Adenosine 5′ monophosphate-activated protein kinase (AMPK) is an enzyme that is known as the body’s “master regulator of energy metabolism.” Why? It works as an energy sensor within our cells. Researchers believe that as we age, AMPK activity significantly decreases. This is one reason why we experience changes in appetite, body weight, energy levels, etc.
Energy depletion (or a lack of cellular energy) is really what stimulates AMPK activity. This causes more of the protein activated protein kinase (AMP) to be produced. That means some of the best AMPK activators are things we think of as beneficial “stressors.” These include calorie restriction, fasting and intense exercise.
Recently, some companies have released “AMPK activator” supplements that claim to have anti-aging effects. Certain supplements might help activate adenosine 5′ monophosphate-activated protein kinase pathways, but limited research is available right now to prove that most supplements are effective.
We do know, however, that natural AMPK activators can offer many benefits. These benefits include reducing inflammation, improving metabolic pathways and supporting healthy aging.
What Is AMPK?
AMPK stands for “adenosine 5′ monophosphate-activated protein kinase.” It is an enzyme present in all living beings that plays an important role in energy balance.
It helps determine your body’s balance between energy consumption and production. The body balances production of AMP by sensing its current AMP to adenosine triphosphate (ATP) ratio. ATP molecules are those that act as a source of fuel within cells. (1) Energy starts as ATP within cells and eventually breaks down into AMP.
Based on your current levels of AMP and ATP, energy production and usage can be altered. This takes place via changes in your appetite, body temperature, desire for physical activity (your energy expenditure), hormone production and other processes.
Where is AMPK found? It is stored throughout tissues in the body, especially those in the brain (including the hypothalamus), liver, fat cells and skeletal muscles. Adenosine 5′ monophosphate-activated protein kinase is influenced by a number of factors, including your genetics, age, diet, sleep patterns, stress levels and exercise habits.
- Regulates Energy Usage and Maintains Homeostasis
- Supports Weight Loss
- Decreases Inflammation
- Improves Metabolic Pathways and Insulin Sensitivity
- Can Improve Physical Performance
- Supports Autophagy and Healthy Aging
- Helps with Hormone Production and Fertility
1. Regulates Energy Usage and Maintains Homeostasis
One of the most important functions of AMPK is regulating energy balance and metabolism. It does this by monitoring cellular energy.
The part of your brain called the hypothalamus is considered your “command center” when it comes to your metabolism. The hypothalamus is a region of the forebrain that coordinates both the autonomic nervous system and the activity of the pituitary gland. It helps maintain homeostasis by controlling energy output, body temperature, thirst, hunger, sleep, emotional activity, hormone production and other bodily activities. (2) Hypothalamic AMPK restores energy balance by making you want to eat more in order to increase energy intake.
To sum up a complex process, when your hypothalamus senses that energy levels are low, adenosine 5′ monophosphate-activated protein kinase is stimulated. Energy expenditure is decreased while appetite is increased since this helps you acquire more energy in the form of calories and use less on energy output. When cellular energy is high, the opposite typically happens. Your body responds by decreasing your appetite and increasing energy expenditure. This can include increased fidgeting, body temperature and sweating associated with movement.
Ghrelin, one of our primary “hunger hormones,” is shown to stimulate AMPK in the hypothalamus. (3) On the other hand, inhibition of adenosine 5′ monophosphate-activated protein kinase in the hypothalamus leads to suppressed appetite. While ghrelin causes increased AMPK in the brain, it inhibits it in fat tissue and the liver.
2. Supports Weight Loss
AMPK can cause changes in hunger and satiety, as well as impact how cells use and store energy.
Studies suggest that adenosine 5′ monophosphate-activated protein kinase can help stimulate fat-burning and weight loss under certain conditions. It helps muscles use more glucose for energy, controls appetite and increases the amount of energy spent on physical activity. Homeostasis controlled in part by AMPK activation can also lead to increased body temperature, reduced inflammation and improved hormone balance. All of those help you maintain a healthy weight. (4)
This works in the opposite direction as well. For example, adenosine 5′ monophosphate-activated protein kinase is tied to adequate thyroid hormone production. When T3 thyroid hormone production is increased, AMPK is activated in muscles.
