Meta Information
ID:aicar
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Interactions
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
AICAR strongly activates AMPK, which promotes glucose uptake into cells, similar to many diabetes drugs. Combining them can cause an additive effect, leading to dangerously low blood sugar (severe hypoglycemia).
Actionable advice:
This should not be used with other diabetes medications like metformin, SGLT2 inhibitors, or insulin due to a high risk of severe hypoglycemia.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
AICAR administration normalized the oral glucose tolerance test and decreased fasting concentrations of glucose and insulin close to the level of the lean animals.
Label source:
PubMed PMID 12086950: Buhl ES et al., Diabetes (2002) - long-term AICAR in insulin-resistant rats
Action type:
avoid
Target id:
/condition/gout-hyperuricemia
Target name:
Gout or High Uric Acid
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
AICAR is broken down through the purine pathway, which significantly increases the production of uric acid. In individuals with a history of gout or high uric acid, this can trigger painful gout attacks or cause kidney stones.
Actionable advice:
AICAR should not be taken with a history of gout or elevated uric acid levels.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Uric acid, the end product of purine metabolism in humans, was the major metabolite of acadesine in plasma and accounted for all of the total, plasma 14C at 6 hours after infusion.
Label source:
PubMed PMID 8227467: Dixon R et al., J Clin Pharmacol (1993) - acadesine (AICA-riboside) disposition and metabolism in healthy men
Source url:
Exact phrase from label:
the incidence of adverse events was similar in the acadesine vs placebo groups, with the exception of a transient increase in serum uric acid in the acadesine group.
Label source:
PubMed PMID 9002496: Mangano DT, JAMA (1997) - meta-analysis of 5 RCTs, 4043 CABG patients
Action type:
avoid
Target id:
/condition/renal-impairment
Target name:
Kidney Disease
Severity:
moderate
Interaction type:
adverse
Nature:
conditional
Temporal spacing:
null
Description:
AICAR and its byproducts, including excess uric acid, are cleared by the kidneys. Impaired kidney function can lead to the accumulation of these substances to toxic levels, worsening both kidney damage and other side effects.
Actionable advice:
AICAR is best avoided in severe kidney impairment. With mild-to-moderate impairment, it is best used cautiously with monitoring of uric acid and kidney function (eGFR/creatinine), reducing the dose or stopping if uric acid or markers of renal stress rise.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Urine and fecal recoveries over 2 weeks accounted for 48% of the total 14C dose, with 44% excreted in urine and 4% in feces. Only 5% of the dose was excreted in urine as intact acadesine. Uric acid was the major metabolite in urine together with small amounts of hypoxanthine.
Label source:
PubMed PMID 8227467: Dixon R et al., J Clin Pharmacol (1993) - renal excretion of acadesine/uric acid
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
The effects of this potent metabolic modulator on fetal development are unknown and could be harmful. It interferes with fundamental cellular processes like growth and energy regulation.
Actionable advice:
AICAR is absolutely contraindicated during pregnancy.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
It is not known if AICAR passes into breast milk, but due to its powerful effects on cellular metabolism, it poses a significant potential risk to a nursing infant.
Actionable advice:
AICAR should not be used while breastfeeding.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
avoid
Target id:
/biomarker/uric-acid
Target name:
Uric Acid Levels
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
AICAR's metabolic breakdown directly and significantly increases the body's production of uric acid, a waste product linked to gout and kidney stones.
Actionable advice:
Regularly monitor uric acid blood levels while using AICAR; discontinue if levels rise significantly.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Uric acid, the end product of purine metabolism in humans, was the major metabolite of acadesine in plasma and accounted for all of the total, plasma 14C at 6 hours after infusion.
Label source:
PubMed PMID 8227467: Dixon R et al., J Clin Pharmacol (1993) - acadesine (AICA-riboside) disposition and metabolism in healthy men
Source url:
Exact phrase from label:
the incidence of adverse events was similar in the acadesine vs placebo groups, with the exception of a transient increase in serum uric acid in the acadesine group.
Label source:
PubMed PMID 9002496: Mangano DT, JAMA (1997) - meta-analysis of 5 RCTs, 4043 CABG patients
Action type:
avoid
Target id:
/intervention/dipyridamole
Target name:
Dipyridamole
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Dipyridamole increases levels of adenosine, a signaling molecule. Since AICAR raises endogenous adenosine levels, their combined use can cause excessive vasodilation, leading to a severe drop in blood pressure (hypotension) and slow heart rate (bradycardia).
Actionable advice:
This combination should be avoided due to the high risk of severe cardiovascular side effects.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Acadesine (AICA-riboside) is a purine nucleoside analog with anti-ischemic properties that is currently being studied (Phase 3) for the prevention of adverse cardiovascular outcomes in patients undergoing coronary artery bypass graft (CABG) surgery.
