Berberine (Coptis chinensis, Hydrastis canadensis) is a natural plant alkaloid that has been used for millennia in traditional Ayurvedic and Chinese medicine to treat diarrhea and gastrointestinal issues.
Berberine is a unique and powerful dietary supplement with nootropic benefits. Research and clinical experience in the last 5 years demonstrates Berberine’s ability to provide positive effects on blood sugar, cholesterol, heart disease, blood pressure, autoimmune disease, inflammation, weight control, gut problems, cancer and Alzheimer’s Disease.
Berberine has recently been shown to help control blood sugar as effectively as the prescription diabetes drug metformin.
But even if you’re not concerned with diabetes or pre-diabetes, you may find benefit in adding Berberine to your nootropic stack. Our modern Western diet is detrimental to overall health. And particularly cognitive health. Berberine can be a powerful ally in achieving and maintaining optimal performance.
Here we’ll explore how Berberine benefits your brain.
Berberine helps:
- Neurotransmitters: Supplementing with Berberine has been shown to increase levels of serotonin, dopamine, norepinephrine in the brain.
- Learning & memory: Berberine preserves Long-Term Potentiation (LTP) in synapses normally lost from diabetes.[i]
- AMPK: Berberine increases adenosine monophosphate-activated protein kinase (AMPK). This enzyme AMPK is the master metabolic switch in each of your cells. When AMPK levels increase you get an energy boost, blood glucose is regulated, insulin sensitivity improves, reduced triglycerides, and increased fat-burning in mitochondria.
Table of Contents
Overview
Berberine (Coptis chinensis, Hydrastis canadensis) is a bright yellow alkaloid extracted from plants such as Indian Barberry (tree turmeric), Oregon Grape and goldenseal.
Other plants containing Berberine used in medical practice include Chinese goldthread, Japanese goldthread, Phellondendron amurense, and the Amur cork tree (Huang Bo).[ii]
Plants containing Berberine have been used in traditional Ayurvedic and Chinese medicine as an antibacterial, anti-inflammatory, anti-diarrheal, anti-microbial, anti-protozoal and immune-enhancing therapy for thousands of years.[iii]
If you’ve only just found out about Berberine, it’s not surprising. This botanical extract came from obscurity to front and center of the dietary supplement market because of recently published research. Of the 4,434 clinical studies for Berberine listed on PubMed, over a third have been published in the last 5 years.[iv]
Berberine is one of the few nootropic supplements known to activate (adenosine monophosphate-activated protein kinase) AMPK. This is especially relevant if you’re diabetic, pre-diabetic, or over-weight. All conditions that negatively affect cognition.
The enzyme AMPK is the metabolic master switch inside each one of your cells.[v] And is critical for regulating cellular metabolism including lipid, glucose and energy imbalances.[vi] AMPK directly influences brain cell energy, function, repair, and maintenance.
Berberine activates AMPK, and AMPK activation boosts fat burning in mitochondria. Studies have shown that supplementing with Berberine prevents fat accumulation in the body.
A study in Phytomedicine had obese human subjects taking 500 mg of Berberine 3-times per day for 12 weeks. The result was a reduction in body weight, blood lipid and hormone levels normalized, and inflammation went down.[vii]
Berberine activates AMPK and increases its phosphorylation (high energy exchange in a brain cell), which elevates the AMP/ATP ratio, and reduces oxygen consumption. This increase is called glycolysis.
This suggests that Berberine enhances glucose metabolism through the stimulation of glycolysis. Which is related to an inhibition of glucose oxidation in mitochondria.[viii] More efficient mitochondria protected from oxidative stress means better brain function and memory.
Berberine supplementation helps control food intake and operates as a memory enhancer. Helping you cut down on weight gain, reduces the likelihood of metabolic syndrome, and helps prevent or control type-2 diabetes.
How does Berberine work in the Brain?
Berberine boosts brain health and function in several ways. But two in particular stand out.
- Berberine normalizes blood sugar. Glucose is the primary source of energy for every cell in your body. Because your brain is so rich in neurons, the demand for energy uses a half of all the sugar energy in your body.
Learning, memory and thinking or cognition are closely linked to glucose levels. And how efficiently your brain uses this fuel source. If there isn’t enough glucose in your brain, neurotransmitters are not produced. And communication between neurons breaks down.
Hypoglycemia, a common problem with diabetes caused by low blood glucose levels leads to a loss of energy for brain function. And is linked to poor attention and cognitive function.[ix]
Problems with blood sugar and type-1 or 2 diabetes affects brain cell connectivity, causes the brain to shrink, and restricts cerebral blood flow. Causing major problems with cognition, and if severe enough, promotes the development of dementia. Berberine helps prevent this cognitive decline by controlling blood sugar and brain cell metabolism.[x]
- Berberine boosts memory. Studies show that Berberine inhibits acetylcholinesterase (AChE) activity and increases glucagon-like peptide (GLP-1)[xi] The enzyme AChE breaks down acetylcholine (ACh) which is critical for concentration, focus and memory. By preventing the breakdown of ACh, more of this neurotransmitter is available for learning, memory and recall.
GLP-1 is a peptide hormone that plays a crucial role in controlling diabetes. And is involved in cognition, learning and neuroprotection. Studies have shown that GLP-1 enhances synaptic plasticity in the hippocampus. And reduces the aggregation of amyloid β protein (Aβ) and the microtubule-associated protein Tau which are associated with Alzheimer’s Disease.[xii]
Increasing GLP-1 with Berberine increases neuroplasticity and reduces protein aggregation resulting in an increase in long-term potentiation. And improved long-term memory.
How things go bad
Most of us in our Western society suffer from chronic nutritional overload.[xiii] Over eating or not eating the right foods in the right amounts messes with the uptake of glucose and fat from our blood for effective energy regulation.
