Mitocarnitine by Cardiovascular Research

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 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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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 ...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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