The incidence of insulin resistance, obesity, and other metabolic disorders have reached massive proportions in industrialized nations. Currently, one of the more popular glucose-lowering drugs available by prescription is metformin. This drug comes with potential side effects, some of which are very serious (1). In this article we are going to talk about metformin alternatives, particularly Berberine and see how it acts as a alternative to metformin. We are going to talk about berberine health benefits and what it actually does as a natural alternative to metformin.
What is Berberine & Where Does it Come From?
Berberine is a plant-based compound that has developed a reputation for being a natural metformin alternative. This is because it can help the body reduce blood sugar levels in multiple ways with relatively few side effects.
Here, we’ll examine a number of berberine’s health benefits and see where it stacks up in terms of its ability to lower blood sugar, improve metabolism, and perform other helpful duties in various systems of the body. We read through mountains of scientific studies and compiled the most important beneficial health information so that you did not have to.
Alternative to Metformin: The Definition of Berberine
Berberine is a phytonutrient and alkaloid compound found in several different plants, including goldenseal, European barberry, phellodendron, coptis, Oregon grape, and tree turmeric (2).
The Chinese Medicine and Ayurveda communities have been aware of the benefits of berberine since ancient times, including its unique ability to lower blood sugar levels. Traditionally, it has been used for the treatment of inflammation, infections, parasites, wound healing, skin and stomach ulcers, indigestion, hemorrhoids, and diarrhea in many geographical regions of the world. Widespread diabetes is relatively a new health concern in history, so past healers didn’t pay much attention to its management during ancient times. (3)(4)
How Exactly is Berberine a Natural Alternative to Metformin?
Berberine Lowers Blood Sugar & Improves Insulin Sensitivity
Berberine lowers blood glucose as much as common drugs used for that purpose. That’s why it’s one of the metformin alternatives.
Supports Insulin Production in the Pancreas
In 2012, a study noted berberine’s ability to decrease glucose and insulin in the blood of humans and animals and strengthen insulin sensitivity throughout the body. (4)
The researchers explained one of the mechanisms behind these benefits as the regulation and repair of pancreatic islet cells. Islets are a group of specialized cells in the pancreas that make several hormones. One of the most important hormones is insulin, which allows your many-body cells to absorb glucose from the circulating blood and use it for cellular energy.
“These results indicate berberine may have a two-way regulation in pancreas islets. In typical type 2 diabetes with notable insulin resistance, berberine lowered blood insulin levels through increasing insulin cellular sensitivity. However, in type 1 diabetes or the late stage of type 2 diabetes characterized by poor β-cell function, berberine was able to increase insulin secretion via repairing destructed or exhausted islets, which may be related to its antioxidant and anti-lipid peroxidation properties.”
Activates the “Metabolic Master Switch” Enzyme
One important glucose-lowering talent of berberine is the ability to activate the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. The AMPK is an enzyme produced in the brain and has earned the nickname of the “metabolic master switch” because it plays an important role in our body’s step-wise pattern of energy metabolism. Defects of this enzyme’s signaling pathway can result in obesity and other metabolic problems in the body. Berberine is known to help activate AMPK which will, in turn, help the body to regulate the metabolism of dietary glucose and fats. (5)
Stimulates Enzymes that Break Down Glucose
In 2014, a study sought to determine whether AMPK activation was the only mechanism by which berberine could lower blood sugar levels and surprisingly found that it was not. They first chemically blocked the AMPK activation pathway and the results showed that even when AMPK was blocked, berberine still lowered blood sugar levels. In addition, metformin had the same effect on blood sugar. The authors concluded that berberine and metformin not only activated the AMPK pathway but they also promote glucose metabolism through the stimulation of glycolysis, which is the breakdown of glucose by enzymes in the body. (6) This is just one of the reasons we consider berberine a natural alternative to metformin. With its ability to lowers blood sugar and improves insulin sensitivity it’s one of the most popular metformin alternatives.
Reduces Breakdown of Certain Carbs & Starches
Berberine is also able to work against diabetes because it works in the same way as alpha-glucosidase inhibitor and alpha-amylase inhibitor drugs (e.g. miglitol and acarbose). These are medications that prevent the digestion of carbohydrates and reduce the impact of dietary carbs on blood sugar levels (7)(8). Specifically, they inhibit enzymes that break down sugars and starches (i.e., glucose). The natural forms of these medications do exist in plants and include curcumin and berberine. (9) So if you’re looking for metforimin alternatives, you could consider natural sources and talk to your doctor to see if Berberine could be one of the best alternatives to metformin for you.
