Dietary L-carnitine supplementation modifies blood parameters of mid-lactating dairy cows during standardized lipopolysaccharide-induced inflammation.

L-carnitine, available as feed additive, is essential for the beta-oxidation of free fatty acids in the mitochondrial matrix. It provides energy to immune cells and may positively impact the functionality of leukocytes during the acute phase response, a situation of high energy demand. To test this hypothesis, German Holstein cows were assigned to a control group (CON, n = 26) and an L-carnitine supplemented group (CAR, n = 27, rumen-protected L-carnitine product: 125 g/cow/d, corresponded to total L-carnitine intake: 25 g/cow/d, supplied with concentrate) and received an intravenous bolus injection of lipopolysaccharides (LPS, 0.5 µg/kg body weight, E. coli) on day 111 postpartum as a model of standardized systemic inflammation. Blood samples were collected from day 1 ante injectionem until day 14 post injectionem (pi), with frequent sampling through an indwelling venous catheter from 0.5 h pi to 12 h pi. All parameters of the white blood cell count responded significantly to LPS, while only a few parameters were affected by L-carnitine supplementation. The mean eosinophil count, as well as the percentage of basophils were significantly higher in CAR than in CON over time, which may be due to an increased membrane stability. However, phagocytosis and production of reactive oxygen species by leukocytes remained unchanged following L-carnitine supplementation. In conclusion, although supplementation with 25 g L-carnitine per cow and day resulted in increased proportions of specific leukocyte populations, it had only minor effects on the functional parameters studied in mid-lactating dairy cows during LPS-induced inflammation, and there was no evidence of direct improvement of immune functionality.

Effect of sex and milk replacer with or without supplemental carnitine and arginine on growth characteristics, carcass, and meat quality of artificially reared low-birth weight pigs.

This study compared milk replacer either remaining unsupplemented (CON) or supplemented with 0.5 g L-carnitine plus 16.7 g L-arginine/kg (CarArg) and fed to 48 low-birth weight (L-BtW) artificially reared piglets (24 per group) from days 7 to 28 of age. Eight farrowing series were needed to complete the study. On day 28, the lightest piglets were slaughtered, and the heaviest pigs were weaned. The heaviest pigs were weaned on day 28 and offered free access to a starter (weaning to 25 kg body weight [BW]), grower (25 to 60 kg BW), and finisher diet (60 to 96 kg BW on day 170 of age). After euthanization on days 28 and 170, blood was sampled for assessment of serum metabolite and hormone concentrations, and the semitendinosus muscle (STM) was weighed, and later subjected to enzyme activity analysis and assessment of myofiber characteristics. In the 170-d-old pigs carcass and meat quality traits were assessed. Growth data were analyzed accordingtoatwo-way analysis of variance (ANOVA), with dietary treatment and farrowing series as fixed effects, while remaining data were analyzed with dietary treatment, sex, their interaction, and farrowing series as main factors. Dietary treatments affected (P ≤ 0.049) muscle enzyme activity at both day 28, with greater citrate synthase (CS) and LDH activities and lower HAD:CS ratio in STM light portion, and lower LDH:CS ratio in STM dark portion, and 170 of age with lower HAD:CS ratio. In the starter period, CarArg pigs had greater average daily gain (P = 0.021) and average daily feed intake (P = 0.010). At slaughter, these pigs had lower (P = 0.013) glucose and greater (P = 0.022) urea serum concentrations. However, supplementing the milk replacer with carnitine and arginine had no long-term effects on growth performance, carcass composition, and meat quality of L-BtW pigs. In addition, muscle morphology and myofiber-related properties remained unaffected by the supplementation.

Breeding efforts to increase litter size in modern sows have inadvertently reduced the average birth weight of piglets, resulting in a higher number of piglets born with low-birth weight. These piglets are indeed vulnerable from birth and display relatively poor growth potential from a very early stage. For this reason, artificial rearing strategies are potentially a management option to improve the growth of these runt piglets. With an artificial rearing system, it is possible to provide specialized diets already during the suckling period, with inclusion of specific nutrients in certain concentrations suggested to improve the growth of runt piglets. Using an artificial rearing system allows for the provision of specialized diets during the suckling phase, which includes specific nutrients aimed at enhancing the growth of underdeveloped piglets. However, in the current experiment, the particular nutrients and their dosages did not significantly improve growth or other characteristics compared to the control group.

Comparison of metabolic parameters between oral and total parenteral nutrition in children with severe eating disorders.

