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AICAR
by Bill Roberts – AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, 5-aminoimidazole-4-carboxamide ribonucleoside, acadesine) is each of several interesting things. First, it’s an important pharmacological research agent, used principally as an AMPK activator. It’s a compound which has shown extremely impressive fat-loss and endurance-enhancing effects in laboratory animals. Further, it has considerable mystique resulting from at least some use by elite European cyclists. And lastly, it’s readily available from research chemical sites and is being personally tried by many, though generally as part of stacks and combined with changes in training and/or diet.
Pause, however, may be given when considering that treatment programs for cyclists reportedly have cost in the tens to hundreds of thousands of Euros, that all reported studies in the scientific literature have used dosing which indeed would be extraordinarily costly when scaled up for human dosing, and that the experience base of bodybuilding usage at far lower doses is equivocal at best.
Mechanism of Action
AICAR’s principal mechanism of action is activation of AMPK (AMP-activated protein kinase.) As is well known, ATP (adenosine triphosphate) is produced by mitochondria as a ready-to-use energy source for biochemical processes in the cell. These processes do not use glucose, fats, or fatty acids directly as energy sources: these must first be metabolized in the mitochondria to yield ATP. When ATP is used for energy, its first product is ADP (adenosine di-phosphate), and then – if the cell is really deprived of immediate sources of energy – finally to AMP (adenosine monophosphate.)
AMP only accumulates as a cell becomes energy-deprived. Accordingly, there’s a system where the cell detects any low energy state from the concentration of AMP that’s present, and activates AMPK in response.
AMPK in turn ramps up conversion of fuel sources, including fatty acids, into ATP, as well as stimulating quite a number of other systems in the cell.
Activating AMPK, therefore, causes the same cellular machinery (so to speak) to be turned on as if the cell were energy deprived, for example from intensive exercise, or from low caloric intake.
AICAR, at sufficient and quite substantial concentration, is effective at activating AMPK and inducing a cellular state as if exercise had been performed, or energy stores were low and fat therefore needed to be burned.
Research Dosages
A number of examples will follow showing AICAR doses uses in research studies, results from treatment, and approximate human equivalent doses, assuming an about-200 lb (90 kg) human for illustration:
In “AMPK and PPARdelta agonists are exercise mimetics“:
Mice, of a strain which is genetically susceptible to obesity and diabetes, were administered AICAR at 500 mg/kg daily for 5 weeks. Their endurance capacity increased by 44%, and expression of 32 genes favorable to metabolism was increased.
Human equivalent dosing would be about 3.2 grams per day, or about 64 vials of product as commonly sold. An example cost of this many 50 mg vials (current as of 2014) would be about $1500.
In “AICAR Administration Causes an Apparent Enhancement of Muscle and Liver Insulin Action in Insulin-Resistant High-Fat-Fed Rats“:
Rats were injected subcutaneously once with AICAR at 250 mg/kg. Improvement in whole body insulin sensitivity both post-injection and at the 24 hour point was comparable to what occurs when a bout of exercise is performed rather than an AICAR injection being given.
Human equivalent dosing would, again, be about 3.2 grams per day.
In “The Full Capacity of AICAR to Reduce Obesity-Induced Inflammation and Insulin Resistance Requires Myeloid SIRT1“:
Both lean and diet-induced-obese mice were administered AICAR at 150 mg/kg daily for 5 weeks. For the lean mice AICAR provided no effect on fat mass or insulin sensitivity, but significant improvement did occur for the diet-induced-obese mice. (Interestingly, the improvement was shown to be associated with reduction of the inflammatory cytokines TNFα, IL-6, and MCP-1, and required the presence of SIRT1, just as an aside, but it helps make sense of the article title.)
Human equivalent dosing would be about 1 gram daily.
Other studies may be found, but dosings will be similar to the above.
Reputed Dosage in Elite Cycling
I do not myself have a direct example known to me personally, but reputedly typical dosage has been about 500 mg/day for about four weeks prior to an event. This is lower than human-equivalent from animal research studies, but not so much so as to strain credulity. (In contrast, for example only 50 mg per day instead of 500 mg absolutely does strain credulity, let alone the 10 mg doses used by some as part of their stacks.)
How to use AICAR
In general I would recommend against using AICAR, but if wishing to do so anyway, I would use 500 mg/day for a limited period of time such as 4 weeks. For almost all persons this would be financially impractical with 50 mg pre-prepared vials. If however able to obtain pure AICAR powder at, for example, $150 per gram and to prepare one’s own IV solutions, such an administration might cost “only” about $75/day.
The purpose would have to be improved endurance capacity; this would be a ridiculous amount to pay for fat loss benefit.
Conclusion
In general, I consider AICAR unsuitable for bodybuilding and general athletic purposes, but it can be suitable for endurance sports when a great deal is at stake. I know of no concrete reason to expect any benefit from AICAR doses at extreme low levels, relative to proven levels, such as 10-50 mg/day, and expect low dose use to be both expensive and unrewarding. In the context of a stack, however, particularly where diet and exercise are changed at the same time, a given user might attribute benefit to the AICAR part of the stack. For this reason, I expect positive claims for low dose use to continue to accumulate.
