Magical Molecule: Berberine
Does nature have another miracle drug up her sleeve?
To help you sort through the details in three videos, here is a summary of Berberine’s mechanisms of action:
Video #1 Berberine: Type 2 Diabetes game changer. What is the mechanism by which Berberine increases the secretion of insulin?
Berberine: Type 2 Diabetes Game Changer
The meta analysis: Frontiers | Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis
Another study: ATP-sensitive K+ channels in pancreatic beta-cells. Spare-channel hypothesis - PubMed
We are looking at why Berberine causes an increase in insulin secretion duration under hyperglycemic conditions, but doesn’t cause an increase of insulin when glucose levels are low, as happens with some drugs, leading to dangerous hypoglycemia.
“Insulin secretory agents are commonly used to treat type 2 diabetes. However, traditional insulin secretory agents such as sulfonylureas and glinides have side effects of hypoglycemia. In recent years, researchers have discovered that berberine can inhibit the voltage-gated k+ channels of pancreatic β cell membrane and promote insulin secretion without causing hypoglycemia, because the glucose-lowering effects of berberine are only under hyperglycemic conditions or in a high-glucose-dependent manner. “
TC: 4:40 Berberine has been used in Chinese medicine for thousands of years. It is available over-the-counter and has an astonishing list of potential health benefits, from improving insulin sensitivity, to reducing blood pressure, anti inflammatory effects, reducing appetite for weight loss, anti-tumour effects, anti-depressant, supports liver function (with a powerful impact on hepatocytes), anti microbial, promotes skin health, reduces age-related macular degeneration, and it is neuro-protective.
All of those benefits are exciting enough, but today I am concentrating on how berberine acts on pancreatic Beta cells.
(Just a note here: Be careful, there are drug interactions with Berberine, which I will cover in the third video.)
It’s complicated to explain so we will go one concept at a time…
First let’s look at the normal function of a beta cell.
The role of pancreatic beta cells is to produce insulin in response to glucose levels. A beta cell could be described as a tiny microscopic “glucometer” that can see the level of glucose and make insulin to keep the glucose level stable.
Our cells in general are negatively charged. The reason for this is that our cells have proteins in them, enzymes that are the machinery of the cell, and those proteins predominantly have a negative charge and give the cell a standard resting negative charge.
This is called “resting potential of minus”. It applies to neurons, muscle cells, hormone secreting cells, as well as the beta cells.
When a cell is at rest it is not active. It is just “sitting around”. It has polarity: negative inside and positive outside.
TC 11:39 When a cell has to function, it must become depolarized. It has to either become positive inside to match the positive outside, or the outside has to become negative to match the inside. Depolarization allows certain functions to happen.
How does that depolarization happen?
In the case of beta cells, we need to trap some positive ions inside which will cause insulin to be released.
TC 13:12 Beta cells are covered with channels on their surface called glucose transporters. They are always open on Beta cells to allow glucose into the cell. They are always open because Beta cells are glucometers and monitor glucose levels. That’s the job of Beta Cells..
TC14:19 There are other microscopic channels on the Beta Cell called “Potassium/ ATP” channels. (KATP) The channel is operated by ATP. The channel releases Potassium from the cell. Potassium is a positive ion.
TC 14:43 Another of many kinds of “voltage-gated” potassium channels on the beta cell is the KCNH6 channel, also allowing the potassium to escape.
TC 15:15 Inside the beta cell are stored vesicles of preproinsulin and there is a door through which insulin can be released from the cell when needed. When glucose levels are high in the cell (via the glucose transporter) then more insulin is released.
TC 15:55 There is another channel called the voltage-gated calcium channel.
Now here is the important part:
16:25 In its resting state the cell is negative inside because of proteins. But potassium is continuously entering the cell, and if it becomes sufficiently concentrated it will depolarize the cell and the cell will start releasing insulin. We don’t want our beta cells to be continuously releasing insulin for no good reason, so the beta cells keep the potassium channels open so that potassium can escape, and the cell can maintain its resting (negative) state.
So, if those channels are closed, the potassium will build up in the cell, which will depolarize it, and it will start releasing insulin.