3. Decreases Inflammation
This enzyme has anti-inflammatory potential. It is shown to promote antioxidant activity, building defenses against factors that accelerate aging, such as a poor diet, chemical/toxin exposure and chronic stress. Studies show that adenosine 5′ monophosphate-activated protein kinase increases the production of certain antioxidant proteins, including NRF2 and superoxide dismutase. (5)
AMPK signaling may also help prevent chronic conditions tied to inflammation, such as cardiovascular disease and diabetes, for several reasons. It can help decrease production of fatty acids, cholesterol, triglycerides and proteins. It’s involved in fatty acid catabolism and stops fatty acid synthesis. This can have positive effects on metabolic/heart health. (6)
4. Improves Metabolic Pathways and Insulin Sensitivity
AMP-activated protein kinase is a major cellular regulator of lipid and glucose metabolism.
In order to maintain homeostasis of blood sugar levels, AMPK activation promotes glucose uptake and utilization. At the same time, it decreases glycogen synthesis. Signaling pathways can increase glucose uptake within muscles so they continue to have a source of fuel. AMP-activated protein kinase also stimulates the breakdown of glucose for energy in order to form more ATP. (7)
Hypothalamic AMPK is capable of increasing glucose production if it senses that cellular energy is low. Glucose is the body’s preferred source of energy. It is used in high quantities by the brain. Adenosine 5′ monophosphate-activated protein kinase can help prevent below-normal blood sugar levels, also called hypoglycemia. Hypoglycemia symptoms include dizziness, weakness, headaches, and fainting.
5. Can Improve Physical Performance
During exercise, AMPK increases glucose uptake and fatty acid oxidation. Another way it regulates energy usage is by supporting mitochondrial activity. This is important for keeping your metabolism high and your muscles fueled.
Due to its potential performance-enhancing effects, certain AMPK-activating substances have even been banned by The World Anti-Doping Agency (WADA). For example, the AMPK activator AICAR is banned by WADA. (8)
6. Supports Autophagy and Healthy Aging
Certain animal studies conducted on worms, fruit flies and rodents have found evidence that AMPK signaling can support cellular renewal and activate autophagy. Autophagy is a physiological process in the body that deals with destruction of cells. 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.” (9)
Adenosine 5′ monophosphate-activated protein kinase 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.
7. Helps with Hormone Production and Fertility
Reproductive hormone production and fertility are highly dependent on energy status. For example, when it’s sensed that the body is being under-fed, over-stressed and and overexerted, sex hormone production (such as estrogen, testosterone and progesterone) is decreased. This leads to issues like irregular periods, infertility, mood changes, sexual dysfunction and more. When adenosine 5′ monophosphate-activated protein kinase senses that the body is nourished and safe, hormonal balance is easier to achieve. (10)
5 Best AMPK Activators
What do AMPK activators do? AMPK activators essentially increase catabolism while decreasing anabolism. Catabolism is the breakdown of complex molecules into simpler ones that helps more energy to be released. Anabolism is the opposite: the synthesis of complex molecules from simpler ones, which increases energy storage. AMPK activators basically work by helping the body utilize nutrients to make more ATP (energy) right away but decrease energy storage to be used at a later time.
The body activates adenosine 5′ monophosphate-activated protein kinase signaling when it’s faced with physical stressors, an increase in stress hormones like cortisol and increased reactive oxidative species. Below is a list of the best AMPK activators.
1. Exercise, Especially High-Intensity Exercise
Vigorous, high-intensity exercise is shown to activate AMPK pathways. At the same time adenosine 5′ monophosphate-activated protein kinase can help with exercise performance. There are a number of ways that AMPK and exercise affect one another. For example, nitric oxide activates AMPK. Exercise keeps your endothelial cells and blood vessels healthy by increasing your body’s production of nitric oxide. (11)
2. Calorie Restriction/Fasting
Calorie restriction and fasting are two of the most powerful ways to boost AMPK signaling. Adiponectin is secreted from fat cells to signal low energy status. This results in increased adenosine 5′ monophosphate-activated protein kinase. On the other hand, overeating based on one’s energy requirements leads to inhibition of AMPK activity. High glucose consumption, elevated insulin levels, high blood sugar levels, high levels of amino acids and high saturated fat intake all decrease adenosine 5′ monophosphate-activated protein kinase. (12)
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. (13) Through AMPK activation, animal/insect studies show that polyphenols can regulate autophagy, decrease bacterial proliferation and increase life span. (14)
High-antioxidant, high-polyphenol foods include: (15)
- fresh vegetables like leafy greens, broccoli, artichokes and green beans
- green tea and other teas
- berries, like blueberries, blackberries, raspberries, bilberries, etc.
