Peak ATP With GlycoCarn by Life Extension

EFFECTIVE

• Cardiovascular disease diagnosis. Adenosine intravenous infusion is FDA-approved for use in cardiac stress testing to diagnose coronary artery disease (CAD). Details: Adenosine is infused at a dose of 0.14 mg/kg/minute for 6 minutes as an adjunct to thallium stress testing in patients who are unable to exercise adequately (15). Caffeine is a competitive antagonist at adenosine receptors and should be avoided for 24 hours prior to the test (9157,11770).
• Paroxysmal supraventricular tachycardia. Adenosine intravenous injection is FDA-approved for acute management of paroxysmal supraventricular tachycardia (PSVT). Details: Adenosine is indicated for termination of PSVT. It is given intravenously as a bolus of 6 mg over 1-2 seconds, followed by 1 or 2 further boluses of 12 mg at 1-2 minute intervals if necessary (15).

POSSIBLY EFFECTIVE

• Cachexia. Intravenous adenosine triphosphate may be beneficial in cachexic patients with various cancers. Oral adenosine has not been evaluated for this purpose. Details: Administering adenosine triphosphate (ATP) intravenously, up to 75 mcg/kg/minute for 30 hours every 2-4 weeks for up to 28 weeks, seems to stabilize body composition, appetite, and dietary intake, and to improve quality of life in people with advanced non-small-cell lung cancer and other tumors (9149,9151,9152).