Let’s say you have just eaten some food and you have high levels of glucose. With higher levels of glucose we want the cells to release insulin. How does that happen?
Glucose freely enters the beta cells and triggers the metabolic pathway that will break down this glucose and make ATP.
A higher ATP level closes the Potassium/ATP channels, keeping the potassium inside the beta cells. Now the potassium levels are building, and they balance out the negative charge, depolarizing the cell. Then the calcium channels open because they are voltage-gated channels and only open at neutral or positive voltage, and calcium rushes in.
Calcium generally is useful to activate neurons, muscles, and hormones, so when the calcium enters the cell it picks up the vesicles of insulin (Those bags in the illustration) and drags them to the cell membrane and they open on the cell membrane surface and the insulin is released.
So far so good…but did you notice in the picture that the KCNH6 channel is still open?
it's not a very big channel so some potassium is still escaping. Imagine if we close this channel as well. Then the potassium would stay trapped for a longer period of time and the cell would continue to release insulin for a longer period of time.
That is what berberine does.
When it is present in the blood, berberine closes the KCNH6 channel and that prolongs the release of insulin when more glucose is present. (hyperglycemic state)
So now the big question: Why does Berberine not cause hypoglycemia like some diabetes drugs do in a low blood sugar state?
Remember there are two channels open at resting state KATP and KCNH6. KATP is the bigger and more functional channel. When there is less glucose present, the potassium is escaping faster than the cell can change polarity.
When berberine is administered, it can close the lesser KCNH6 channel, but KATP is still open so the potassium is still escaping faster than the cell can depolarize so the insulin will not be released.
It is only in the higher glucose state (Hyperglycemic) that the KATP channel will close and with the addition of berberine, it will cause the cell to secrete insulin for longer.
Brilliant! That’s what you want if you are a diabetic.
But of course, please don’t take this as medical advice. Consult with your doctor.
Now let’s look at how Berberine impacts the liver and metabolic health.
Video #2: Berberine: Liver and Metabolic Health
Here are the studies we will discuss: https://pubmed.ncbi.nlm.nih.gov/19800084/; and https://pubmed.ncbi.nlm.nih.gov/21304897/
Berberine has diverse effects. Next, I will discuss the glucose lowering effect and the liver healing effect.
On the cell surface are insulin receptors.
Insulin receptors are the gatekeepers for glucose channels. The receptor has a structure that crosses the cell membrane and appears on the inside of the cell where it interacts with the enzymes inside the cell. When insulin binds with the receptor on the outside, it is like ringing a doorbell: the button is on the outside, and the bell is inside.
Berberine increases the number of insulin receptors. How? It works on the nucleus of a cell and increases the production of messenger RNA for insulin receptors so when the messenger RNA comes out of the nucleus it will go to the ribosomes and ribosomes will produce more insulin receptors; those insulin receptors will then be expressed on the surface of the cell. This is called upregulation of the insulin receptors. There are many mechanisms that upregulate insulin receptors. Berberine is one of them.
That means that the circulating insulin molecules have a lot more doorbells to ring and have more chances to cause an effect inside the cell so this is what we will call an improvement in insulin sensitivity or a reduction in insulin resistance.
Beautiful magical molecule.
Berberine isn’t alone in it’s impact on insulin resistance, there are actually more mechanisms for that, for example the insulin receptors become less operational when fatty acids start
binding at the receptor portal inside the cell and when the inflammatory markers start interfering with the operation of the cell's internal mechanisms. That would also be insulin resistance so just having more receptors is not the only solution for insulin resistance.
We will get to that when we find out how berberine helps reduce fatty acids and that would also reduce insulin resistance.
But first…here are a few of Berberine’s effects:
Berberine acts on the electron transport chain in the mitochondria. (Go here for a discussion on electron transport chain) Within the mitochondria there are some enzymes present on the inner membrane of the mitochondria that are called electron transport chains. Electron transport chain is a set of enzymes that work with each other to produce energy. The very first enzyme in that set is called “complex one”.
The first thing to remember is that berberine acts on complex one of the electron transport chain inside the mitochondria
Remember, metformin does that too, so this behavior of metformin and berberine is very similar .
