Critical update for the clinical use of L-carnitine analogs in cardiometabolic disorders

Mingorance, Carmen; Rodríguez‐Rodríguez, Rosalía; Justo, María Luisa; Sotomayor, Marı́a Álvarez de; Herrera, Marcelino

doi:10.2147/vhrm.s14356

Cited by 19 publications

(18 citation statements)

References 69 publications

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“…The acylcarnitines themselves are seemingly attractive candidates; however, the weight of evidence at this stage suggests that these metabolites function in a homeostatic capacity to relieve mitochondrial stress (Figure 1) (Muoio et al, (in press), Mingorance et al, 2011; Noland et al, 2009; Power et al, 2007). Another hypothesis that has gained momentum in recent years centers on the premise that mitochondrial-derived ROS modulate insulin signaling (Bloch-Damti and Bashan, 2005; Evans et al, 2005).…”

Section: Mitochondrial Stress: a Contemporary View Of The Randle Cyclementioning

confidence: 99%

Lipid-Induced Mitochondrial Stress and Insulin Action in Muscle

2012

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Summary The interplay between mitochondrial energetics, lipid balance and muscle insulin sensitivity has remained a topic of intense interest and debate for decades. One popular view suggests that increased oxidative capacity benefits metabolic wellness; based on the premise that it is healthier to burn fat than glucose. Attempts to test this hypothesis using genetically-modified mouse models have produced contradictory results; and instead link muscle insulin resistance to excessive fat oxidation, acylcarnitine production and increased mitochondrial H2O2 emitting potential. Here, we consider emerging evidence that insulin action in muscle is driven principally by mitochondrial load and redox signaling rather than oxidative capacity.

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Section: Mitochondrial Stress: a Contemporary View Of The Randle Cyclementioning

confidence: 99%

Lipid-Induced Mitochondrial Stress and Insulin Action in Muscle

2012

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“…Many clinical trials have suggested acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC), two naturally occurring carnitine derivates, as potential strategies in the management of peripheral arterial disease (PAD), heart and cerebral ischemia, and congestive heart failure [35]. The beneficial effects of PLC on PAD, particularly in alleviating intermittent claudication, have been widely studied.…”

Section: Cam Effects On the Cardiovascular System And Cvd Risk Facmentioning

confidence: 99%

“…The beneficial effects of PLC on PAD, particularly in alleviating intermittent claudication, have been widely studied. It is generally agreed upon that PLC is able to improve exercise tolerance in terms of increasing the maximum walking distance in patients suffering from intermittent claudication as well as to improve most measures of quality of life (overall physical activity, pain while walking, and psychological activity) [35]. The recent Trans-Atlantic Inter-Society Consensus II update recommends the use of PLC in combination with physical training to improve the symptoms associated with PAD [35].…”

Section: Cam Effects On the Cardiovascular System And Cvd Risk Facmentioning

confidence: 99%

“…It is generally agreed upon that PLC is able to improve exercise tolerance in terms of increasing the maximum walking distance in patients suffering from intermittent claudication as well as to improve most measures of quality of life (overall physical activity, pain while walking, and psychological activity) [35]. The recent Trans-Atlantic Inter-Society Consensus II update recommends the use of PLC in combination with physical training to improve the symptoms associated with PAD [35]. However, it has recently been reported that the long-term administration of PLC to patients with intermittent claudication did not result in a statistically significant improvement in peak treadmill performance or quality of life as compared with exercise alone [35].…”

Section: Cam Effects On the Cardiovascular System And Cvd Risk Facmentioning

confidence: 99%

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Complementary and Alternative Medicine and Cardiovascular Disease: An Evidence-Based Review

Rabito

Kaye

2013

Evidence-Based Complementary and Alternative Medicine

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Complementary and alternative medicine (CAM) plays a significant role in many aspects of healthcare worldwide, including cardiovascular disease (CVD). This review describes some of the challenges of CAM in terms of scientific research. Biologically-based therapies, mind-body therapies, manipulative and body-based therapies, whole medical systems, and energy medicine are reviewed in detail with regard to cardiovascular risk factors and mediation or modulation of cardiovascular disease pathogenesis. CAM use among patients with CVD is prevalent and in many instances provides positive and significant effects, with biologically-based and mind-body therapies being the most commonly used treatment modalities. More rigorous research to determine the precise physiologic effects and long-term benefits on cardiovascular morbidity and mortality with CAM usage, as well as more open lines of communication between patients and physicians regarding CAM use, is essential when determining optimal treatment plans.

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“…Carnitine derivatives are potent antiradical agents and may protect tissues from oxidative damage [10], [11]. Acetyl-L-carnitine (ALC) (a carnitine derivative) possesses similar physiological functions but better bioavailability and antioxidant capacity compared with carnitine [12].…”

Section: Introductionmentioning

confidence: 99%

Acetyl-l-Carnitine and Oxfenicine on Cardiac Pumping Mechanics in Streptozotocin-Induced Diabetes in Male Wistar Rats

Wang

et al. 2013

PLoS ONE

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IntroductionIn the treatment of patients with diabetes, one objective is an improvement of cardiac metabolism to alleviate the left ventricular (LV) function. For this study, we compared the effects of acetyl-l-carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine palmitoyltransferase-1 inhibitor) on cardiac pumping mechanics in streptozotocin-induced diabetes in male Wistar rats, with a particular focus on the pressure-flow-volume relationship.MethodsDiabetes was induced by a single tail vein injection of 55 mg kg−1 streptozotocin. The diabetic animals were treated on a daily basis with either acetyl-L-carnitine (1 g L−1 in drinking water) or oxfenicine (150 mg kg−1 by oral gavage) for 8 wk. They were also compared with untreated age-matched diabetic controls. LV pressure and ascending aortic flow signals were recorded to calculate the maximal systolic elastance (E max) and the theoretical maximum flow (Q max). Physically, E max reflects the contractility of the myocardium as an intact heart, whereas Q max has an inverse relationship with the LV internal resistance.ResultsWhen comparing the diabetic rats with their age-matched controls, the cardiodynamic condition was characterized by a decline in E max associated with the unaltered Q max. Acetyl-l-carnitine (but not oxfenicine) had reduced cardiac levels of malondialdehyde in these insulin-deficient animals. However, treating with acetyl-l-carnitine or oxfenicine resulted in an increase in E max, which suggests that these 2 drugs may protect the contractile status from deteriorating in the diabetic heart. By contrast, Q max showed a significant fall after administration of oxfenicine, but not with acetyl-L-carnitine. The decrease in Q max corresponded to an increase in total vascular resistance when treated with oxfenicine.ConclusionsAcetyl-l-carnitine, but not oxfencine, optimizes the integrative nature of cardiac pumping mechanics by preventing the diabetes-induced deterioration in myocardial intrinsic contractility associated with unaltered LV internal resistance.

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Critical update for the clinical use of L-carnitine analogs in cardiometabolic disorders

Cited by 19 publications

References 69 publications

Lipid-Induced Mitochondrial Stress and Insulin Action in Muscle

Lipid-Induced Mitochondrial Stress and Insulin Action in Muscle

Complementary and Alternative Medicine and Cardiovascular Disease: An Evidence-Based Review

Acetyl-l-Carnitine and Oxfenicine on Cardiac Pumping Mechanics in Streptozotocin-Induced Diabetes in Male Wistar Rats

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