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If you’re interested in natural health remedies, you may have heard of berberine. But what does the research actually say about berberine?
In this article, we’ll take a closer look at the science behind this popular supplement and explore what benefits it may realistically offer. From its potential effects on blood sugar and cholesterol to its anti-inflammatory properties, we’ll delve into the evidence and separate fact from fiction when it comes to berberine.
What is berberine?
Berberine is a natural alkaloid compound that can be found in various plants, including:
- Goldenseal (Hydrastis canadensis)
- Oregon grape (Mahonia aquifolium)
- Barberry (Berberis vulgaris)
- Tree turmeric (Berberis aristata)
- Chinese goldthread (Coptis chinensis)
- Phellodendron (Phellodendron amurense)
- European barberry (Berberis vulgaris)
- Greater celandine (Chelidonium majus)
These plants have been used in traditional medicine for centuries, and their active ingredient, berberine, has been shown to have a variety of health benefits, including anti-inflammatory and anti-diabetic effects.
In fact, many of these herbs owe a lot of their beneficial properties to the fact that they contain berberine.
So if you’ve ever been interested in trying one of these herbs before, you might be better off just getting pure berberine than trying to get an extract of one of these herbs.
For example taking a goldenseal tincture or European barberry extract is mostly beneficial thanks to the berberine, and because purified berberine removes any contamination or harmful impurities that might be found in the raw goldenseal or European barberry herbs, I’d suggest you cut straight to the chase and take berberine instead.
Berberine vs Dihydroberberine
Now most supplements will use the berberine HCl form, which is generally the form you should look for when using berberine.
This form is not well absorbed by the body, in fact, most of it is not absorbed at all, and much of it is metabolized by the liver, rendering it useless.
So researchers have looked for ways to improve its absorption into the body. One such form is the creation of dihydroberberine, a derivative of berberine that appears to be much better absorbed than regular berberine.
Dihydroberberine is far less common and much more difficult to find as a supplement, and is several times more expensive than berberine HCl, so is this improved form worth it?
Well the study that compared the two surprisingly did not find any improvement in blood sugar control with dihydroberberine.
So even though significantly more berberine was absorbed, it had no additional benefits.
This tells me that berberine likely has an upper limit, and taking more than the standard dose of berberine HCl is not likely going to be any better.
At that point, the only benefit of dihydroberberine would be the possibility that you could take less dihydroberberine and achieve similar effects.
However, the cost difference is still too large, and the regular berberine HCl dose, which would be around 500 mg 2-4 times a day or a total of 1 to 2 grams a day, is more than enough to achieve benefits, and still be much cheaper than trying to take a smaller dose of dihydroberberine.
Berberine vs Metformin
It doesn’t necessarily mean you can’t take berberine if you’re taking a diabetes medication like metformin, just that you should ask your doctor first for guidance. In fact, studies have combined and compared metformin with berberine before.
There is interest in both because they’re both AMPK activators, and seem to provide some similar health benefits. Metformin is just a stronger AMPK activator.
Studies have compared the two and found pretty similar effects on blood sugar control in diabetics.
For cholesterol control however, berberine seems to have the upper hand. Most evidence would suggest that berberine is better than metformin at helping to lower cholesterol levels.
People taking berberine are also less likely to have side effects than those taking metformin, and tolerate it better overall.
We can also roughly compare berberine’s weight loss effects with metformin, and find that both produce similar but small overall effects on weight, with perhaps metformin being slightly more effective for weight loss.
Now metformin is better absorbed than berberine in the body but with similar effects on blood sugar, and with berberine having more effects on cholesterol, you might be wondering why the heck doctors don’t just recommend berberine for diabetics instead of metformin.
There are a few reasons why. For one, there’s still much more robust research behind metformin, and even though berberine has some smaller studies behind it, the research behind metformin is far greater.
Secondly, everyone can make berberine supplements, and their standardization is all over the place. If you take a supplement that says 500 mg of berberine, you may actually be getting 200 mg, or 600 mg.
You just don’t know if a pill of berberine is actually giving you a good dose of berberine or if there might be impurities or contamination, since supplements are rarely independently tested.
You see, berberine is available without a prescription, and can be purchased over the counter as a supplement, while metformin is by prescription only, and is considered a medication.
If a doctor prescribes you 500 mg of metformin, you’re getting 500 mg of metformin. Medications require far more rigorous testing for purity and dosing than supplements.
Also if your doctor has prescribed you something, they’ll be able to better monitor your progress and adherence to the medication, to make sure what they’re recommending is actually working for you.
Finally, generic metformin also tends to be quite cheap, while berberine supplements can range from moderately cheap to very expensive.