When the electron transport chain complex one is blocked or reduced in its activity because berberine has bound to it, the function of the electron transport chain will be reduced. The function of the electron transport chain (ETC) is to make ATP …energy… plus its function is to consume oxygen, so oxygen is consumed, nutrients are consumed, and ATP is produced and carbon dioxide is produced.
The result of berberine’s impact on complex one is that oxygen consumption and ATP production are reduced. The cell reacts to having less energy by finding glucose molecules that are sitting in the cell and breaking them down. That is called glycolysis. The benefit of glycolysis is that the concentration of the glucose inside the cell will be reduced which will allow more glucose to enter more easily because the glucose concentration has to be greater outside and lesser inside for the glucose to move in.
So by causing upregulation of glycolysis, berberine promotes the uptake of glucose from the environment inside the cell and the cell gets more energy. Outside the cell the glucose levels will be reduced so hyperglycemia will diminish because glucose uptake is improved.
It is important to note that this behavior of berberine is independent of insulin. This particular study actually shows the insulin signaling pathway was not altered in the liver so this is an insulin independent pathway.
TC12:16 Berberine increases AMP kinase levels. Because ATP is reduced, AMP increases. As this ratio becomes altered with the deficiency of ATP, an enzyme called AMP kinase senses the reduction of ATP and then triggers activities to improve the energy in the cell.
One such activity is that the AMP kinase enzyme will trigger the movement of glucose receptors from the vesicles to the surface of the cell so the cell will now express more glucose transporters, which allows more glucose to enter.
To sum up this part: Berberine has caused glycolysis, promoting expression of more glucose channels and enabling the cell to pick up more glucose. This is not just hepatic; this would affect peripheral channels as well, resulting in lower glucose in the environment and a reduction in hyperglycemia.
Nature is Magical.
But we aren’t finished yet…
TC15:45 As berberine has reduced energy production, the nucleus of the cell senses the reduced energy and it says I should not make all kinds of proteins I should only do the most essential work. Remember ATP is the money of the cell… if we run low on money we will do the most essential things and not spend money on less essential things. The cell behaves the same way. Take away its energy. It's going to spend the energy on the most important thing. So the nucleus starts focusing only to make essential messenger RNAs to keep the cell functional but not make extra vacant enzymes. In that process the nucleus starts to produce less messenger RNA for making the enzymes called PEPCK and G6Pase which are deemed to not be the most essential.
In our liver, when we are in a fasting state (for example in the morning when you wake up or any time you're fasting) we still need glucose to be maintained at 80 milligram per decilitre, the basal glucose level. So how is that maintained?
Our liver makes glucose. That is what is called gluconeogenesis…synthesis of glucose by our own body. You don't have to eat glucose to make glucose. It is the liver who's going to make glucose in the fasting state. The problem is those of us that have developed diabetes actually already have glucose in the body but that glucose is not entering the cells because of the peripheral insulin resistance. So the liver thinks we don't have glucose and abnormally starts making glucose. Now we are getting glucose running around in the body and causing damage by sticking to various proteins and enzymes and disrupting their function, and the liver is also now producing glucose. So in normal healthy individuals, when there is enough glucose, and insulin is present, the liver will not make glucose.
The function of Phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G6Pase)is to help make new glucose from pyruvate. Insulin inhibits that function and blocks gluconeogenesis.
Berberine does that too, by down-regulating the production of messenger RNA for PEPCK and G6PAS, berberine reduces these enzymes which reduces glucose production.
This is hugely important for diabetes.
TC 21:31 To review: Outside the cell, Insulin attaches to the receptor. Inside the cell there is a receptor called insulin receptor response substrate or insulin receptor. This response substrate will cause another enzyme called PI3K to be activated which in turn causes another enzyme which is the hub of the insulin response system called AKt to be activated. When AKt is activated it brings more GLUT4 to the surface (which berberine does as well through the AMPK pathway) and more GLUT4 on the surface means there will be more glucose coming in the cell, which is what insulin wants to happen. Insulin wants a cell to take up glucose.
