This one’s a doozy. But in this write-up, we’ll examine the many benefits of Berberine including improved insulin sensitivity, and if it can replace Metformin (Glucophage) as a safer alternative.

What is Metformin?

Metformin, aka Metformin HCL, aka Metformin hydrochloride, aka Glucophage, is a drug given to people with non-insulin dependent type 2 diabetes to help bring down their blood glucose levels and improve insulin sensitivity. In other words, their body still makes insulin, it just stinks at using it. (1)

It can also sometimes be used in conjunction with insulin in non-insulin dependent type 2 diabetes, and even rarely in select patients with insulin dependent type 2 diabetes. (2)

What does metformin do?

Metformin works to lower your blood glucose levels. It does this in a couple ways.
1) cuts down on the amount of glucose your liver kicks out
2) improves your insulin sensitivity, specifically how sensitive your muscles are to insulin
3) cuts down on how much glucose you absorb through the food you eat. (1, 3)

Metformin's use in bodybuilding.

There are legit uses for metformin in bodybuilding, and they're very similar and/or directly related to why it is beneficial for diabetics. I mean who doesn't want to have awesome insulin sensitivity, right? Your muscles are more sensitive to insulin so they scoop up glucose better, allowing for that pump we all love. Your muscles can then make better use of that nutrition they're holding after you damage them after training. It helps your body make much better use of glucose, which will allow users to eat more carbs without worrying as much about it turning to fat. And, because extended HGH use can cause cause a rise in insulin resistance (4), Metformin can help mitigate this shitty side effect of HGH.

However, metformin is not without it's own set of side effects.

Side effects of Metformin

From drugs.com (5). You can read the giant list on your own, but here are the highlights.
- abdominal pain
- decreased appetite
- diarrhea
- fast/shallow breathing
- fever/chills
- lower back pain
- muscle pain/cramping
- painful urination
- lethargy
- anxiety
- blurred vision
- confusion
- depression
- seizures
- shakiness
- slurred spray
- tightness in chest
- loss of strength
- excess gas in stomach or intestines
- flu like symptoms

1-10% hypoglycemia
Very rare >0.01% Lactic acidosis (serious shit)

That ends it for drugs.com.

Top those off with what should concern us hormone-wise:
- decrease total and free testosterone in non-diabetic men (6)
- downregulation of androgen receptors (not desensitizing the receptors... literally gets rid of androgen receptors… gross) (7)

Now if you're on exogenous testosterone anyway those two are probably a wash, but I wouldn't fuck with the stuff if you're natty, and DEFINITELY not during PCT.

"But wait! Could there be a herbal OTC alternative that is just as, or possibly even more effective than metformin?"

Well little Jimmy, there is! You may be in luck. Let me tell you about Berberine.

What is berberine?

Berberine is an extract from a berry shrub called Berberis Vulgaris, aka common Barberry, aka European barberry, aka Barberry, hailing from Southern Europe, Africa and Western Asia. (8)

It's being studied for its anti-aging, anti-diabetic and anti-cancer properties. And all it takes is a quick Google to see that more and more diabetics have been successfully replacing their metformin with berberine.

Using berberine in place of metformin?

So how did I stumble on this shit? You may or may not be asking yourself... I was researching new ways to increase my insulin sensitivity. I already do the standards like improving omega 6:3 ratio, drinking apple cider vinegar, green tea, cutting out simple carbs, etc. and thought "well, what do diabetics do?” I started looking at supps for diabetics and researching the ingredients, and found two very strong candidates. One being berberine and the other gymnemma (maybe another post one day? We’ll see. This was a lot of fucking work).

Berberine was the strongest since there were tons of articles, controlled medical studies, and forum posts of diabetics and doctors claiming berberine was just as effective as metformin, with some swapping out one for the other with great success. You can do the googling yourself if you want to hear the personal accounts or read the articles, but I'll sum it up for you, mainly the medical studies since the proof is in the pudding.

Studies show berberine's effects not only match metformin, but can eclipse it....
Ok, here's where the fun shit starts. Although we don't really hear about it, scientists have been sciencing the balls out of Berberine and its comparability to Metformin for years...

In one study, 74 patients (there were a few more, but a couple dropped out and others where kicked out for being lazy with their drugs and not following directions, because why would they?) with newly diagnosed type 2 diabetes were split into two groups. One group received 500mgs of Berberine three times daily after meals, and Group B received 500mg of Metformin three times daily after meals. I'm going to copy and paste this part instead of summarizing so I don't fuck it up:

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).(9)

So that's what's up...

