L-carnitine enhances extracellular matrix synthesis in human primary chondrocytes.

Osteoarthritis (OA) is one of the most common degenerative joint disease for which there is no cure. It is treated mainly with non-steroidal anti-inflammatory drugs to control the symptoms and some supplements, such as glucosamine and chondroitin sulphate in order to obtain structure-modifying effects. Aim of this study is to investigate the effects of L-carnitine, a molecule with a role in cellular energy metabolism, on extracellular matrix synthesis in human primary chondrocytes (HPCs). Dose-dependent effect of L-carnitine on cartilage matrix production, cell proliferation and ATP synthesis was examined by incubating HPCs with various amounts of molecule in monolayer (2D) and in hydromatrix scaffold (3D). L-Carnitine affected extracellular matrix synthesis in 3D in a dose-dependent manner; moreover, L-carnitine was very effective to stimulate cell proliferation and to induce ATP synthesis, mainly in 3D culture condition. In conclusion, L-carnitine enhances cartilage matrix glycosaminoglycan component production and cell proliferation, suggesting that this molecule could be useful in the treatment of pathologies where extracellular matrix is degraded, such as OA. To our knowledge, this is the first study where the effects of L-carnitine are evaluated in HPCs.

Propionyl-L-carnitine in Leriche-Fontaine stage II peripheral arterial obstructive disease.

Peripheral arterial obstructive disease (PAOD) of the lower limbs affects 5% of the adult population. Uncontrolled arteriopathy is established due to a microcirculatory deficit, which may be present despite a good Winsor index and which leads to exhaustion of the functional microcirculatory reserve. The target of this study was to examine possible improvements in microvascular and tissue homeostasis by the administration of propionyl-L-carnitine (PLC). A total of 26 patients were enrolled in this study, aged 65 +/- 15 years; two males were diagnosed at stage IIA and 17 males and seven females at stage IIB PAOD. The main criterion of inclusion was the worsening of walking distance during the last month. In this study the duration of therapy was 33 days. PLC was administered in three flasks, each containing 300 mg in 250 cc saline by continuous infusion. The following parameters were measured before and after treatment: pain-free and maximum walking distance (measured on a treadmill at 3.2 km/hr with a gradient of 12%), recovery time from pain after maximum walking distance, ankle-brachial index by means of the Doppler apparatus, and evaluation of the microcirculation using capillaroscopy. The results showed that therapy with PLC was effective at restoring activity of skeletal muscle in ischemic conditions. In particular, capillaroscopy showed improvement in the angioarchitecture in the microcirculation fields, expressed as increased numbers of visible capillaries and diminution in the time of loss of sodium fluorescein marker. The clinical data showed increased walking distance and diminished time to recover from pain, and the clinical improvement correlated with improved microcirculatory function. From these preliminary data has emerged an indication of therapy with PLC for chronic obstructive arteriopathy of the lower limbs at stage II. Further studies with higher numbers of patients and more controlled variables are planned.

Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue.

Fatigue is one of the conditions most frequently complained by the elderly. There are few effective treatment options for patients with chronic fatigue syndrome. To determine the efficacy, tolerability and impact on the fatigue, as well as on cognitive and functional status of elderly subjects with acetyl L-carnitine (ALC), 96 aged subjects (>70 years, range 71-88) were investigated (50 females and 46 males; mean age 76.2+/-7.6 and 78.4+/-6.4 years, respectively). They met four or more of the Holmes major criteria or at least six of Fukuda minor criteria. Fatigue was measured with the Wessely and Powell [Wessely, S., Powell, R., 1989. Fatigue syndromes: a comparison of chronic postviral fatigue with neuromuscular and affective disorders. J. Neurol. Neurosurg. Psychiatry 52, 940-948] scores, with the fatigue severity scale. At the end of the treatment, we observed a decrease of physical fatigue: 6.2 (p<0.001), of mental fatigue: 2.8 (p<0.001), of severity fatigue: 21.0 (p<0.001) and improvements in functional status: 16.1 (p<0.001) and cognitive functions: 2.7 (p<0.001). By the end of the treatment, significant differences between the two groups were found for the following parameters: muscle pain -27% versus -3% (p<0.05); prolonged fatigue after exercise: 51% versus -4% (p<0.0001); sleep disorders: 28% versus 4% (p<0.05); physical fatigue: 7 versus -0.5 (p<0.0001); mental fatigue: -3.3 versus 0.6 (p<0.0001); fatigue severity scale: -22.5 versus 1.2 (p<0.0001); functional status 17.1 versus 0.6 (p<0.0001); mini mental state examination (MMSE) improvements: 3.4 versus 0.5 (p<0.0001). Our data show that administering ALC may reduce both physical and mental fatigue in elderly and improves both the cognitive status and physical functions.