TC 22:13 In addition to that AKT blocks an enzyme called FOX01or Forkhead box zero one. When FOX01 is blocked it reduces the production of PEPCK and G6Pase and gluconeogenesis is reduced. That is the insulin pathway.
Berberine does not actually activate the insulin pathway, but independent of the insulin pathway it can reduce the production of PEPCKand G6Pase and thereby reduce gluconeogenesis.
What a wonderful gift berberine gives to the to the liver because not only is less glucose that would cause hyperglycemia produced, but also this glucose can then be converted into fatty acids and accumulate in the liver.
So far we have four mechanisms of action for Berberine:
the insulin receptor expression mechanism
glycolysis increase
GLUT4 receptor expression
gluconeogenesis reduction
But wait, there’s more!!
This one is the best:
TC23:33
Insulin comes and attaches to the insulin receptor that causes the receptor substrate (on the inside of the cell) to become activated causing PI3k to be activated. That causes AKT to be activated which then blocks two more proteins called TSC1 and TSC2. These proteins usually keep mTORC1 enzyme blocked. When insulin blocks TSC enzyme, then mTORC1 becomes disinhibited and it activates SREBP 1C and S6K .
TC 24:28(We’ll Leave the S6K function out. It’s not relevant to berberine function)
SREBP 1c in turn causes fatty acid synthase enzyme to become activated and that would start converting fatty acids to lipids, or lipogenesis.
So insulin brings glucose into the cell especially for the liver then helps convert the energy into lipids
This mechanism goes wrong in diabetics because now it is converting unnecessary fats.
Guess what berberine does?
TC 25:25 When Berberine reduces energy (ATP) in the cell and that causes the nucleus to produce less enzymes, one of the enzymes that is also deemed less essential in the presence of berberine is SREBP 1c. The reduction in SREBP 1c reduces fatty acid synthase enzyme which then reduces fatty acid synthesis, then we have less lipogenesis and we have less hepatic steatosis. Hepatic steatosis is fatty liver.
Then over time, it would continue to chip away at the fatty acids by reducing the production of fatty acids and the production of triglycerides, and it also helps reduce cholesterol.
All of those functions result in improved hepatocyte function and when liver cell function improves then liver cells do not unnecessarily engage in hyperglycemia because now the liver cells can understand that there is insulin, plus they can understand that they do not need to make more glucose, so gluconeogenesis is controlled, plus fatty acid production is controlled, and the whole metabolic state becomes stabilized.
Some of those functions are immediate. Glucose control is immediate depending upon how much glucose is present and how much berberine is present and what other factors are in play. Liver healing is a long-term effect but it is a very important effect .
TC 29:20
So just a quick summary:
Berberine works to reduce gluconeogenesis independent of the insulin pathways for gluconeogenesis and lipogenesis but it interferes with those pathways in a positive way. In addition to that it causes glycolysis or glucose breakdown. In addition to that it causes more glucose uptake from the environment by increasing the insulin receptors which would also reduce hyperglycemia outside the cell. New gluconeogenesis will be reduced, new lipid formations will be reduced, existing glucose will be taken up and the cells would become happy cells.
NB: Please make sure you talk to your doctor before you run out and start taking berberine, because it has interactions with blood thinners and other medications and can augment some diabetic medications, and you have to be careful. Hypoglycemia can be very dangerous.
A list of links for this discussion can be found at the end of this post.
Next is a discussion of the side effects and the drug interactions…
Here is the video:
Berberine Side Effects and Toxicity
Do not take at all in combination with:
Cyclosporine. Berberine might decrease how quickly the body breaks down cyclosporine. This might increase the effect and side effects of cyclosporine.
Be cautious with:
dextromethorphan(Robitussin) Berberine might decrease how quickly the body breaks down dextromethorphan as berberine modulates liver enzymes so do not break down o other drugs that fast causing those drugs to accumulate and have a more potent effect. Some of these potencies might cross the toxicity window threshold and cause toxicity.
Losartan(Cozaar) The liver activates losartan to make it work. Berberine might decrease how quickly the body activates it which might decrease the effect of losartan.