POSSIBLY INEFFECTIVE

• Myocardial Infarction (MI). Intravenous or intracoronary adenosine does not seem to be beneficial for acute coronary syndrome. Oral adenosine has not been evaluated for this purpose. Details: A meta-analysis of 17 clinical studies in patients with acute coronary syndrome undergoing revascularization shows that administration of intracoronary or intravenous adenosine does not reduce major adverse cardiac events when compared with placebo. Adenosine also does not reduce all-cause death, non-fatal MI, or heart failure when compared with placebo. However, adenosine is associated with an increased risk of atrioventricular block (111744). The interpretation of these findings is limited by the heterogeneity of the included studies. In addition, most studies were in patients treated with percutaneous coronary intervention; the generalizability of these results to patients treated with thrombolysis is unclear.
• Postoperative nausea and vomiting (PONV). Parenteral adenosine does not seem to be beneficial for PONV. Oral adenosine has not been evaluated for this purpose. Details: A meta-analysis of 4 clinical studies shows that adenosine, administered intravenously or intrathecally, does not reduce PONV when compared with placebo (97981).
• Postoperative pain. Parenteral adenosine does not seem to be helpful for postoperative pain. Oral adenosine has not been evaluated for this purpose. Details: A meta-analysis of 9 clinical studies shows that adenosine, administered intravenously or intrathecally, does not reduce postoperative pain scores when compared with placebo (97981).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. It is unclear if topical adenosine is beneficial in patients with androgenic alopecia. Details: Preliminary clinical research shows that topical application of adenosine 0.75% solution to the scalp twice daily for 6 months does not improve hair growth in males with androgenic alopecia. However, patients applying topical minoxidil 5% (Rogaine) also experienced no improvement at 6 months, with over 97% of patients in each group reporting less than 30% hair growth in the affected area (93689).
• Athletic performance. It is unclear if oral adenosine triphosphate is beneficial for improving athletic performance. Details: Preliminary clinical research in healthy males performing 10 repeated sprinting bouts shows that taking adenosine triphosphate (PEAK ATP, TSI USA, Inc) 400 mg orally daily for 2 weeks prior to the exercise increases muscle excitability during the first two bouts and attenuates reductions in power output and muscle excitability during the final three bouts when compared with placebo (97982).
• Erectile dysfunction (ED). Oral adenosine monophosphate has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking adenosine monophosphate 200 mg plus arginine aspartate 8 grams orally 1-2 hours prior to sexual intercourse improves erectile function and sexual satisfaction scores when compared with placebo in patients with erectile dysfunction (93690). It is not clear if this effect is due to adenosine, arginine, or the combination.
• Hearing loss. Oral adenosine triphosphate has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with idiopathic sudden sensorineural hearing loss shows that taking adenosine triphosphate 300 mg orally daily with vitamin B12 1.5 mg orally daily for 8-16 weeks is associated with modestly reduced hearing loss after 4-6 months when compared with taking this combination for less than 8 weeks (104924). The validity of this finding is limited by the observational nature of the study and the lack of a control group.
• Herpes labialis (cold sores). It is unclear if intramuscular adenosine monophosphate is beneficial in patients with herpes labialis. Oral adenosine has not been evaluated for this purpose. Details: Preliminary clinical research shows that a gel formulation of adenosine monophosphate 1.5-2 mg/kg IM every other day for a total of 9-12 injections might accelerate the healing of cold sores and reduce the risk of recurrence (9590). The validity of these findings is limited by the lack of a control group.
• Herpes zoster (shingles). It is unclear if intramuscular adenosine monophosphate is beneficial in adults with herpes zoster. Oral adenosine has not been evaluated for this purpose. Details: Preliminary clinical research in adults with shingles shows that giving adenosine monophosphate in a gel formulation, 100 mg IM three times weekly for 4 weeks, increases the number of patients classified as pain-free at 4 weeks by 45% and might also accelerate viral clearance when compared with placebo (9155,10067).
• Lung cancer. Intravenous adenosine triphosphate does not seem to be beneficial in patients with advanced non-small-cell lung cancer (NSCLC). Oral adenosine has not been evaluated for this purpose. Details: One very small clinical study in adults with advanced NSCLC shows that giving adenosine triphosphate in at least 3, 96-hour infusions at a dose of 50 mcg/kg/min or more does not induce complete or partial responses when compared to baseline (9154).
• Neuropathic pain. It is unclear if intrathecal adenosine is beneficial for experimentally-induced neuropathic pain. Oral adenosine has not been evaluated for this purpose. Details: Preliminary clinical research in healthy volunteers with areas of allodynia and hyperalgesia induced by topical capsaicin shows that giving single doses of intrathecal adenosine 0.5-2 mg modestly reduces these areas (9157). The clinical significance of this finding is unclear.
• Porphyria cutanea tarda. It is unclear if oral adenosine monophosphate is beneficial in patients with porphyria cutanea tarda. Details: A case series of 21 patients with porphyria cutanea tarda shows that taking adenosine monophosphate 160-200 mg orally daily for at least 4 weeks resolves or reduces symptoms, including photosensitivity, hyperpigmentation, and hypertrichosis, and decreases urinary and fecal excretion of porphyrins, when compared to baseline (106423). The validity of these findings is limited by the lack of a control group.
• Pulmonary hypertension. Adenosine given by central venous infusion might be beneficial in patients who develop pulmonary hypertension during cardiac surgery. Details: Preliminary clinical research in patients who develop pulmonary hypertension during cardiac surgery shows that giving a central venous infusion of adenosine, 50 mcg/kg/minute for 15 minutes after weaning from cardiopulmonary bypass, produces pulmonary vasodilation and reduces mean pulmonary arterial pressure (106424). The validity of these findings is limited by the lack of a control group. More evidence is needed to rate adenosine for these uses.

