AICAR

Key Benefits#

• AMPK activation mimics aerobic exercise adaptations
• Increased fat oxidation and endurance
• Mitochondrial biogenesis (PGC-1alpha)
• Improved insulin sensitivity and glucose metabolism
• Anti-inflammatory effects
• Potential cardiac protection during ischemia
• Synergistic with actual exercise training
• Reduces hepatic glucose production

Mechanism of Action#

AICAR is converted intracellularly to AICAR monophosphate (ZMP), a potent AMPK activator. AMPK activation triggers a cascade mimicking exercise adaptations: increased fatty acid oxidation, enhanced glucose uptake in muscle, inhibition of fat synthesis, mitochondrial biogenesis via PGC-1alpha activation, and improved insulin sensitivity. In animal studies, AICAR administration increased running endurance by 44% without exercise training, making it WADA-prohibited.

Dosing Protocols#

Side Effects#

• Hypoglycemia risk
• Lactic acidosis at high doses (animal data)
• Injection site irritation

Contraindications#

Competitive athletes (WADA banned). Pregnancy or breastfeeding. Hypoglycemia risk. Limited human safety data.

Storage#

Lyophilized powder: store at −20°C. Reconstituted: refrigerate at 2–8°C, use within 14 days.

Featured In Stacks#

1. 1.
   FNDC5/Irisin-dependent renoprotection of resistance training in myocardial infarction-induced Type 2 cardiorenal syndrome

   Fu W, Lin J, Lin W, Zeng K · PloS one · 2026PubMed Verified

2. 2.
   Zinc Depletion Increases Susceptibility to AMPK-Induced Atrophic Responses in C2C12 Myotubes

   Imoto T, Ishizaka J, Tamura Y · Pathophysiology : the official journal of the International Society for Pathophysiology · 2026PubMed Verified

3. 3.
   The AMPK activator A769662 promotes ferroptosis and suppresses disulfidptosis by inhibiting SLC7A11

   Misono U, Ishida N, Fumuro A, Katoh H · Biochemical and biophysical research communications · 2026PubMed Verified

4. 4.
   Ketamine ameliorates postpartum depression-like behaviors in rats exposed to sevoflurane during pregnancy through the AMPK/SIRT1/NLRP3 pathway

   Xue H, Yang X, Kuai S, Zhang Y, Jia Y, Wu Z et al. · Journal of affective disorders · 2026PubMed Verified

5. 5.
   Vitamin A-activated PPARγ signaling enhances intramuscular fat accumulation by overriding AMPK-mediated inhibition in late-fattening beef cattle

   Yang X, Zhang C, Tan J, Zhang J, Cui J, Fan Y et al. · Journal of animal science and biotechnology · 2026PubMed Verified

6. 6.
   AMPK promotes TFEB transcriptional activity through dephosphorylation at both MTORC1-dependent and -independent sites

   Negoita F, Fraguas Bringas C, Hellberg K, Luda KM, Liu H, Li Z et al. · Autophagy · 2026PubMed Verified

7. 7.
   AICAR attenuates ischemia-reperfusion-induced AKI by modulating AMPK-TXNIP-NLRP3 pathway and energy metabolism

   Gan L, Li W, Zhang Y, Zeng J, Xu B · Cellular and molecular life sciences : CMLS · 2026PubMed Verified

8. 8.
   Investigating the Effects of Morin and Aminoimidazole Carboxamide Ribonucleotide on the AMPK/mTOR/ULK1 Signaling Pathway in Breast Cancer Cell Line (MCF-7)

   Khorsandi L, Fakhredini F, Azandeh SS, Bijan-Nejad D, Karimi S, Rezaei-Tazangi F et al. · Advanced biomedical research · 2025PubMed Verified

9. 9.
   Nicorandil ameliorates cardiac microcirculation in hypertensive myocardial infarction via LKB1/AMPK signaling activation

   Wang W, Wang S · Pakistan journal of pharmaceutical sciences · 2026PubMed Verified