Medication Changed by the liver enzymes cytochrome p450. “Because berberine goes to the liver, it can modulate the liver cell enzymes and that can cause those drugs that are broken down by the liver cells enzymes, for example cytochrome p450, to have longer but prolonged duration of action or even higher potency.”
Berberine might lower blood sugar levels, so taking berberine along with diabetes medications might cause blood sugar to drop too low. Monitor your blood sugar closely.
medications that slow blood clotting. Berberine can act as a weak blood thinner but when it is combined with other blood thinners it can potentiate their effect by modulating the liver enzymes. That might increase the risk of bruising and bleeding.
Metformin (glucophage) Berberine might increase the amount of Metformin in the body which may increase its effect and side effects. This interaction seems to occur when the berberine is taken around two hours before metformin. Taking berberine and Metformin at the same time doesn't appear to increase the amount of Metformin in the body.
Midazolam(Versed) the body breaks down midazolam to get rid of it . Berberine can decrease how quickly the body breaks it down; this might increase the effect and side effects of midazolam.
Pentobarbital (Nembutal) Pentobarbital is a medication that can cause sleepiness. Berberine might also cause sleepiness and drowsiness. Taking berberine with pentobarbital might cause too much sleepiness.
Sedatives. Berberine might cause sleepiness and slow breathing. Sedatives can also cause sleepiness and slow breathing. Taking berberine with sedatives might cause breathing problems and/or too much sleepiness.
Tacrolimus(Prograf) is removed from the body by the liver. Berberine might slow down the body's ability to remove tichrolymers this might increase the effect and side effect of trichrolymers and there are more interactions with certain supplements so please read this paper:
https://medlineplus.gov/druginfo/natu…
Meanwhile let’s look at another paper:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643735/
Let’s look at some of the pharmacokinetics of Berberine.
Berberine has low bioavailability. Lesser than 5 percent is absorbed due to an enzyme called P-glycoprotein which appears to contribute to its poor absorption by actively expelling the alkaloids on the Lumen mucosal cells.
Imagine there is a person sitting in a house and then an Amazon driver brings something and imagine if they push that thing in the house, then this person from inside throws it back out so that is what this enzyme does with alkaloids. Berberine is a kind of alkaloid so when the berberine is absorbed by the cells, this enzyme sitting inside actively rejects it and throws it back out.
Berberine is primarily metabolized by liver and excreted through bile, that means through the GIT, stools and very tiny amount in the urine
In a rat non-comartmental model, unbound berberine is transported to bile through active transport and it is metabolized by a p450 enzyme system in the liver with Phase 1 demethylation and Phase 2 glucuronidation .
Intestinal bacterial flora takes a role in enterohepatic circulation and enterohepatic circulation means that something present in the intestine is absorbed from the intestine, taken up in the blood, circulated to liver, then the liver puts it in bile and moves it back into the intestine. This is called enterohepatic circulation where things are excreted in the bile then reabsorbed, excreted then reabsorbed and so on. In that process some of the material also escapes towards stools and is excreted. On the other hand a very small amount of unchanged berberine is eliminated in urine so the question is how small let me show you in this study:
https://pubmed.ncbi.nlm.nih.gov/7795781/
The authors detected berberine in plasma, urine, and bile. Bile will represent berberine in the enteropathic circulation and being eliminated through stools, the plasma would represent the berberine present in the blood, and urine will represent berberine excreting through the urine. In plasma 18.1 nanogram per milliliter in urine, 2.3 nanogram, and in bile 90.4 nanogram. So the majority in bile, a very tiny amount 2.3 in urine and in plasma 18.1
The authors say:
“Standard doses of berberine are generally well tolerated and eventual adverse events are rare and mild. On the contrary, high doses have been associated with arterial hypotension, dyspnea, flu-like symptoms, gastrointestinal discomfort, constipation, and cardiac damage. The most studied side effects are those in the gastrointestinal system. Berberine and derivatives can also produce gastric lesions.
The safety issue of berberine mostly involves the risk of some pharmacological interaction. In fact, berberine displaces bilirubin from albumin about 10-fold better than phenylbutazone, thus any herb containing large amounts of berberine should be avoided in jaundiced infants and pregnant women. Berberine displaces warfarin, thiopental, and tolbutamide from their protein-binding sites, increasing their plasma levels ”
Berberine is absolutely not recommended to be taken by Children and pregnant women.