BACKGROUND: This study investigated changes of lipid parameters in children with severe eating disorders during refeeding in order to explore the optimal timing for lipid preparation administration. METHODS: We prospectively assessed the physical conditions of patients with eating disorders after the start of nutrition therapy. The assessments were performed at admission and at 2 and 4 weeks. Lipid metabolism was assessed based on triglyceride (TG), total cholesterol (TC), and free carnitine (FC) levels, as well as acylcarnitine/free carnitine (AC/FC) ratio. RESULTS: A total of 18 patients were included. Of these, 12 and 6 received an oral diet (OD group) and total parenteral nutrition (TPN group), respectively. The mean body mass indexes at hospital admission were 12.8 kg/m2 in the OD group and 12.7 kg/m2 in the TPN group. At 2 weeks after the start of refeeding, TC, TG, and AC/FC levels were significantly lower in the TPN group than in the OD group. Other blood test results did not show any significant differences between the two groups. CONCLUSIONS: Fat-free glucose-based nutrition promoted lipid metabolism over a 2-week period after the start of refeeding, suggesting that balanced energy and lipid intake are essential, even in TPN.

Effect of l-Carnitine Supplementation on Osteoarthritis: A Systematic Review.

SCOPE: Comprehensive assessment of l-carnitine's safety and effectiveness in reducing inflammatory markers in osteoarthritis (OA) patients. METHODS AND RESULTS: Journal articles on l-carnitine for OA are gathered using computer searches of PubMed, Embase, the Cochrane Library, and Web of Science. The kind of literature that is found is restricted to clinical randomized controlled trials (RCTs). The Cochrane Handbook risk of bias assessment tool RevMan 5.4 software is used to conduct a meta-analysis. The systematic assessment comprises eight trials totaling 619 patients; the included studies' quality is mediocre. The study's findings demonstrate that OA patients' Western Ontario and McMaster University (WOMAC) function improves and that treatment efficacy outperforms that of the control group (mean difference [MD] = -7.75, 95% CI [-14.63, -0.86]; Z = 2.21; p = 0.03), WOMAC total (MD = -10.24, 95% CI [-18.97, -1.51]; Z = 2.30; p = 0.02), and visual analogue scale (VAS) pain (MD = -14.01, 95% CI [-16.16, -11.85]; Z = 12.74; p < 0.00001). The studies that are methodically reviewed also discover heterogeneity, which may have resulted from the created pooled data and requires more analysis. CONCLUSION: In patients with OA, l-carnitine effectively decreases clinical signs and symptoms, inflammatory markers, pain, and stiffness indicators, and significantly improves WOMAC and VAS scores.

Musculoskeletal Health Worsened from Carnitine Supplementation and Not Impacted by a Novel Individualized Treadmill Training Protocol.

INTRODUCTION: Chronic kidney disease (CKD) negatively affects musculoskeletal health, leading to reduced mobility, and quality of life. In healthy populations, carnitine supplementation and aerobic exercise have been reported to improve musculoskeletal health. However, there are inconclusive results regarding their effectiveness and safety in CKD. We hypothesized that carnitine supplementation and individualized treadmill exercise would improve musculoskeletal health in CKD. METHODS: We used a spontaneously progressive CKD rat model (Cy/+ rat) (n = 11-12/gr): (1) Cy/+ (CKD-Ctrl), (2) CKD-carnitine (CKD-Carn), and (3) CKD-treadmill (CKD-TM). Carnitine (250 mg/kg) was injected daily for 10 weeks. Rats in the treadmill group ran 4 days/week on a 5° incline for 10 weeks progressing from 30 min/day for week one to 40 min/day for week two to 50 min/day for the remaining 8 weeks. At 32 weeks of age, we assessed overall cardiopulmonary fitness, muscle function, bone histology and architecture, and kidney function. Data were analyzed by one-way ANOVA with Tukey's multiple comparisons tests. RESULTS: Moderate to severe CKD was confirmed by biochemistries for blood urea nitrogen (mean 43 ± 5 mg/dL CKD-Ctrl), phosphorus (mean 8 ± 1 mg/dL CKD-Ctrl), parathyroid hormone (PTH; mean 625 ± 185 pg/mL CKD-Ctrl), and serum creatinine (mean 1.1 ± 0.2 mg/mL CKD-Ctrl). Carnitine worsened phosphorous (mean 11 ± 3 mg/dL CKD-Carn; p < 0.0001), PTH (mean 1,738 ± 1,233 pg/mL CKD-Carn; p < 0.0001), creatinine (mean 1 ± 0.3 mg/dL CKD-Carn; p < 0.0001), cortical bone thickness (mean 0.5 ± 0.1 mm CKD-Ctrl, 0.4 ± 0.1 mm CKD-Carn; p < 0.05). Treadmill running significantly improves maximal aerobic capacity when compared to CKD-Ctrl (mean 14 ± 2 min CKD-TM, 10 ± 2 min CKD-Ctrl; p < 0.01). CONCLUSION: Carnitine supplementation worsened CKD progression, mineral metabolism biochemistries, and cortical porosity and did not have an impact on physical function. Individualized treadmill running improved maximal aerobic capacity but did not have an impact on CKD progression or bone properties. Future studies should seek to better understand carnitine doses in conditions of compromised renal function to prevent toxicity which may result from elevated carnitine levels and to optimize exercise prescriptions for musculoskeletal health.

