Update 6/6/23. Berberine has been used for thousands of years, but these days the supplement most mostly used to lower total cholesterol and LDL levels and reduce blood sugar levels. It's been proposed as a natural PCSK9 inhibitor which, if true may make it an alternative for those who don't want to take injectable LDL cholesterol-lowering medications like Repatha. So, does it really work? This review will look at the proof and help you decide which supplement -and amount to take -may be right for you.
What Is Cholesterol?
Contrary to popular belief, cholesterol is not all evil. The body actually makes it because it serves many important functions. Cholesterol is a part of all cells in the body and it helps maintain cell integrity. It is also a precursor to vital hormones such as:
- Testosterone
- Estrogen
- Progesterone
- Aldosterone
- Cortisol
In addition, cholesterol helps make:
- Vitamin D
- Vitamin A
We know heart disease is not just about the total amount of cholesterol you have. Both LDL and HDL levels are important too.
- LDL (low-density lipoprotein / bad cholesterol)
- HDL (high-density lipoprotein / good cholesterol)
Think of LDL as a truck that takes excess cholesterol away from the bloodstream and returns it to the liver, where it can be recycled. Think of HDL as like a truck that delivers cholesterol to the bloodstream, where cells can use that cholesterol to make hormones, and vitamins, incorporate it into cell membranes, etc.
While LDL is often called bad and HDL is usually called good, remember both are needed to keep the body healthy. That said, when LDL levels get too high, more cholesterol is delivered to the blood than is needed. Just as when garbage piles up in your neighborhood isn't picked up regularly, cholesterol can start to pill up. This can increase plaque formation inside blood vessels, one of the forerunners of heart disease.
What is PCSK9 (Repatha & Praulent)?
PCSK9 refers to proprotein convertase subtilisin kexin 9. It's a protein enzyme on the surface of LDL receptors of liver cells that interferes with the removal of LDL cholesterol from the blood. In other words, you don't want a lot of PCSK9 in the blood. Low PCSK9= less bad cholesterol.
Anything that could knock out or lower PCSK9 levels would increase LDL receptors on liver cells so those receptors could best remove LDL cholesterol from the blood. This is how drugs like Repatha and Praulent work. Both Praulent and Repatha are known as PCSK9 inhibitors. Studies have shown that inhibiting PCSK9 with these medications can significantly lower LDL cholesterol levels in humans. The lower the LDL level in the blood, the lower your risk of heart disease and heart attacks.
Prescription PCSK9-inhibiting drugs work differently than statins like Lipitor and Crestor which have been around since the 1990s. Statins work by interfering with an enzyme (called HMG-CoA reductase) that makes cholesterol. Ironically, statins also tend to increase PCSK9, which may help explain why they are less effective in some people.
So, What's The Problem?
Self-injectable medications like Repatha are expensive (costing over $1000 US dollars per month). Some people may not like injecting themselves with a needle (even a small needle). Another thing is the potential for side effects such as intense muscle pain, which some have reported from these injectable medications.
So, is there a natural way to reduce PCSK9 levels without the side effects of injectable medicines?
This is where Berberine comes in.
What Is Berberine & How Does It Compare
Berberine is an organic compound found in some plants, such as goldenseal and Indian barberry (tree turmeric). While used in China since the 1950s to treat diarrhea, these days, most people take it to self-treat high cholesterol levels and diabetes, and non-alcoholic fatty liver disease.
There is evidence it works too.
For example, one review of 27 previous investigations noted berberine plus a healthy lifestyle was effective at lowering both blood sugar levels and A1C more than lifestyle changes alone. It seems to do this by increasing insulin sensitivity and altering the microbiome to a more favorable composition.
In those with heart disease, PCOS, and high lipid levels, another review has noted berberine can lower total cholesterol, LDL, and triglycerides as well as raise HDL levels too. While results can vary, the following changes have been seen with supplementation:
- Total cholesterol: 13 mg/dl decrease
- LDL: up to about 11 mg /dl decrease
- Triglycerides: up to about 9mg/dl decrease
- HDL: up to about 12 mg/dl increase
In cholesterol-lowering studies, about 1000 mg per day has been used.
Video Review
Watch on my Youtube channel if you prefer.
Berberine: Natural PCSK9 Inhibitor?
Given its ability to reduce cholesterol levels, some have wondered why. While it's suggested berberine lowers blood sugar by increasing the number of insulin receptors on cells (exercise does this, too), it's likely there are other mechanisms of action.
Another way berberine may work is by acting as a natural PCSK9 inhibitor. This is similar to how injectable drugs like Repatha and Praluent work, although remember, berberine is a dietary supplement that's taken orally.
To test this theory, researchers gave berberine to mice with high cholesterol levels. They observed berberine reduced PCSK9 levels in the mice by about 50%. The mice also had lower LDL levels too. Researchers in Norway noted berberine lowered PCSK9 levels in human liver cells by almost 90%. Human studies need to confirm these results.