These compounds also decrease glucose transportation into the body because following the intake of a regular meal, food is digested in the mouth and stomach and transported across the intestinal epithelium layer into the bloodstream. These compounds work at the layer of cells which facilitate food absorption in the intestines.
Prevents the Liver from Creating Too Much Glucose
The liver is the main site in the body for making and storing glucose. This function is key during times of starvation (between meals) and fasting. Berberine has also been found to inhibit gluconeogenesis, or the production of glucose that takes place in the liver. (10)
How Berbereine, as an Alternative to Metformin, Supports Metabolism
The same mechanisms that allow berberine to control blood sugar levels and cellular insulin sensitivity also allow it to be good for the overall metabolism of carbs and fats.
If you’ve read this article from the beginning, you would know that berberine inhibits glucose production in the liver and glucose digestion in the belly. It activates the enzyme, AMPK, which regulates fat and sugar metabolism. It also repairs and supports islet cells, the clusters of cells in the pancreas that produce insulin.
May Promote Weight-Loss
In one study, obese human subjects ingested 500mg of berberine three times a day for 12 weeks. The study subjects reportedly lost an average of five pounds (2.3kg). They also were found to have lost more cholesterol and triglyceride than they would have through other traditional weight loss methods. (11)
Another study of humans with metabolic syndrome led to a greater weight loss in the same amount of time. In three months, their body mass indices (BMI) dropped from an average of 31.5 to 27.4, allowing them to decrease from anobese to overweight status. They were noted for taking 300mg of berberine, three times a day. Insulin resistance most likely played a role in the amount of weight loss seen in this group. (12)
A 6-month study of metformin and weight loss followed 154 patients who took up to 500mg of berberine twice a day.. They also lost a considerable amount of weight, especially those with high insulin resistance. To the contrary, the untreated participants actually gained weight. (13)
Berberine as one of the metformin alternatives has multiple mechanisms of action that help regulate metabolism and cause weight loss.
AMPK triggers the production of new mitochondria (pictured)
In 2014, a review of studies examined berberine’s anti-inflammatory effects in those with metabolic disorders like diabetes, which is also considered an inflammation disorder. In their analysis, researchers noted a large number of antioxidant and anti-inflammatory activities in human and animal subjects. (14)
Kills Bacteria, Viruses & Fungi
A number of scientific studies have revealed berberine’s ability to kill bacteria, viruses, fungi, and parasites. There are actually too many to mention here; however, here are some key notable ones to consider.
- In 2014, a study noted berberine’s ability to fight candida overgrowth, a fungal infection that begins in the digestive system and can spread to all other body systems. (15)
- In 2011, a rodent study demonstrated the reduction of the mortality rate of the influenza virus from 90% to 55%. (21)
- In 2005, researchers found that berberine helped certain antibiotics fight the deadly methicillin-resistant staphylococcus aureus (MRSA) bacteria in a synergistic pattern compared to controls. (16)
Quickens Wound Healing
Berberine’s anti-bacterial and anti-inflammatory effects have also demonstrated key properties which can help wounds heal more quickly.
Promotes Heart Health & Lowers Cholesterol
Factors such as high blood sugar, high triglycerides, and unhealthy cholesterol levels can increase the risk of heart disease. Berberine is noted to reduce all three and also elevates the level of healthy cholesterol. (17)
In 2003, a long-term study published results suggesting that berberine significantly improved the survival rate of people who previously suffered from heart failure. (18)
Lowers Fat Build-Up in the Liver
In 2013, an analysis of scientific studies examined berberine’s ability to reduce fat storage in the liver. Researchers confirmed the existence of this ability and recommended that more studies be conducted to determine how this biological property is achieved. (19)
May Improve Mood
In 2008, a research study demonstrated the increased levels of serotonin (19%), dopamine (52%), and norepinephrine (29%) in the brains of rats within 15 days of using berberine. (20)
In 2019, researchers examined existing studies and noted numerous ways in which berberine improves mood, especially in patients with mood disorders. (22)
Encourages Good Gut Bacteria Balance
3D Image of Intestinal Bacteria
In 2010, a study of adult men of all ages, shapes, and sizes linked excessive amounts of certain types of “bad bacteria” in the gut with type 2 diabetes. (23)
In 2018, in an analysis of existing studies, researchers pointed out several connections between metabolic disorders like diabetes and the gut bacteria ecosystem. They blame the current high levels of diabetes on a modern diet saturated with carbohydrate-rich and fat-rich processed foods and a lack of eating fiber. Healthy bacteria found in the gut feed on the fiber and create short-chain fatty acids (SCFA’s) which are known to reduce inflammation. People with diabetes are known to have lower levels of gut bacteria that create SCFA’s. All of these factors, combined with the overuse of antibiotics, have led to more diabetic cases than in previous periods of history. (24)
The same researchers have also noted other chemicals produced by healthy bacteria of the gut that can help prevent metabolic disorders, support the immune system and regulate other organs in all systems of the body.
