Effects of Reducing L-Carnitine Supplementation on Carnitine Kinetics and Cardiac Function in Hemodialysis Patients: A Multicenter, Single-Blind, Placebo-Controlled, Randomized Clinical Trial.

L-carnitine (LC) supplementation improves cardiac function in hemodialysis (HD) patients. However, whether reducing LC supplementation affects carnitine kinetics and cardiac function in HD patients treated with LC remains unclear. Fifty-nine HD patients previously treated with intravenous LC 1000 mg per HD session (three times weekly) were allocated to three groups: LC injection three times weekly, once weekly, and placebo, and prospectively followed up for six months. Carnitine fractions were assessed by enzyme cycling methods. Plasma and red blood cell (RBC) acylcarnitines were profiled using tandem mass spectrometry. Cardiac function was evaluated using echocardiography and plasma B-type natriuretic peptide (BNP) levels. Reducing LC administration to once weekly significantly decreased plasma carnitine fractions and RBC-free carnitine levels during the study period, which were further decreased in the placebo group (p < 0.001). Plasma BNP levels were significantly elevated in the placebo group (p = 0.03). Furthermore, changes in RBC (C16 + C18:1)/C2 acylcarnitine ratio were positively correlated with changes in plasma BNP levels (ß = 0.389, p = 0.005). Reducing LC administration for six months significantly decreased both plasma and RBC carnitine levels, while the full termination of LC increased plasma BNP levels; however, it did not influence cardiac function in HD patients.

Reduced home cage and social activity in Pou3f2⊿ mice.

Pou3f2/Brn2 is a transcription factor that helps to determine the cellular identity of neocortical or hypothalamic neurons. Mammalian Pou3f2 contains three homopolymeric amino acids that are not present in amphibian Pou3f2. These amino acids contribute to monoamine function, which may play specific roles in mammalian development and behavior. Previous work has indicated that Pou3f2⊿ mice, which lack the homopolymeric amino acids, exhibited declined maternal activity and impaired object and spatial recognition. The current study, analyzed weight gain, brain development, home cage activity, social interaction, and response to novel objects in Pou3f2⊿ mice to determine which aspects of behavior were affected by monoamine dysregulation. Compared to their wild type counterparts, Pou3f2⊿ mice showed decreased social interaction and reduced home cage activity during their active phase. However, they showed normal weight gain, brain development, and responses to novelty. These results indicate that monoamine dysregulation in Pou3f2⊿ mice may specifically affect basal activity and social development, without altering non-social motivation.

Effects of switching from oral administration to intravenous injection of l-carnitine on lipid metabolism in hemodialysis patients.

BACKGROUND: Carnitine deficiency may contribute to cardiovascular disease (CVD) in patients with hemodialysis (HD). Dyslipidemia plays a role in CVD and its prevalence is also high in HD patients. We examined here the effects of switching from oral administration (PO) to intravenous (IV) injection of l-carnitine on lipid metabolism in patients with HD. METHODS: Nine HD patients who had received l-carnitine orally (900 mg/day) for 1 year were enrolled in this study. We examined whether lipid parameters were improved by switching to IV injection therapy of 1000 mg l-carnitine. RESULTS: IV injection of l-carnitine for 1 week significantly increased total, free and acyl carnitine levels both before and after HD. Switching to IV injection therapy for 1 and 4 weeks decreased serum free fatty acid (FFA) (322 ± 104 versus 261 ± 124 µmol/L) and increased high-density lipoprotein-cholesterol levels (1.46 ± 0.49 versus 1.63 ± 0.62 mmol/L), respectively. Change in FFA values from the baseline (ΔFFA) was positively correlated with the Δacyl/free carnitine ratio (r (2) = 0.553, P = 0.022). CONCLUSION: This study demonstrated that switching to IV l-carnitine therapy from oral supplementation improved lipid profiles, thus supporting the clinical utility of IV administration of l-carnitine for the treatment of patients on HD.