Metformin, Berberine, and the Power of AMPK

Metformin and berberine are two compounds that have shown beneficial effects in diabetes management and metabolism regulation, and both have a relationship with AMP-activated protein kinase (AMPK).

Introduction

It has become fashionable to take metformin for longevity because it is a drug that stimulates the anti-aging enzyme AMPK.

Metformin is so powerful that people with diabetes who take metformin live longer compared to people without diabetes.

But I would like to emphasize that there is a natural active ingredient (which is not a drug) that has similar effects, and this is Berberine.

I am going to provide you with a comparative summary of both products.

First I will talk about what it means to activate the AMPK (AMP activated protein kinase) pathway. This is an enzyme that plays a crucial role in regulating energy metabolism. Activating AMPK helps to:

1. Increase glucose uptake by muscle cells.
2. Reduce glucose production in the liver.
3. Improve insulin sensitivity.
4. Stimulate fatty acid oxidation.

AMPK has also been linked to longevity and resistance to cellular stress, earning it the nickname “anti-aging enzyme.”

Metformin

Metformin is a drug commonly used to treat type 2 diabetes. Its main mechanism of action is the activation of AMPK, which leads to a reduction in glucose production in the liver and an improvement in insulin sensitivity. By activating AMPK, metformin also promotes fatty acid oxidation and decreases lipid synthesis.

Berberine

Berberine is a natural compound found in various plants and has also been traditionally used in medicine. Like metformin, berberine activates AMPK. This activation contributes to improving insulin sensitivity, lowering blood glucose levels and regulating lipid metabolism. In addition, berberine has anti-inflammatory and antioxidant effects.

Effects on Longevity

Observational studies have suggested that people with diabetes who take metformin may have a life expectancy similar to or even longer than people without diabetes. A notable study published in 2014 in Diabetes, Obesity and Metabolism found that diabetic patients treated with metformin had higher survival compared to non-diabetics and diabetics treated with sulfonylureas.

Possible Longevity Mechanisms

Possible mechanisms through which AMPK activation might influence longevity include:

1. Reduction of oxidative stress: which would reduce cell damage.
2. Inflammation: Reducing chronic inflammation, a factor associated with many age-related diseases.
3. Mitochondrial function: Improve mitochondrial function and biogenesis, promoting more efficient energy metabolism.
4. Autophagy: Activating AMPK can induce autophagy, a cellular cleansing process that removes damaged and dysfunctional components, preventing the accumulation of cell damage that can lead to aging-related diseases.

Autophagy can help cells deal with oxidative stress, an important factor in aging and chronic disease, while the elimination of damaged mitochondria (mitophagy) is particularly crucial for maintaining mitochondrial function and reducing the production of reactive oxygen species (ROS). In other words, by activating autophagy (point 4) we would also improve other processes related to longevity.

Autophagy is crucial for removing misfolded proteins and protein aggregates, which are hallmarks of neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

What is Berberine?

It is a natural active ingredient extracted from the plant Berberis vulgaris or Berberis aristata , also commonly called barberry. This plant has a fruit that is called Barberries in English. They are similar to red fruits, and are even regularly sold dried as raisins and can be added to salads, although it is a little difficult to find them because in our country they are not as common as raisins.

Barberry is one of the plants that contains berberine and has had a long history in the Eastern and Western medical tradition. It has been used for 3000 years.

Berberine Studies

New experimental and animal studies have indicated the beneficial effects of this plant on blood pressure and lipid profiles, as well as its anti-inflammatory properties (Ebrahimi-Mamaghani et al., 2009)

Various parts of the plant are used in medicine, including the bark, root, rhizomes, stem, leaves, and fruit (Arayne et al., 2007).

Berberine can act as an activated protein kinase (AMPK) and can increase the ratio of AMP to ATP and inhibit ATP biosynthesis in the mitochondria.

Due to the multiple properties of the root and fruit of barberry to control the complications of diabetes, reducing and controlling lipid profiles and liver enzymes, and its evident antioxidant and anti-inflammatory properties, as well as its ability to influence the secretion of thyroid hormones. , so this plant can be considered as a candidate drug for the prevention and control of cardiovascular diseases, diabetes, thyroid disorders and liver diseases

This is a conclusion drawn from the publication Avicenna J Phytomed. 2015 November-December; 5(6): 485–497.

Summary of Metformin and Berberine Actions:

Metformin:

• Mechanism of Action: Metformin activates AMP-activated protein kinase (AMPK), which improves insulin sensitivity and reduces hepatic glucose production. It also promotes autophagy, a process crucial for cell renewal and longevity (Hone Health).
• Hypoglycemic Effects: Metformin is widely recognized for its ability to lower blood glucose levels, being a first-line treatment for type 2 diabetes (Ask Dr. Nandi | Official Site).
• Additional Benefits: Although metformin may improve the lipid profile and have a modest effect on blood pressure reduction, its main benefits focus on glycemic control (Hone Health) (Ask Dr. Nandi | Official Site).

Berberine:

• Mechanism of Action: Similar to metformin, berberine also activates AMPK, enhancing the oxidation of glucose and fatty acids, and reducing hepatic glucose production (BioMed Central) (Frontiers).
• Hypoglycemic Effects: Berberine significantly reduces fasting glucose, postprandial glucose, and HbA1c levels, comparable to traditional hypoglycemic medications. Its combination with OHAs enhances this effect (BioMed Central) (Frontiers) (JSTAGE).
• Additional Benefits: Berberine has more pronounced effects on lowering triglycerides and LDL cholesterol, and may increase HDL cholesterol. In addition, it has antihypertensive effects, anti-inflammatory properties, and benefits on the gut microbiome (Frontiers) (Hone Health).
• Clinical Studies: A recent trial showed that high-purity berberine administered at 500 mg three times daily for 12 weeks significantly improved glycemic control markers without noticeable adverse effects (BioMed Central).

Advantages or disadvantages of taking one or the other

Methotformin is a drug with many clinical studies in its use in metabolic syndrome. Berberine, although it has been used for thousands of years, has fewer studies at the clinical level because it is a natural product, which does not require a prescription.

In recent years, berberine is emerging as an attractive new agent in the treatment of metabolic syndrome, as it shares many characteristics with metformin. However, poor oral bioavailability may limit its application.

On the other hand, metformin can cause adverse gastrointestinal reactions and berberine its side effects are more tolerable and controllable (usually gastrointestinal upset). So in the event that you are refractory or intolerable to metformin, berberine can be used as an alternative agent or additive to increase tolerance and minimize side effects.

Consistent with this, a study in a six-month trial with 60 patients with T2DM randomly divided groups of berberine and metformin or metformin alone and better efficacy was observed in the combination treatment group.

It is postulated that the synergistic action of berberine and metformin is attributed to similar antidiabetic mechanisms despite the different transporters and metabolism. Therefore, the combination of these two products could allow the reduction of the dose of each of them at the individual level to solve problems such as the oral bioavailability of berberine and the side effects of each separately.

Conclusion

Both metformin and berberine activate AMPK, leading to improvements in glucose and lipid metabolism. This common pathway is critical for its antidiabetic effects and its potential in the treatment of metabolic conditions. Research continues to explore its mechanisms and potential benefits.