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18. Doctor's Note: Should People without Diabetes Take Metformin for Longevity and Neuroprotection

Updated: Jun 27, 2023

Author: Ting ZHOU, MD, Endocrinologist, Peking Union Medical College Hospital, China


As everyone knows, metformin is a very common medication for diabetes patients. As long as there are no specific contraindications, such as impaired liver or kidney function or severe gastrointestinal reactions, it is generally considered the first-line treatment for type 2 diabetes.

Metformin is an old drug that has been used for over 60 years and is still in clinical use, which also indicates its safety. With increased experience in its use and further research, in recent years, besides its blood sugar-lowering effect, other benefits for individuals have been discovered. Today, I would like to share these findings with you for your reference.



1. Anti-aging effects of metformin As we age, various tissues and organs in the human body undergo aging, which is irreversible. In a certain sense, some chronic diseases, including diabetes, are closely related to aging. Previously, type 2 diabetes patients were generally older, and their pancreatic beta-cell function decline was also associated with aging. However, due to unhealthy lifestyles accelerating this process, it is now observed that many younger individuals are affected by type 2 diabetes, although older adults still constitute the majority. In fact, the causes of human aging are very complex, and one of the reasons is related to AMPK (AMP-activated protein kinase). AMPK is a protein kinase that plays a crucial role in cellular energy metabolism. With age increasing, AMPK activity gradually decreases. AMPK is present in various cells, especially in the brain, muscles, liver, and fat cells. It typically detects the level of energy metabolism within cells and responds accordingly. When activated, AMPK promotes fat breakdown and fatty acid oxidation, generating ATP to provide energy for cells. Cellular aging is associated with cellular energy metabolism, and as cells age, energy metabolism levels decrease. Current research has found that metformin can enhance AMPK activity, increase cellular stress defense capabilities, improve cellular self-renewal through autophagy, and also improve insulin sensitivity and reduce inflammation, thereby achieving an anti-aging effect. Animal experiments have demonstrated that nematodes treated with metformin exhibit higher AMPK activity and about a 20% increase in lifespan compared to the untreated control group. In addition to pharmaceutical interventions affecting AMPK activity, we can also promote it through exercise, especially strength training and resistance exercise. Furthermore, research has found that mild fasting can also promote AMPK activity. It has also been discovered that metformin can prevent DNA glycation and mitochondrial dysfunction, promote DNA repair, and similarly slow down aging. In fact, certain studies have even shown that some diabetic patients taking metformin have longer lifespans compared to healthy individuals without diabetes.


2. Protective effects of metformin on the central nervous system

In recent literature, there have been many reports suggesting the potential role of metformin in preventing neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The possible reasons for this are mainly focused on metformin's ability to activate AMPK. One of the main functions of AMPK activation is the clearance of accumulated misfolded proteins in brain cells, and the accumulation of proteins (such as β-amyloid) leads to brain cell death and neurodegenerative diseases. Many animal and laboratory studies have shown that metformin has a delaying effect on such diseases. These studies indicate that metformin reduces the levels of enzymes that produce β-amyloid, reduces the harmful effects of β-amyloid on brain cell function, and decreases the levels of alpha-synuclein. In 2016, a human study showed that taking 1000 mg of metformin twice a day for 12 months improved the memory of a group of elderly individuals with mild cognitive impairment, which is considered a precursor to Alzheimer's disease. Some researchers refer to Alzheimer's disease as type 3 diabetes, although this has not yet been internationally recognized.

Whether metformin will become the next "wonder drug" remains uncertain, but it does indeed have beneficial effects on many diseases. However, like any medication, metformin also has some side effects. The most common are gastrointestinal reactions, where some patients may experience nausea, vomiting, abdominal pain, and diarrhea, and some may experience weight loss. For overweight patients, this can be seen as a positive aspect, and in most cases, gastrointestinal reactions gradually become tolerable over time. Secondly, metformin can interfere with the absorption of vitamin B12, increasing the risk of vitamin B12 deficiency. Decreased levels of vitamin B12 can lead to elevated homocysteine levels, which can worsen cardiovascular and cerebrovascular damage. Individuals using metformin should actively supplement with vitamin B12, at least 300 micrograms of methylcobalamin per day, and monitor their homocysteine levels. In rare cases, metformin may potentially cause lactic acidosis, especially in patients with impaired liver or kidney function.



Although metformin has certain effects in anti-aging, neuroprotection, anti-inflammatory, and antioxidant aspects, the evidence from large-scale evidence-based medicine is not sufficient, and more evidence needs to be obtained. In clinical practice, indications should be well understood, and side effects should not be overlooked. In fact, there is still a long way to go in understanding the human body and diseases.



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