The result is an accumulation of cellular waste and damaged proteins. Impairing genes that should help us live longer and boosting genes that cause inflammation.
As the cells in our body and brain consistently deal with over-nourishment, the enzyme AMPK decreases.[xiv] Resulting in weight gain, diabetes, neurodegenerative disease and ultimately, premature death.
Decreases in AMPK activity results in:
↓ Chronic inflammation
↓ Accelerated aging
↑ High cholesterol and triglycerides
↑ Increased belly fat
↓ Insulin resistance
↓ Mitochondrial insufficiency and dysfunction
↓ Neurodegeneration
The consequences to brain function of low AMPK activity results in decreased alertness, brain fog, slower thinking, poor memory and a decline in mood.
Berberine to the rescue
Berberine has been used for thousands of years as treatment for bacterial infections, fungus, protozoa, viruses, chlamydia and candida. It helps protect against cholera and E coli. It is used as an anti-diarrheal, and to reduce inflammation.
Up until just a few years ago, you’d find Berberine in the pharmacy section for gastrointestinal issues.
In the last 5 years, research has shown Berberine to be effective for treating diabetes, metabolic syndrome, inflammation and even cancer.
Berberine is gaining a reputation for its anti-diabetic effects. Helping to prevent or treat type-2 diabetes. It helps with glucose metabolism, maintenance of healthy lipid levels (LDL & HDL cholesterol), improves insulin sensitivity, helps lower blood pressure, weight management, the immune system, and boosts cognition.
Research shows that Berberine may provide anti-aging benefits by extending the life of telomeres.[xv] And studies have found it’s able to suppress the growth of several different types of tumor and cancer cells.[xvi]
Reviews from those using Berberine frequently mention a lift in mood. Likely because it provides a significant increase in the neurotransmitters dopamine, norepinephrine and serotonin.
Berberine may also help prevent Alzheimer’s disease because of its effects on β-amyloid pathways, and the enzyme that degrades acetylcholine, acetylcholinesterase.[xvii]
How does Berberine feel?
If you start feeling shaky between meals, get a little dizzy or nauseous, or feel like your mood has taken a sudden turn south – you may want to try Berberine.
Many neurohackers report how supplementing with Berberine has made a dramatic change in how they feel. And their quality of life.
It may take up to a month to begin feeling dramatic changes in how you feel. Many report seeing or feeling positive changes within days.
Sugar cravings disappear. No sugar crashes late afternoon. Energy levels rise and stamina increases.
Many find that thinking is easier and quicker. Brain fog is no longer a problem. And mood is much better.
Berberine helps with weight loss so you may find your waist getting smaller. It may not be a dramatic difference but you’ll feel better.
Many people report a greater improvement in symptoms when switching from metformin or statins to Berberine.
Berberine is proven to help regulate blood sugar. Your friends and family will thank you for no longer subjecting them to mood swings.
Berberine can increase neurotransmitter levels. So a boost in dopamine and serotonin may put you in a better mood.
Many report skin conditions or gastrointestinal issues brought on by stress are no longer a problem. Less indigestion and heart burn.
If you have blood sugar issues, you may not realize how bad you feel until you start feeling better by adding Berberine to your nootropic stack.
The Research
A lot of the research lately has centered around using Berberine to treat various problems associated with diabetes. So why is this important to the nootropics community?
The latest figures released by the CDC in the United States reported that 29 million people have diabetes. This number was up from 26 million in 2010. The CDC went on to say that one in four people with diabetes don’t know they have it.[xviii]
Another 86 million adults in the USA are pre-diabetic. That’s one in three American adults. Pre-diabetic means blood sugar levels are higher than normal but not high enough to be classified as type-2 diabetes.
And this is not just an American problem. The World Health Organization reports that as of 2014, 422 million people worldwide are dealing with type-2 diabetes.[xix] I imagine that just like in the USA, hundreds of millions more are pre-diabetic.
Now let’s take a quick look at how diabetes affects the brain. Those with type-2 diabetes are more apt to get Alzheimer’s or some other form of dementia. If you’re diabetic or pre-diabetic, learning, executive function and psychomotor performance all suffer.[xx]
All the brain functions affected by diabetes and its causes can be repaired and maintained with the use of the right nootropics.
The most important nootropic supplement in the management of diabetes is Berberine. And its effects on brain function will help anyone working on brain optimization.
Berberine improves learning & memory
Problems with memory are often associated with how brain cells use glucose, by oxidative stress, and cholinergic dysfunction. Research has found that treatment with antihyperglycemics that affect blood sugar (glucose), antioxidants and cholinergic agonists boosted memory.
Berberine works as an antioxidant, and is an acetylcholinesterase (AChE) inhibitor. A study in India was done with diabetic rats with severe learning and memory problems. The rats were given 25 – 100 mg/kg of Berberine twice daily for 30 days. Learning and memory improved along with lower hyperglycemia, less oxidative stress, and more cholinergic activity.[xxi]
Diabetes kills brain cells (apoptosis), negatively affects synaptic plasticity and long-term potentiation in the brain. Which causes problems with learning and memory. Researchers in Iran working with diabetic rats were able to restore learning and memory with 100 mg/kg of Berberine per day.[xxii]
Researchers in Korea gave Berberine to rats 30 minutes before injecting them with scopolamine. The team found that daily dosing of Berberine improved the memory impairment caused by scopolamine.
Digging deeper, the researchers learned that Berberine increased cholinergic activity, restored Brain-Derived Neurotrophic Factor (BDNF), and cAMP-response element-binding protein mRNA expression in the hippocampus. And Berberine also significantly decreased proinflammatory cytokines like interleukin-1β, tumor necrosis factor-α and cyclooxygenase-2 mRNA in the hippocampus.[xxiii]
Berberine as an anti-depressant
While not considered a first-line treatment for depression, several neurohackers report the “side effect” of a better mood when supplementing with Berberine. We have some clinical evidence from animal trials that could explain this antidepressant effect of Berberine. But no human clinical trials.