According to a Chinese study in 2011, berberine that does not get absorbed and used by the body may suppress “bad” gut bacteria and inhibit their reproduction. Some of these bacterial strains can help create the conditions for diabetes. Berberine that does get absorbed may help suppress these strains, too, but the scientists were mainly looking at the berberine that stayed in the digestive system. (25)
The researchers cited a study showing that berberine does not suppress healthy probiotic strains in the lactobacillus and bifidobacterium groups. These groups include most of the healthy strains that you will find in probiotic supplements, yogurt, and other probiotic-rich foods. They also pointed out another study of a probiotic milk beverage slowing down a number of diabetic symptoms in rats consuming high amounts of fructose. By suppressing bad bacteria, berberine inadvertently supports the growth of probiotics.
Reduces the Severity of Acne
In 2012, an Iranian study of adolescents with moderate to severe acne demonstrated the lowering of their Michaelson’s acne severity scores by an average of 45% in four weeks compared to a placebo. The subjects used 600mg of oral barberry extract daily. (33)
Berberine vs. Metformin: Is Berberine the Metformin Alternative?
First of all, let us remind you that this article is not intended to be a substitute for a comprehensive diagnosis and sound medical advice from your doctor. Secondly, below is some great news and key findings associated with the biological impact of berberine.
In 2008, a study followed 36 adults for three months who were newly diagnosed with type 2 diabetes. Subjects were randomly assigned berberine or metformin. Both showed similar effectiveness at lowering blood sugar levels. However; berberine worked better than metformin in regards to fat metabolism. (26)
In part B of the study, data from 48 adults with “poorly controlled” type 2 diabetes was collected and analyzed. Berberine demonstrated improved blood sugar and cholesterol levels as well as fat metabolism. The only side effects reported were temporary gastrointestinal symptoms: passing gas, gas pains, diarrhea, and constipation. There was no damage noted to the function of the liver or kidneys. (26)
Given such results, the medical scientists concluded that berberine, “may serve as a new drug candidate in the treatment of type 2 diabetes.” They noted its low cost and relatively good safety profile compared to established drugs with similar effects. They also recommended new studies embracing a larger share of the diabetic patient population. (26)
In 2015, an analysis of scientific studies published in the Journal of Ethnopharmacology compared the effects of berberine on those with type 2 diabetes. Researchers looked at 27 randomized controlled clinical trials with a total of 2,569 patients participating. These were placebo studies. Some also compared results of berberine to placebos with and without exercise programs and other “lifestyle interventions.” Others compared berberine with oral drugs that lower blood sugar levels. (27)
The researchers concluded that berberine with lifestyle intervention was more effective at lowering blood glucose compared to lifestyle intervention alone with placebo. Berberine showed additional positive effects on blood sugar when combined with similar pharmaceutical drugs. Their conclusion was that berberine’s ability to lower blood sugar is as effective as conventional treatments. They also recommended berberine for those who can’t afford traditional pharmaceutical drugs while also calling for more studies to resolve remaining unanswered questions. (27)
Clinical Verdict: Berberine does appear to act as a natural alternative to glucose-lowering drugs like metformin, but remember: Always consult with your healthcare provider before treating any disease with nutrients. Healthcare providers have the testing resources and expertise to offer a proper clinical diagnosis. If you have a complex health condition or multiple illnesses, they are also better equipped to detect these things and advise you accordingly.
Berberine vs Metformin Side Effects
Metformin Side Effects
Common Side Effects
From Drugs.com: (1)
“Commonly reported side effects of metformin include: lactic acidosis, diarrhea, nausea, vomiting, and flatulence. Other side effects include: asthenia, and decreased vitamin B12 serum concentration.”
The same website recommends telling your doctor if you experience the above problems after taking metformin. Other common side effects to watch for include muscle cramps, painful urination, stomach pain or discomfort, fever, chills, sleepiness, and appetite loss.
Less Common Side Effects
Less common effects of metformin include cold sweats, anxiety, dizziness, blurry vision, fast or irregular heartbeat, headache, confusion, slurred speech, difficulty breathing, weakness, and a few others.
