AMPK is a genetic master switch that controls our metabolism and is found in every cell of our body. Because metabolism is the essence of life, activating AMPK becomes critical to living a longer and healthier life.
We’ll give you a quick overview of AMPK, the benefits of activating it, and how you can naturally boost your levels to reap its benefits in this article.
Contents
1. What is AMP-Activated Protein Kinase (AMPK)
AMPK, which stands for adenosine monophosphate activated protein kinase, is an enzyme found in our cells that is essential for energy metabolism.
It detects the amount of energy (the number of ATP molecules) in a cell and helps regulate responses when it becomes too low or too high.
It is synthesized in a variety of tissues, including the liver, brain, fat cells, and muscle.
2. Metabolism and AMPK activation
The chemical reactions that occur in your cells to sustain life are referred to as your metabolism. Some of these reactions use stored energy to build things up, a process known as anabolism, whereas others break things down, releasing energy that can be stored for later use, a process known as catabolism.
Catabolism minus anabolism results in people’s body weight.
Catabolism is the breaking down of compounds to release energy.
Energy starts as ATP within cells and eventually breaks down into AMP.
ATP (Adenosine tri-phosphate) is an important molecule found in all living things. Think of it as the “energy currency” of the cell. If a cell needs to spend energy to accomplish a task, the ATP molecule splits off one of its three phosphates, becoming ADP (Adenosine di-phosphate) + phosphate. The energy holding that phosphate molecule is now released and available to do work for the cell.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4973318/
Normally, it’s up to here. But, when the cell needs even more energy(e.g. exercise, stress, hunger), and it splits off another phosphate, so it goes from ADP, adenoside di-phosphate, to AMP, adenosine mono-phosphate.
When the ratio of AMP in the body increases, that is when AMPK is activated to help restore balance to our cells. Although its primary role is in energy metabolism it is becoming more clear that AMPK has even more benefits at the cellular level.
3. 9 Health Effects of AMPK Activation
1) Supports Autophagy and Healthy Aging
Japanese cell biologist Yoshinori Ohsumi won the Nobel Prize in Medicine in 2016 for his research on how cells recycle and renew their content, a process called autophagy.
https://www.nobelprize.org/prizes/medicine/2016/ohsumi/facts/
Autophagy is the process of recycling cellular components. This process promotes molecular and cell subunit quality control by degrading damaged or misfolded proteins and even damaged mitochondria.
Certain animal studies conducted on worms, fruit flies and rodents have found evidence that AMPK signaling can support cellular renewal and activate autophagy.
As a 2015 article published in the journal Cell Metabolism puts it, “When energy supply is low, organisms respond by slowing aging and increasing resistance to diverse age-related pathologies.”
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4287273/
AMPK seems to help regulate processes that turn over destroyed cell organelles, damaged mitochondria and other degraded material in order to form new cells. In this way, AMPK helps the body age and deal with stress in a healthier way. Autophagy needs to be upscaled and increased as free radicals/oxidative stress take a toll on cells.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4973318/
“It is known that AMPK activity in muscle is ‘dialed down’ with aging in humans, so this may be an important cause of muscle loss during aging,” according to another study.
Researchers can now try to adapt exercise regimens and existing drugs to switch on AMPK in muscle more effectively now that they know AMP-activated protein kinase (AMPK) is essential for maintaining muscle mass with aging. The development of new selective AMPK pathway activators in muscle may also be effective in preventing muscle loss with aging.
https://doi.org/10.1016/j.cmet.2015.05.016
2) Improves Metabolic Pathways and Insulin Sensitivity
AMP-activated protein kinase is a key regulator of lipid and glucose metabolism in the cell.
AMPK activation promotes glucose uptake and utilization in order to maintain blood sugar homeostasis. Simultaneously, it reduces glycogen synthesis. Signaling pathways can increase glucose uptake within muscles, ensuring that they have a constant source of fuel. AMP-activated protein kinase also promotes the breakdown of glucose for energy, resulting in the formation of more ATP.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3696539/
If hypothalamic AMPK detects a lack of cellular energy, it can increase glucose production. Glucose is the body’s preferred energy source. The brain makes extensive use of it. Adenosine 5′ monophosphate-activated protein kinase can help prevent hypoglycemia, or low blood sugar levels. Symptoms of hypoglycemia include dizziness, weakness, headaches, and fainting.
