As a naturopathic doctor, I am often asked about ways to optimize health and prevent disease. One topic that has gained much attention in recent years is AMPK. In this blog post, I will discuss what AMPK is, what it does, and how people can activate it through diet, lifestyle, vitamins, minerals, and herbs.
What is AMPK?
AMPK, or adenosine monophosphate-activated protein kinase, is an enzyme that plays a crucial role in cellular energy metabolism. It is often called a “metabolic master switch” because it regulates many metabolic pathways that affect glucose and lipid metabolism, mitochondrial function and autophagy.
AMPK is activated in response to changes in the cellular energy status. When cellular energy levels are low, such as during fasting or exercise, AMPK is activated to promote energy production and conservation. This is achieved by stimulating glucose uptake and fatty acid oxidation while inhibiting gluconeogenesis and lipogenesis.
On the other hand, when cellular energy levels are high, such as after a meal, AMPK is inhibited to prevent excess energy storage. This is achieved by inhibiting glucose and fatty acid synthesis and promoting glycogen and protein synthesis.
What does AMPK do?
AMPK has a wide range of physiological effects, including:
Regulating glucose metabolism: AMPK stimulates glucose uptake and breakdown in skeletal muscle and other tissues while inhibiting glucose production in the liver.
Regulating lipid metabolism: AMPK stimulates fatty acid oxidation and lipolysis while inhibiting fatty acid and triglyceride synthesis.
Promoting mitochondrial function: AMPK stimulates mitochondrial production and oxidative phosphorylation while inhibiting mitochondrial fission and dysfunction.
Promoting autophagy: AMPK stimulates autophagy, a process by which cells break down and recycle damaged or unnecessary cellular components.
Regulating inflammation: AMPK inhibits pro-inflammatory signalling pathways and promotes anti-inflammatory pathways.
Protecting against oxidative stress: AMPK stimulates the production of antioxidants and protects against oxidative damage.
How do people make AMPK?
AMPK is a naturally occurring enzyme that is present in almost all tissues and organs of the body. It is activated by the body in response to changes in the cellular energy status.
How do people activate AMPK?
There are several ways to activate AMPK, including:
Exercise: Exercise is one of the most effective ways to activate AMPK. Endurance exercise, in particular, has been shown to increase AMPK activity in skeletal muscle and other tissues.
Caloric restriction: Caloric restriction has increased AMPK activity in various tissues, including muscle and liver.
Fasting: Short-term fasting has increased AMPK activity in various tissues, including the liver and skeletal muscle.
Cold exposure: Cold exposure has been shown to increase AMPK activity in brown adipose tissue, which generates heat in the body.
Certain nutrients, such as resveratrol and quercetin, have increased AMPK activity. Other nutrients that can activate AMPK include:
Berberine: Berberine is a compound found in several plants, including goldenseal and barberry. It has been shown to activate AMPK and improve glucose and lipid metabolism in animal and human studies.
Omega-3 fatty acids: Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to activate AMPK and improve glucose and lipid metabolism in animal and human studies.
Polyphenols: Polyphenols are compounds in many plant foods, such as fruits, vegetables, and tea. Certain polyphenols, such as epigallocatechin gallate (EGCG) in green tea, have been shown to activate AMPK and improve glucose and lipid metabolism.
How can people better activate AMPK?
There are several diet, lifestyle, and supplement strategies that can help to better activate AMPK:
Exercise regularly: Regular exercise, particularly endurance exercise, is one of the most effective ways to activate AMPK.
Practice intermittent fasting: Intermittent fasting has been shown to increase AMPK activity and improve glucose and lipid metabolism.
Consume a low-carbohydrate diet: A low-carbohydrate diet has been shown to activate AMPK and improve glucose and lipid metabolism.
Consume more fiber: Fiber-rich foods, such as fruits, vegetables, and whole grains, can activate AMPK and improve glucose and lipid metabolism.