Health benefits
Berberine has been the subject of extensive research, and several potential health benefits have been associated with its use. Here are some of the notable ones:
- Blood Sugar Regulation: Berberine has shown promise in helping regulate blood sugar levels by improving insulin sensitivity and reducing glucose production in the liver. It may be beneficial for individuals with type 2 diabetes or those at risk of developing the condition.
- Cholesterol and Lipid Management: Studies suggest that berberine may help lower total cholesterol, LDL cholesterol (the “bad” cholesterol), and triglyceride levels while increasing HDL cholesterol (the “good” cholesterol). This effect on lipid metabolism may contribute to cardiovascular health.
- Antioxidant and Anti-inflammatory Effects: Berberine exhibits strong antioxidant properties, helping protect cells from oxidative stress and damage caused by free radicals. It also possesses anti-inflammatory properties, which may be beneficial for various inflammatory conditions.
In diabetes
The most promising benefits of berberine are related to its ability to help diabetics. Here are some of the possible ways (based on animal and human studies) in which berberine helps with blood sugar control:
- Increases insulin receptor expression: Berberine can increase insulin receptor expression in peripheral blood lymphocytes, which helps to improve insulin sensitivity and reduce blood glucose levels in patients with type 2 diabetes.
- Activates AMPK: Berberine can activate AMPK, which stimulates glucose uptake in skeletal muscles, increases the oxidation of fatty acids in adipose tissue, and reduces the production of glucose in the liver, all of which help to lower blood glucose levels.
- Increases GLP-1 secretion: Berberine can increase GLP-1 secretion, an incretin that plays a role in the maintenance of glycemic control, which helps to lower blood glucose levels.
- Modulates PPAR expression: Berberine can increase PPAR-alpha and PPAR-delta expression, which help to improve lipid metabolism, but reduce PPAR-gamma expression in the liver of diabetic rats, which helps to reduce insulin resistance and lower blood glucose levels.
- Inhibits aldose reductase: Berberine might inhibit aldose reductase, which could help to prevent nerve and eye damage in people with diabetes.
The primary way berberine helps with blood sugar control and reduces inflammation in diabetics, is by helping to stimulate a protein called AMP-activated protein kinase, or simply AMPK.
Activating AMPK does a number of different things in the body, like reducing the amount of glucose the liver produces and pours into the bloodstream.
The overall effect is helping to reduce sugar in the blood, and reducing inflammation, particularly in those with metabolic diseases like diabetes.
Side effects
So despite regular berberine being poorly absorbed, the evidence would suggest that you don’t need too much berberine to be absorbed for it to be effective.
In fact, taking too much berberine is one of the common ways side effects occur. Most of them are related to gastrointestinal issues, such as stomach pain, gas, bloating, and nausea. Here are some potential side effects of berberine supplements:
- Gastrointestinal symptoms: Berberine may cause gastrointestinal side effects such as diarrhea, constipation, nausea, vomiting, and abdominal pain.
- Hypotension: Berberine may lower blood pressure in some people, which can cause dizziness, lightheadedness, and fainting.
- Headaches: Some people may experience headaches as a side effect of berberine supplements.
However, when taken at a reasonable dose, berberine is pretty well tolerated.
Interaction with medications
Berberine does interact with numerous medications, since berberine affects the metabolism in the liver. So if you’re taking any medication, particularly drugs that also interact with the liver like cyclosporin, you need to ask your doctor if it’s safe to use.
Berberine can also theoretically lower blood sugar and blood pressure levels, so if you’re taking any diabetes medication or blood pressure medication, you should also work with your doctor to make sure your blood sugar or blood pressure doesn’t get any unexpected drops.
Here is a list of possible drug interactions with berberine:
- Anticoagulant/antiplatelet drugs: Berberine may increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
- Antidiabetes drugs: Berberine may increase the risk of hypoglycemia when taken with antidiabetes drugs.
- Antihypertensive drugs: Berberine might have additive effects when taken with antihypertensive drugs.
- CNS depressants: Berberine might increase the sedative effects of CNS depressants.
- Cyclosporine: Berberine can increase serum levels of cyclosporine, and these two drugs should not be taken together.
- CYP2C9 substrates: Berberine may increase serum levels of drugs metabolized by CYP2C9.
- CYP2D6 substrates: Berberine may increase serum levels of drugs metabolized by CYP2D6.
- CYP3A4 substrates: Berberine may increase serum levels of drugs metabolized by CYP3A4.
- Dextromethorphan: Berberine may increase serum levels of dextromethorphan.
- Losartan: Berberine might reduce the therapeutic effects of losartan by decreasing its conversion to its active form.
- Midazolam: Berberine can reduce metabolism of midazolam, which may increase the risk of severe adverse effects.
- Pentobarbital: Berberine might increase the sedative effect of pentobarbital.