Another study (that i would have had to purchase for the details, but we at least get the abstract) proved that Berberine given to humans with type 2 diabetes lowered their fasting blood glucose, hemoglobin A1C (super important measure in diabetes), triglyceride, and insulin levels similar to the level Metformin and Rosiglitazone does. It did this by increasing the expression of the insulin receptor (aka improving sensitivity). It also improved liver enzymes and liver function. Again, I don't wanna mess this part up:

Our results confirmed the activity of BBR on InsR in humans and its relationship with the glucose-lowering effect. Together with our previous report, we strongly suggest BBR as an ideal medicine for T2DM (Type 2 diabetes mellitus). (10)

But wait, there's more!

Another study investigated Berberines effect on both metabolic disorders like diabetes and cardiovascular disease. It not only confirmed what the other studies found, that's it's awesome at lowering glucose, nutrient partitioning and improving insulin sensitivity to the same level as metformin, BUT also demonstrated effects on the AMPK activity involved in cardiovascular disorders. Concluding...

In fact, widely used drugs, including statins, metformin and rosiglitazone, execute CV protective effects though the activation of AMPK. The demonstrated efficacy in dyslipidemia and the promising antiarrhythmic activity make BBR a candidate for further study to provide new insights for therapeutic purpose. (11)

Another study used only 24 people with metabolic syndrome. 12 got 500mg of Berberine 3 times a day before meals, the other 12 got a placebo. No change was shown in the placebo group. The Berberine group had a 36% remission of metabolic disorder, their waist shrunk, systolic blood pressure, total insulin secretion and triglycerides all were lowered, and insiulin sensitivity improved. (12)

Wham-O!

Lipid improvement? Yes please!

Yet another study looked at Berberines effect on the blood lipid profile. The study gave subjects two 500mg doses a day of either Berberine or placebo for 3 months. Then they took them off for 2 months as a “wash out period”, then started up the treatment again for another 3 months. Results?

A decrease of body weight and BMI was observed after the run-in period. Berberine reduced total cholesterol, triglycerides and LDL cholesterol and increased HDL cholesterol after 3 months from randomization and compared with placebo. After the washout period, lipid profile worsened; afterward, when berberine was reintroduced, lipid profile improved again both compared with the washout period, and with placebo. (13)

They concluded it was effective and safe for low risk patients.

I know... You're all like "Holy shit, D... are there ANY downsides?!"

Dangers/sides of berberine?

Berberine has an extremely low toxicity – Yay!

Some gastrointestinal discomfort was found for a few patients in one of the studies above (I think (9)?). That was mitigated by dropping the dose to 300mgs 3 times daily instead of 500mgs. So you may experience cramping, diarrhea, or nausea. (I didn't, but you might)

I found these drug interactions in another article about sides and stacks that already did the research for me and cited said research in the article (14)

• Berberine lowers blood sugar and can increase the effects of other drugs that perform the same task.

• Berberine inhibits cytochromes CYP2D6, CYP2C9, and CYP3A4. These cytochromes are the targets of a large number of medications, so check that you're not taking something that targets one of those.

• "Berberine has a powerful effect on anion transporter proteins in the cell membrane. A few medications use these transporters to access your cells and deliver their effects. One important medication is Metformin" (14)

• Dangerous interaction with macrolide antibiotics. "The Berberine toxicity occurs at hERG channels in the heart. There is a potential for serious negative health effects in these interactions. (14)"

So don't mix it with any of those.

Also, webMD says don't give it to babies. So don't do that either. But really, you'd kind of be an asshole if you did anyway...

The one downside I can find is that it's bioavailability isn't super awesome. In fact it's the opposite of super awesome. In theory, if the bioavailability can be improved, maybe less can be taken and that would cut down on anyone experiencing gastrointestinal issues. BUT I found a way that should improve that too!

Improving bioavailability

While the studies dosed orally and it still worked, we can make it even better. Studies show that P-glycoprotein is a real cock-block when it comes to absorbing Berberine in the intestines, and that the use of a P-glycoprotien inhibitor increased absorption 6-fold in rats (15).

Problem solver? Milk Thistle! Studies show that milk thistle (silymarin) does a good job at inhibiting p-glycoprotein, therefore improving Berberine’s bioavailability. (16, 17)

They sell one Berberine supp on Amazon with silymarin (the active ingredient in milk thistle that does all the great things milk thistle is known for) already in it. But you can also just take it together with it if you have it around... which I'm sure a lot of you do.