The data is low but for a newborn if the pregnant woman is taking it and if it goes to the child, then because berberine separates the bilirubin from albumin the bilirubin that is separated will go to the brain. Because a child's brain system is still being developed the blood-brain barrier cannot really stop the bilirubin from coming into the brain tissue and if bilirubin goes into the brain tissue it will bind to the brain tissue and cause kernicterus which in babies can cause brain damage or even death. So berberine itself may be safe for the woman herself, but it can be dangerous for the child. Don't give berberine to children or to pregnant mothers. Berberine is teratogenic for the child and that is of course a No-No.
More on Safety:
Effects on the heart like low blood pressure slow heart rate and abnormal heart rhythms may occur with doses higher than 27.5 Milligram per kilogram.
Allergic reactions have been reported.
This paper: https://www.drugs.com/npp/barberry.html adds more adverse reactions that shouldn’t be ignored.
“ caution is warranted in the presence of cardiac arrhythmias … there are documented adverse effects including uterine stimulant effect…” which can cause abortion.
Toxicology
“Symptoms of poisoning are characterized by lethargy, stupor and daze, vomiting and diarrhea, and nephritis. A median lethal dose (LD50) for berberine was noted as 27.5 mg/kg in humans. Berberine showed mutagenicity in yeast cells and Ames test, while a phototoxic reaction between berberine alkaloid and ultraviolet A (UVA) light has been described.”
So in a 70 kilogram person, 1924 milligrams so that can become toxic so just be careful.
This study https://www.drugs.com/breastfeeding/goldenseal.html looks at safety of goldenseal during breastfeeding:
“Goldenseal (Hydrastis canadensis) root contains berberine and other isoquinoline alkaloids. Goldenseal has traditionally been used as an anti-infective both systemically and topically, although high-quality studies of its efficacy and safety are lacking. It has also been used to mask illicit drugs in the urine, although it appears to be ineffective with modern laboratory methods. Goldenseal has been used topically by nursing mothers to treat sore nipples. No data exist on the excretion of any components of goldenseal into breastmilk or on the safety and efficacy of goldenseal in nursing mothers. Berberine can displace bilirubin from serum albumin, causing concern about exposure of newborn infants, because bilirubin can build up in the infant's brain, causing brain damage. However, the extent of berberine's passage from the mother to the infant is unknown. Most sources recommend avoiding exposure of neonates to goldenseal via breastfeeding or otherwise.”
More on effects on kidneys:
“Abnormal lipid metabolism in renal tubular epithelial cells contributes to renal lipid accumulation and disturbed mitochondrial bioenergetics which are important in diabetic kidney disease.”
In diabetic kidney disease the nephrons that are making urine, the surface cell epithelial cells of microscopic tiny tubes, become filled with lipids and that is how the mitochondria get damaged, and the kidney damage starts occurring so…
“These data suggested that berberine alleviates diabetic renal tubulointerstitial injury through improving high glucose-induced reduction of fatty acid oxidation, alleviates lipid deposition, and protects mitochondria in tubular epithelial cells.”
So berberine seems to be, from this paper's point of view alleviating the pathology
of diabetic kidney, so this is a very important paper.
And another:
“Berberine ameliorates chronic kidney injury caused by atherosclerotic renal vascular disease through the suppression of nuclear Factor KB signaling Pathways in rats”
This is very interesting. It is a very similar thing to Ivermectin. I was trying to figure out
If berberine will cause damage to the kidneys, and these papers allude to a possibility of berberine actually helping.
“Berberine (BBR) regulates cholesterol metabolism and exerts antioxidant effects. Accordingly, we hypothesized that BBR treatment may ameliorate ARD-induced kidney injury through its cholesterol-lowering effect and also suppression of the pathways involved in oxidative stress, inflammation and NFκB activation.”
And?
“We conclude that BBR can improve hypercholesterolemia and redox status in the kidney, eventually ameliorating chronic renal injury in rats with ARD, and that BBR can act against proinflammatory and profibrotic responses through suppression of the NFκB signaling pathway.”