Similar to L-Deprenyl, Berberine seems to be a monoamine oxidase-A (MAO-A) inhibitor.[xxiv] The enzyme MAO is involved in the degradation of norepinephrine and dopamine in the brain. And research has shown that an overabundance of MAO-A and B happens as you get older. Inhibiting MAO-A increases norepinephrine and dopamine in your brain. Which in turn improves your mood.
Research with mice showed that supplementing with Berberine increased norepinephrine (31%), serotonin (47%) and dopamine (31%) in the whole brain. Increasing these major neurotransmitters is certainly going to have a positive effect on mood.
Major depression and anxiety have long been treated as a dysfunction of the GABA, serotonin and glutamate systems in the brain. And while SSRI’s and other prescription antidepressants have had some success in treating anxiety and depression, full remission of symptoms has not happened.
Some of the latest research has shown that sigma-receptors play a role in depressive disorders. And companies are working on developing drugs that modulate the sigma-1 receptor.[xxv] Turns out that Berberine is a modulator of sigma-1 receptors.[xxvi]
Berberine as good as metformin for diabetes
Probably the most celebrated clinical evidence for Berberine is its ability to control blood sugar and lipid metabolism in diabetes. Berberine stimulates the uptake of glucose into cells, improves insulin sensitivity and reduces glucose production in the liver.
This famous study was done in China with adults diagnosed with type-2 diabetes. In study A, patients were randomly assigned treatment of Berberine or metformin 3-times per day for 3 months. The hypoglycemic effect of Berberine was similar to that of metformin. Both decreased hemoglobin A1c, fasting blood glucose and plasma triglycerides.
In study B, 48 type-2 diabetic adults were supplementing with Berberine for 3 months. Results were similar to the study A group. But the researchers noted that total cholesterol, and LDL-cholesterol decreased significantly as well.
The researchers concluded that Berberine is a potent hypoglycemic agent with beneficial effects on lipid metabolism.[xxvii] But without the increased risk of death from heart attack by using metformin.
Dosage Notes
Recommended dose of Berberine is 900 – 1,500 mg per day.
Berberine has a short half-life, so you need to dose it several times a day to keep stable levels in your blood.
When you first start supplementing with Berberine, you may experience diarrhea, the sweats, or even vomiting. This supplement is a powerful antibiotic. The good news is it only kills the ‘bad’ bacteria in your gut. Not the good bacteria like prescription antibiotics. But when those bad bacteria decide to leave your body, it may not be pleasant.
You may be able to avoid an unpleasant reaction to Berberine by starting with a lower dose at first. And work your way up.
The debate continues on how bioavailable Berberine actually is. Recent reports suggest that it’s not detectable in blood because it’s absorbed so quickly into cells. But several clinical studies suggest Berberine is poorly absorbed. And this can be counteracted with the sodium caprate that comes in coconut oil.[xxviii]
Take your nootropic stack containing Berberine with a tablespoon of virgin, unrefined coconut oil and problem solved.
It’s best to split your dose so you’re taking 500 mg of Berberine 3-times per day. Preferably about 30 minutes before meals to prevent the glucose and lipid spike the comes with eating a meal.
Side Effects
If you are dealing with a medical condition or are taking any medication (including antibiotics), you should speak with your doctor before taking Berberine. Especially if you’re currently using blood-sugar lowering medication.
Diabetics who are controlling blood sugar with insulin must use caution because Berberine can lower blood sugar. I’ve seen more than one review of someone remarking, “dropped my blood sugar extremely low!”.
If you’re dealing with low blood pressure be careful using Berberine because it can lower blood pressure.
If you’re pregnant or nursing you should NOT use Berberine.
Berberine inhibits cytochromes P450 (CYP3A4, CYP2D6 and 2C9) in your liver.[xxix] Which means it can cause a substantial increase in the bioavailability of certain drugs and nootropics. Which can be dangerous. You may need to lower your dosage of certain drugs to prevent this potential toxicity. Or avoid Berberine altogether.
Berberine affects muscle protein synthesis and causes muscle atrophy.[xxx] So if you’re worried about muscle loss, don’t use Berberine. Or amp up your exercise program to counteract these effects.
Berberine has a very good safety profile. The primary side effects are related to digestion like cramps, diarrhea, gas, constipation or stomach pain.
As with any nootropic, start with the lowest recommended dose and you’ll likely avoid any problems. And spreading your dose throughout the day helps avoid side effects.
Available Forms
Berberine is available as a powder, and in capsules as Berberine HCl (hydrochloride) or Berberine Sulfate.
One company claims that the sulfate version is superior because once the sulfate is removed during digestion, it can participate in “phase II detoxification reactions in the liver”. I cannot find any science to back up this claim.
If you choose the powder form, you’d be wise to put it in capsules because Berberine is an ammonium salt alkaloid. Which tastes nasty.
I’ve tried several different brands of Berberine, but keep coming back to and using Amazing Formulas Berberine by Amazing Nutrition® based and manufactured in Carlstadt, New Jersey.
Studies with animals show that Berberine could cause DNA damage promoting tumor growth. This DNA damage can be avoided by using Milk Thistle with Berberine. The radical-scavenging and antioxidant properties of the compound silymarin in Milk Thistle appears to counteract this effect.[xxxi]
Nootropics Expert Recommendation
Berberine 900 – 1,500 mg per day
I recommend using Berberine as a nootropic supplement.
Your body does not make Berberine on its own. So to get its benefits you must take it as a supplement.
Berberine is especially helpful for those dealing with diabetes, high cholesterol, obesity, gut bacterial overgrowth, and Alzheimer’s.
Berberine is a powerful nootropic supplement. It may help reduce sugar cravings, avoid that afternoon energy slump, boost energy levels, reduce brain fog, improve your mood and tame digestive issues.