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POSSIBLY EFFECTIVE

• Angina. Oral propionyl-L-carnitine may improve myocardial ischemia and exercise capacity in patients with chronic, stable angina. Details: In patients with chronic, stable angina, taking propionyl-L-carnitine 500 mg three times daily orally for 4-6 weeks seems to produce small improvements in myocardial ischemia and exercise capacity (1579,1580,1581). In one study, exercise duration was increased by 5% when compared with placebo. However, angina attacks were not affected (1580). In another study, the number of angina attacks was reduced by approximately 67% when compared with placebo, although there was no change in nitroglycerin use (1581).
• Cardiovascular disease (CVD). Intravenous propionyl-L-carnitine may improve left ventricular function and decrease myocardial ischemia. Details: In patients with chronic myocardial ischemia, intravenous administration of single doses of propionyl-L-carnitine 15 mg/kg may improve left ventricular function and cardiac output, as well as decrease myocardial ischemia (1571,1572,1573). In one study, left ventricular fraction increased by 18% when compared with placebo (1573).
• Congestive heart failure (CHF). Oral propionyl-L-carnitine may improve left ventricular function and exercise capacity in patients with class II or III CHF. Details: In patients with class II or III CHF, taking propionyl-L-carnitine 500 mg three times daily for up to 6 months seems to improve left ventricular function and exercise capacity (1575,1582,1583). Some research has found that exercise time increases by up to approximately 26% (1575,1583) or by an additional minute when compared with placebo (1582). Also, ejection fraction is improved by 13% when compared with placebo (1583).
• Intermittent claudication. Oral and intravenous propionyl-L-carnitine may improve walking capacity and quality of life in some patients with intermittent claudication and peripheral vascular disease. Details: A meta-analysis, as well as individual clinical trials, suggest that taking oral propionyl-L-carnitine 1-4 grams daily in divided doses increases walking distance by up to 45 meters when compared with placebo (1434,1435,1436,1576,10456,94439,94446). One study suggests an increase in walking time of 1.33 minutes (94446). Taking propionyl-L-carnitine 1-3 grams daily over 6 months also seems to improve quality of life when compared with placebo. Oral propionyl-L-carnitine might be more effective in individuals with the ability to walk shorter distances, specifically less than 250 meters, at baseline (1436). One small clinical study failed to show a benefit when propionyl-L-carnitine 2 grams daily was added to exercise; however, it may not have been adequately powered to detect a difference between groups (94443). Intravenous propionyl-L-carnitine also increases claudication distance and maximal walking distance when given as a single dose of 600 mg or daily doses of 600 mg for 4 days. Maximal walking distance increases by 28% to 42% when compared with placebo (1437).
• Ulcerative colitis. Oral propionyl-L-carnitine may improve clinical response and remission rates in patients with mild to moderate ulcerative colitis. Details: In patients with mild to moderate ulcerative colitis receiving conventional therapy, clinical research shows that taking colonic-release propionyl-L-carnitine tablets 0.5-1 gram twice daily for 4 weeks improves clinical response and remission rates (94447,94448,94449). Clinical response and clinical remission occur in 55% to 72% of patients treated with propionyl-L-carnitine when compared with baseline or placebo (94447,94448). In one study, propionyl-L-carnitine increases the rate of clinical response by 44% when compared with placebo. However, a significant difference in remission rate when compared with placebo was lacking (94448).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related testosterone deficiency. Oral propionyl-L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in older males shows that taking propionyl-L-carnitine 2 grams, in combination with acetyl-L-carnitine 2 grams, daily for 6 months seems to attenuate symptoms of androgen decline. The combination appears to be similar to testosterone for improving sexual dysfunction, depression, and fatigue (12353). It is unclear if these findings are due to propionyl-L-carnitine, acetyl-L-carnitine, or the combination.
• Athletic performance. It is unclear if oral glycine propionyl-L-carnitine is beneficial for improving athletic performance in young resistance-trained males; the available research is mixed. Details: Some clinical research shows that taking a specific ingredient called glycine propionyl-L-carnitine (GlycoCarn, Sigma Ta Health Sciences, S.p.A.) 4.5 grams as a single dose 90 minutes before testing improves peak anaerobic power by 4% to 16% in repeated cycling sprints when compared with placebo (94444). However, taking 1.5, 3, or 4.5 grams of this product daily for 28 days does not improve anaerobic performance of repeated high speed high intensity bouts when compared with placebo. Additionally, preliminary research shows that taking 3 grams or 4.5 grams daily might actually be detrimental to performance. However, the study size was too small for definitive conclusions (94445). The reason for the discrepancy between studies is not clear. However, it is possible that a single dose prior to exercise is more effective than repeated dosing.
• Androgenic alopecia. Topical propionyl-L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in males and females with androgenic alopecia shows that applying 1 mL of a combination lotion (TRINOV Lozione Anticaduta Uomo/Donna, Fidia Farmaceutici s.p.a.) containing undisclosed quantities of propionyl-L-carnitine, gamma-linolenic acid, and S-equol to the scalp daily for 6 months increases total hair count and the proportion of actively growing hair to senescent hair, but not hair diameter, when compared with baseline (100348). The validity of these findings is limited by the lack of a comparator group. Also, it is unclear if these effects are due to propionyl-L-carnitine, the other ingredients, or the combination.
• Crohn disease. It is unclear if oral propionyl-L-carnitine is beneficial in patients with mild to moderate Crohn disease. Details: A small clinical study in patients with mild to moderate Crohn disease receiving conventional therapy shows that taking colonic-release propionyl-L-carnitine tablets 1 gram twice daily for 4 weeks results in clinical remission in 75% of patients (94447). The validity of this study is limited by the lack of a comparator group.
• Chronic fatigue syndrome (CFS). It is unclear if oral propionyl-L-carnitine is beneficial in patients with CFS. Details: Preliminary clinical research in patients with CFS shows that taking propionyl-L-carnitine 2 grams daily for 6 months improves general fatigue in up to 63% of patients when compared with baseline. The combination of propionyl-L-carnitine and acetyl-L-carnitine appears to be less effective than either supplement alone, with only 37% of patients taking this combination achieving improvement when compared with baseline (11788).
• Erectile dysfunction (ED). Oral propionyl-L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In males with ED and diabetes, combination therapy with propionyl-L-carnitine and sildenafil may improve erectile function better than sildenafil alone. In males unresponsive to 8 uses of sildenafil, adding propionyl-L-carnitine 2 grams daily to continued twice weekly doses of sildenafil 50 mg seems to improve erections and successful intercourse attempts more than sildenafil alone (12682). Also, preliminary clinical research in adults with ED shows that taking a specific combination of propionyl-L-carnitine 250 mg, niacin 20 mg, and arginine 2500 mg daily (Ezerex, Sigma-Tau) for 3 months substantially improves erections in 46% of patients and modestly improves sexual function in 37% of patients (94442). It is unclear if these findings are due to propionyl-L-carnitine, other ingredients, or the combination.
• Peyronie disease. Oral propionyl-L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with advanced or resistant Peyronie disease shows that receiving the combination of oral propionyl-L-carnitine 2 grams daily with injectable verapamil for 3 months improves erectile function by 42% compared with no change in a group receiving oral tamoxifen with injectable verapamil. The need for surgery was reduced from 27% in the tamoxifen group to 2% in the propionyl-L-carnitine group. Pain was reduced in 97% of all patients (12683). It is unclear if these findings are due to propionyl-L-carnitine, verapamil, or the combination. More evidence is needed to rate propionyl-L-carnitine for these uses.