- olive oil
- red wine
- herbs and spices like cinnamon, turmeric, etc.
- Nuts like pecans
4. Certain Supplements
What are the best AMPK activator supplements and medications? One of the most researched AMPK activators is metformin. Metformin is a prescription antidiabetic drug used to manage type 2 diabetes.
How does metformin activate adenosine 5′ monophosphate-activated protein kinase? Studies show that metformin activates AMPK in liver cells (hepatocytes). This causes fatty acid oxidation to be induced, lipogenic enzymes to be suppressed, fat burning to be stimulated and glucose uptake to be increased. In other words, metformin basically works to fight diabetes and fatty liver conditions by decreasing fat production and liver glucose production. (16) Aspirin can also cause increased AMPK activity and fatty acid breakdown.
AICAR is another product, known as an “exercise pill,” that naturally activates AMPK. It has been shown to improve exercise performance in various mammals, including humans and racehorses. (17) As of 2011, AICAR officially is considered a banned substance in the World Anti-Doping Code.
Additionally, certain herbs and botanical blends are used to boost AMPK. However, less is known about how exactly these work. A number of AMPK activator formulas are now available to purchase over the counter as supplements. Yet there are limited trials showing that they work and are safe to used in the long term when used in combination.
AMPK activator supplements can include: (18)
- Alpha lipoic acid — an antioxidant that increase insulin sensitivity
- Polyphenol antioxidants, such as resveratrol, anthocyanins, quercetin, EGCG, genistein and curcumin found in things like green tea, blueberries, grapes, soybeans, vegetables and turmeric
- Berberine — may have anti-diabetic/hypoglycemic effects and help to treat PCOS
- Burdock — may help lower blood glucose levels and improve metabolism
- Red sage
- Omega-3 fish oil
- Apple cider vinegar
- Adaptogen herbs, such as astralagus and rhodiola
- Medicinal mushrooms, such as reishi mushroom and cordyceps
5. Exposure to Very Cold Temps
AMPK is present in brown adipose (fat) tissue. This fat plays a role in regulating metabolic state and body temperature. In animal studies, chronic cold exposure (more than seven days) was shown to cause a progressive increase in brown adipose tissue AMPK activity. (19)
While it’s pretty unrealistic that people would expose themselves to seven days or more of uncomfortably cold temperatures to boost AMPK, some believe that cryotherapy can have similar effects. (20) Cryotherapy is a cold-exposure technique that uses liquid nitrogen or argon gas to reduce inflammation, ease pain and help with exercise recovery.
AMPK Activator Side Effects
What are possible side effects of AMPK activation? There’s still more to learn about how AMPK signaling might affect the risk for certain diseases, such as neurological disorders and cancer. Overall, studies show mixed results. Some indicate that increased AMPK may raise the risk for some conditions. Others show it might reduce the risk.
It’s important to use caution if you choose to try any AMPK activator supplements, since the quality of supplements is not tightly regulated or controlled. To be safe, look at the side effect profile of each supplement you take to determine any potential negative effects.
More research is needed to show how different supplement combinations affect energy balance. Until we have more information, be sure to purchase quality products from reputable manufacturers and follow dosage directions carefully. You should also speak with your doctor before beginning to take any new supplement if you take medication to treat a chronic health problem.
- AMPK stands for “adenosine 5′ monophosphate-activated protein kinase.” It is an enzyme that plays an important role in energy balance.
- This enzyme helps determine your balance between energy production and consumption.
- Adenosine 5′ monophosphate-activated protein kinase is stored throughout tissues in the body, especially the brain (including the hypothalamus), liver, fat cells and skeletal muscles. It is influenced by a number of factors, including your genetics, age, diet, sleep patterns, stress levels and exercise habits.
- Adenosine 5′ monophosphate-activated protein kinase can help regulate energy usage, maintain homeostasis, support weight loss, decrease inflammation, improve metabolic pathways and insulin sensitivity, aid physical performance, support autophagy and healthy aging, and help with hormone production and fertility.
- The best AMPK activators are intense exercise, fasting/calorie restriction, high-antioxidant foods, certain supplements and medications, and cold exposure.