You can safely take up to 1,500 mg of Berberine daily if needed. But dosed 500 mg at a time and preferably before you eat.
I use and recommend Amazing Formulas Berberine which is made in the USA in a facility that tests each batch of product they produce.
You can help absorption by taking Berberine with a tablespoon of unrefined coconut oil (for the sodium caprate). And I recommend taking it with 175 mg of Milk Thistle extract each time to avoid possible DNA damage from long-term use.
[i] Ye L., Wang F., Yang R.H. “Diabetes impairs learning performance and affects the mitochondrial function of hippocampal pyramidal neurons.” Brain Research. 2011 Sep 9;1411:57-64 (source)
[ii] Tillhon, M.; Guamán Ortiz, L.M.; Lombardi, P.; Scovassi, A.I. Berberine: New perspectives for old remedies. Biochemical. Pharmacology. 2012, 84, 1260–1267. (source)
[iii] Vuddanda P.R., Chakraborty S., Singh S. “Berberine: a potential phytochemical with multispectrum therapeutic activities.” Expert Opinion on Investigational Drugs. 2010 Oct;19(10):1297-307. (source)
[iv] Schor J. “Clinical Applications for Berberine” Natural Medicine Journal December 2012 Vol. 4 Issue 12 (source)
[v] Winder W.W., Hardie D.G. “AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes.” American Journal of Physiology. 1999 Jul;277(1 Pt 1):E1-10. (source)
[vi] Srivastava R.A., Pinkosky S.L., Filippov S., Hanselman J.C., Cramer C.T., Newton R.S. “AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases.” Journal of Lipid Research. 2012 Dec;53(12):2490-514. (source)
[vii] Hu Y. et. El. “Lipid-lowering effect of berberine in human subjects and rats” Phytomedicine Volume 19, Issue 10, 15 July 2012, Pages 861-867 (source)
[viii] Yin J., Gao Z., Liu D., Liu Z., Ye J. “Berberine improves glucose metabolism through induction of glycolysis.” American Journal of Physiology, Endocrinology and Metabolism. 2008 Jan;294(1):E148-56. (source)
[ix] “Sugar and the Brain” Harvard Mahoney Neuroscience Institute neuro.hms.harvard.edu (source)
[x] Yin J., Xing H., Ye J. “Efficacy of berberine in patients with type 2 diabetes mellitus.” Metabolism. 2008 May;57(5):712-7 (source)
[xi] Hwang J.T., Kwon D.Y., Yoon S.H. “AMP-activated protein kinase: a potential target for the diseases prevention by natural occurring polyphenols.” New Biotechnology. 2009 Oct 1;26(1-2):17-22. (source).
[xii] Perry T., Lahiri D.K., Sambamurti K., Chen D., Mattson M.P., Egan J.M, Greig N.H. “Glucagon-like peptide-1 decreases endogenous amyloid-beta peptide (Abeta) levels and protects hippocampal neurons from death induced by Abeta and iron.” Journal of Neuroscience Research. 2003 Jun 1;72(5):603-12. (source)
[xiii] Ford ES, Dietz WH. “Trends in energy intake among adults in the United States: findings from NHANES.” American Journal of Clinical Nutrition. 2013;97(4):848-53. (source)
[xiv] Coughlan K.A., Valentine R.J., Ruderman N.B., Saha A.K. “Nutrient excess in AMPK downregulation and insulin resistance.” Journal of Endocrinology, Diabetes and Obesity. 2013; 123(7):2764–72. (source)
[xv] Zhang W.J., Ou T.M., Lu Y.J., Huang Y.Y., Wu W.B., Huang Z.S., Zhou J.L., Wong K.Y., Gu L.Q. “9-Substituted berberine derivatives as G-quadruplex stabilizing ligands in telomeric DNA.” Bioorganic & Medicinal Chemistry. 2007 Aug 15;15(16):5493-501. (source)
[xvi] Sun Y., Xun K., Wang Y., Chen X. “A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs.” Anticancer Drugs. 2009 Oct;20(9):757-69. (source)
[xvii] Huang L., Luo Z., He F., Shi A., Qin F., Li X. “Berberine derivatives, with substituted amino groups linked at the 9-position, as inhibitors of acetylcholinesterase/butyrylcholinesterase.” Bioorganic & Medical Chemistry Letters. 2010 Nov 15;20(22):6649-52. (source)
[xviii] “Diabetes Latest” Centers for Disease Control and Prevention cdc.gov (source)
[xix] “Diabetes” World Health Organization November 2016 who.int (source)
[xx] Seaquist E.R. “The Final Frontier: How Does Diabetes Affect the Brain?” Diabetes. 2010 Jan; 59(1): 4–5. (source)
[xxi] Bhutada P., Mundhada Y., Bansod K., Tawari S., Patil S., Dixit P., Umathe S., Mundhada D. “Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes.” Behavioral Brain Research. 2011 Jun 20;220(1):30-41. (source)
[xxii] Kalalian-Moghaddam H., Baluchnejadmojarad T., Roghani M., Goshadrou F., Ronaghi A. “Hippocampal synaptic plasticity restoration and anti-apoptotic effect underlie berberine improvement of learning and memory in streptozotocin-diabetic rats.” European Journal of Pharmacology. 2013 Jan 5;698(1-3):259-66 (source)
[xxiii] Lee B., Sur B., Shim I., Lee H., Hahm D.H. “Phellodendron amurense and Its Major Alkaloid Compound, Berberine Ameliorates Scopolamine-Induced Neuronal Impairment and Memory Dysfunction in Rats.” Korean Journal of Physiology & Pharmacology. 2012 Apr;16(2):79-89 (source)
[xxiv] Kulkarni S.K., Dhir A. “On the mechanism of antidepressant-like action of berberine chloride.” European Journal of Pharmacology. 2008 Jul 28;589(1-3):163-72 (source)
[xxv] Kulkarni S.K., Dhir A. “sigma-1 receptors in major depression and anxiety.” Expert Review of Neurotherapeutics. 2009 Jul;9(7):1021-34. (source)
[xxvi] Caliceti C., Rizzo P., Cicero A.F.G. “Potential Benefits of Berberine in the Management of Perimenopausal Syndrome” Oxidative Medicine and Cellular Longevity. 2015; 2015: 723093. (source)
[xxvii] Yin J., Xing H., Ye J. “Efficacy of berberine in patients with type 2 diabetes mellitus.” Metabolism. 2008 May;57(5):712-7. (source)
[xxviii] Lv X.Y. et. Al. “Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine” AAPS PharmSciTech. 2010 Mar; 11(1): 372–382. (source)
