What Athletes Should Know About AICAR and Other Prohibited AMP Activated Protein Kinase Activators

In recent years, AICAR has been in the news a number of times as a novel substance athletes have turned to for performance enhancement. However, this substance is both prohibited in sport and a health risk because it’s not approved for therapeutic use in humans anywhere in the world.

Here’s what athletes should know about AICAR and other prohibited AMP activated protein kinase activators.

What is AICAR?

AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) is a substance produced naturally by the body that stimulates AMP activated protein kinase (AMPK), a protein that regulates metabolism in a variety of ways. AMPK acts as an energy regulator and is activated during exercise or other circumstances that use up cellular energy.

The AMPK-stimulating AICAR can also be synthesized in a lab and is being evaluated in preclinical research and human clinical trials as a therapeutic agent to treat certain metabolic disorders in humans.

How do AICAR and AMPK impact performance?

Once activated by AICAR, AMPK works to make energy more available. For example, it increases the usage of fat for energy and causes cells to make more mitochondria (the cells’ powerhouses or energy creators). AMPK basically ensures that the various tissues in the body don’t run out of energy.

There are many circumstances that activate AMPK naturally, including hypoxia (low oxygen levels during exercise or at elevation), hypoglycemia (low blood sugar with exercise or fasting), the use of cellular energy during muscle contraction, and anything that disrupts energy creation within cells.  

The effects of activating AMPK are extremely complex since it is involved in so many different metabolic pathways of the body. To date, the medical community has not found a way to target AMPK in a way that allows for the treatment of diseases in humans, although research has suggested it plays a role in diabetes, heart disease, and cancer. 

Why is AICAR on the World Anti-Doping Agency (WADA) Prohibited List?

AICAR is prohibited because it’s an AMPK activator, which are prohibited at all times under the category of Hormone and Metabolic Modulators on the WADA Prohibited List because of their potential performance-enhancing effects. 

Are there health risks to using AICAR?

Some articles refer to AMPK activators as “exercise-in-a-pill” in the hope that using an AMPK activator will cause the same changes in the body as exercise. However, the truth is much more complex.

Too much activation of AMPK, or activating it in the wrong tissue, can cause serious side effects, including neurodegeneration, or preventing cells from dividing. The accumulation of naturally-occurring AICAR in the body is also associated with metabolic disorders in humans.

However, AICAR has not been extensively studied in people. For this reason and many others, AICAR is an experimental compound that is not yet approved for therapeutic use in humans and should not be used by any athletes.

Can I get a TUE for AICAR?

No, athletes cannot get a TUE for AICAR because it is not approved for use in humans anywhere in the world. AICAR is not available as a medication, so your doctor should not prescribe it for you under any circumstance.

More questions?

For questions about specific products, substances, and methods, contact USADA’s Drug Reference Line at drugreference@usada.org or call (719) 785-2000, option 2.