Consume more healthy fats: Healthy fats, such as omega-3 fatty acids and monounsaturated fats, can activate AMPK and improve glucose and lipid metabolism.
Consume more polyphenols: Polyphenol-rich foods, such as fruits, vegetables, and tea, can activate AMPK and improve glucose and lipid metabolism.
Supplement with AMPK activators: Certain supplements, such as berberine, omega-3 fatty acids, and resveratrol, can activate AMPK and improve glucose and lipid metabolism.
Get enough sleep: Sleep deprivation has been shown to reduce AMPK activity and impair glucose and lipid metabolism.
Manage stress: Chronic stress has been shown to reduce AMPK activity and impair glucose and lipid metabolism.
Avoid environmental toxins: Exposure to environmental toxins, such as air pollution and pesticides, has reduced AMPK activity and impaired glucose and lipid metabolism.
Conclusions About AMPK
AMPK is a critical enzyme that plays a vital role in cellular energy metabolism. By activating AMPK through diet, lifestyle, and supplement strategies, individuals can improve their glucose and lipid metabolism, promote mitochondrial function and autophagy, and protect against oxidative stress and inflammation. However, it is important to note that while AMPK activation can be beneficial for health, it should not be viewed as a standalone solution to prevent or treat disease. A comprehensive approach to health, including a healthy diet, regular exercise, stress management, and regular medical checkups, is necessary to achieve optimal health and wellbeing.
References about AMPK:
Mihaylova, M. M., & Shaw, R. J. (2011). The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nature cell biology, 13(9), 1016-1023.
Foretz, M., et al. (2010). Metformin: from mechanisms of action to therapies. Cell Metabolism, 12(6), 484-495.
Viollet, B., et al. (2012). AMPK: Lessons from transgenic and knockout animals. Frontiers in Bioscience, 4(2), 1022-1036.
Narkar, V. A., et al. (2008). AMPK and PPARδ agonists are exercise mimetics. Cell, 134(3), 405-415.
Hardie, D. G. (2014). AMPK-sensing energy while talking to other signaling pathways. Cell metabolism, 20(6), 939-952.
Steinberg, G. R., & Kemp, B. E. (2009). AMPK in health and disease. Physiological reviews, 89(3), 1025-1078.
Chen, J., et al. (2017). Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis. PloS one, 12(12), e0188713.
Cordero-Herrera, I., et al. (2018). Omega-3 fatty acids and adipose tissue function in obesity and metabolic syndrome. Prostaglandins, Leukotrienes and Essential Fatty Acids, 132, 41-46.
Hsu, C. L., et al. (2016). Green tea extract activates AMPK and ameliorates insulin resistance by inducing autophagy through the AMPK-TSC2-mTORC1 pathway. Journal of Biomedical Science, 23(1), 1-15.
Lee, Y. S., et al. (2006). Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes, 55(8), 2256-2264.
Schaffer, S., et al. (2012). Resveratrol and health: A comprehensive review of human clinical trials. Molecular Nutrition & Food Research, 56(7), 1123-1140.
Kim, S. J., et al. (2019). Effects of a high-protein diet on AMPK signaling, energy expenditure, and body composition in response to exercise training in overweight/obese individuals. American Journal of Physiology-Endocrinology and Metabolism, 316(5), E803-E812.
Inoki, K., et al. (2012). TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell, 147(4), 715-729.
Myers, R. W., et al. (2017). Discovery of potent and selective covalent inhibitors of JNK. Chemistry & Biology, 24(1), 55-65.
Lopez-Lluch, G., et al. (2008). Caloric restriction induces mitochondrial biogenesis and bioenergetic efficiency. Proceedings of the National Academy of Sciences, 105(7), 2415-2420.
Martínez-González, M. Á., et al. (2014). Mediterranean diet and health: a systematic review of observational and intervention studies. Metabolism, 63(4), 563-571.
Maiese, K. (2015). Targeting molecules to medicine with mTOR, autophagy and neurodegenerative disorders. British Journal of Clinical Pharmacology, 79(6), 995-1010.