[xxix] Guo Y., Chen Y., Tan Z.R., Klaassen C.D., Zhou H.H. “Repeated administration of berberine inhibits cytochromes P450 in humans.” European Journal of Clinical Pharmacology. 2012 Feb;68(2):213-7 (source)
[xxx] Wang H., Liu D., Cao P., Lecker S., Hu Z. “Atrogin-1 affects muscle protein synthesis and degradation when energy metabolism is impaired by the antidiabetes drug berberine.” Diabetes. 2010 Aug;59(8):1879-89 (source)
[xxxi] Dunnick J.K., Singh B., Nyska A., Peckham J., Kissling G.E., Sanders J.M. “Investigating the potential for toxicity from long-term use of the herbal products, goldenseal and milk thistle.” Toxicology and Pathology. 2011 Feb;39(2):398-409 (source)
Hi David! Super happy to run into your article. As a holistic nutritionist, I was looking for something that was extremely informative as every other article says the same thing at the bare minimum. So thanks for putting this out there! I am curious about the side effects you listed as it’s my first time taking these. The first time I ended up really sick. I actually ended up having a pancreatitis attack and then in bed for a week with absolutely no solid bowel movements. I new it was partially due to the berberine because I only change things up one at a time when I add something new in. I decided to give.it another shot today, and I immediately got intense acid reflux which I literally never get. I am a bit perplexed as to why this is happening. If you could shed any light on this, I would absolutely appreciate it. I only took 500mg once. Hope you’re having a wonderful day!
Linn, when you first start supplementing with Berberine, you may experience diarrhea, the sweats, or even vomiting. This supplement is a powerful antibiotic. The good news is it only kills the ‘bad’ bacteria in your gut. Not the good bacteria like prescription antibiotics. But when those bad bacteria decide to leave your body, it may not be pleasant.
The only way around this is either not using Berberine, or using a lower dose until your system is cleaned up.
Hi David, Greetings from NZ. Firstly I would thank you for your work and sharing it. Great work.
I am 73 years old , prediabetic, ( take 1000mg metformin ) slightly overweight, fatty liver disease ( I quit alcohol). Have been taking vitamins , minerals and herbs for years. I have been taking 3mg melatonin mainly for dementia prevention and as an antioxidant, but also for sleep I guess.
I had been taking berberine for year or so (500mg) but ran out. When I ordered some more from vitacost I did some more research on it, and thus found your video and comprehensive website. I decided to up the dose to 2×500 and I now take my silimarin with it and MTC oil. I developed a hip problem late last year and have problems walking. It manifests as pain down the front of my leg, and across to the groin. By using a stick and walking like an “old man” I sort of improved the discomfort. However since starting the berberine the pain is markedly reduced. It is early days but I am quite surprised. I thought I was destined for a hip replacement. I cannot think what else to attribute the improvement to. On the Vitacost site they have customer feedback, and one person said berberine fixed her knee problem, said it was life changing. What are your thoughts about this?? :-).
Another thing that happened was my “melatonin dreams” (vivid.. I quite enjoy them) suddenly became so vivid and crazy that they were disturbing. Two nights in a row. I switched to a lower dose (750mcg slow release from Life Extension) which we happen to have. And the problem seems to have stopped. Have you ever heard of this.. maybe the berberine is increasing the power of the melatonin??
As an aside.. melatonin is prescription only in NZ and you will pay $1 a pill if you can get it. We smuggle it in from the USA for 10c a pill. It is sold freely in Australia.. so go figure. We get all of our suppliments from iherb and vitacost at much better prices.. even including shipping and now NZ VAT.
Thanks, David Swan
David, Berberine is a potent anti-inflammatory which could manifest in ways your suggest.
Melatonin is another story altogether. Please see my review for melatonin for more detail: https://nootropicsexpert.com/melatonin/. Better to get a natural source of melatonin by using Tart Cherry Juice from concentrate.
David, I’m a late onset type1 diabetic with high LDL cholesterol. My naturopath
added Berberine to my supplements and it does help keep my blood sugar in stable range. However I’ve been feeling nauseous and constipated since starting it I did move to taking 2-3 times a day with meals pretty quickly. Are there some ways to address this and still be able to take it? I’m disappointed as I’ve never had side effects to anything! Thanks. Helene
Helene, the only thing recommended to take with Berberine is Milk Thistle extract because it counters problems with long-term usage of Berberine.
I’d scale back my dosage if I was you. And use only one capsule per day for awhile. Once your system gets accustomed to it you can increase the number of daily doses.
More recent studies have also shown that high dose Omega-3s (EPA & DHA) help lower LDL Cholesterol without messing with HDL Cholesterol.
Hello Mister Tomen,
Thank you for the videos that you post on youtube and for the detailed transcripts on your site.
But there’s an error on this one.
“Similar to L-Deprenyl, Berberine seems to be a monoamine oxidase-A (MAO-A) inhibitor”
L-Deprenyl, Selegiline is classified as a MAO-B inhibitor.
In high doses, It can inhibits MAO-A.