Label source:
PubMed PMID 8227467: Dixon R et al., J Clin Pharmacol (1993) - acadesine characterized as an adenosine-regulating agent
Action type:
avoid
Target id:
/class/mtor-inhibitors
Target name:
mTOR Inhibitors (e.g., Rapamycin)
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
null
Description:
AICAR activates AMPK, which naturally inhibits the mTOR pathway, while drugs like rapamycin inhibit mTOR directly. Using them together results in a powerful, dual-pronged suppression of mTOR, which could enhance intended effects but also increase side effects like impaired healing or immune suppression.
Actionable advice:
It is worth being aware that this combination strongly inhibits mTOR, potentially amplifying both benefits and side effects.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
the western blotting results revealed that AICAR stimulated AMPK activation and inhibited angiogenesis and inflammation possibly by subsequently suppressing mTOR phosphorylation.
Label source:
PubMed PMID 30856534: Jiang L et al., Biomed Pharmacother (2019) - AICAR acts via the AMPK-mTOR pathway
Action type:
informational_none
Target id:
/intervention/intermittent-fasting
Target name:
Fasting or Caloric Restriction
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Fasting naturally activates AMPK as cellular energy levels drop. AICAR artificially enhances this same pathway, potentially deepening the metabolic benefits of a fasted state but also increasing the risk of hypoglycemia.
Actionable advice:
This is best used with caution during fasting periods, and it is a good idea to monitor blood glucose closely to prevent it from dropping too low.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
During acute starvation, autophagy is rapidly engaged by AMPK (AMP-activated protein kinase) activation and MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) inhibition to maintain energy homeostasis and cell survival.
Label source:
PubMed PMID 33734022: Paquette M et al., Autophagy (2021) - starvation engages AMPK (the pathway AICAR activates)
Action type:
monitor
Target id:
/class/nephrotoxic-agents
Target name:
Drugs Harmful to Kidneys (e.g., NSAIDs)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
AICAR increases uric acid, which can be stressful for the kidneys. Combining it with other drugs known to be hard on the kidneys (nephrotoxic) may compound the risk of kidney injury.
Actionable advice:
Extreme caution is warranted when combining this with other potentially kidney-damaging agents, and it is worth monitoring renal function.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Exact phrase from label:
Uric acid, the end product of purine metabolism in humans, was the major metabolite of acadesine in plasma and accounted for all of the total, plasma 14C at 6 hours after infusion.
Label source:
PubMed PMID 8227467: Dixon R et al., J Clin Pharmacol (1993) - acadesine (AICA-riboside) disposition and metabolism in healthy men
Action type:
monitor
Target id:
/dietary/purine-rich-foods
Target name:
High-Purine Foods
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Foods high in purines (like organ meats, sardines, and some game meats) are broken down into uric acid. Consuming these foods while taking AICAR adds to the already high uric acid load, increasing the risk of gout.
Actionable advice:
Strictly limit or avoid high-purine foods to minimize the risk of dangerously high uric acid levels.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Exact phrase from label:
Uric acid, the end product of purine metabolism in humans, was the major metabolite of acadesine in plasma and accounted for all of the total, plasma 14C at 6 hours after infusion.
Label source:
PubMed PMID 8227467: Dixon R et al., J Clin Pharmacol (1993) - acadesine (AICA-riboside) disposition and metabolism in healthy men
Action type:
avoid
Target id:
/dietary/alcohol-acute
Target name:
Alcohol (Acute Consumption)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Alcohol consumption can independently raise uric acid levels and increase the risk of hypoglycemia. These effects are additive with those of AICAR, increasing the risk of both gout and low blood sugar.
Actionable advice:
Alcohol consumption is best avoided or strictly limited while using AICAR.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Exact phrase from label:
Uric acid, the end product of purine metabolism in humans, was the major metabolite of acadesine in plasma and accounted for all of the total, plasma 14C at 6 hours after infusion.
Label source:
PubMed PMID 8227467: Dixon R et al., J Clin Pharmacol (1993) - acadesine (AICA-riboside) disposition and metabolism in healthy men
Action type:
avoid
Target id:
/intervention/exercise
Target name:
Exercise
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
0
Description:
Both strenuous exercise and AICAR are powerful activators of the AMPK pathway. Taking AICAR before a workout may enhance endurance and the metabolic benefits of exercise, but it is a banned performance-enhancing substance for this reason.
Actionable advice:
If used, taking it approximately one hour before exercise may amplify metabolic effects.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Unexpectedly, even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%.
Label source:
PubMed PMID 18674809: Narkar VA et al., Cell (2008) - AICAR is an orally active AMPK agonist and exercise mimetic
Action type:
separate