Recall that metformin can cause lactic acidosis. Extreme cases of lactic acidosis caused by metformin have caused dangerously low blood pressure, hypothermia, and death. Some extreme cases began with minor symptoms like “malaise, myalgia, respiratory distress, somnolence, and abdominal distress.” (1)
Metformin may be a bad idea if you have advanced cirrhosis of the liver because it can increase the risk of lactic acidosis. Both metformin and berberine may be OK, or even beneficial if you have other liver conditions, but you need to consult your doctor about this. (29)(30)
A 13-year study of the effects of long-term metformin use compared to a placebo, published in 2016, revealed vitamin B12 deficiency and anemia as common side effects. Those low in B12 had a higher likelihood of developing peripheral neuropathy. The dose was 850mg twice a day. Patients were enrolled in a diabetes program. (28)
In a 2015 study, medical scientists performed a multicenter, randomized, controlled, open-label phase II trial with blinded outcome assessment on stroke patients with impaired glucose intolerance. Regarding the study side effects, the researchers noted:
“That 19 patients were randomly assigned metformin and 9 patients in this group had side effects, mostly gastrointestinal, leading to the permanent discontinuation of4 patients after 3–10 weeks.” (31)
Berberine Side Effects
Berberine is widely revered as an alkaloid that lowers blood glucose levels significantly with relatively few side effects. It’s a natural alternative to metformin.
You may recall from the 2008 study mentioned above that some berberine patients taking 500mg three times a day experienced passing gas (19%), abdominal pains (3.4%), diarrhea (10.3%), and constipation (6.9%). However, these effects were only temporary. (26)
Another negative side effect of berberine is that if you are currently taking other substances that lower blood sugar levels, like metformin, the combination of the drugs may cause your blood sugar level to go too low. Therefore, make sure to consult your doctor if you think you might be in this category.
On the other hand, some medical scientists note that berberine can work synergistically with other substances that lower blood sugar, at least at specific dosages. However, don’t turn yourself into a human drug lab without proper medical supervision.
You also want to be cautious when taking berberine with herbs and drugs with blood-thinning properties, or if you have a history of overly low blood pressure. (32)
If you want to use berberine to treat a disease like diabetes, then you definitely will want to talk to your doctor first. Do this regardless of whether you currently use drugs, herbs, or extracts of any kind.
Please also consult your doctor if you are pregnant or breastfeeding and wish to supplement your nutritional intake with berberine. There is a possible link between berberine and brain damage in fetuses and other health risks in newborn babies. (32)
Berberine Dosage – How Much Should I Take?
Berberine is well absorbed by the body and also metabolized in the liver. This means that it’s absorbed and used by the body very quickly. After a few hours, routine blood tests will only detect very small amounts within the bloodstream. This means that you will need to take berberine after every meal to have a constant supply in your body. This is why studies involving people with diabetes often take a dosage of 500mg three times a day. But don’t take more than 500mg at any one time, as this can sometimes produce gastrointestinal side effects.
Make sure to choose a pure berberine supplement as well, as many brands are known to sell weaker complexes that will not be as effective.
How Long Does Berberine Take To Work?
You might notice consistently lower blood sugar levels after about one week of use, but this effect may not become apparent for three or four weeks.
The length of time required for berberine to show health benefits may vary according to the benefit you are seeking and the conditions within your body.
Where To Buy Berberine?
At Intelligent Labs, we have produced an ultra-pure berberine supplement in capsules which deliver a clinically recognized 500mg dosage. Our third-party lab testing consistently ensures the purity of the product and the accuracy of the labeling.
Berberine is a good natural substance for reducing blood sugar levels and increasing insulin cellular sensitivity with relatively few side effects. It has demonstrated quite a few numbers of positive health benefits outside of its anti-diabetic and cholesterol-lowering properties. This plant-based phytonutrient is touted in multiple scientific studies as a natural alternative to metformin and other drug substances that decrease blood sugar levels.
If you are interested in its many other health benefits, please read our other article on berberine biological properties.
This article is for educational purposes only and is not intended to be a substitute for sound medical advice from your doctor or clinical results from your medical lab. Diagnosis and treatment of a medical condition is the result of a subtle intellectual process conducted by a well-informed person, especially if you have multiple conditions or any medical condition that affects more than one system in the body. We don’t promise that berberine, or any other supplement, can treat or cure any of your diseases, but we do proudly offer credible information so that you can make informed decisions about your current health.
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