10. 10.
    Exercise-induced differential transcriptional output of AMPK signalling improves axon regeneration and functional recovery

    Behera S, Ghosh Roy A · The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026PubMed Verified

11. 11.
    MFN2 interacts with phosphorylated AMPK to mediate mitophagy in MCF-7 cells

    Zhai S, Huang Z, An C, Gao L, Chen T · The international journal of biochemistry & cell biology · 2026PubMed Verified

12. 12.
    AMPK as a central regulator of metabolic memory: mechanisms and therapeutic opportunities

    Khan WA, Garg SS, Banyal K, Gupta J · Journal of diabetes and metabolic disorders · 2026ReviewPubMed Verified

13. 13.
    Investigation of exercise-mimetic bioactive molecules as modulators of MMP activity and expression in cancer cells

    Vo HVT, Patton GN, Park JS, Kim SJ, Kim N, Lee HJ · Journal of enzyme inhibition and medicinal chemistry · 2026PubMed Verified

14. 14.
    AdipoRon Suppresses Multiple Myeloma Proliferation Through AMPK-Mediated Metabolic Reprogramming and Apoptosis Induction

    Wang Z, Su X, Guo R, Han Y, Zhang J · IUBMB life · 2026PubMed Verified

15. 15.
    Mechanistic study of miR-148a-3p-mediated AMPK/mTOR/S6-dependent autophagy in hepatitis B virus replication

    Liu J, Sheng Y · Virus genes · 2026PubMed Verified

16. 16.
    Intermittent exercise alleviates MI-induced renal injury in mice via IGF-1

    Zhu W, Bo W, Ma Y · Frontiers in physiology · 2025PubMed Verified

17. 17.
    N-nitrosodimethylamine increased glucose production by promoting hyperglycemia in hepatocyte via AMPK signaling pathway in vivo and in vitro

    Wang W, Xi S, Wang Y · Drug and chemical toxicology · 2026PubMed Verified

18. 18.
    Transcriptome analysis of Pantoea rara mutants reveals the underlying complexity of bacterial phosphate solubilization

    Hone H, Li T, Wood JL, Kaur J, Sawbridge T · Microbiology spectrum · 2026PubMed Verified

19. 19.
    Wharton's jelly mesenchymal stem cell-derived conditioned media inhibits colon cancer cells via activating AMPK/mTOR-mediated autophagy

    Dayer D, Akbari-Jonoush Z, Mahdavi R, Amari A, Keshavarz-Zarjani A, Khorsandi L · Molecular biology research communications · 2026PubMed Verified

20. 20.
    Methotrexate Exhibits a Dual Role in Regulation of CD4(+) T Follicular Helper (Tfh) Cell Differentiation and Activity

    Chakraborty S, Khamaru P, Daptary AH, Mukherjee S, Ghosh S, Bhattacharyya A · Scandinavian journal of immunology · 2025PubMed Verified

21. 21.
    The AMPK-FOXO signaling regulates the transcriptional response of 4EBP to pesticide stress in Tribolium castaneum

    Guan D, Wang Z, Liu C, Ge H, Zhou M, Fang S et al. · Pesticide biochemistry and physiology · 2026PubMed Verified

22. 22.
    Common and distinct roles of AMPKγ isoforms in small-molecule activator-stimulated glucose uptake in mouse skeletal muscle

    Biswas D, Espino-Gonzalez E, Ahwazi D, Freemantle JB, Ehrlich AM, Jomard C et al. · Molecular metabolism · 2026PubMed Verified

23. 23.
    Defective autophagy and AMPK inactivation drive ferroptosis in diabetic kidney disease

    Matsui S, Yamamoto T, Takabatake Y, Takahashi A, Namba-Hamano T, Matsuda J et al. · Diabetologia · 2026PubMed Verified

24. 24.
    Lactate-Induced Lipid Accumulation in Hepatocytes through GPR81 Activation