“Inhibiting MAO-A increases norepinephrine and dopamine in your brain.”
Inhibiting MAO-A increases serotonin and norepinephrine, not dopamine.
At high doses Moclobemide, a MAO-A inhibitor can increases dopamine by inhibiting MAO-B.
Respectfully.
Fawzi, thank you for your feedback. But did you read the paragraph following that one? And did you read the abstract I linked to as well? https://pubmed.ncbi.nlm.nih.gov/18585703/
I read all the article.
A very instructive one.
Hi David,
Greetings from Malaysia. Thanks for the wonderful YT video on berberine on berberine as it’s packed with so much vital info. Recently, I came across two berberine formulations on eBay and would be grateful if you could help me puzzle out this issue :
{1} berberine HCL 10:1 extract
{2} 97% pure extract [standardized?]
Which of the two is the more potent one? I get the impression that {2} is an ordinary standardized extract but not as concentrated as {1}. What do you say?
Kindest regards, Cjuan
Cjuan, I’d say athe 97% extract was more potent. But either way, as long as the company is trustworthy and tests their product, you’re going to get a powerful Berberine supplement. This nootropic is not to be messed with. So please read the side effects section of this review carefully.
Does all forms of Berberine have the same benefits for alzheimers? Theres so many forms! Berberis Vulgaris, Berberis Aris, whats the form to take for Alzheimers?
Cy, you’re looking for Berberine HCl (hydrochloride) or Berberine Sulfate. I use and recommend this one: https://amzn.to/3fDxCQc
Im trying the brand from Toniiq. This time im also trying it with Milk Thistle to help with absorbtion. Ive tried different brands. Even amazing formulas. I dont notice a great dip on blood sugar. Im hopeing the milk thistle will help.
Cy, the Milk Thistle is not for better absorption. It’s to product from DNA damage from long-term use. To boost absorption I suggest trying a low dose of Piperine or BioPerine.
Both Milk Thistle & Berberine are very low in bioavailability. Silibin is better than Silymarin while the best milk thistle extract with highest bioavailability is Siliphos Milk Thistle* which sells at iherb [dot]com. In the case of berberine, a formulation described as ‘dihydroberberine’** has been found to be 5x more bioavailable – it is still rather expensive at present.
* Natural Factors, Siliphos Phytosome, Clinical Strength Milk Thistle, 160 mg
Cjuan, ’tis true and thanks for sharing. Here is the clinical data for Milk Thistle: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098397/. And for Berberine: https://pubmed.ncbi.nlm.nih.gov/18285556/
I bought some berberine and was going to buy Milk thistle but I t said not to use if you have allergies to rag weed. Have you heard of people having trouble with the milk thistle? Also I did low carb last year and went off metformin. With the pandemic I ate too much sugar and my blood sugar went back up so I went back on metformin. Do I take both together or just one or the other?
Thanks!
Bonnie, Berberine is as powerful as Metformin so should not be used together.
And avoid using Milk Thistle if you are allergic to plants in the asteraceae family, such as ragweed, daisies, marigolds and chrysanthemums. Because it could cause anaphylactic shock which can be deadly.
Ive currently got my mom on Berberine and serrapeptase and platexia. Oh my gosh!! I cant believe the improvement my mom is makeing on high dose serrapeptase!!! I know its got to be the serrapeptase. But it might be a combo of the platexia , serrapeptase from source naturals and the berberine from Toniiq. But she basically went from hardly answering my questions to freely answering my questions!!! I dont know if Serrapeptase is considered a nootropic or not?? But. SO FAR it is amazeing!! I read it eats brain plaque and arterial plaque.
Cy, Serrapeptase is a proteolytic enzyme so I would not consider it a nootropic. But if it’s working as you describe congrats on a good find.
Hi David,
Thanks for the great article.
You make the statement “The good news is it only kills the ‘bad’ bacteria in your gut. Not the good bacteria like prescription antibiotics”.
I just had my gut biome tested, and given the diversity of all of the bacteria present, could you explain how berberine accomplishes this? For example, here is an article which has a chart of predominant “bad” and “good” bacteria in the human gut. Notice that several of the species are considered neutral.
Thanks again for this article.
Matthew, I haven’t a clue how Berberine only goes after the ‘bad’ bacteria in the gut. Only that it does and it’s one of reasons why it’s been used in Chinese and Ayurvedic medicine for a long time: https://www.ncbi.nlm.nih.gov/pubmed/26092760.
My area of expertise is the human brain and that’s where I spend most of my research time. You’d need to search places like PubMed for Berberine’s antimicrobial properties and see if anyone has figured out how it works.
Hi David,
You said absorption will be better when we take berberine with unrefined coconut oil. But the thing is i always have high cholesterol and coconut oil is bad for me. so please do u think of any other supplements that will increase berberine absorption without raising blood cholesterol.
Thanks
Mahmoud, Berberine is fat-soluble so you must take it with a healthy oil. It’s the fat that takes it through cell walls. Any healthy fat will work. Even the fat that’s in a meal.
hi David; diagnosed type 1 an a half diabetes at 55, now 63 been on 2 insulins now for 7 or 8 years, am interested in berberine , will give it a try, mine is crazy, drs scratch there heads always health, fitness addict whole life, never over weight, no pre diabetes , just boom your type 1, or lada they call it , have endless searched for cures, slightly obcessed to find a cure , not to mention sick of needles an endless checking bld. sugar. no s all day ! anyway thx for this info, can’t wait to try. thx Scott
Would you tell me your opinion on switching to Berberine for Metfomin as used to extend lifespan described in David Sinclair PHD book “Lifespan”? Metformin: Anti Aging Drug? (David Sinclair Book LIFESPAN – Part 4) https://www.youtube.com/watch?v=_ofoy4RQjwQ (8:54 min) I would take Coconut oil and Milk thistle with the Berberine.