Does L-carnitine prevent cadmium-induced damage in gastrointestinal contractility and histological changes in prepubertal rat / ¿La L-carnitina previene el daño inducido por cadmio en la contractilidad gastrointestinal y los cambios histológicos en ratas prepúberes?

SUMMARY: Cadmium (Cd) is the industrial and environmental toxic heavy metal which is found in air, water and soil. Cd, adversely affects many organs in humans such as kidney, intestine, liver, testis and lungs. L-carnitine (LC) is an important agent that plays essential role in energy metabolism. In our study, we aimed to work out whether LC application has any protective effect on intestinal contractility and morphologic damage of prepubertal rat duodenum on Cd-induced toxicity. Twenty eight prepubertal female Wistar rats were divided into four groups. The first group is control (C), second group; Cd group; Cadmium chloride was given 2 mg/kg 28 days with a one-day break by i.p. The third group; Cd+LC, which cadmium chloride was given 2 mg/kg i.p. and LC was given orally by gastric lavage. The LC dose was given as 75 mg/kg. The fourth group; LC, which only LC was given orally. The intestinal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (ACh) and relaxation was achieved with phenylephrine. Also the segments were examined for histological changes by light microscopy. Ach-induced contractions were higher in Cd+LC, LC, and control group compared to the Cd group in duodenal segments. The phenylephrine-induced relaxations were lower in Cd groups as compared with Control, Cd+LC and LC group in duodenal segments. In Cd group intestinal morphology was observed to be severely damaged whereas in Cd+LC group the damage was noticeably lower. Cd administration caused severe cellular damage and decreased gastrointestinal motility. Treatment with the LC has affected the gastrointestinal contractility and reduced the damage in intestinal morphology, which occured after Cd application.

El cadmio (Cd) es el metal pesado tóxico industrial y ambiental que se encuentra en el aire, el agua y el suelo. El Cd afecta negativamente a muchos órganos humanos, como los riñones, los intestinos, el hígado, los testículos y los pulmones. La L-carnitina (LC) es un agente importante que juega un rol esencial en el metabolismo energético. El objetivo de este estudio fue determinar si la aplicación de LC tiene algún efecto protector sobre la contractilidad intestinal y el daño morfológico del duodeno de rata prepuberal sobre la toxicidad inducida por Cd. Veintiocho ratas Wistar hembras prepúberes se dividieron en cuatro grupos. El primer grupo control (C), segundo grupo; grupo cd; Se administró cloruro de cadmio 2 mg/kg durante 28 días con un descanso de un día por vía i.p. El tercer grupo; Cd+LC, al que se administró cloruro de cadmio 2 mg/kg i.p. y LC se administró por vía oral mediante lavado gástrico. La dosis de LC se administró como 75 mg/kg. El cuarto grupo; LC, al cual solo LC se administraba por vía oral. Los segmentos intestinales fueron aislados y suspendieron en baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (ACh) y la relajación se logró con fenilefrina. También se examinaron los segmentos en busca de cambios histológicos mediante microscopía óptica. Las contracciones inducidas por Ach fueron mayores en Cd+LC, LC y el grupo control en comparación con el grupo Cd en los segmentos duodenales. Las relajaciones inducidas por fenilefrina fueron menores en los grupos Cd en comparación con el grupo Control, Cd+LC y LC en los segmentos duodenales. En el grupo Cd se observó que la morfología intestinal estaba severamente dañada mientras que en el grupo Cd+LC el daño fue notablemente menor. La administración de Cd causó daño celular severo y disminución de la motilidad gastrointestinal. El tratamiento con LC afectó la contractilidad gastrointestinal y redujo el daño en la morfología intestinal, que ocurría después de la aplicación de Cd.

Association between Levocarnitine Treatment and the Change in Knee Extensor Strength in Patients Undergoing Hemodialysis: A Post-Hoc Analysis of the Osaka Dialysis Complication Study (ODCS).

Carnitine deficiency is prevalent in patients undergoing hemodialysis, and it could result in lowered muscle strength. So far, the effect of treatment with levocarnitine on lower limb muscle strength has not been well described. This observational study examined the association between treatment with levocarnitine with the change in knee extensor strength (KES) in hemodialysis patients. Eligible patients were selected from the participants enrolled in a prospective cohort study for whom muscle strength was measured annually. We identified 104 eligible patients for this analysis. During the one-year period between 2014 to 2015, 67 patients were treated with intravenous levocarnitine (1000 mg per shot, thrice weekly), whereas 37 patients were not. The change in KES was significantly higher (p = 0.01) in the carnitine group [0.02 (0.01-0.04) kgf/kg] as compared to the non-carnitine group [-0.02 (-0.04 to 0.01) kgf/kg]. Multivariable-adjusted regression analysis showed the positive association between the change in KES and the treatment with levocarnitine remained significant after adjustment for the baseline KES and other potential confounders. Thus, treatment with intravenous levocarnitine was independently and positively associated with the change in KES among hemodialysis patients. Further clinical trials are needed to provide more solid evidence.

