6 Ways to Boost AMPK Activation

What is AMPK Activation?

AMPK activation refers to the stimulation and increased activity of AMP-activated protein kinase (AMPK), a crucial enzyme that plays a central role in cellular energy homeostasis. This activation occurs in response to conditions indicating an energy deficit within the cell, such as low levels of adenosine triphosphate (ATP) and elevated levels of adenosine monophosphate (AMP). When activated, AMPK initiates a cascade of intracellular events aimed at restoring energy balance, including promoting energy production processes like glucose uptake and fatty acid oxidation while inhibiting energy-consuming processes such as cell growth and lipid synthesis. AMPK activation is a key cellular mechanism to adapt and respond to fluctuations in energy availability, ensuring efficient energy utilization and metabolic regulation.

Practical Ways to Boost AMPK

• Stop snacking. Allow the body to enter a mini-fast between meals (at least 6 hours). Exercising during this time, even if it’s a 10-minute walk, will expedite the onset of the energy deficit that’s needed to activate AMPK. Walking for just a few minutes after a meal, and even taking standing breaks while sitting, can kickstart this energy shift. Read the article here. 
• Caloric restriction (CR) is the most extensively studied dietary method to up-regulate AMPK. Ample research has shown that limiting calorie intake, even modestly, enhances insulin sensitivity and metabolic regulation.1, 6 In practice, caloric restriction is difficult to deploy because of low patient compliance. Alternative protocols involving alternate day fasting (ADF) may offer similar health benefits with better long-term adherence. Modest reductions in overall energy intake can also activate AMPK, but it’s important to allow blood sugar to drop sufficiently between meals to engage it. 
• Exercise is perhaps the most sustainable and well-supported method. Any exercise will suffice, as long as it burns calories and creates a temporary energy deficit. It’s important to avoid snacking before or during the workout. 
• CR mimetics (CRMs) are small molecules that may partially recapitulate the cellular effects of CR.9, 10 CRMs lacked a unified definition until 2014 when Madeo and colleagues defined them as substances that inhibit protein acetylation, which “tunes up” metabolism, mitochondrial renewal and longevity pathways.9 To learn more, here is a short article describing CRMs.
• Polyphenols in fruits, berries, green tea and other plant foods support the AMPK-SIRT1 axis and other pathways related to cardiometabolic health.8
• Berberine supports insulin receptor function and signaling, in part, by supporting AMPK activation. Human clinical trials have shown significant metabolic health benefits after 4-12 weeks of daily supplementation with 1000-1500 mg/day.7 Berberine has very poor oral bioavailability, but new delivery systems can overcome this limitation. Dihydroberberine: AMPK Activator is 5x more bioavailable and 2x longer lasting than regular berberine.

SUMMARY & KEY POINTS

• AMPK is a master metabolic sensor that enhances mitochondrial function, insulin signaling and glucose metabolism.
• Lifestyle interventions that create energy deficits, such as caloric restriction and exercise, are well-established modalities that activate the AMPK-SIRT1 axis.
• Dihydroberberine can provide a significant boost to AMPK and/or SIRT1 activity. Polyphenols from fruits and vegetables are also supportive.

Other than being instrumental in metabolic health, AMPK activation can also influence longevity in the following ways:

1. Cellular Repair and Maintenance: AMPK activation promotes autophagy, a cellular process that removes damaged or dysfunctional components, contributing to overall cellular health and longevity.

2. Mitochondrial Function: AMPK activation enhances mitochondrial biogenesis and function. Healthy mitochondria are crucial for energy production and play a role in cellular longevity.

3. Reduced Inflammation: AMPK activation has anti-inflammatory effects, helping to mitigate chronic inflammation, which is linked to various age-related diseases. By modulating inflammatory pathways, AMPK supports overall health and longevity.

4. DNA Repair: AMPK activation is associated with enhanced DNA repair mechanisms. This supports genomic stability and reduces the risk of mutations that can contribute to aging and age-related diseases.

5. Stress Resistance: AMPK activation increases cellular stress resistance. Cells that are better equipped to handle various stressors, including oxidative stress, may be more resilient and less prone to damage over time.

6. Caloric Restriction Mimicry: AMPK activation mimics some of the effects of caloric restriction, a dietary approach linked to increased longevity in various organisms. This includes improvements in metabolic health, cellular repair processes, and stress resistance.

1. Herzig S, Shaw R. Nat Rev Mol Cell Biol 19, 121–135 (2018). 

2. Burkewitz K, Zhang Y, Mair WB. Cell Metab. 2014 Jul 1;20(1):10-25.

3. Smith BK, Steinberg GR. Curr Opin Clin Nutr Metab Care. 2017 Jul;20(4):248-253.

4. Nakamura S, Yoshimori T. Autophagy and Longevity. Mol Cells. 2018 Jan 31;41(1):65-72.

5. Dai H, Sinclair DA, Ellis JL, Steegborn C. Pharmacol Ther. 2018 Aug;188:140-154.

6. Johnson, Distelmaier Diabetes 2016 Jan;65(1):74-84.

7. Och A, Och M, Nowak Molecules 2022 Feb;27(4): 1351.

8. Zhang S, Xu M, Zhang W Int J Mol Sci. 2021Jun; 22(11): 6110.