3) Supports fat burning
AMPK outside of the brain increases fat burning, and this pathway can result in weight loss.
AMPK can alter hunger and satiety, as well as how cells use and store energy. Under certain conditions, adenosine 5′ monophosphate-activated protein kinase may help stimulate fat-burning and weight loss, according to research. It increases the amount of energy spent on physical activity by assisting muscles in using more glucose for energy. Homeostasis, which is influenced in part by AMPK activation, can result in increased body temperature, decreased inflammation, and improved hormone balance. All of these things contribute to your ability to maintain a healthy weight.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2658714/
4) Decreases Inflammation
This enzyme may have anti-inflammatory properties. It has been shown to increase antioxidant activity, thereby strengthening defenses against factors that speed up aging, such as poor diet, chemical/toxin exposure, and chronic stress. According to research, adenosine 5′ monophosphate-activated protein kinase increases the production of antioxidant proteins such as NRF2 and superoxide dismutase.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4936058/
For a variety of reasons, AMPK signaling may also aid in the prevention of chronic inflammatory diseases such as cardiovascular disease and diabetes. It can aid in the reduction of fatty acid, cholesterol, triglyceride, and protein production. It participates in fatty acid catabolism and inhibits fatty acid synthesis. This has the potential to improve metabolic and cardiovascular health.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3494254/
5) Helps with Hormone Production and Fertility
AMPK stimulates the production of sex hormones in a variety of animal species.
The production of reproductive hormones and fertility are highly dependent on energy status. For example, when the body is underfed, overstressed, or overexerted, sex hormone production (such as estrogen, testosterone, and progesterone) is reduced. This causes problems such as irregular periods, infertility, mood swings, sexual dysfunction, and more. Hormonal balance is easier to achieve when adenosine 5′ monophosphate-activated protein kinase detects that the body is well-nourished and safe.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4500899/
6) Can Improve Physical Performance
AMPK increases glucose uptake and fatty acid oxidation during exercise. It also regulates energy usage by promoting mitochondrial activity. This is essential for maintaining a healthy metabolism and fueling your muscles.
Certain AMPK-activating substances have even been banned by The World Anti-Doping Agency due to their potential performance-enhancing effects (WADA). WADA, for example, has banned the AMPK activator AICAR.
https://pubmed.ncbi.nlm.nih.gov/28407446/
7) Helps With Oxygen Delivery
AMPK activation may protect against acute breathing instability during hypoxia (low oxygen) at altitude or during sleep. In mice, AMPK deficiency causes breathing dysfunction during hypoxia.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5003690/
Variations in AMPK gene components have been discovered in high-altitude Andean populations, presumably to improve survival in low-oxygen environments.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4166715/
8) Increases Blood Flow
By stimulating nitric oxide release in blood vessels, AMPK plays a critical role in increasing blood flow via vasodilation (blood vessel widening).
https://pubmed.ncbi.nlm.nih.gov/25869500/
9) Benefits the Heart
AMPK activation is also beneficial in the prevention of cardiovascular disease.
https://pubmed.ncbi.nlm.nih.gov/27815596/
4. Best AMPK Activators
1) Exercise, Especially High-Intensity Exercise
AMPK pathways have been shown to be activated by vigorous, high-intensity exercise. Simultaneously, adenosine 5′ monophosphate-activated protein kinase can improve exercise performance. AMPK and exercise influence each other in a variety of ways. Nitric oxide, for example, activates AMPK. Exercise promotes the health of your endothelial cells and blood vessels by increasing your body’s production of nitric oxide.
https://pubmed.ncbi.nlm.nih.gov/12941758/
2) Calorie Restriction/Fasting
Fasting (16~18 hours, minimum 12 hours) and calorie restriction are two of the most effective ways to increase AMPK signaling. Adiponectin is a hormone secreted by fat cells to indicate a low energy status. As a result, adenosine 5′ monophosphate-activated protein kinase levels rise. Overeating based on energy requirements, on the other hand, inhibits AMPK activity. Adenosine 5′ monophosphate-activated protein kinase is decreased by high glucose consumption, elevated insulin levels, high blood sugar levels, high amino acid levels, and high saturated fat intake.