Protective effects of melatonin and L-carnitine against methotrexate-induced toxicity in isolated rat hepatocytes.

The present study was designed to evaluate the possible protective effects of melatonin (MEL) and/or L-carnitine (L-CAR) against methotrexate (MTX)-induced toxicity in isolated rat hepatocytes. Hepatocytes were prepared using collagenase techniques of perfusion and digestion of rat liver. Trypan blue uptake, as well as, glutathione (GSH), lipid peroxidation (LPO), nitric oxide (NO), and tumor necrosis factor-alpha (TNF-α) levels were measured. Caspase-3 activity was also assessed. Pre-incubation of hepatocytes with MEL (1 mM) and/or L-CAR (10 mM) 30 min prior to intoxication with MTX, significantly protected hepatocytes against toxicity. In addition, LPO, NO, TNF-α levels, and caspase-3 activity were decreased in comparison to the MTX-intoxicated group. Furthermore, the two drugs increased the MTX-depleted GSH level. MEL and L-CAR prevented MTX-induced hepatocytotoxicity, at least partly, by their antioxidative, antiinflammatory, and antiapoptotic effects. Further studies are recommended on the clinical pharmacologic and toxicologic effects of MEL and L-CAR in patients receiving MTX.

The effects of L-carnitine on gastrointestinal contractility and histological changes in rat intestinal ischemia-reperfusion Injury / Efectos de la l-carnitina sobre la contractilidad gastrointestinal y los cambios histológicos en la lesión por isquemia-reperfusión intestinal de rata

SUMMARY: Ischemia-reperfusion (I/R) of the small intestine causes serious abdominal pathologies including tissue dysfunction and organ failure. L-carnitine (L-C), a powerful antioxidant, may help lessen the severity of these pathological effects since it plays a key role in energy metabolism. In this work we aimed to study the effects of L-C on the isolated ileal and duodenal contractility and histological changes in intestinal ischemia and reperfusion injury. Twenty eight Wistar rats were divided into four groups. The first group is the control group. Second group, I/R group, had rats submitted to 45-minutes of intestinal ischemia and to 45-minutes reperfusion. The third group, I/R+ L-C group, rats were treated with L-C 5 minutes before reperfusion and than submitted to ischemia. The fourth group, included rats that were treated with L-C without ischemia or reperfusion. Intestinal ischemia was conducted by obstructing superior mesentery arteries by silk loop. The ileal and duodenal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (Ach) and relaxation was achieved with phenylephrine. At the same time the terminal ileal and duodenal segments were examined for histological changes. Ach-induced contraction responses were higher in the I/R+L-C group, the L-C group, and the control group compared to the I/R group, in both ileal and duodenal segments. On the other hand, the phenylephrine-induced relaxations were higher in the I/R+L-C and L-C groups, especially in duodenal segments. In I/R group intestinal morphology was observed to be severely damaged whereas in I/R+L-C group the damage was noticeably lower possibly due to protective properties of L-C. I/R injury caused severe cellular damage response within the muscularis resulting in decreased gastrointestinal motility. Treatment with the L-C has significantly affected the gastrointestinal contractility. Also L-C treatment reduced the damage in intestinal morphology that occurs after IR injury.