Benefits of taking berberine instead of metformin?

A lot less possible sides, no known dangers for the kidney and it's cheaper. And legal. And OTC. No effect on Natural Test, or Free Test, or androgen receptors, or TSH... So there you have it.

But, will it perform as well for bodybuilding purposes?

Will it work for our purposes?

Ahhh the million dollar question... and the one that I did ZERO research on aside for trying it myself. In theory, yes. Unlike all of our other "tools", we use metformin at "normal" studied dosages. Berberine works just as well and extremely similarly to metformin in diabetics and normal people, so why not for bodybuilding purposes? Want to keep your muscles fuller during low carb dieting? Try berberine! GH use got your insulin sensitivity down? Try berberine! etc. etc.

I tried it for 2 months and I leaned out and had great pumps. That being said, I was also on 535mg of Test and 50mgs of Anavar at the time... so that would have happened anyway. But maybe it added to it? Not really a fair way to test it. I ordered more and will be giving it another go now that I'm off and will update this post with the results. In theory, I should be able to get a better pump, eat more carbs without gaining fat, or trim my waist a bit if I stick to normal carbs... just like one would report with metformin. Alas (Alas? Did I come over on the Mayflower?), only time will tell.

I will say that a couple times I didn't eat carbs in the morning while taking it on cycle. I felt a little hypo and it was fixed by taking in 30g of some simple carbs. Maybe in my head? Can't be 100% sure, but I'd like to think not.

Be a Guinea Pig with me!

I'd love for anyone interested to give this supplement a shot and report back with the details. Especially metformin guys, for an even better comparison! If you report back with your experience here or in a PM, I'll make sure to keep this updated with real world results (or lack there of). I'm sure there are varying qualities of this product out there on the market, and only the real shit will give us real answers, so go with a brand you trust!

I enjoyed putting this together. I hope you guys enjoyed reading it and found it informative. I know it was long and possibly boring to anyone that isn't me.

And I REALLY hope that I can update this in a couple months with some of your experiences in a final section to properly wrap it up. Maybe something good will come out of it.

Thanks to Makwa for encouraging me to write this. No homo.

Citations:

1. WebMD - Drugs - Metformin HCL (http://www.webmd.com/drugs/2/drug-11285-7061/metformin-oral/metformin-or...)

2. Combination therapy with insulin and metformin (https://www.ncbi.nlm.nih.gov/m/pubmed/15251717/)

3. Glucophage (Metformin) and Diabetes (http://www.diabetes.co.uk/diabetes-medication/glucophage.html)

4. Growth hormone replacement therapy induces insulin resistance by activating the glucose-fatty acid cycle (https://www.ncbi.nlm.nih.gov/m/pubmed/12679422/)

5. Drugs.com - Metformin side effects (https://www.drugs.com/amp/sfx/metformin-side-effects.html)

6. Effects of short term metformin administration on androgens in normal men.
   (http://cat.inist.fr/?aModele=afficheN&cpsidt=13918081)

7. Metformin represses androgen-dependent and androgen-independent prostate cancers by targeting the androgen receptor.
   (https://www.ncbi.nlm.nih.gov/m/pubmed/25894097/)

8. Wikipedia - Berberis Vulgaris (https://en.wikipedia.org/wiki/Berberis_vulgaris)

9. Efficacy of Berberine in Patients with Type 2 Diabetes (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410097/)

10. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression (http://www.sciencedirect.com/science/article/pii/S0026049509003163)

11. Cardiovascular and metabolic effects of Berberine (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999047/#!po=54.9180)

12. Effect of Berberine Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion (http://online.liebertpub.com/doi/pdf/10.1089/met.2012.0183)

13. Effects of berberine on lipid profile in subjects with low cardiovascular risk. (https://www.ncbi.nlm.nih.gov/m/pubmed/23441841/)

14. Taking Berberine? Look out for these 3 sides and 3 great stacks! (https://liftmode.com/blog/berberine-side-effects/#_ftn4)

15. The involvement of P-glycoprotein in berberine absorption (https://www.ncbi.nlm.nih.gov/m/pubmed/12530470/)

16. Herbal modulation of P-glycoprotein (https://www.ncbi.nlm.nih.gov/m/pubmed/15072439/)

17. Inhibition of P-glycoprotein by natural products in human breast cancer cells (https://link.springer.com/article/10.1007%2FBF02977349?LI=true)