- Tacrolimus: Berberine has been associated with increased blood levels of tacrolimus, which may require a reduction in tacrolimus dosage.
Uses in specific health conditions
Diabetes
Berberine has shown the most promise in reducing blood glucose levels in people with type 2 diabetes, and may even provide additional benefits when taken with conventional medications.
Clinical research suggests that taking berberine orally in doses of 500 mg 2-3 times daily for 2-4 months can reduce glycated hemoglobin, fasting plasma glucose, and postprandial glucose in subjects with type 2 diabetes when compared with placebo.
Large meta-analyses show that taking berberine in combination with lifestyle interventions can reduce FPG, PPG, and HbA1c levels, with reductions ranging from 10-16 mg/dL, 27-34 mg/dL, and 0.4% to 0.7%, respectively.
Moreover, taking berberine in combination with oral hypoglycemic drugs has been found to lower FPG, PPG, and HbA1c levels by 12-19 mg/dL, 18-24 mg/dL, and 0.6% to 0.9%, respectively, when compared with hypoglycemic drugs alone.
High cholesterol
Taking berberine orally, alone or with other ingredients, has been shown to reduce total cholesterol, LDL cholesterol, and triglycerides while increasing HDL cholesterol levels in clinical research.
Meta-analyses have shown that berberine can reduce total cholesterol by 21-32 mg/dL, triglycerides by up to 34 mg/dL, and LDL cholesterol by 23-26 mg/dL while increasing HDL cholesterol by 2-3 mg/dL when compared with placebo or lifestyle interventions.
Berberine alone was found to be as effective as simvastatin in one meta-analysis. In combination with lipid-lowering drugs, berberine can lower total cholesterol by 10-15 mg/dL, LDL cholesterol by up to 9 mg/dL, and triglycerides by up to 30 mg/dL when compared with lipid-lowering drugs alone.
PCOS
Berberine might be helpful for women who have polycystic ovary syndrome (PCOS) and insulin resistance. It can lower blood sugar, cholesterol, and testosterone levels and increase the level of HDL cholesterol and sex hormone binding globulin.
Berberine can also improve certain lipid parameters when compared to metformin, and might be effective in increasing clinical pregnancies and live births before in vitro fertilization (IVF).
However, there are conflicting results on whether berberine can increase live birth rates when combined with letrozole for ovarian stimulation.
Weight loss
According to two meta-analyses, taking berberine in daily doses ranging from 300 to 3000 mg for anywhere from 1 to 24 months can lead to modest weight loss in obese individuals.
These reductions include roughly 3 kg of body weight, a decrease in body mass index (BMI) of 0.3 to 0.5 kg/m2, and a waist circumference decrease of about 1 to 3 cm compared to baseline.
It’s worth noting that the studies were generally small and varied in quality, with some significant differences, so it’s possible that more research is needed to confirm the findings.
So some doctors are understandably cautious, however I do believe a good quality berberine supplement can be a suitable alternative to blood sugar control in those with metabolic conditions like diabetes or PCOS.
Blood sugar control is also hypothesized to be the primary way that berberine helps people lose weight, since the other weight loss mechanisms have not been well established in humans.
This helps your body to better convert the carbohydrate that you eat into energy to be used, rather than being stored as fat.
As a result, it’s people with blood sugar issues to begin with that are going to benefit the most, and likely lose the most weight from taking berberine.
It’s not going to be super significant, and if you don’t have any blood sugar issues you may not even notice it.
How to use it for weight loss
To summarize, berberine can be a useful alternative to metformin, and help those with diabetes to control their blood sugar levels and manage their cholesterol levels.
It may also help you to lose a little weight, but don’t expect miracles.
If you do decide to try it, you should look for a quality berberine supplement. It doesn’t have to be dihydroberberine, but it should be independently tested for purity and dose.
Finally, while berberine is relatively safe to take at standard doses, you should still ask your doctor, especially if you’re taking other medication.
Top supplement choices
- Berberine (dihydro) – 2 to 4 caps / day
- Berberine (generic) – 2 to 3 caps w/ meals
- Berberine (Thorne) – 1 to 2 caps w/ meals
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See also
- The Real Benefits of Bee PollenBee pollen is rich in nutrients and a good superfood, but research shows it has little benefits on any actual health conditions.
- The Real Benefits of TurmericTurmeric may help with blood sugar management and fatty liver disease but likely will not cause actual weight loss.
- The Benefits of MoringaMoringa may not have significant effects on diabetes or cholesterol. Its most well-researched benefit is likely supporting lactation.
- The Benefits of AshwaghandaAshwagandha is well-known for its benefits in reducing stress and anxiety, with most of the research coming from India and the Middle East.
- The Benefits of SchisandraThe clinical evidence supporting schisandra’s medicinal benefits is too weak. However, it shines as a nutritious functional food.