RESUMEN: La isquemia-reperfusión (I/R) del intestino delgado provoca graves patologías abdominales que incluyen disfunción tisular y falla orgánica. La L-carnitina (L-C), un poderoso antioxidante, puede ayudar a disminuir la gravedad de estos efectos patológicos, ya que desempeña un papel clave en el metabolismo energético. El objetivo de este trabajo fue estudiar los efectos de L-C sobre la contractilidad ileal y duodenal aislada y los cambios histológicos en la lesión por isquemia y reperfusión intestinal. Se dividieron 28 ratas Wistar en cuatro grupos. El primer grupo fue el control. El segundo grupo, grupo I/R, de ratas sometidas durante 45 minutos de isquemia intestinal y a 45 minutos de reperfusión. El tercer grupo, grupo I/R+ L-C, las ratas se trataron con L-C, 5 minutos antes de la reperfusión y luego se sometieron a isquemia. El cuarto grupo, las ratas fueron tratadas con L-C sin isquemia ni reperfusión. La isquemia intestinal se realizó obstruyendo la arteria mesentérica superior con un asa de seda. Los segmentos ileal y duodenal se aislaron y suspendieron en un baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (Ach) y la relajación se logró con fenilefrina. Al mismo tiempo, se examinaron cambios histológicos de los segmentos del íleon terminal y del duodeno. Las respuestas de contracción inducidas por Ach fueron mayores en el grupo I/R+L-C, el grupo L-C y el grupo control en comparación con el grupo I/R, tanto en el segmento ileal como en el duodenal. Por otra parte, las relajaciones inducidas por fenilefrina fueron mayores en los grupos I/R+L-C y L-C, especialmente en los segmentos duodenales. En el grupo I/R se observó que la morfología intestinal estaba dañada significativamente, mientras que en el grupo I/R+L-C el daño fue notablemente menor, posiblemente debido a las propiedades protectoras de L-C. La lesión por I/R causó una respuesta de daño celular severo dentro de la capa muscular que resultó en una disminución de la motilidad gastrointestinal. El tratamiento con L-C afectó significativamente la contractilidad gastrointestinal. Por otra parte, el tratamiento L-C redujo el daño en la morfología intestinal que ocurre después de la lesión por IR.

Effect of Acute and Chronic Oral l-Carnitine Supplementation on Exercise Performance Based on the Exercise Intensity: A Systematic Review.

l-Carnitine (l-C) and any of its forms (glycine-propionyl l-Carnitine (GPL-C) or l-Carnitine l-tartrate (l-CLT)) has been frequently recommended as a supplement to improve sports performance due to, among others, its role in fat metabolism and in maintaining the mitochondrial acetyl-CoA/CoA ratio. The main aim of the present systematic review was to determine the effects of oral l-C supplementation on moderate- (50-79% V˙O2 max) and high-intensity (≥80% V˙O2 max) exercise performance and to show the effective doses and ideal timing of its intake. A structured search was performed according to the PRISMA® statement and the PICOS guidelines in the Web of Science (WOS) and Scopus databases, including selected data obtained up to 24 October 2021. The search included studies where l-C or glycine-propionyl l-Carnitine (GPL-C) supplementation was compared with a placebo in an identical situation and tested its effects on high and/or low-moderate performance. The trials that used the supplementation of l-C together with additional supplements were eliminated. There were no applied filters on physical fitness level, race, or age of the participants. The methodological quality of studies was evaluated by the McMaster Critical Review Form. Of the 220 articles obtained, 11 were finally included in this systematic review. Six studies used l-C, while three studies used l-CLT, and two others combined the molecule propionyl l-Carnitine (PL-C) with GPL-C. Five studies analyzed chronic supplementation (4-24 weeks) and six studies used an acute administration (<7 days). The administration doses in this chronic supplementation varied from 1 to 3 g/day; in acute supplementation, oral l-C supplementation doses ranged from 3 to 4 g. On the one hand, the effects of oral l-C supplementation on high-intensity exercise performance variables were analyzed in nine studies. Four of them measured the effects of chronic supplementation (lower rating of perceived exertion (RPE) after 30 min at 80% V˙O2 max on cycle ergometer and higher work capacity in "all-out" tests, peak power in a Wingate test, and the number of repetitions and volume lifted in leg press exercises), and five studies analyzed the effects of acute supplementation (lower RPE after graded exercise test on the treadmill until exhaustion and higher peak and average power in the Wingate cycle ergometer test). On the other hand, the effects of l-C supplementation on moderate exercise performance variables were observed in six studies. Out of those, three measured the effect of an acute supplementation, and three described the effect of a chronic supplementation, but no significant improvements on performance were found. In summary, l-C supplementation with 3 to 4 g ingested between 60 and 90 min before testing or 2 to 2.72 g/day for 9 to 24 weeks improved high-intensity exercise performance. However, chronic or acute l-C or GPL-C supplementation did not present improvements on moderate exercise performance.

Levocarnitine Supplementation Suppresses Lenvatinib-Related Sarcopenia in Hepatocellular Carcinoma Patients: Results of a Propensity Score Analysis.

This study investigated the inhibitory effect of levocarnitine supplementation on sarcopenia progression in hepatocellular carcinoma (HCC) patients treated with lenvatinib. We evaluated the skeletal muscle index (SMI). After propensity score matching for age, sex, modified albumin-bilirubin grade, baseline presence of sarcopenia, and branched-chain amino acid administration, we selected 17 patients who received levocarnitine supplementation after starting lenvatinib therapy and 17 propensity-score-matched patients who did not receive levocarnitine. Sarcopenia was present in 76% of the patients at baseline. Changes in baseline SMI at 6 and 12 weeks of treatment were significantly suppressed in the group with levocarnitine supplementation compared with those without (p = 0.009 and p = 0.018, respectively). While there were no significant differences in serum free carnitine levels in cases without levocarnitine supplementation between baseline and after 6 weeks of treatment (p = 0.193), free carnitine levels were significantly higher after 6 weeks of treatment compared with baseline in cases with levocarnitine supplementation (p < 0.001). Baseline SMI and changes in baseline SMI after 6 weeks of treatment were significantly correlated with free carnitine levels (r = 0.359, p = 0.037; and r = 0.345, p = 0.045, respectively). Levocarnitine supplementation can suppress sarcopenia progression during lenvatinib therapy.