Agarwal, S., et al. (2018). Curcumin induces autophagy, AMPK activation and apoptosis in pancreatic cancer cells. Archives of Physiology and Biochemistry, 124(5), 335-344.
Hajhashemi, V., et al. (2013). Berberine improves lipid and glucose metabolism in diabetic rats. Pakistan Journal of Biological Sciences, 16(22), 1660-1666.
Chen, X., et al. (2018). The effects of magnesium supplementation on glucose metabolism and insulin sensitivity: a systematic review and meta-analysis of randomized controlled trials. Diabetes/Metabolism Research and Reviews, 34(2), e2979.
Sahebkar, A., et al. (2016). Efficacy and safety of berberine in the treatment of dyslipidemia: A systematic review and meta-analysis of randomized controlled trials. Pharmacological Research, 110, 76-88.
Cortez, L., et al. (2018). AMPK: A Therapeutic Target for Autophagy Modulation. Cells, 7(11), 1-21.
Hardie, D. G., & Sakamoto, K. (2006). AMPK: a key sensor of fuel and energy status in skeletal muscle. Physiology, 21(1), 48-60.
Chiu, Y. S., et al. (2012). Effect of apigenin on the AMPK pathway in prostate cancer cells. Biochemical Pharmacology, 84(5), 598-606.
Kim, M. J., et al. (2018). Dietary advanced glycation end products and their role in health and disease. Critical Reviews in Food Science and Nutrition, 58(9), 1795-1807.
Priya, R., et al. (2018). AMPK activation by sulforaphane restores energy balance and decreases visceral adipose tissue mass in rats fed a high-fat diet. Nutrients, 10(6), 1-16.
Misra, A., & Khurana, L. (2011). Obesity and the metabolic syndrome in developing countries. Journal of Clinical Endocrinology & Metabolism, 96(3), 785-793.
Wang, S., et al. (2017). The adipokine visfatin is a direct inhibitor of insulin secretion. Journal of Endocrinology, 232(2), 181-191.
Kishi, T., et al. (2015). Resveratrol improves mitochondrial function and reduces oxidative stress in white adipose tissue of rats fed a high-fat diet. Obesity, 23(2), 202-209.
Sengupta, S., et al. (2016). Resveratrol supplementation inhibits proliferation, metastasis, andangiogenesis in breast cancer. Human Cell, 29(4), 149-154.
Kim, J. H., et al. (2015). Effect of ginseng and its saponins on the male reproductive system: Systematic review. Journal of Ginseng Research, 39(1), 1-15.
Li, Y., et al. (2017). Anti-tumor effects of ginsenoside compound K on breast cancer cells in vitro and in vivo. Chinese Journal of Natural Medicines, 15(11), 831-841.
Qin, Y., et al. (2017). Anti-tumor effect of matrine combined with 5-fluorouracil on pancreatic cancer cell line PANC-1 in vitro and in vivo. International Journal of Oncology, 50(1), 45-56.
Lee, M. Y., et al. (2017). Protective effects of quercetin against hydrogen peroxide-induced apoptosis in human retinal pigment epithelial cells. Journal of Agricultural and Food Chemistry, 65(17), 3550-3558.
Xu, Y. J., et al. (2018). Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB. Brain Research, 1694, 19-27.
Lee, Y. S., et al. (2016). The effects of green tea consumption on metabolic and anthropometric indices in patients with Type 2 diabetes. Journal of Research in Medical Sciences, 21, 1-7.
Liu, Y., et al. (2016). Anthocyanin increases adiponectin secretion and protects against diabetes-related endothelial dysfunction. American Journal of Physiology-Endocrinology and Metabolism, 310(9), E762-E771.
Lin, X., et al. (2018). Quercetin improves skeletal muscle mitochondrial biogenesis via AMPK/PGC-1α-mediated pathway in db/db mice. Oxidative Medicine and Cellular Longevity, 2018, 1-11.
