Berberine and Metformin for Longevity

14 September 2018 (1 August 2018)
Connie Packer


Aging and shortening of life are associated with the body’s decreasing ability to refresh and repair itself over time. As the human body ages, there is decreased rebuilding of structure such as bone and muscle, decreased turnover of cellular contents (autophagy), and decreased suppression of oxidation. By maintaining the body’s ability to repair itself, life may be extended.

There are various ways to support the body's repair function and adopt a longevity lifestyle, including changes to exercise and diet. According to anti-aging research, two geroprotectors that may support the body's repair function are the supplement berberine and the drug metformin.


Berberine is a compound found in various plants such as the barberry shrub. Berberine supplementation has been shown to support healthy blood sugar. And it has also been observed to support healthy cardiovascular function.

Berberine reviews typically note that the compound may not be well absorbed when taken as an oral supplement. And that may contribute to berberine side effects related to gastrointestinal discomfort. Studies are being done to improve absorption. Methods to increase absorption may include encapsulation in nanotubes, using an additive such as milk thistle to inhibit the cellular transporter P-glycoprotein, and developing more water soluble derivatives that still maintain its functionality.

Is berberine anti-aging? Berberine has been associated with increased lifespan in flies, potentially by slowing a metabolic pathway that causes inflammation and increasing activity of the AMPK enzyme. And that has motivated researchers to explore the use of berberine to combat aging in humans.


Metformin is a compound originally derived from French lilac. The most common metformin uses are related to blood glucose control, therefore most of the human research on metformin includes participants with type 2 diabetes. At least part of its effect is credited to its influence on increasing the activity of the AMPK enzyme. The most common metformin side effects are gastrointestinal, including abdominal discomfort, lack of appetite, bloating, and diarrhea.

Is metformin anti-aging? Researchers have observed that metformin treatment has potentially decreased mortality in people with type 2 diabetes. Metformin has been shown to improve healthspan and lifespan in mice. And a metformin aging clinical trial, the TAME study (Targeting Aging with Metformin), is testing the potential to extend healthy years of life for humans.

Comparing Berberine vs Metformin

Berberine and metformin may both support healthy blood sugar, and more similarities can be found when looking at cellular level effects.

Both compounds appear to increase AMPK activity. The AMPK enzyme is biologically stimulated when there is a deficit of energy, like during fasting or exercise. By stimulating AMPK, the cell works to increase its access to energy, by facilitating glucose and fatty acid uptake from the blood, increasing fat and glycogen breakdown, and inhibiting both glucose and fat storage. AMPK acts by directly phosphorylating enzymes for a more immediate effect, and also by phosphorylating the transcription factors of enzymes, giving it a longer lasting effect. Both berberine and metformin increase the cellular uptake of energy compounds and break down energy storage.

In addition to stimulating AMPK activity, glucose consumption is increased by influencing the electron transport chain. Metformin and berberine can each inhibit complex 1 of the electron transport chain. By doing so, the process becomes less efficient at producing ATP, thereby wasting energy and potentially mimicking a restricted calorie diet.

Side-by-side comparative research on their mechanisms of action is limited, but it appears that the different compounds have different areas of influence. Berberine has been shown to decrease total cholesterol and LDL cholesterol while metformin has been shown to decrease fatty acids, triglyceride, and LDL cholesterol.

Can you take berberine and metformin together? They may actually complement each other. For example, when using berberine with metformin, berberine may support healthy levels of lactic acid -- at least it helped in mice, when using berberine and metformin together.

In summary, reviewing berberine compared to metformin, we can observe that the two compounds vary in structure and have different points of action, which results in some variability, but they share some general effects. And given that berberine and metformin affect some of the same metabolic pathways, it may be worthwhile to include both in studies related to human longevity.

Using Berberine and Metformin

Although more research is required to confirm the extent to which berberine and metformin may contribute to healthy life extension, they appear to be among the most promising geroprotectors presently available.

Metformin is a pharmaceutical that requires a prescription in the United States. If you're interested in using it, talk with your doctor.

Berberine supplements are readily available on the market without a prescription. When selecting a berberine supplement, look for one that incorporates a method to increase absorption, and buy it from a company that responsibly seeks out quality suppliers.

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