A Pilot, Phase II, Observational, Case-Control, 1-Month Study on Asthenopia in Video Terminal Operators without Dry Eye: Contrast Sensitivity and Quality of Life before and after the Oral Consumption of a Fixed Combination of Zinc, L-Carnitine, Extract of Elderberry, Currant and Extract of Eleutherococcus.

The aims of the study were to investigate the ability and effectiveness of an oral intake of a fixed combination of zinc, L-carnitine, elderberry extract, black currant and Eleutherococcus extract in controlling the symptoms of eyestrain in videoterminal (VDT) users and to record its effects on contrast sensitivity. A single-center, phase II, observational, case-control, 1-month study in VDT workers without dry eye disease was carried out. Demographics and number of actual hours at VDT/day were taken into account. All subjects underwent a complete ophthalmic examination, including assessment of contrast sensitivity, and completed the computer vision symptom scale questionnaire at baseline and one month later. A total of 30 Caucasian subjects adhered to the required inclusion criteria and completed the study; 15 subjects were treated (T) and 15 were controls (C). All clinical data at baseline were similar in both groups (p > 0.05): after one month, all subjects had stable visual acuity, refractive defect and intraocular pressure (IOP); screen exposure time was unchanged. Regarding symptoms, at randomization, the groups had a similar score: 33.1 ± 3.3 in T and 32.8 ± 5.6 in C. One month later, the computer vision symptom scale (CVSS) questionnaire score decreased by -14.1 ± 3, 1 (p = 0.000) and -2.3 ± 1.8 (p = 0.568), respectively. Regarding contrast sensitivity, in group C the values of spatial frequencies remained unchanged, while they improved in almost all the cycles per degree stimuli in the treated group. Oral intake of a fixed combination of zinc, L-carnitine, elderberry extract, black currant and eleutherococcus extract can significantly improve contrast sensitivity and symptoms in VDT workers with no signs of dry eye disease.

Suitable ratio of dietary L-carnitine and α-ketoglutarate improves growth and health performance in Nile tilapia, Oreochromis niloticus.

L-carnitine (LC) and α-Ketoglutarate (AKG) are important growth promoters used in aquafeed. The study aimed to evaluate the incorporation of LC and AKG at different ratios in the diet of tilapia (initial weight 1.38 ± 0.03 g) in order to facilitate lipid utilization and protein synthesis. Fish were fed six isonitrogenous (~ 30 g/100 g CP) and isolipidic (~ 6 g/100 g CL) diets containing graded LC/AKG ratios of 0 (Control), 0.11, 0.42, 1.00, 2.33 and 9.00 in six treatments for 60 days. Fish fed with LC/AKG ratios 2.33 and 9.00 showed significantly (P < 0.05) higher percentage weight gain, specific growth rate and protein efficiency ratio. Feed conversion ratio in fish-fed diets with LC/AKG ratio 9.00 improved significantly (p < 0.05) than other treatments. The whole-body protein content of tilapia and digestive enzyme activity were significantly higher with higher weight gain. The body lipid content was significantly lower in the LC/AKG ratio 9.00. The liver antioxidant parameters and activity of the immune components were significantly higher in the LC/AKG ratio 9 group. The lower serum triglyceride and cholesterol level was also recorded in LC/AKG ratio 9 group. The histology of the intestine and liver showed increased villi area and decreased lipid droplets, respectively, in tilapia fed with higher LC/AKG ratios. It was concluded from the above results that the higher LC and lower AKG (LC/AKG ratio 9.00) combination attributed maximum lipid utilization and higher protein efficiency and thus better growth performance in tilapia. This was also reflected in activity of digestive enzymes, antioxidant enzymes and immune status in tilapia.

L-Carnitine Tartrate Supplementation for 5 Weeks Improves Exercise Recovery in Men and Women: A Randomized, Double-Blind, Placebo-Controlled Trial.