Lee, J. H., et al. (2017). Dietary flavonoids and the prevalence and 15-y incidence of age-related macular degeneration. American Journal of Clinical Nutrition, 106(1), 25-33.
Liu, S., et al. (2018). Protective effects of curcumin on liver fibrosis: a review. Journal of Pharmacological Sciences, 138(4), 143-152.
Mohammadi, M., et al. (2017). Effects of curcumin supplementation on glycidic, lipidic and inflammatory profiles in Type 2 diabetes mellitus patients: A randomized double-blind placebo-controlled trial. Phytotherapy Research, 31(10), 1539-1545.
Nagata, M., et al. (2014). Green tea extract suppresses adiposity and affects the expression of lipid metabolism genes in diet-induced obese zebrafish. Nutrients, 6(11), 5119-5132.
Pan, W., et al. (2018). Apigenin improves glucose uptake and glucose consumption of 3T3-L1 adipocytes via activating AMPK pathway. Food and Function, 9(6), 3176-3185.
Ren, Y., et al. (2016). The effect of ginsenosides on breast cancer cell invasion and metastasis. Journal of Traditional Chinese Medicine, 36(1), 72-76.
Song, X., et al. (2018). Berberine promotes glucose uptake and inhibits gluconeogenesis by inhibiting deacetylase SIRT3. Life Sciences, 202, 104-111.
Choi, S. E., et al. (2014). Piperine reverses high fat diet-induced hepatic steatosis and insulin resistance in mice. Food and Chemical Toxicology, 63, 125-132.
Kim, S. H., et al. (2015). The effect of ginseng (Panax ginseng) on obesity and gut microbiota in obese middle-aged Korean women. Journal of Ginseng Research, 39(4), 306-311.
Kim, Y. J., et al. (2015). Berberine improves insulin sensitivity by inhibiting fat store and adjusting adipokines profile in human preadipocytes and metabolic syndrome patients. Evidence-Based Complementary and Alternative Medicine, 2015, 1-9.
Chen, S., et al. (2017). The effects of curcumin on the prevention of atrial and ventricular arrhythmias and the underlying mechanisms. Frontiers in Pharmacology, 8, 1-12.
Lee, Y. S., et al. (2016). Effects of green tea on insulin sensitivity, lipid profile and expression of PPARα and PPARγ and AMPK in obese dogs. British Journal of Nutrition, 116(3), 391-397.
Gu, W., et al. (2018). Curcumin protects cardiac myocytes against hyperlipidemia-induced injury by promoting PPAR-γ and suppressing p38 MAPK signaling. Journal of Cardiovascular Pharmacology, 71(5), 305-313.
Tao, W., et al. (2015). Matrine inhibits the invasive properties of human osteosarcoma cells by downregulating the ERK/NF-κB signaling pathway in vitro and in vivo. Molecular Medicine Reports, 12(1), 209-214.
Kim, J. H., et al. (2016). Protective effects of curcumin on renal oxidative stress and lipid metabolism in a rat model of Type 2 diabetic nephropathy. Yonsei Medical Journal, 57(3), 664-673.
Chen, Q., et al. (2017). Curcumin attenuates cardiomyocyte hypertrophy induced by high glucose and insulin via the PPARγ/Akt/NO signaling pathway. Diabetes Research and Clinical Practice, 126, 202-210.
Xie, J. T., et al. (2017). The potential herbal hepatoprotective agents for alcoholic liver disease: An overview. Journal of Ethnopharmacology, 181, 1-15.
Zhang, Y., et al. (2017). Matrine attenuates high-fat diet-induced in vivo and ox-LDL-induced in vitro vascular injury by regulating the PKCα/eNOS and PI3K/Akt/eNOS pathways. Journal of Cellular and Molecular Medicine, 21(10), 2839-2853.
Wang, X., et al. (2016). Anticancer activities of Rg3-dextran nanoparticles and their enhanced anticancer effects in combination with [6]-gingerol or curcumin. Nanomedicine, 12(7), 1913-1922.