If wishing to evaluate AICAR for yourself, I’d strongly recommend keeping all other factors essentially the same, either the same as presently or as you have done before.
by Bill Roberts – AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, 5-aminoimidazole-4-carboxamide ribonucleoside, acadesine) is each of several interesting things. First, it’s an important pharmacological research agent, used principally as an AMPK activator. It’s a compound which has shown extremely impressive fat-loss and endurance-enhancing effects in laboratory animals. Further, it has considerable mystique resulting from at least some use by elite European cyclists. And lastly, it’s readily available from research chemical sites and is being personally tried by many, though generally as part of stacks and combined with changes in training and/or diet.
Pause, however, may be given when considering that treatment programs for cyclists reportedly have cost in the tens to hundreds of thousands of Euros, that all reported studies in the scientific literature have used dosing which indeed would be extraordinarily costly when scaled up for human dosing, and that the experience base of bodybuilding usage at far lower doses is equivocal at best.
Mechanism of Action
AICAR’s principal mechanism of action is activation of AMPK (AMP-activated protein kinase.) As is well known, ATP (adenosine triphosphate) is produced by mitochondria as a ready-to-use energy source for biochemical processes in the cell. These processes do not use glucose, fats, or fatty acids directly as energy sources: these must first be metabolized in the mitochondria to yield ATP. When ATP is used for energy, its first product is ADP (adenosine di-phosphate), and then – if the cell is really deprived of immediate sources of energy – finally to AMP (adenosine monophosphate.)
AMP only accumulates as a cell becomes energy-deprived. Accordingly, there’s a system where the cell detects any low energy state from the concentration of AMP that’s present, and activates AMPK in response.
AMPK in turn ramps up conversion of fuel sources, including fatty acids, into ATP, as well as stimulating quite a number of other systems in the cell.
Activating AMPK, therefore, causes the same cellular machinery (so to speak) to be turned on as if the cell were energy deprived, for example from intensive exercise, or from low caloric intake.
AICAR, at sufficient and quite substantial concentration, is effective at activating AMPK and inducing a cellular state as if exercise had been performed, or energy stores were low and fat therefore needed to be burned.
Research Dosages
A number of examples will follow showing AICAR doses uses in research studies, results from treatment, and approximate human equivalent doses, assuming an about-200 lb (90 kg) human for illustration:
In “AMPK and PPARdelta agonists are exercise mimetics“:
Mice, of a strain which is genetically susceptible to obesity and diabetes, were administered AICAR at 500 mg/kg daily for 5 weeks. Their endurance capacity increased by 44%, and expression of 32 genes favorable to metabolism was increased.
Human equivalent dosing would be about 3.2 grams per day, or about 64 vials of product as commonly sold. An example cost of this many 50 mg vials (current as of 2014) would be about $1500.
In “AICAR Administration Causes an Apparent Enhancement of Muscle and Liver Insulin Action in Insulin-Resistant High-Fat-Fed Rats“:
Rats were injected subcutaneously once with AICAR at 250 mg/kg. Improvement in whole body insulin sensitivity both post-injection and at the 24 hour point was comparable to what occurs when a bout of exercise is performed rather than an AICAR injection being given.
Human equivalent dosing would, again, be about 3.2 grams per day.
In “The Full Capacity of AICAR to Reduce Obesity-Induced Inflammation and Insulin Resistance Requires Myeloid SIRT1“:
Both lean and diet-induced-obese mice were administered AICAR at 150 mg/kg daily for 5 weeks. For the lean mice AICAR provided no effect on fat mass or insulin sensitivity, but significant improvement did occur for the diet-induced-obese mice. (Interestingly, the improvement was shown to be associated with reduction of the inflammatory cytokines TNFα, IL-6, and MCP-1, and required the presence of SIRT1, just as an aside, but it helps make sense of the article title.)
Human equivalent dosing would be about 1 gram daily.
Other studies may be found, but dosings will be similar to the above.
Reputed Dosage in Elite Cycling
I do not myself have a direct example known to me personally, but reputedly typical dosage has been about 500 mg/day for about four weeks prior to an event. This is lower than human-equivalent from animal research studies, but not so much so as to strain credulity. (In contrast, for example only 50 mg per day instead of 500 mg absolutely does strain credulity, let alone the 10 mg doses used by some as part of their stacks.)
How to use AICAR
In general I would recommend against using AICAR, but if wishing to do so anyway, I would use 500 mg/day for a limited period of time such as 4 weeks. For almost all persons this would be financially impractical with 50 mg pre-prepared vials. If however able to obtain pure AICAR powder at, for example, $150 per gram and to prepare one’s own IV solutions, such an administration might cost “only” about $75/day.
The purpose would have to be improved endurance capacity; this would be a ridiculous amount to pay for fat loss benefit.
Conclusion
In general, I consider AICAR unsuitable for bodybuilding and general athletic purposes, but it can be suitable for endurance sports when a great deal is at stake. I know of no concrete reason to expect any benefit from AICAR doses at extreme low levels, relative to proven levels, such as 10-50 mg/day, and expect low dose use to be both expensive and unrewarding. In the context of a stack, however, particularly where diet and exercise are changed at the same time, a given user might attribute benefit to the AICAR part of the stack. For this reason, I expect positive claims for low dose use to continue to accumulate.
If wishing to evaluate AICAR for yourself, I’d strongly recommend keeping all other factors essentially the same, either the same as presently or as you have done before.
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