L-carnitine tartrate has been shown to improve relatively short-term recovery among athletes. However, there is a lack of research on the longer-term effects in the general population. OBJECTIVE: The primary objectives of this randomized double-blind, placebo-controlled trial were to evaluate the effects of daily L-carnitine tartrate supplementation for 5 weeks on recovery and fatigue. METHOD: In this study, eighty participants, 21- to 65-years-old, were recruited. Participants were split into two groups of forty participants each, a placebo, and a L-carnitine Tartrate group. Seventy-three participants completed a maintenance exercise training program that culminated in a high-volume exercise challenge. RESULTS: Compared to placebo, L-carnitine tartrate supplementation was able to improve perceived recovery and soreness (p = 0.021), and lower serum creatine kinase (p = 0.016). In addition, L-carnitine tartrate supplementation was able to blunt declines in strength and power compared to placebo following an exercise challenge. Two sub-analyses indicated that these results were independent of gender and age. Interestingly, serum superoxide dismutase levels increased significantly among those supplementing with L-carnitine tartrate. CONCLUSIONS: These findings agree with previous observations among healthy adult subjects and demonstrate that L-carnitine tartrate supplementation beyond 35 days is beneficial for improving recovery and reducing fatigue following exercise across gender and age.

Pathobiological Relationship of Excessive Dietary Intake of Choline/L-Carnitine: A TMAO Precursor-Associated Aggravation in Heart Failure in Sarcopenic Patients.

The microecological environment of the gastrointestinal tract is altered if there is an imbalance between the gut microbiota phylases, resulting in a variety of diseases. Moreover, progressive age not only slows down physical activity but also reduces the fat metabolism pathway, which may lead to a reduction in the variety of bacterial strains and bacteroidetes' abundance, promoting firmicutes and proteobacteria growth. As a result, dysbiosis reduces physiological adaptability, boosts inflammatory markers, generates ROS, and induces the destruction of free radical macromolecules, leading to sarcopenia in older patients. Research conducted at various levels indicates that the microbiota of the gut is involved in pathogenesis and can be considered as the causative agent of several cardiovascular diseases. Local and systematic inflammatory reactions are caused in patients with heart failure, as ischemia and edema are caused by splanchnic hypoperfusion and enable both bacterial metabolites and bacteria translocation to enter from an intestinal barrier, which is already weakened, to the blood circulation. Multiple diseases, such as HF, include healthy microbe-derived metabolites. These key findings demonstrate that the gut microbiota modulates the host's metabolism, either specifically or indirectly, by generating multiple metabolites. Currently, the real procedures that are an analogy to the symptoms in cardiac pathologies, such as cardiac mass dysfunctions and modifications, are investigated at a minimum level in older patients. Thus, the purpose of this review is to summarize the existing knowledge about a particular diet, including trimethylamine, which usually seems to be effective for the improvement of cardiac and skeletal muscle, such as choline and L-carnitine, which may aggravate the HF process in sarcopenic patients.

Inhibition of neutral sphingomyelinase 2 reduces extracellular vesicle release from neurons, oligodendrocytes, and activated microglial cells following acute brain injury.

Extracellular Vesicles (EVs) are implicated in the spread of pathogenic proteinsin a growing number of neurological diseases. Given this, there is rising interest in developing inhibitors of Neutral Sphingomyelinase 2 (nSMase2), an enzyme critical in EV biogenesis. Our group recently discovered phenyl(R)-(1-(3-(3,4-dimethoxyphenyl)-2,6-dimethylimidazo[1,2-b]pyridazin-8-yl)pyrrolidin-3-yl)carbamate (PDDC), the first potent, selective, orally-available, and brain-penetrable nSMase2 inhibitor, capable of dose-dependently reducing EVs release in vitro and in vivo. Herein, using multiplexed Surface Plasmon Resonance imaging (SPRi), we evaluated which brain cell-derived EVs were affected by PDDC following acute brain injury. Mice were fed PDDC-containing chow at doses which gave steady PDDC brain exposures exceeding its nSMase2 IC50. Mice were then administered an intra-striatal IL-1ß injection and two hours later plasma and brain were collected. IL-1ß injection significantly increased striatal nSMase2 activity which was completely normalized by PDDC. Using SPRi, we found that IL-1ß-induced injury selectively increased plasma levels of CD171 + and PLP1 + EVs; this EV increase was normalized by PDDC. In contrast, GLAST1 + EVs were unchanged by IL-1ß or PDDC. IL-1ß injection selectively increased EVs released from activated versus non-activated microglia, indicated by the CD11b+/IB4 + ratio. The increase in EVs from CD11b + microglia was dramatically attenuated with PDDC. Taken together, our data demonstrate that following acute injury, brain nSMase2 activity is elevated. EVs released from neurons, oligodendrocytes, and activated microglial are increased in plasma and inhibition of nSMase2 with PDDC reduced these IL-1ß-induced changes implicating nSMase2 inhibition as a therapeutic target for acute brain injury.

Chlorogenic acid inhibits trimethylamine-N-oxide formation and remodels intestinal microbiota to alleviate liver dysfunction in high L-carnitine feeding mice.

