AICAR Side Effects

AICAR is an amino acid sequence that can be synthesized in the laboratory, but is an analogue of adenosine monophosphate (a natural molecule). Its primary function, based on which it achieves all its potential beneficial effects, is the selective activation of AMP-activated protein kinase (AMPK) in various types of predominantly connective tissue such as adipose, muscle tissue, and liver cells.

Another crucial function of AICAR is its regulatory properties, primarily in glucose and lipid metabolism, as well as in the control of anabolic processes. In addition to the aforementioned properties, it also has a possible anti-inflammatory effect based on the ability to inhibit proinflammatory cytokines. Thanks to all those properties, AICAR can potentially be used as part of therapy for various conditions and diseases.

About the Peptide

AICAR is also known as Acadesine due to its structural similarity to adenosine monophosphate. As mentioned, its main function is to activate AMP-activated protein kinase (AMPK), and all its further properties and positive effects on the body are based on this function. This peptide can detect energy levels in certain tissues and is always activated in conditions of reduced energy availability.

In addition, AICAR accelerates and improves the differentiation of mesenchymal stem cells (the basic cells of connective tissue that are inactive) into mature cell forms that possess activity. Inhibition of certain enzymes such as acetyl-CoA carboxylase and malonyl-CoA and an increase in the rate of fatty acid oxidation and glucose uptake are just some of the effects that may be applied to the treatment of various conditions. AICAR is therefore considered a potential treatment for type 2 diabetes and metabolic syndrome, as well as many autoimmune diseases and other inflammatory conditions. It may also be used in ischemic cardiovascular disease after a heart attack or in case of heart failure. The peptide also has antioxidant properties that could potentially be used to slow down the signs of aging. Numerous studies are underway on the use of this compound.

How Does a Peptide Work?

If AICAR were used as part of a treatment for type 2 diabetes and metabolic syndrome, its mechanism of action would be based on possible anti-inflammatory properties. In the case of this disease, insulin receptors become resistant to insulin. Therefore, the glucose we get from food cannot enter the cells and remains unused in the blood, which results in high blood sugar levels. Reduced insulin receptor sensitivity leads to inflammation in adipose tissue. However, as AICAR potentially has an anti-inflammatory effect, therapy with this peptide could reduce the resulting inflammation and reduce insulin resistance, increasing the sensitivity of their receptors on cells.

There are various assumptions that this peptide can also serve as a cardioprotective agent and be a potential heart attack prevention and part of heart failure treatment. When patients eat unhealthy food, there is an accumulation of LDL (better known as bad cholesterol) on the walls of blood vessels. In response, the body sends a lot of macrophages, and over time, atherosclerotic plaque is formed, the rupture of which leads to a heart attack.

The mechanism of action of AICAR is reflected in the control of lipid metabolism and, therefore, the prevention of cholesterol accumulation and subsequent heart failure. In addition, due to its possible anti-inflammatory properties, it could improve the condition of patients suffering from various cardiovascular diseases that are based on inflammation. Thus, AICAR may be used both as a therapeutic and prophylactic agent. The anti-inflammatory effect is often mentioned in the prevention and treatment of various diseases, so the question arose about how this property is realized.

Based on various studies, scientists have concluded that AICAR may be able to inhibit the secretion and activity of various pro-inflammatory cytokines that promote the creation of inflammation (mainly interleukin-1β). This property is extremely useful and can be applied to various conditions based on this type of process, including some autoimmune diseases. Most of all, the properties mentioned that could be used in the therapy of many states and diseases are actually based on the primary function of this peptide, which is the selective activation of AMP-activated protein kinase.

Chemical Structure

The structure of AICA ribonucleotide is shown in the figure. Its structure contains:

• nine carbon atoms,
• fifteen hydrogen atoms,
• four nitrogen atoms,
• eight oxygen atoms,
• phosphorus atom.

Its chemical name is (1R)-1-(5-Amino-4-carbamoyl-1H-imidazol-1-yl)-1,4-anhydro-D-ribitol 5-(dihydrogen phosphate).

Side Effects

Muscle Atrophy

AMPK can increase the expression of genes specific to the process of autophagy (known as ATG). The enzyme achieves this effect by activating a specific transcription factor (FoxO3), thus leading to the initiation of autophagy, which can ultimately lead to skeletal muscle atrophy. Since AICAR is the main activator of this enzyme, the unwanted effect of muscle loss can occur after its use.

Metabolic Problems

Although AICAR as an AMPK activator has metabolic regulatory properties, chronic activation of this enzyme can lead to serious consequences such as obesity, hyperphagia, and even disruption of endogenous hormone secretion. Studies have shown that it can also impair adipose tissue formation and decrease pancreatic β-cell function.
Problems with Gastrointestinal Tract

Various adenosine monophosphate analogs that activate AMPK, such as AICAR, can cause gastrointestinal problems and symptoms such as nausea, abdominal pain, bloating, constipation, or Dwhen administered in higher-than-recommended doses.
Other Side Effects

Excessive activation of AMPK (which can occur with the use of AICAR or other adenosine monophosphate analogues) or activation of this enzyme in the wrong tissue can cause serious side effects such as neurodegenerative disorders and other neurological symptoms or prevent cells from actively dividing through the process of mitosis as they normally do in a healthy organism. If previously consumed, AICAR accumulates in the body, severe metabolic disorders can occur, some of which have already been mentioned.
Is AICAR Safe to Use?

Even if certain side effects can occur if AMPK is chronically activated or activation occurs in the wrong tissue, AICAR, as an activator of this enzyme, shows more potentially beneficial effects that can be applied as part of treatment for certain diseases. The mentioned side effects do not have a significant clinical impact because they occur extremely rarely and in cases when the peptide was not applied according to the recommended dose and indications. Moreover, scientists assume this peptide is completely safe for use if used as directed. AICAR will certainly be the subject of research in the future to further determine the ratio of benefit and harm.