Propionyl-L-carnitine supplement health benefit and medical uses

Propionyl-L-carnitine is a short-chain fatty ester of carnitine and a naturally occurring substance required in mammalian energy metabolism. Although the mechanism of action of Propionyl-L-carnitine remains incompletely understood, it appears that its cardiovascular effects are in part related to vasodilatation and enhanced blood flow.

Propionyl-L-carnitine and claudication
Levo Propionyl-carnitine improves the effectiveness of supervised physical training on the absolute claudication distance in patients with intermittent claudication.
Angiology. 2008 Feb-March. Angiology Care Unit of University Hospital of Padua, Italy.
The mechanisms by which supervised physical training improves walking ability in patients with intermittent claudication are microcirculatory, rheological, and metabolic. The main mechanism of levo propionyl carnitine is metabolic; it increases the walking ability in claudicants, providing an additional energy to the ischemic muscle by an anaplerotic activity. Therefore, the current study was carried out to ascertain whether the combined treatment has a synergistic effect. The results confirm the effectiveness of supervised physical training in patients with intermittent claudication, and we recommend the use of propionyl carnitine during the exercise training program, at least in patients with severe claudication. Finally, underlining the similar mechanisms of physical training and LPC treatment, the study suggests that a cycle of propionyl l carnitine infusions could be advised in patients with severe claudication who cannot be included, for various reasons, in an exercise rehabilitation program.

Heart disease and blood flow
Propionyl-L-Carnitine Improves Postischemic Blood Flow Recovery and Arteriogenetic Revascularization and Reduces Endothelial NADPH-Oxidase 4-Mediated Superoxide Production.
Arterioscler Thromb Vasc Biol. 2010 Jan 7. Stasi MA, Scioli MG, Arcuri G, Mattera GG, Lombardo K, Marcellini M, Riccioni T, De Falco S, Pisano C, Spagnoli LG, Borsini F, Orlandi A. General Pharmacology and Oncology Department Sigma-Tau, Pomezia, Rome, Italy; Anatomic Pathology, Tor Vergata University, Rome, Italy; Experimental Medicine and Biochemical Sciences, Tor Vergata University of Rome, Italy; Institute of Genetics and Biophysics, CNR, Napoli, Italy.
The beneficial effect of the natural compound propionyl-L-carnitine (PLC) on intermittent claudication in patients with peripheral arterial disease is attributed to its anaplerotic function in ischemic tissues, but inadequate information is available concerning action on the vasculature. We investigated the effects of PLC in rabbit hind limb collateral vessels after femoral artery excision, mouse dorsal air pouch, chicken chorioallantoic membrane, and vascular cells by angiographic, Doppler flow, and histomorphometrical and biomolecular analyses. PLC injection accelerated hind limb blood flow recovery after 4 days (P<0.05) and increased angiographic quadriceps collateral vascularization after 7 days Histomorphometry confirmed the increased vascular area, with unchanged intramuscular capillary density. PLC-induced dilatative adaptation, and growth was found associated with increased inducible nitric oxide synthase and reduced arterial vascular endothelial growth factor and intracellular adhesion molecule-1 expression. PLC also increased vascularization in air pouch and chorioallantoic membrane (P<0.05), particularly in large vessels. PLC increased endothelial and human umbilical vascular endothelial cell proliferation and rapidly reduced inducible nitric oxide synthase and NADPH-oxidase 4-mediated reactive oxygen species production in human umbilical vascular endothelial cells; NADPH-oxidase 4 also regulated NF-kappaB-independent intracellular adhesion molecule-1 expression. Our results provided strong evidence that PLC improves postischemic flow recovery and revascularization and reduces endothelial NADPH-oxidase-related superoxide production. We recommend that Propionyl-L-Carnitine should be included among therapeutic interventions that target endothelial function.

