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AMPK Activators: Everything you need to know, definition, Pathways, Benefits, and List of Natural AMPK activators

AMPK Activator for longevity

We can’t avoid the aging process, but we can impact to slow it down in a healthy way. However, slowing down aging or having a healthy way to achieve that is the key to being healthy overall. According to many scientists and many types of research done, several pathways can help us prolongs health and lifespan. AMPK is one of the best ways to maximize longevity, by restoring the energy to the cells. AMPK regulates the activities of many important metabolic enzymes. It protects cells from the stress that causes ATP depletion by shutting down ATP-consuming biosynthetic pathways. The AMPK is known to improve healthy aging.

What is AMPK?

AMPK stands for 5′ AMP-activated protein kinase or 5′ adenosine monophosphate-activated protein kinase. As the name suggests, it is regulated by AMP (adenosine monophosphate), i.e. the AMP: ATP ratio. This means that when this ratio increases, AMPK becomes activated. Because it is activated by AMP it is considered as an “energy sensor” to the cells, meaning when there is a lack of energy in the cells for completing their job, AMPK is activated to restore that energy. AMPK is an enzyme that has a crucial role in homeostasis, energy metabolism and has been used as a therapeutic target for many metabolic diseases such as cancer, Alzheimer’s, and age-related conditions.


AMPK and mTOR are discovered to be involved in having healthy aging and longevity. mTOR is the mammalian target of rapamycin. It is also called a master controller of protein synthesis. When mTOR is high it promotes cell growth, which can also lead to stimulating cancer cell growth. When is low, it can maintain the body in balance and cause autophagy as well. Autophagy is a process that removes and recycles damaged cells within the body to form new and healthy tissues. This process helps in slowing down aging. Therefore, the main goal is to keep mTOR low.

The AMPK and mTOR pathways interact with each other by complex mechanisms. Besides amino acids and IGF-1 (insulin-like growth factor 1), mTOR is activated by AMPK too. mTORC1 is a protein complex in mammals that is sensitive to rapamycin. AMPK tends to inhibit the activation of mTORC1 by rapid and direct phosphorylation of two proteins. By suppressing this protein complex, it regulates cell growth.

AMPK pathway

AMPK is involved in cell metabolism, energy metabolism, autophagy, and cell growth. AMPK pathway promotes ATP production, so when cellular stress occurs, which inhibits ATP production, the AMP:ATP ratio is changed, and the AMPK pathway is activated. Due to its role in energy regulation, the AMPK pathway takes place as a potential therapeutic solution for metabolic syndrome, diabetes type 2, and obesity.

AMPK activator

One way to activate AMPK is by high levels of AMP and ADP in the cells. When lots of ATP molecules are converted into AMP molecules, AMPK activation occurs. AMPK is also activated by low glucose levels, increased levels of intracellular Ca2+, and DNA damage. Certain pharmaceutical drugs can activate AMPK, such as metformin, which we will discuss further. Natural food, vegetables, fruit, including food rich in omega3s can help in AMPK activation.

AMPK weight loss

Activated AMPK will help you to lose weight by burning fat. AMPK promotes a healthy life, by losing weight more effectively which in return protects you from developing serious diseases in the future such as diabetes type 2, heart disease, and many other health and age-related conditions. When AMPK is activated, it improves insulin sensitivity to the cells and helps to utilize glucose as a fuel. You can naturally stimulate AMPK by diet and exercise. Low carbs levels and fasting are some of the ways to increase AMPK activation. In both diets, there is reduced glucose intake, which directly impacts weight loss. The absence of glucose triggers the AMPK activation.

Metformin AMPK

Metformin is known to extend lifespan in mice and fight aging. Besides natural ways and food, taking pharmaceutical drugs like metformin can help you in AMPK activation. Metformine is a drug used worldwide in the treatment of diabetes type 2. However, metformin is a low-potency drug used in high doses with modest efficiency. AMPK can help to improve the beneficial effects of metformin. Metformine promotes AMPK activation in the liver by inhibiting gluconeogenesis, leading to decreased glucose production.

Berberine AMPK

Berberine is the best natural compound to support sugar blood health. Activation of AMPK improves the beneficial effects of berberine in controlling diabetes, insulin, and sugar levels. Berberine lowers triglycerides and cholesterol levels in the blood and improves the LDL and HDL cholesterol ratio. In the liver, it activates the AMPK and affects the genes that are responsible for energy metabolism. This helps in non-alcoholic fatty liver disease and improves your overall health.

AMPK activator foods and the strongest AMPK activator

Many vegetables and fruit can activate AMPK. Food rich in omega3s, like fish oil ad fish, can activate AMPK by reducing inflammation in the body. Polyphenols can also stimulate the activation of AMPK. They are antioxidants, found in many vegetables and fruit. Other food that activates AMPK, include green tea, berries, nuts, cocoa, grapes, pomegranate, red wine, onions, grapefruit, garlic, peppers, curcumin, and many others.

Due to the many trials that are done, metformin happens to be the strongest AMPK activator with strong effects and high oral bioavailability.

Mechanism of action

AMP, LKB1, and exercising are great ways to activate AMPK. AMPK inhibits mTOR, which actually phosphorylates and inactivates it. By this process, it inhibits protein synthesis. Another thing that AMPK does is activate ULK1, a protein involved in autophagy. By activation of this protein, AMPK stimulates the autophagy pathway. Furthermore, AMPK activates ATGL, which stands for adipose triglyceride lipase, involved in fatty acid catabolism. Additionally, AMPL inhibits ACC and HMG-CoA, which means it inhibits fatty acids synthesis and cholesterol synthesis respectively.

AMPK activators list

Some of the indirect AMPK activators include metformin, Thiazolidinediones, polyphenols, α-lipoic acid, ginsenoside, and so on. Direct AMPK activators include 5-Aminoimidazole-4-carboxamide riboside, salicylate, PT-1, compound-13, benzimidazole, MT 63–78, and others.

Natural AMPK activator

You can activate AMPK by natural AMPK activators such as resveratrol, cerberine, berberine, curcumin, salvianolic acid B., crocin, naringenin, ginsenosides, quercetin, and so on.

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