Eating a high-fat diet increases compounds called lipopolysaccharides. Lipopolysaccharides are pro-inflammatory, and they increase PCSK9 levels too. Researchers in China noted 4 weeks of berberine supplementation prevented the rise in PCSK9 in mice that were also given lipopolysaccharides. In addition, the mice had lower LDL levels too.
In one of the few human studies published, researchers in Italy split 270 people into groups receiving either a statin medicine or a dietary supplement containing 500 mg of berberine, 10 mg of policosanol, and 200 mg of red yeast rice. After 3 months of use, they noted a reduction in LDL levels by about 10%. The effect was attributed to reductions in PCSK9 levels. Problems with this include:
- Before and after PCSK9 levels were not tested.
- Red yeast rice can also reduce LDL cholesterol due to its natural statin component.
Most of the berberine/PCSK9 research is limited to cell studies and laboratory animals for the moment.
Berberine vs. Repatha
Because drugs like Repatha and Praluent are injected, they are very effective at reducing PCSK9 levels. It's unlikely that an oral berberine supplement would lower LDL cholesterol as well as drugs do. But, given the high cost of these medications ($12-$14K per year) and the reports of severe muscle pain, berberine may be a consideration to discuss with a doctor.
Pro/ Con: Berberine vs. PCSK9 Inhibitor Drugs
| Berberine | Drugs (Repatha, etc.) |
| Human studies show it works | Human studies show it works |
| Inexpensive | Expensive |
| Taken orally | Taken by injection |
| No significant side effects reported in healthy people | Significant side effects reported |
| No prescription required | Prescription required |
Remember, the optimal dosage to significantly lower PCSK9 in humans is not known. Most research is limited to lab animal research. As such, it may take some experimentation to see if and how much works for you. Studies looking at lowering LDL levels generally use 500-1000 mg of berberine per day. The amount you use may be less or more than this. This is another reason why the supplement should be used in conjunction with regular blood tests performed by your doctor.
Combining the supplement with healthy lifestyle changes will likely magnify the effects of the supplement.
Can Berberine Help You Lose Weight?
Berberine has been called Nature's answer to Ozempic on social media. Ozempic, a diabetes medication, is very popular because it also has been shown to promote weight loss. This leads to shortages in Ozempmic. Berberine appears to lower blood sugar, similar to Ozempic, and clinical studies on people have also indicated it may help people lose weight. Various studies have revealed people may lose between 5 and 11 pounds when taking berberine for up to three months. See this video for more insights and how much might work.
Berberine Side Effects
When taken orally, the supplement is generally regarded as safe in healthy people. Side effects in healthy individuals appear mild for the most part such as constipation and GI discomfort. Because it has a bitter taste, some report a bad taste in the mouth after taking the supplement. This is temporary. Here are some general guidelines and suggestions when using this supplement. This list is not complete, so always check with your doctor first:
- Start with less than recommended for the first week to see what your side effects are
- Avoid while pregnant and breastfeeding. Berberine can pass from mother to baby and may cause contractions of the uterus.
- Stop taking at least 2 weeks before having surgery
- The supplement may interact with blood thinner medicines
- Berberine seems to interfere with the enzymes that break down medications. This could lead to medications breaking down too quickly or too slowly. Speak to your doctor if you take any prescription or non-medication.
- Berberine can reduce blood sugar levels. It may interact with medications that treat diabetes.
- The supplement may interact with dietary supplements that lower blood sugar levels.
When combined with diet and exercise, berberine has been shown to reduce blood pressure more than lifestyle changes alone. This tells us the supplement may reduce blood pressure and might interact with blood pressure medications.
Like all supplements, when in doubt, talk to your doctor first if you have health issues.
What To Look For And Watch Out For
Look for Berberine HCL. That's the form most supplements contain. Effective dosages range from 500 mg to 1000 mg per day. Supplements usually provide 1000 mg in two capsules. Some supplements may be large making them difficult for some to swallow. If this is the case, open the capsules and mix the powder with juice or other liquid. Remember, berberine can have a bitter taste which may alter the flavor of what you mix it with.
Be careful with goldenseal supplements. While the compound is found goldenseal, it's also true goldenseal has many other ingredients too. So far, only the berberine compound has been shown to reduce PCSK9 levels.
Here are 2 supplements I investigated for quality (they contain what they are supposed to):
It may take 1-4 months to see reductions in LDL and blood sugar levels. The effects of supplements are optimal when combined with healthy lifestyle modifications like eating better and exercising.
Does Berberine Lower PCSK9?
There is evidence berberine can reduce PCSK9 levels, although most evidence involves lab animals and cell cultures. This at least partially explains berberine's ability to lower LDL levels in humans which human clinical studies have documented. The effect would likely be less than injectable anti-cholesterol medications like Repatha and Praluent so for the very best results; supplements should be combined with a healthy lifestyle eating, and exercise to maximize benefits.