize that it may well be those pills responsible for effects in spite of the diet.

But another thing that's rather pervasive in the community is the use of supplements often accompanied by sanctimonious braggadocio regarding how the "diet" enabled a person to come off of all medications!

Berberine has been making the rounds in LC/diabetic circles, and for good reason.  It works!  There's been a veritable sheetload of legit scientific studies on the stuff.   So ... this then begs the question of whether it matters that someone takes, say, prescription Metformin or buys a supplement such as the berberine containing Glycosolve.  
Yeah, Jimmy Moore again!  ;-)

As with most of his various posts in favor of low carbing and it's supposedly universally positive impact on his health, Jimmy's n=1 experiments -- from the product testing on up through his nutty ketosis experiments -- often reveal some negative things going on.  Key among these are that for much of the past year and a half  (perhaps longer), Jimmy has had elevated fasting glucose.  His readings have been above 100 mg/dL enough days that if he were under regular medical care, a "prediabetes" diagnosis would almost certainly appear on his charts.  For most of that time, one might attribute that to his weight fluctuations and basically gaining 55 lbs in the latter half of 2011/early 2012.  

While he might have blamed the occasional glucose excursion from the fake low carb items, ingestion of carbs ultimately has little or no influence on fasting blood glucose, and elevated FBG is generally attributed to hepatic insulin resistance.  He was asked once about it and whether or not he'd considered taking metformin  (he was on it briefly in 2008 despite having no indications of insulin resistance at the time).  His response:  
... I’ve always suspected I was on the borderline of being insulin resistant/prediabetic anyway. Obviously something metabolic has been going on to make the weight struggles happen. It will be interesting to see if the blood sugar levels normalize as the experiment continues on. As for Metformin, I tried it for a month a few years back and it didn’t seem to help me–and gave me a big tummy ache all the time. I know they have a CR version now that’s supposed to be better for that. I’m just skittish about trying it and I hate taking prescription medications for ANYTHING.
Here are the links to Jimmy's six monthly updates for nutty ketosis:  onetwothreefourfive and six.   His fasting blood glucose levels are all over the map as we see from the compilation of the first three months below.

While he certainly had his fair share of normal readings in this time, there are also a goodly number of concerning readings.  So in month three, 
Again, that dastardly Chinese buffet meal in Indiana hit me hard with a blood sugar reading of 111, but the rest of the month got remarkably better. You’ll see towards the end of July and in early August I had blood sugar readings in the upper 70s/low 80s. I started taking a blood glucose stabilizing supplement called Glycosolve (made with berberine shown in this study to lower blood sugar levels) that has helped me manage my blood sugar. My results aren’t perfectly in the 70s/80s all the time yet, but that’s my goal. It’ll be interesting to see if my higher blood sugar levels are only showing up in the morning (Dawn Phenomena maybe?) or if the nighttime testing will also be higher. We’ll know next time I update.
As I demonstrated with the Google Scholar search linked above, there's quite a bit of peer review clinical research on berberine.  It has been demonstrated to have pharmaceutical-grade effects on FBG and postprandial glucose.  According to Jimmy's link, this is due to berberine's action upregulating insulin receptors and overall improving liver function.  By "pharmaceutical-grade" I mean that the effect is one of magnitude of effect that would be desired for a pharmaceutical agent.   Here's another study (two actually) that compare berberine to metformin and berberine in combination with other diabetes therapies.   In Study A, subjects were given either 500 mg berberine or metformin, 3X daily at meal times.  The results over 13 weeks?  {bullet-pointed for clarity}
  • In newly-diagnosed diabetic patients, berberine reduced blood glucose and lipids (Table 2). 
  • There were significant decreases in HbA1c (by 2%; P < 0.01), FBG (by 3.8 mmol/L; P < 0.01) and PBG (by 8.8 mmol/L; P < 0.01) in the berberine group. 
  • The FBG (or PBG) declined progressively during the berberine treatment, reaching a nadir that was 3.7 mmol/L (or 8.7 mmol/L) below baseline by week 5, and remained at this level until the end of the study (Fig 1A). 
  • Triglycerides and total cholesterol decreased by 0.24 mmol/L (P < 0.05) and 0.57 mmol/L (P < 0.05) with berberine treatment. 
  • It seemed there was a declining trend of HDL-C and LDL-C; however, no significant differences between week 1 and week 13 were observed in the berberine group. 
  • 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).
Repeate, note to diabetics in the audience -- this berberine stuff looks to be "for real"!! However, taken in conjunction with other meds, there must have been some instances of stomach upset, sometimes seen with metformin, as reduction of the dose to 300 mg was mentioned for some subjects who experienced this side effect. 