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LIKELY SAFE ...when adenosine is used intravenously and appropriately. Adenosine injection (Adenocard, Adenoscan) is an FDA-approved prescription drug (15).

POSSIBLY SAFE ...when adenosine triphosphate (ATP) is used intravenously and appropriately. ATP appears to be safe in intravenous doses of 75 mcg/kg per minute for 30 hours given every 2 weeks for 28 weeks (9149,9154). There is insufficient reliable information available about the safety of adenosine when used orally or intramuscularly.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally and appropriately at doses up to 3 grams daily for up to 6 months (1434,1435,1436,1437,94439,94446,94447,94448). ...when single intravenous doses of 15 to 30 mg/kg are used under appropriate medical supervision (1571,1572,1573,1575).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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CARBAMAZEPINE (Tegretol) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Carbamazepine might increase the risk of heart block when used concomitantly with adenosine.  Details Carbamazepine and adenosine can both cause heart block. Giving them concurrently might produce an additive effect (15).

DIPYRIDAMOLE (Persantine) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = D Dipyridamole can increase the therapeutic and toxic effects of adenosine.  Details Dipyridamole decreases the metabolism of adenosine. Intravenous infusion of adenosine in patients who are taking dipyridamole can cause dizziness, bradycardia, and syncope. Dipyridamole should be discontinued for several days prior to a cardiac stress test using adenosine (12209).