    Nguyen G, Yu JH, Pham PTM, Lai TL, Park SY, Kim KW et al. · Diabetes & metabolism journal · 2025PubMed Verified

25. 25.
    Impaired AMP-Dependent Protein Kinase-Mediated Neutrophil Extracellular Trap Clearance by Aged Macrophages in Sepsis-Induced Liver Injury

    Guan Z, Bai Y, Ji X, Li F, Zhou B, Zhong W et al. · Anesthesia and analgesia · 2025PubMed Verified

26. 26.
    AICAR Inhibits Insulin-Stimulated Glucose Uptake in 3T3-L1 Adipocytes via an AMPK-Independent, ZMP-Dependent Mechanism

    Alshuweishi Y, Binzomah Alghamdi F, Patrick K, Salt IP · Cells · 2025PubMed Verified

27. 27.
    AMP-activated protein kinase-Caspase 6 axis regulation alleviates the combined apoptotic damage caused by deoxynivalenol and fumonisin B1 in mammary glands

    Cao L, Li G, Liu K, Gao W, Dong Y, Yang Z et al. · NPJ science of food · 2025PubMed Verified

28. 28.
    5-Aminoimidazole-4-carboxamide-1- β -d-ribofuranoside ameliorates lipotoxicity through enhanced reticulophagy in HepG2 cells

    Krishnan U A, Venkataraman AC, Ramachandran V · Biotechnology and applied biochemistry · 2025PubMed Verified

29. 29.
    AICAr Inhibition of cardiomyocyte autophagy promotes p62-dependent NRF2 expression and protection against doxorubicin toxicity

    Fassett EK, Mayer B, Fassett JT · Cellular and molecular life sciences : CMLS · 2025PubMed Verified

30. 30.
    Purine Nucleotide Precursors in Preventing Myocardial Ischemia-Reperfusion Injury

    Musial PT, Badtke PA, Zabielska-Kaczorowska MA · International journal of molecular sciences · 2025ReviewPubMed Verified

31. 31.
    Quercetin alleviates ethanol-induced hepatocyte senescence by interacting with glycinamide ribonucleotide transformylase

    Huimin C, Shufen P, Zhaoyu C, Jiaxin L, Li C, Xingzhu Y et al. · Food research international (Ottawa, Ont.) · 2025PubMed Verified

32. 32.
    When is a sample a urine sample? Markers for urine sample authenticity assessment in sports drug testing

    Piper T, Geyer H, Huelsemann F, Mareck U, Walpurgis K, Fusshoeller G et al. · Bioanalysis · 2025ReviewPubMed Verified

33. 33.
    Sacubitril/Valsartan Ameliorates Inflammation and Oxidative Stress in Hypertensive Heart Disease by Upregulating CAMKK2 Protein and Modulating the AMPK/AKT/GSK-3β Axis

    Yang YJ, Li JS · The Kaohsiung journal of medical sciences · 2025PubMed Verified

34. 34.
    A novel long non-coding RNA, Lnc-GAS7, modulates myosin heavy chain isoform switching via AMPK signaling in ovine muscle

    Tan D, Chen Y, Han X, Fu Y, Chen J, Lai C et al. · International journal of biological macromolecules · 2025PubMed Verified

35. 35.
    AMPKα2 signals amino acid insufficiency to inhibit protein synthesis

    Mao Y, Cui M, Jiang Y, Yu H, Wang M, Li G et al. · Cell metabolism · 2026PubMed Verified

36. 36.
    Allopurinol Treatment Improves Cognitive Skills, Adaptive Behavior, and Biochemical Markers in Young Patients With Adenylosuccinate Lyase Deficiency

    Rousselot-Pailley B, Semeraro M, Marquant F, Robel L, Gitiaux C, Kaminska A et al. · Journal of inherited metabolic disease · 2025Clinical TrialPubMed Verified

37. 37.
    GPR75 knockdown alleviates mitochondrial dysfunction in hippocampal neurons via AMPK pathway in diabetic mice