They didn't use the word “curative”, or “treats”. They use the word “ameliorates” so I cannot say anything more than that. I cannot say berberine would help fix the kidney but I would use the same word here for the study that for chronic kidney disease, berberine actually ameliorates the injury in that kidney caused by ARD.
So it's a beautiful mechanism.
The Summary
Not in pregnant women. It may be safe for the woman but not safe for the child;
not in children, even born children, because for the first two years of their life, children are still developing parts of their brain tissues. Berberine can cause the bilirubin to be separated and go to the brain and cause brain damage;
Then there are some drugs for which berberine has interactions. See the list above;
drugs which are working with cytochrome p450 enzyme system can be potentiated and that potentiation may even reach toxic levels if the accumulation is too much;
berberine has a very tiny excretion through urine. The majority of berberine is in enterohepatic circulation that means it is excreted through stools and in that process of being present in the GIT it is going to modulate microbiota plus microbiota is going to modulate this substance as well;
For the kidneys it seems like it is actually more helpful. Now for the first time I use this word “helpful”. The words they used were “alleviate” or “ameliorate” so this is my word “helpful”. There is no study behind that. I want to be very very careful with the words here so it seems to be “helpful” for diabetic or atherosclerotic kidney disease.
Stay tuned for another article in this series coming up….
Reference List:
Berberine is an insulin secretagogue targeting the KCNH6 potassium channel | Nature Communications
https://www.nature.com/articles/s4146...
AMP-activated protein kinase - Wikipedia
https://en.wikipedia.org/wiki/AMP-act...
Frontiers | Cerebral Gluconeogenesis and Diseases
https://www.frontiersin.org/articles/...
Phosphoenolpyruvate carboxykinase - Wikipedia
https://en.wikipedia.org/wiki/Phospho...
Gluconeogenesis - Wikipedia
https://en.wikipedia.org/wiki/Glucone...
Metformin - Wikipedia
https://en.wikipedia.org/wiki/Metformin
Sterol regulatory element-binding protein 1 - Wikipedia
https://en.wikipedia.org/wiki/Sterol_...
The Role of Mammalian Target of Rapamycin (mTOR) in Insulin Signaling - PMC
https://www.ncbi.nlm.nih.gov/pmc/arti...
mTORC1 activates SREBP-1c and uncouples lipogenesis from gluconeogenesis | PNAS
https://www.pnas.org/doi/10.1073/pnas...
Insulin Signaling Pathway | Antibodies.com
https://www.antibodies.com/insulin-si...
Regulation of SREBP by insulin signaling pathway | Download Scientific Diagram
https://www.researchgate.net/figure/R...
The role of the KATP channel in glucose homeostasis in health and disease: more than meets the islet - PMC
https://www.ncbi.nlm.nih.gov/pmc/arti...
Frontiers | Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis
https://www.frontiersin.org/articles/...
ATP-sensitive K+ channels in pancreatic beta-cells. Spare-channel hypothesis - PubMed
https://pubmed.ncbi.nlm.nih.gov/2452107/
Show less
Berberine: MedlinePlus Supplements
https://medlineplus.gov/druginfo/natu...
Study progress of berberine for treating cardiovascular disease - PMC
https://www.ncbi.nlm.nih.gov/pmc/arti...
What is berberine used for?
https://www.drugs.com/medical-answers...
Barberry Uses, Benefits & Dosage - Drugs.com Herbal Database
https://www.drugs.com/npp/barberry.html
Goldenseal use while Breastfeeding | Drugs.com
https://www.drugs.com/breastfeeding/g...
Frontiers | Berberine Reduces Lipid Accumulation by Promoting Fatty Acid Oxidation in Renal Tubular Epithelial Cells of the Diabetic Kidney
https://www.frontiersin.org/articles/....
Berberine Ameliorates Chronic Kidney Injury Caused by Atherosclerotic Renovascular Disease through the Suppression of NFκB Signaling Pathway in Rats | PLOS ONE
Excellent - thank you - will share with my PCP - he's a D.O. Internal Med.