3) High-Antioxidant Foods
What about when you’re not fasting? What are the best AMPK activator foods? Studies show that high-antioxidant foods, especially those with polyphenols, help activate adenosine 5′ monophosphate-activated protein kinase. Polyphenols can lower lipids by activating AMPK. They benefit those at risk for hyperlipidemia, atherosclerosis and diabetes. Through AMPK activation, animal/insect studies show that polyphenols can regulate autophagy, decrease bacterial proliferation and increase life span.
https://pubmed.ncbi.nlm.nih.gov/16873680/
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005034
High-antioxidant, high-polyphenol foods include:
- Fresh vegetables like leafy greens, broccoli, artichokes and green beans
- Green tea and other teas
- Coffee
- Cocoa
- Berries, like blueberries, blackberries, raspberries, bilberries, etc.
- Grapes
- Olive oil
- Pomegranate
- Apples
- Red wine
- Onions
- Herbs and spices like cinnamon, turmeric, etc.
- Nuts like pecans
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5343824/
4) Certain Supplements
Which AMPK activator supplements and medications are the most effective? Metformin is one of the most extensively studied AMPK activators. Metformin is a prescription diabetes medication used to treat type 2 diabetes.
Metformin activates adenosine 5′ monophosphate-activated protein kinase in what way? Metformin has been shown in studies to activate AMPK in liver cells (hepatocytes). This stimulates fatty acid oxidation, suppresses lipogenic enzymes, stimulates fat burning, and increases glucose uptake. In other words, metformin fights diabetes and fatty liver disease by lowering fat production and glucose production in the liver. (16) Aspirin can also increase AMPK activity and the breakdown of fatty acids.
Certain herbs and botanical blends are also used to increase AMPK activity. However, little is known about how these work. A variety of AMPK activator formulas are now available as supplements over the counter. Despite this, there have been limited trials that show they work and are safe to use in the long term when used in combination.
The FDA has not approved these supplements for medical use, and there is a general lack of solid clinical research. Regulations establish manufacturing standards but do not guarantee their safety or effectiveness. Before beginning any supplementation program, consult with your doctor.
Nonetheless, numerous polyphenols have been found in cell and animal studies to activate AMPK. The top three ingredients with the most research results are as follows.
- Alpha lipoic acid is an antioxidant that improves insulin sensitivity.
- Red grape Resveratrol
- Berberine may have anti-diabetic/hypoglycemic effects and aid in the treatment of PCOS.
Introducing Exipure
5) Exposure to Very Cold Temps
Brown adipose tissue (Brown fat) contains AMPK. This fat is involved in the regulation of metabolic state and body temperature. Chronic cold exposure (more than seven days) was shown in animal studies to cause a progressive increase in brown adipose tissue AMPK activity.
https://pubmed.ncbi.nlm.nih.gov/17272339/
While it’s unlikely that people would expose themselves to uncomfortably cold temperatures for seven days or more in order to boost AMPK, some believe cryotherapy can have similar effects. Cryotherapy is a cold-exposure technique that uses liquid nitrogen or argon gas to reduce inflammation, relieve pain, and aid in the recovery process after exercise.
5. AMPK Activator Side Effects
What are the potential consequences of AMPK activation? There is still much to learn about how AMPK signaling may influence the risk of certain diseases like neurological disorders and cancer. Overall, studies yielded conflicting results. According to some, increased AMPK may increase the risk of certain conditions. Others show that it may reduce the risk.
If you decide to try any AMPK activator supplements, you should proceed with caution because the quality of supplements is not tightly regulated or controlled. To be on the safe side, review the side effect profile of each supplement you take to identify any potential negative effects.
More research is required to determine how various supplement combinations affect energy balance. Until we have more information, make sure to buy quality products from reputable manufacturers and carefully follow dosage instructions. If you take medication to treat a chronic health problem, you should also consult your doctor before starting any new supplement.