    Liu M, Liu L, Liu W, Yu H, Yu S, Liu Z et al. · International immunopharmacology · 2025PubMed Verified

38. 38.
    Potential Role of Aerobic Exercise in Attenuating Diabetic Cardiomyopathy via Modulation of P2X4-Mediated NLRP3 Inflammasome Activation and Pyroptosis

    Liu Z, Yang Y, Song L, Ruan X, Li X, He Y et al. · Journal of innate immunity · 2025PubMed Verified

39. 39.
    AMPK activation mitigates α-synuclein pathology and dopaminergic degeneration in cellular and mouse models of Parkinson's disease

    Kim Y, Lee JS, Son S, Park S, Oh H, Choi YK et al. · Neuropharmacology · 2025PubMed Verified

40. 40.
    CD137L promotes immune surveillance in melanoma via HLTF regulation

    Liang L, Zhu L, Li X, Zhou W, Zhang Y, Hung MC et al. · Nature communications · 2025PubMed Verified

41. 41.
    Ex vivo Lung Perfusion Enhances Donor Lung Preservation in Mice via Hippo Signaling Activation

    Huang R, Zhao Z, Liu S, Li M, Wang Y, Hu Y et al. · American journal of respiratory cell and molecular biology · 2025PubMed Verified

42. 42.
    AMPK regulates BK-channel current in CA1 hippocampal neurons

    Esquivel-Garcia R, Bravo-Martinez J, Bermeo K, Arenas I, Garcia DE · Biochimica et biophysica acta. General subjects · 2025PubMed Verified

43. 43.
    Cardiovascular and renal effects of 5-aminoimidazole-4-carboxyribonucleoside (AICAR) in the deoxycorticosterone acetate (DOCA)-salt rat model of hypertension

    Dennis MR, Zozobrado L, Reinartz DM, Foster T, Gauthier MM, Wilson JE et al. · Life sciences · 2025PubMed Verified

44. 44.
    Temozolomide-Derived AIC Is Incorporated into Purine Synthesis in Glioblastoma

    Sowers ML, Baljinnyam T, Herring JL, Chang-Gu B, Hackfeld LC, Tang H et al. · Chemical research in toxicology · 2025PubMed Verified

45. 45.
    Cardioprotective effects of AMPK activation in H1N1 influenza virus infection

    Leumi S, McFadden M, Kumar N, Mattoo SS, Roettger J, Speaks S et al. · bioRxiv : the preprint server for biology · 2025PubMed Verified

46. 46.
    Glycyrrhizin alleviates contrast-induced acute kidney injury via inhibiting HMGB1-mediated renal tubular epithelial cells ferroptosis

    Tian FY, Liu K, Tang ZY, Zhou G, Zhou GL, Chen RF et al. · Renal failure · 2025PubMed Verified

47. 47.
    Exploring Cirrhosis: Insights into Advances in Therapeutic Strategies

    Wiacek M, Adam A, Studnicki R, Zubrzycki IZ · International journal of molecular sciences · 2025ReviewPubMed Verified

48. 48.
    Sophocarpine prevents LPS and IFN-γ-stimulated oxidative stress and neuroinflammation of BV-2 microglia by regulating the AMPK/NF-κB signaling pathway

    Guo S, Li T, Luan L, Deng J, Luo Y · Neurological research · 2025PubMed Verified

49. 49.
    Diverse Inhibitors of De Novo Purine Synthesis Promote AICAR-Induced AMPK Activation and Glucose Uptake in L6 Myotubes

    Dolinar K, Miš K, Šopar K, Šutar M, Božič M, Kolar M et al. · BioFactors (Oxford, England) · 2025PubMed Verified

50. 50.
    Reprogramming of Myeloid Responses to Volumetric Muscle Loss via Engineered Protein Nanoparticles

    Castor-Macias JA, Piotto C, Rudy P, Guzman SD, Chang A, Larouche JA et al. · ACS nano · 2025PubMed Verified