Erectile dysfunction or impotence
Effect of propionyl-L-carnitine, L-arginine and nicotinic acid on the efficacy of vardenafil in the treatment of erectile dysfunction in diabetes.
Curr Med Res Opin. 2009 Sep; Gentile V, Antonini G, Antonella Bertozzi M, Dinelli N, Rizzo C, Ashraf Virmani M, Koverech A. Dipartimento di Urologia U Bracci, Sapienza University of Rome, Italy.
The association of diabetes-related vascular damage and the role of metabolic factors in erectile dysfunction are well known in the literature. The compounds propionyl-L-carnitine (PLC), L-arginine (L-Arg) and nicotinic acid have numerous metabolic actions which have been reported to improve endothelial function. This study investigated the administration of the combination of these three compounds alone and in association with an inhibitor of 5-phosphodiesterase (5PDE), vardenafil, on endothelial function in diabetic patients with erectile dysfunction. A total of 40 patients aged between 50 and 60 years with insulin-dependent diabetes (IDDM) for 3-4 years were selected from 509 patients presenting with erectile dysfunction. The patients were randomly subdivided into four groups of ten to be treated for 12 weeks. Group A was administered one sachet each day of test formulation containing PLC, L-Arg and nicotinic acid (Ezerex); group B with one 20 mg capsule of vardenafil (Levitra) twice a week; group C was treated with one sachet each day of the test formulation plus vardenafil 20 mg twice a week. Group D was administered placebo capsules twice weekly. Endothelial function was evaluated by examining flow-mediated dilation (FMD) and erectile function was estimated with the International Index of Erectile Function (IIEF5) questionnaire in all subjects. At the end of treatment group A showed an increment of 2 points in the IIEF5; group B showed an increment of 4 points; group C, the group which was administered all the treatments, showed an increment of 5 points, and group D, treated with placebo, showed no increment in the IIEF5. Although there was a small number of subjects in this study the data suggest that the test formulation may improve the endothelial situation in diabetes. The test formulation together with vardenafil was better than the 5PDE inhibitor alone, but further studies are needed to confirm these findings.

Transplantation
Propionyl-L-carnitine prevents early graft dysfunction in allogeneic rat kidney transplantation.
Kidney Int. 2008 December. Azzollini N, Cugini D, Cassis P, Pezzotta A, Gagliardini E, Abbate M, Arduini A, Peschechera A, Remuzzi G, Noris M. Azzollini N, Cugini D, Cassis P, Pezzotta A, Gagliardini E, Abbate M, Arduini A, Peschechera A, Remuzzi G, Noris M. Department of Immunology and Organ Transplantation, Ospedali Riuniti-Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Ischemia-reperfusion injury is an important cause of graft failure. Because carnitine regulates substrate flux and energy balance across membranes which may be deranged in ischemia we determined whether its use was effective in preventing kidney injury in an allogeneic transplant model. Brown Norway rats received a Lewis rat kidney transplant and were then treated with cyclosporine A to avoid rejection. The grafts were stored in Belzer solution supplemented with propionyl-L-carnitine during the cold ischemia period. Compared to rats receiving untreated kidneys but with equal cold ischemia times, the post-transplant serum creatinine values of the carnitine-treated transplants were significantly lower. Histological evaluation 16 h after transplant showed that propionyl-L-carnitine significantly inhibited tubular necrosis and neutrophil infiltration of the allografts and improved the 3 month graft survival. Treated transplants also had decreased lipid peroxidation, inducible nitric oxide synthase expression and protein nitration compared to the untreated grafts. Post-transplant serum creatinine levels were significantly reduced and graft survival was slightly prolonged in rats not receiving cyclosporine A treatment and transplanted with a kidney treated with propionyl-L-carnitine. The efficacy of propionyl-L-carnitine to modulate ischemia-reperfusion injury during transplantation suggests that its use in human transplantation is worth testing.

Absorption
Comparison of pharmacokinetics of L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine after single oral administration of L-carnitine in healthy volunteers.
Clin Invest Med. 2009 Feb 1; The Affiliated Hospital of Medical College, Qingdao University, Qingdao, China.
To investigate the pharmacokinetics of L-carnitine and its analogues, acetyl-L-carnitine and propionyl-L-carnitine in healthy volunteers after single L-carnitine administration. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. L-carnitine has a greater maximum plasma concentration than acetyl-L-carnitine and propionyl-L-carnitine. L-carnitine also has a longer half-life than ALC and propionyl-L-carnitine. These data may have important implications in the designing of dosing regimens for L-carnitine or its analogues, such as ALC or propionyl-L-carnitine.