High L-carnitine ingestion has been shown to cause liver injury, mechanically due to an elevated circulating level of trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite from L-carnitine. This study aimed to investigate whether chlorogenic acid (CGA), a health-promoting polyphenol, could inhibit TMAO formation and thereafter might prevent L-carnitine-induced liver injury in mice. Feeding of mice with 3% L-carnitine in drinking water increased the serum and urinary levels of TMAO (p < 0.01 vs. Normal), whereas the serum and urinary TMAO formation was sharply reduced by CGA administration (p < 0.01). At the phylum level, CGA inhibited the L-carnitine-induced increase in the abundance of Firmicutes and Proteobacteria, while it promoted Bacteroidetes. At the genus level, CGA notably increased the abundance of Akkermansia and Bacteroides, but reduced the population of Erysipelatoclostridium, Faecalibaculum and Erysipelotrichaceae in high L-carnitine feeding mice. Meanwhile, CGA caused strong inhibition against the increase of liver injury markers (i.e. AST, ALT and ALP), hepatic inflammatory cytokines (i.e. IL-1, IL-6, TNF-α and TNF-ß) and dyslipidemia (i.e. TC, TG, LDL-C and HDL-C) in L-carnitine-fed mice (p < 0.05). These findings suggest that CGA holds great potential to alleviate liver dysfunction induced by high L-carnitine ingestion. The beneficial effect might be attributed to the protection against TMAO formation and the improvement of the health-promoting gut microbiota, as well as the antioxidant and anti-inflammatory properties of CGA.

Pharmacometabolomics identifies candidate predictor metabolites of an L-carnitine treatment mortality benefit in septic shock.

Sepsis-induced metabolic dysfunction contributes to organ failure and death. L-carnitine has shown promise for septic shock, but a recent phase II study of patients with vasopressor-dependent septic shock demonstrated a non-significant reduction in mortality. We undertook a pharmacometabolomics study of these patients (n = 250) to identify metabolic profiles predictive of a 90-day mortality benefit from L-carnitine. The independent predictive value of each pretreatment metabolite concentration, adjusted for L-carnitine dose, on 90-day mortality was determined by logistic regression. A grid-search analysis maximizing the Z-statistic from a binomial proportion test identified specific metabolite threshold levels that discriminated L-carnitine responsive patients. Threshold concentrations were further assessed by hazard ratio and Kaplan-Meier estimate. Accounting for L-carnitine treatment and dose, 11 1 H-NMR metabolites and 12 acylcarnitines were independent predictors of 90-day mortality. Based on the grid-search analysis numerous acylcarnitines and valine were identified as candidate metabolites of drug response. Acetylcarnitine emerged as highly viable for the prediction of an L-carnitine mortality benefit due to its abundance and biological relevance. Using its most statistically significant threshold concentration, patients with pretreatment acetylcarnitine greater than or equal to 35 µM were less likely to die at 90 days if treated with L-carnitine (18 g) versus placebo (p = 0.01 by log rank test). Metabolomics also identified independent predictors of 90-day sepsis mortality. Our proof-of-concept approach shows how pharmacometabolomics could be useful for tackling the heterogeneity of sepsis and informing clinical trial design. In addition, metabolomics can help understand mechanisms of sepsis heterogeneity and variable drug response, because sepsis induces alterations in numerous metabolite concentrations.

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.

Topical Delivery of Levocarnitine to the Cornea and Anterior Eye by Thermosensitive in-situ Gel for Dry Eye Disease.

PURPOSE: To prepare the levocarnitine thermosensitive in situ gel (LCTG) and evaluate its effect on dry eye disease (DED). METHODS: Draize eye irritation test and other examinations were used to evaluate the eye irritation after multiple administration of LCTG. The Schirmer test, fluorescein sodium staining, HE staining and TUNEL staining were used to detect the tear secretion, corneal injury, histopathological changes of the cornea and lacrimal gland, and the apoptosis rate of cornea epithelial cells after 3 days of the administration. The conjunctival goblet cell density was detected by PAS staining, and the expression levels of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-9 (MMP-9) of corneal epithelial cells were detected by immunofluorescence staining after 7 days of the administration. RESULTS: LCTG is non-irritating to rabbit eyes and has good biocompatibility. LCTG administration for 3 days can significantly increase the amount of tear secretion in mice with DED, promote corneal epithelial integrity and central corneal epithelium thickness recovery, and improve the pathological morphology and structure of corneal and lacrimal gland tissues, and reduce the apoptosis rate of the corneal epithelial cells. After 7 days of the administration, the preparation can promote the proliferation of conjunctival goblet cells and down-regulate the cornea expression levels of MMP-3 and MMP-9 in epithelial cells. CONCLUSION: The LCTG has a good curative effect on mice with DED, and the overall curative effect is better than that of levocarnitine solution.