METHYLXANTHINES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Methylxanthines are competitive antagonists of adenosine and can block its pharmacologic effects.  Details The methylxanthines, aminophylline, caffeine, and theophylline, can block the effects of adenosine by acting as competitive antagonists at adenosine cell surface receptors (9157). It is recommended that methylxanthines be avoided for 24 hours prior to cardiac stress tests (11770).

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ACENOCOUMAROL (Sintrom) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, propionyl-L-carnitine might increase the anticoagulant effects of acenocoumarol.  Details L-carnitine, the parent compound of propionyl-L-carnitine, might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant similar to warfarin, but shorter-acting (9878,12165). There are at least two case reports of INR elevation when L-carnitine was taken with acenocoumarol. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product (12165). It is unclear if such an interaction would also occur with propionyl-L-carnitine.

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, acetyl-L-carnitine might decrease the effectiveness of thyroid hormone replacement.  Details L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting entry of thyroid hormone into the nucleus of cells (12761). Taking L-carnitine also seems to diminish some of the symptoms of hyperthyroidism (8047). It is unclear if such an interaction would occur with propionyl-L-carnitine.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, propionyl-L-carnitine might increase the anticoagulant effects of warfarin.  Details L-carnitine, the parent compound of propionyl-L-carnitine, might increase the anticoagulant effects of acenocoumarol, a shorter-acting oral anticoagulant similar to warfarin (9878,12165). There is not enough information to know whether this interaction occurs with propionyl-L-carnitine and warfarin.

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General ...Intravenously, the prescription form of adenosine can cause cardiovascular and respiratory adverse effects. When used orally or intramuscularly, no adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Intravenously: Chest pain, dizziness, dyspnea, facial flushing, headache, hypotension, nausea, nervousness, numbness, paresthesias, and tingling.
Serious Adverse Effects (Rare):
Intravenously: Arrhythmias, first- and second-degree heart block, hypersensitivity reactions, myocardial infarction, ST segment depression, and ventricular tachycardia.

Cardiovascular ...Intravenously, adenosine causes chest pain, palpitations, hypotension, and supraventricular tachycardia (15,9148). Intravenous adenosine has also been associated with arrhythmias, fatal or nonfatal cardiac arrest, ventricular tachycardia, and myocardial infarction (15). Intravenously, adenosine triphosphate (ATP) causes chest pain, particularly at doses greater than 50 mcg/kg per minute (9154).

Dermatologic ...Intravenously, adenosine causes flushing in up to 44% of patients in clinical research (15). Topically, folliculitis and pruritus can occur after application of adenosine to the scalp (93689).

Gastrointestinal ...Intravenously, adenosine can cause abdominal discomfort (15).

Neurologic/CNS ...Rapid intravenous injection of adenosine can cause headache, lightheadedness, insomnia, and anxiety (9148,9151,9152,9154,9158). New onset seizures, including tonic-clonic seizures, have also occurred (15). Intrathecally, adenosine has been reported to cause headache (9157).

Pulmonary/Respiratory ...Intravenously, adenosine can cause dyspnea, bronchospasm, bronchoconstriction, and respiratory arrest (15). Intravenously, adenosine triphosphate (ATP) causes dyspnea, which can be severe, particularly at doses greater than 50 mcg/kg/minute (9154).

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General ...Orally, propionyl-L-carnitine is well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, gastric pain, nausea, and vomiting. A metabolite of propionyl-L-carnitine has been reported to cause a fishy odor of the urine, breath, and sweat.

Gastrointestinal ...Orally, nausea, vomiting, diarrhea, and gastric pain have been reported with propionyl-L-carnitine use (1579,1580,1582,12682,94439,94443).

Musculoskeletal ...Orally, back pain was reported more frequently with propionyl-L-carnitine when compared with placebo in one clinical trial (94443).

Neurologic/CNS ...Orally, asthenia has been reported with propionyl-L-carnitine use (1579,1580,1582).

Pulmonary/Respiratory ...Orally, bronchitis was reported more frequently with propionyl-L-carnitine when compared with placebo in one clinical trial (94443).

Other ...Orally, one of the metabolites of propionyl-L-carnitine can cause the urine, breath, and sweat to have a fishy odor (12756).

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