My personel history is I am 80 years old had a stroke in 2012 that partialy affected my right side muscle control, but not my thinking. I am a member of Mensa and a few other high IQ groups, have written several books since my stroke among them “How To Thrive And Prosper After A Stroke, 2nd Ed.” https://www.amazon.com/How-Thrive-Prosper-After-Stroke-ebook/dp/B07FC65CQ3 I was diagnosed recently with Afib which caused a lowered ability to breath, and a 4 day stay in the hospital where after much testing I was prescribed with Metropolol, Losartan, and Warfarin as needed – a nurse monitors my INR number. I quit taking Furosamide and Potasium CL. I am currently experiencing weight gain in my abdomen. Supplements I currently take are Magnesium, vitamin C, Zinc, vitamin D, a multi vitamin, and Glucosamine/MSM. I anticipate taking NMNs and Resveratrol in the near future.
David, I started using Berberine on the recommendation of my doctor for insulin resistance and possible pre-diabetes. He refused to prescribe metformin because Berberine would work just as well according to him.
Turns out he and the clinical trials are right. My labs are normal, I’m no longer insulin resistant nor worry any longer about diabetes.
Berberine works.
Hi David, thanks for all you do
Berberine inhibits cytochromes P450 (CYP3A4, CYP2D6 and 2C9) in your liver.[xxix] Which means it can cause a substantial increase in the bioavailability of certain drugs and nootropics. Which can be dangerous. You may need to lower your dosage of certain drugs to prevent this potential toxicity. Or avoid Berberine altogether.
This comment has me a little worried. I am not sure what it means and which types of nootropics would be a problem. Is there a way for me to research or can you give me a class or type this would be a problem with?
JQ, Several nootropics act as cytochrome inhibitors in your liver. And you need to be aware this in case it affects you.
This is no different than the warnings you hear about avoiding using grapefruit juice if you are on statins, blood pressure meds, organ-transplant rejection drugs, some abnormal heart rhythm drugs, and anti-anxiety drugs. Because drinking it while on these drugs could severely either amplify their effects, or negate their effects depending on the cytochrome.
It is exactly the same principle with Berberine affecting the same cytochromes as grapefruit juice does. For some drugs and a few nootropics it could be particularly dangerous for certain people.
Whether berberine causes muscle atrophy is debatable, because at least one study showed the opposite effect:
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0100918
One possible resolution of the contradiction is this: “Muscle atrophy was induced by berberine injection. Oral administration of berberine led to improvement of muscle atrophy. The actual effects of berberine remain to be explored.” The quote is from here:
https://www.sciencedirect.com/science/article/pii/S2211383512000871#s0065
Jim, that is encouraging news and I appreciate that you found this. I’ve been using Berberine for a couple of years for insulin resistance and it’s an important part of my stack. For thousands of others as well. So thank you.
I’d like to take Berberine for depression but am thin and don’t want to lose muscle mass or testosterone, which may be a side affect. My fasting glucose is 111 consistently. 5.6 long term. My cholesterol dropped from 264 to 231 but not sure how? Rates good. Will I see any affect is I take 250 mg 2 times a day?
Evelyn, Berberine is probably not the best option for depression especially in your case. This is a very powerful nootropic even at the dosages you suggest.
Please read this post for all possible causes of depression and some tips on how to figure out what may work for you: https://nootropicsexpert.com/best-nootropics-for-depression/
Hi, I’m a bit confused about the milk thistle extract dosing. I just bought the extract and instructions recommend 3 ml/day which is equivalent to 18 mg/day (according to the instructions paper that comes with the product). However David, you recommend “175 mg of Milk Thistle extract each time”. It seems a huge difference, so what may I be missing here? Thanks for the post by the way. A great and thorough coverage of the subject.
Mariano, in this case I’d stay with the manufacturer’s recommended dosages.
David, what is your opinion on berberine dose at 600mg per serving? I’ve seen multiple companies on amazon selling it at that dose. Would it be ok to do 1 of those two times daily?
Gregory, many have good success with 600 mg Berberine twice a day. Personally, I need to use twice that much to keep my insulin resistance under control.
But for long-term you need to stack it with Milk Thistle because studies show it’ll damage DNA. So use it with Milk Thistle extract and your good.
David, I usually take NAC instead of milk thistle for liver protection. I like to drink. Your thoughts??
Phillip, if you drink you’ll have better protection by using NAC along with Milk Thistle:
https://www.ncbi.nlm.nih.gov/pubmed/22308119
https://www.ncbi.nlm.nih.gov/pubmed/12508366
https://www.lifeextension.com/magazine/2019/1/milk-thistle-promotes-liver-detoxification/page-01
About your Berberin review:You have been right. Berberine alleviates ischemic arrhythmias via recovering depressed I(to) and I(Ca) currents in diabetic rats.
https://www.ncbi.nlm.nih.gov/pubmed/22188769
Thanks David. I was kind of leaning towards conclusion as well; seeds can be inconsistent…at best. Then there was the whole thing of those extra ingredients, of which I had never really heard of them being used for that purpose. I ended up ordering their berberine and the Nature’s Way milk thistle you mentioned earlier in another reply. I suppose that with diabetes on BOTH sides of my family, along with a few cases of being on both sides of EACH family, it’s probably fortunate that I came across this stuff, despite my sugar levels always being in the acceptable range.
Is amazeing formulas brand still a good brand of berberine? I read they changed the formula number and the pills look smaller and different color. Do you still use this brand?
Cy, that is still the brand of Berberine I use and it’s working for me.
David, on a related note, is the Amazing Formulas brand of Liver Support Formula a good idea to take along with their berberine? Or is it overkill and would it be better to stick with the Nature’s Way Milk Thistle? I should note I will also be taking MLP 2x/day as well. And, would modafinil @ 50-100 mg taken midway between the MLP doses be advisable or should it be avoided?