So the first question that comes to mind, and this is irrelevant to whether this is Jimmy or anyone else, is whether there's really any distinction to be made in the act of "taking something" to regulate glucose.  To me the only difference that matters is between taking something that is effective vs. nothing.  Indeed in any study on the impact of diet on something, all supplements and/or medications should be either standardized across the board or discontinued entirely.  But potential side effects aside, there's no difference between taking an effective molecule extracted from a plant vs. an effective molecule developed by a pharmaceutical company in the lab.  

Well, it does appear that berberine may be effective for Jimmy as evidenced by his lowered FBG's in months 4 through 6.  (Note the vertical scale expansion exaggerates fluctuations these three months).

A definite improvement, he attributes at least partially to Glycosolve:
Did you notice that something miraculous happened with my morning fasting blood sugar readings this month? THEY NORMALIZED!!! My average reading was probably around 83 which I’ll take every day of the week. ... As I shared with you in last month’s update, I started taking a blood glucose stabilizing supplement called Glycosolve 2-3 times a day which I am sure is contributing to these rockin’ blood sugar numbers.
That's great, but perhaps Glycosolve is entirely responsible for them, and improving on some hepatic insulin resistance Jimmy might otherwise be inducing with his ketogenic diet and intermittent fasting.  The fact of the matter is, according to the study I posted, Jimmy is taking a "drug" to normalize his blood sugar.   And although berberine has been studied as a cholesterol-lowering substance, it doesn't appear to be doing much for him in that department.

I intend to do a follow-up post on the pros and cons of taking pharmaceuticals vs. OTC supplements vs. pharmaceuticalized supplements.   The Cliff Notes is that there are real differences in costs (often surprisingly in favor of the pharmaceutical) , reliability, efficacy, etc.  Sometimes the supplement is the better choice, sometimes the pharmaceutical, but always it's a cost/benefit/risk balance for each individual to weigh for themselves.

In the case of berberine, the doses of supplements are on the order of those used in various studies on its effectiveness.  Good!  It's not horribly expensive, depending on your source, roughly 50cents to a dollar a day.  Good!   But compared to the metformin Jimmy likes to avoid because it's a "drug" -- it's rather expensive.  Generic versions of metformin are among the $4/month scripts offered by many places, and even the "top of the line" name brand version rivals the cost of Glycosolve.  That comes backed with literally decades worth of clinical trials and widespread usage amongst millions of diabetics with no known dangerous side effects to my knowledge.  This part is just food for thought for those considering a tablet of metformin vs. berberine.    For the record, personally I'd consider berberine if I had the health issues it can help with.  

The use of natural products for the treatment of metabolic diseases has not been explored in depth despite the fact that a number of modern oral hypoglycemic agents such as metformin are derivatives of natural plant products.  Although several traditional medicines have been reported to have antidiabetic effects, the molecular targets of such compounds have not been revealed, and a careful analysis of their mode of action in animal models has not been undertaken. In the present study, we have focused on berberine because this natural product has been reported in the Chinese literature and several recent studies to have beneficial effects in human type 2 diabetes, although its mechanism of action is not known.
Bottom line here.  Taking berberine is akin to taking a pharmaceutical agent to improve glucose metabolism.  Since its action is as effective and in some ways more effective than metformin, any boasting or back patting by anyone taking this supplement, and not "prescription meds", is a bunch of hot air.  There is evidence for different mechanisms of action that deserve further investigation.  Neat stuff, actually!!  But ....

