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:  one, two, three, four, five 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 HbA_1c (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 HbA_1c, 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.  

I'm going to close this out with this study:  Berberine, a Natural Plant Product, Activates AMP-Activated Protein Kinase With Beneficial Metabolic Effects in Diabetic and Insulin-Resistant States.  

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.