Larry, what is in Amazing Formula’s “liver support formula”? Milk Thistle is used to help mitigate the DNA damage caused by long-term Berberine use.
Milk Thistle (seed)
Dandelion (root)
Yellow Dock (root)
Beet (root)
Larry, I’d be more confident if it was Milk Thistle extract. With just Milk Thistle seed you’re not guaranteed any protection.
Dan,
Do you take the milk thistle at the same time as you take the berberine?? Just curious
Trudi, yes I take Milk Thistle each time I use Berberine.
Hello David,
As a type 2 Diabetic, it was a no-brainer to add Berberine to my daily stack. You were absolutely not kidding when pointing out how powerful it is, particularly its antibiotic effect. I did get nauseous and vomited the first time but subsequently my stomach has not reacted badly, so clearly there was bad gut bacteria that needed to be flushed out.
My concern now is how to phase out the 1000 Mgs of Metformin yet maintain glucose control without going overboard. I’d discuss it with my primary physician at Kaiser but you know how that will go. I would appreciate any suggestions you might have on how to phase out Metformin while phasing in Berberine.
Dan, best I can offer is to take a look at the clinical trials comparing Metformin with Berberine. And see what dosage they use.
If it was me I suppose I’d try reducing my prescription by a 1/4 or 1/2 and taking the appropriate amount of Berberine. But making sure I got my labs done real soon to see how it was going.
What is your Milk Thistle dosage?
I’ve been using Nature’s Way Milk Thistle which is standardized to 80% Silymarin at 175 mg 3-times per day.
Hello David,
I’m currently taking 20mg of Citalopram for Anxiety/Depression. Recently, I’ve noticed that my fasting blood sugar is around 110, whereas it was in the normal range before I started taking Citalopram.
I’ve read that SSRI’s can increase risk of developing Type 2 Diabetes and it seems that I’m in the pre diabetic stage now. Diabetes doesn’t run in my family either.
Can I take Berberine to help manage may blood glucose levels, or should I be wary of Serotonin Syndrome? Your article states that Berberine increases serotonin and increases Citalopram’s action and possible side effects.
I will ask my Doctor about this, but you know how it is. They usually know absolutely nothing about supplements or their interactions with pharmaceutical drugs. Maybe I can get off of the Citalopram as Berberine has antidepressive actions. Any insight? Thanks.
Nathan, Berberine does seem to raise serotonin, norepinephrine and dopamine levels. But I haven’t seen any contraindication on taking it with a SSRI. Do a little more research on your own and if you decide to try it start with the lowest dose and see how you feel. Look up the symptoms of “excess serotonin” so you know what to watch for.
And you may also want to try alpha lipoic acid: https://nootropicsexpert.com/alpha-lipoic-acid/ for pre-diabetes.
Hi David,
Love all the info you have provided re berberine. Is there much of a reaction between berberine and zolpidem tartrate (ambien?). I take it at night to get some much needed sleep (insomnia).
I have been taking berberine for the past few months and feel fine, but there is so much conflicting info out there. And, you sound like you are so familiar with Berberine!
Thanks,
Jennifer Tash
Jennifer, the only issue with using Berberine and zolpidem is that Berberine is a CYP3A4 inhibitor. Which means it significantly increases the action of zolpidem.
On the other hand, Berberine may be able to counteract some of the memory inhibiting side effects of zolpidem. But don’t take them at the same time. Berberine should be dosed earlier in the day.
And some animal studies show that long-term use of Berberine could cause DNA damage. But this can be counteracted by using Milk Thistle.
Hi David,
I’m a 52 year old woman, have been diagnosed with insulin resistance. I was taking metformin, but wanted to try a natural approach, so from my research I stumbled on berberine, which I am about to start taking. I’m hurtling towards the menopause also and have also decided to try and take a more natural approach towards that, so I no longer take HRT, instead using a supplement called DIM, which apparently addresses hormone imbalances i.e. Oestrogen dominance. I am very interested in purchasing Mind Lab Pro to help address the long term problems I’ve been experiencing with energy levels, brain fog, memory, lack of motivation etc, but concerned that the combination of the different supplements mentioned above may not be compatible. Are you able to comment on this pls.
Many thanks,
Lisa, I personally use Mind Lab Pro twice a day and Berberine for insulin resistance daily as well. My brain works better and my body’s use of insulin is now normal.
Hi David,
The price of berberine seems to vary considerably between suppliers, which may have to do with quality. Can you please tell me which brand you use.
Graeme, my favorite berberine so far is made by Amazing Nutrition: https://amzn.to/2wpjkOo. It works for me and has been consistent for the year I’ve been using it.
Hi David,
Could you provide a citation of berberine and heart arrhythmia? The studies I’m seeing indicate that berberine could actually inhibit development of arrhythmia.
Love your site and thank you for all of your work!
Jared, seems to be plenty of studies on berberine and the heart. Here’s two of them:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643735/
https://www.ncbi.nlm.nih.gov/pubmed/11607041
Right, but don’t both of these studies show that berberine is useful against arrhythmia? I’m asking because I want to be sure before I begin supplementing with berberine, undecylinic acid, and betaine combined.
‘The cardiovascular effects of berberine suggest its possible clinical usefulness in the treatment of arrhythmias and/or heart failure.’
Whereas your post says ‘If you have heart problems you may want to avoid using Berberine. Because supplementing with this nootropic could cause heart arrhythmia.’
It is very possible that this is over my head, but aren’t these opposite?
Thanks again
Jared, you are absolutely right and thank you for pointing this out. I did the research for Berberine primarily for brain health and optimization. Clearly I made a mistake about it’s affect on heart arrhythmia. I’ll correct it right now.
Berberine alleviates ischemic arrhythmias via recovering depressed I(to) and I(Ca) currents in diabetic rats.
https://www.ncbi.nlm.nih.gov/pubmed/22188769