Anyone taking berberine might as well as being taking metformin in terms of improvements one attributes to the diet they're following while doing so.   Berberine is a pharmacologically active compound.  Period.  Just because it has not been pharmaceuticalized is irrelevant.

Berberine seems to be a supplement worthy of consideration that is effective in doses that have been tested and are in line with the potency of supplements that include it.  It apparently has a long history of use in Chinese medicine and such.  But don't kid yourself or others.  It IS a "clinical intervention", a "molecular therapy", a "medical treatment", a "fill-in-the-blank".    

A final note vis a vis Jimmy's use of berberine.  That during the first few months of rapid weight loss on a demonstrably ketogenic diet, his fasting blood glucose levels failled to stabilize would be concerning to me were I him.  He's now effectively taking an antidiabetic medication to control his fasting glucose levels despite following a super low carb diet.  It will be interesting to see what happens when he goes off the Glycosolve.


Anonymous said…
Hi, Jimmy's BG readings in months 1-3 look stable to me if you consider variation typical in home testing.

Also, elevated FFA decreases beta cell function. No IR required. If you are going keto or LC, mild FBG increase should be expected.
Anonymous said…
When you prepare your blog entry about over-the-counter supplements vs. pharmaceuticals, don't forget this:

Once upon a time, it had some fairly useful free information. Now, I think you have to pay for the info. Nevermind, it's still useful stuff. I could be totally wrong about this, but I think the quality of stuff produced by a pharmaceutical company is better because that industry is more tightly regulated.
CarbSane said…
Hi stew,

I agree, variation is typical, but his FBG had been around 100 for quite some time, and over 110 several days in this time frame. This would garner him a prediabetic diagnosis.

Not sure I agree on the FFA and beta cell function. High FFA increases basal insulin, a feedback loop to keep FFA release in check. If you're in FFA causing reduced beta cell function? Not good man!
CarbSane said…
I tend to agree in general ... of course there will be exceptions. I'm torn especially with pharmaceutical grade supplements. On the one hand, the supps are cheaper and often just as effective, OTOH, you know what your are getting with the pharma-grade. The biggest thing I'm cautious about is when a plant-derived compound is specifically effective (e.g. can be shown to impact gene expression, enzyme production, enzyme activity,etc.etc.) I'd tend towards the pharma version.
Puddleg said…
Could it be that what Jimmy is supplementing here is like the concentrated, carb-free essence of the PLANTS he is not eating?
Berberine also has antidepressant effects, kills pathogens, and so on.
Aaron said…
Evelyn, I'm not sure why you mention Jimmy anymore. You've already acknowledged he's way too entrenched into his online empire to have any kind of change of heart (even if it would help him). Regardless of what anyone says, fasting blood glucose over 100 is bound to be bad.

We will never know if he is eating too many snacks, eating too much, or just eating way too much fat than is healthy for an individual without impeccable genetics.

I'm sure Jimmy's issue more than anything is a lack of exercise and meal frequency (with a caloric excess).

Even people who think they are totally going to crash with carbs just don't know physiology unless they are a type 1 diabetic. A person's liver/muscles are so ready for glucose after exercise and glycogen depletion that I'm sure the same could be said for Jimmy's if he'd just move around some more.

I also think that he'd probably benefit from less meals in a day (2 or even 1). That would allow for his insulin to moderate in between meals.

I'd bet any amount of money that if he ate a low to moderate monounsaturated diet with tubers/rice and veggies he tolerates he have wonderful lab results AS LONG AS HE EXERCISED.
Jason Sandeman said…
I'm not sure why people end up pussing out from Metformin. Sure, there's a bit of heartburn while you get used to it, (especially with a fatty meal in the beginning.) I take 3 x 500g per day, and really - it's no big deal.
I think Jimmy doesn't want to take the Met because of the connotations of what it will mean. To be honest, while Jimmy's average FBS is "prediabetic," the trend indicates some WAY more serious going on. In his shoes, I'd be worried about pancreatic fatigue.
He has bragged before about his statetorea from his fat fasts - pancreatic problems present that symptom.
In any case, there is definitely something going on there. I'm a T1D who takes evil pharma drugs - and my FBS are normal. Yes, they are prediabetic levels - but they are normal, EVEN if I hit a Chinese buffet.

Oh, one other thing - in a case where a person had pancreatic dysfunction, a high carb meal will definitely affect a FBS. It's not "dawn" phenomenon like the joker is claiming, it's liver dumping glycogen to cover the excess insulin load. That's the main function of Metformin - to stop the liver from dumping glucose and allowing the insulin to do its job. A regular person won't have to worry as much, as first phase insulin covers that glucose dump. In Jimmy's case, you can see he is having problems with that liver dump. It explains his NAFLD symptoms, his attrotius lipids, his FBS and his weight problems.
To bad he is a dumbass. A 4$/month "drug" would solve his problems - and curb his appetite as a
blogblog said…
The scientific literature shows that exercise is FAR more beneficial than weight loss with regard to health benefits.

Two of my siblings are heavy drinkers and ex-smokers. Both are diligent exercisers. They have very few health problems.

My very sedentary sister who has never smoked and doesn't drink has appalling health.
CarbSane said…
At least metformin is "allowed" in LC circles, unlike the evil insulin ;-) Still everyone seems to be in a rush to get off meds so they can say so, I suppose. I can certainly understand the desire not to have to take meds, but sometimes they are warranted. It's a common story on forums, overweight person goes LC, loses a bunch of weight, BG's normalize a bit, goes off meds, complain how fasting BG is still wonky. Rationalizing begins.

To clarify, there's no evidence that a "prediabetic range" FBG is harmful, it's the evidence, as you point out, of underlying issues. It looks like the berberine is working for him. And judging from the literature I've been reading, it should help his liver out.

Unknown said…
People put a lot of effort into finding a "hack" that will give them health while avoiding the necessity of exercising.

river rance said…
What effect does JM's testosterone supplementation have on any of his fat loss/muscle gain or his most recent high fat diet that he seems to be raving about? You can't make this stuff up! He's off the rails. From about a year ago:

You might be asking “Why is raising testosterone levels so important?” That’s an excellent question and it’s one my fellow health pioneer and Paleo blogger/podcaster extraordinaire Robb Wolf addressed in an epic blog post he wrote last month entitled “Paleo and Testosterone.” Take time to read and absorb all the information there when you have a chance. It’s a lot more technical (translated: “nerdy”) than what I’m sharing here today, but incredibly invaluable. In fact, it was that post that got me to seriously start taking a look at whether this was MY problem. It turns out this could be EXACTLY what I’ve been dealing with regarding low sperm count and motility and my struggles to lose body fat around the middle of my body in recent years when my legs and upper body look completely normal. I’m trying not to get too excited about this just yet, but the sense of at least knowing what is going on and attempting to do something about it has me more ecstatic than I’ve been since losing 180 pounds on low-carb in 2004.
CarbSane said…
Aaron, so long as he remains an arbiter of information in this community, posts like this one will continue. He just toured Australia promoting this nutty ketosis stuff on their dime. One would think you couldn't make that sort of stuff up, but there are a lot of gullible people out there.

He's been eating a pretty consistently low carb diet for going on 9 years now, and he was relatively healthy in 2005 ... two years in and 190 lbs down. Since then his health has deteriorated on the diet he promotes as healthy.

Right now he feels great because everyone feels great when they've lost a lot of weight and adoring fans are complimenting you left and right and you're no longer lugging around 50 lbs. But he is not healthy and he can't blame his past diet for that.

Yep Unknown, that seems to be an activity engaged in with the most zeal in the low carb community! I'm happy to see he's playing frisbee golf, but with his sedentary job that brings his activity level to "low". On his recent trip on a vid his wife mentioned he went on a long walk that morning. 5-6K = <4 miles = a "good walk", but hardly worthy of special mention as "long". Of course Tom Naughton is impressed by such feats!
CarbSane said…
He's coy now about testosterone. I think the last report was that his levels were normalized and he stopped taking it? Not sure on that. Interestingly when he went "Paleo and Testosterone", he got up to 306 lbs.

How anyone takes him seriously is beyond me. Talk about getting cause and effect wrong again and again.
Galina L. said…
My FBS is also on elevated side very early in the morning, but it is back to norm after 10 am (if I don't start exercising), so, if I don't want a strange number on my blood test, I just go to a blood testing lab after 10 am. In mine case not ketosis, but the adaptation to the fasting and especially to the exercising in a fasted state caused elevated FBS. There is a bonus though - my blood sugar doesn't fall too low nowadays and a delay in eating doesn't cause a headache or any other discomfort like uncontrollable desire to eat.
CarbSane said…
BTW, I am actually rather amazed so many older women put up with Jimmy's shenanigans. He had his RMR measured in 2005 too, and it was like 2300 cal/day. For the most sedentary person that would put TDEE at around 3000 cal/day. Anyone who cannot maintain that level of intake has some other problem, period. Even 2500 cal/day is a LOT of food when calories are "well spent".

Someone on FB just asked me if I was familiar with a woman's website. I remember her from Jimmy's forum in 2009. She has finally busted through a years long stall to lose 60 lbs (after losing 17 lbs initially). How? She eats like a bird. 1000 cal/day. That will be what she has to eat for all eternity. I would caution her about that but she thinks I'm just a biotch so why bother.

This is one of the things with low carb and why I find the Ebbeling study so infuriatingly misleading and all of the metabolic advantage stuff equally so. Yes, LC tends to produce faster weight loss, but it also is the only diet I know of where staunch advocates and adherents will regain -- not all, but some. Part of this is that I believe it suppresses metabolism over the long haul. Jimmy was exercising 5 hours a week back when he had his RMR measured, so was likely keeping that metabolism up by the sheer force of calories consumed (and protein).

I'd love to know what his RMR was circa March 2009. That was the last time he was somewhat weight stable for around 6 months around 240 lbs and reporting only refereeing and the occasional recreational volleyball for exercise. I am willing to wager he's damaged his metabolism with carb restriction and aggravated that with his sedentary job.

I really have to fight that myself, and blogging is not my job! It sounds so silly, but one semester years ago I taught entirely online. It was horrible for my weight. You don't realize how even the little things add up -- getting dressed for public consumption, walking to your car, walking into work, for me pacing/standing for several hours in front of a class, walking between classes in different buildings, for most walking to the cafeteria for lunch, perhaps walking down the hall to use the rest room, walking to a break room, walking back to the car, walking back into the house. Now, that is not much. I would not describe my job as laborious or active, and lately using the Symposiums (you write on computer screen and it's projected on screen) means even less active standing in one place (but it beats writing on a board for any number of reasons in terms of students, so if available, it's sort of a must do thing). But all of that adds up.

CarbSane said…
Jimmy is doing some sort of "spontaneous IF" -- he eats only once every 12 to 24 hours. The only reason I mention his FBG at all is that if he were to report those numbers on any other diet, the carbs in the diet would be blamed. Clearly he can't blame the carbs and it's just another part of the puzzle of what appears to be deteriorating liver health (and perhaps he has non-alcoholic fatty pancreas as well).

This berberine looks promising Galina. You've mentioned you also get pp spikes with not a whole lot of carbs. Worth looking into, but I'd discuss with the doc if you are taking other meds.
river rance said…
" my fellow health pioneer and Paleo blogger/podcaster extraordinaire Robb Wolf"
That's the line that had me laughing. And I often laugh at his nonsense. Sadly real people looking for real answers to their health issues believe this "circus clown". I find that very very sad.
Galina L. said…
The only med I am taking is the Armour thyroid. BTW about supplements - I am normally taking a magnesium supplement because it is highly recommended by everyone (it is good for mental health, for allergies, for everything, ..., unlike starches, everybody agrees on magnesium), but I didn't take it for about 2 months without feeling any difference in how I feel. Of course, it may be not enough to deplete my body from it , but such experience made me wonder, how many people just take whatever is recommended by others. Of course, berberine is a different matter because it is so close to Metphormine. It is my guess, but I suspect that the use of Metphormine by a person who is well adapted to ketosis may cause the training of the liver to be even more efficient with making sugar. I could be wrong.

I own a glucosemeter only for one year and a half, so the only BS readings I have are FBS data during previous years from tests done twice a year during reqular check-up. I asked my doc's office to give me the information, and I had a chance to notice that my FBS was steadily rising getting closer and close to the upper range.It didn't caught my doc's attention(or mine). The last test before I radically change my diet 5 years ago, after gaining 26 lb in one year, gave the FBS=99, then in 6 months after intense initial weight loss it dropped to 69, then 71. Nowadays it is something like 96 after 10 am, if the test is done after 12 pm in a fasted state, it is 84. If I start exercising without eating , it will be 118 - 121 . At least my BS numbers have some explanation now.

You encouraged me to talk with my doctor. What do you think he is supposed to say? To sent me to the glucose tolerance test and declare me a diabetic if I forget to do carbo-loading several days in advance, to check glucated hemoglobin? I noticed my mom didn't have a good pp numbers when I checked her 1.5 years ago(like close to 170 one hour after eating an oatmeal or a wholegrain sandwich.).
Anonymous said…

' Metformin has recently gained much attention as it appears to reduce cancer incidence and improve prognosis of patients with diabetes. In vitro data and animal studies support these findings from human epidemiological studies. Metformin has multiple potential mechanisms by which it inhibits cancer development and growth.'
Diana said…
Agree w/you completely about "going off the meds" while swallowing boatloads of supplements. But - this berberine stuff intrigues me.

I recently began taking amino acid supplements (plus SAM-e) and it has improved my mood. So I am not so dismissive of supps as I used to be.

What is the diff between berberine and barberry bark? The latter appears to be much more cheap than the former.
CarbSane said…
Hey Diana, Barberry bark contains other stuff, berberine is isolated from that.
Although it's more expensive, I think I'd go for the berberine for blood sugar control as there's better chance of getting consistent dose.
CarbSane said…
Yeah, "health pioneer"??? LOL. Yes, "circus clown" is more like it, and it is very very sad there are people going to him for advice. Even listening to his podcasts has gotten pretty bad as he injects his bias left and right. How do you know you're getting something worth listening to? Jimmy gets VERY quiet.

CarbSane said…
Sorry, I might be misremembering, or you may have mentioned your Mom's pp glucose before and I confused it with yours. I was also under the impression you still took some meds for migraines. That was the only reason for my rec to talk to doc before taking something like berberine. Not that you should go talk to your doc! Berberine is for all intents and purposes, a drug. I say that as opposed to Mg which is a supplement -- it's involved in metabolism and deficiency can be a problem (and certain conditions increase requirements). Not that it's dangerous, heck it could be safer than metformin for all I know, but there's not a lot of info out there on how it interacts with other stuff.
Galina L. said…
Yes, you are right, sometimes I take meds for migraine(ergots) , I have to do it probably every other month. Somehow I mentally dismissed not-regularly taken things. Allergies are my second main health problem, most of the time any medication I take makes allergies to come back, so I am very motivated to keep anything pharmacological to minimum, and ergots are pretty bad in that regard , and often I have to combine it with Claritine (oops, another med). I resumed magnesium citrate after coming back to USA. I just decided to live the magnesia I took to Russia for my mom. I brought her some, but calculated it will not last till my next visit. They sell magnesium citrate in pharmacies in the form of powder which tastes horrible and my mom refused to take it.

From my experience I can guess that berberine may increase migraine frequency in people who are prone to migraines because BS falling too low is one of triggers. For that reason the adaptation to fasting was so beneficial in my case. Migraine is not the only condition that can worsen due to the low blood sugar, people who experience episodes of hypoglycemia really suffer from it.
Diana said…
I ordered this:

Because it was SO cheap. I can't believe it contains 500 mgs of barberry bark. It would have to be some kind of extract.
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