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Background: Depression is a serious public health concern due to its prevalence and associated discomfort, dysfunction, morbidity, and economic impact. Depression is more prevalent in women than in males. There is a need to investigate the course of depressive disorders in India to identify the necessity and duration of ongoing treatment. Studies should also assess cost-effective treatment strategies that can be easily implemented in primary care settings to successfully treat depression. Methods: This study aimed to estimate the Serum L-Acetyl Carnitine (LAC) levels in depressive episodes, mainly to find a correlation between the levels and depression and also to correlate the values to the severity of depression with a depression rating scale like Montgomery–Åsberg Depression Rating Scale (MADRS). LAC levels were estimated using an enzyme-linked immunosorbent assay kit. Results: A cross-sectional study was conducted with 60 individuals after obtaining their informed consent. This included 30 cases of diagnosed depression and 30 age and sex-matched normal controls. The diagnosed depressive episodes were rated in MADRS, and a score was assigned based on the same. The results were tabulated and statistically analyzed. The mean age of the case group was 41.37 ± 11.32 and control group was 41.50 ± 14.37. The incidence of depressive symptoms was higher in females (53%) than males (47%). The incidence of depressive symptoms was higher in the 41–50-year age group than in any other group. The acetyl carnitine-LAC levels were significantly decreased in patients with depressive episodes (950.7 ± 902.7) compared to the control (1799.6 ± 67.1), respectively. The Pearson’s correlation shows there is a strong negative correlation between the MADRS score and the levels of acetylcarnitine in the cases which was statistically significant, P < 0.001. Conclusions: LAC may have an important role in the pathophysiology of depression by its epigenetic action on metabotropic glutamate receptors and the decrease in the brain tissue may induce depressive symptoms, and consequently, their supplementation causes a rapid antidepressant effect. Hence, it could be a useful biochemical marker for the diagnosis of depression and also an effective for the treatment of depression.

Background: Depression is a serious public health concern due to its prevalence and associated discomfort, dysfunction, morbidity, and economic impact. Depression is more prevalent in women than in males. There is a need to investigate the course of depressive disorders in India to identify the necessity and duration of ongoing treatment. Studies should also assess cost‑effective treatment strategies that can be easily implemented in primary care settings to successfully treat depression. Methods: This study aimed to estimate the Serum L-Acetyl Carnitine (LAC) levels in depressive episodes, mainly to find a correlation between the levels and depression and also to correlate the values to the severity of depression with a depression rating scale like Montgomery–Åsberg Depression Rating Scale (MADRS). LAC levels were estimated using an enzyme-linked immunosorbent assay kit. Results: A cross-sectional study was conducted with 60 individuals after obtaining their informed consent. This included 30 cases of diagnosed depression and 30 age and sex-matched normal controls. The diagnosed depressive episodes were rated in MADRS, and a score was assigned based on the same. The results were tabulated and statistically analyzed. The mean age of the case group was 41.37 ± 11.32 and control group was 41.50 ± 14.37. The incidence of depressive symptoms was higher in females (53%) than males(47%). The incidence of depressive symptoms was higher in the 41–50-year age group than in any other group. The acetyl carnitine-LAC levels were significantly decreased in patients with depressive episodes (950.7 ± 902.7) compared to the control (1799.6 ± 67.1), respectively. The Pearson’s correlation shows there is a strong negative correlation between the MADRS score and the levels of acetylcarnitine in the cases which was statistically significant, P < 0.001. Conclusions: LAC may have an important role in the pathophysiology of depression by its epigenetic action on metabotropic glutamate receptors and the decrease in the brain tissue may induce depressive symptoms, and consequently, their supplementation causes a rapid antidepressant effect. Hence, it could be a useful biochemical marker for the diagnosis of depression and also an effective for the treatment of depression [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a primary psychiatric illness worldwide; there is a dearth of new mechanistic models for the development of better therapeutic strategies. Although we continue to discover individual biological factors, a major challenge is the identification of integrated, multidimensional traits underlying the complex heterogeneity of depression and treatment outcomes. Here, we set out to ascertain the emergence of the novel mitochondrial mediator of epigenetic function acetyl-L-carnitine (LAC) in relation to previously described individual predictors of antidepressant responses to the insulin-sensitizing agent pioglitazone. Herein, we report that i) subjects with MDD and shorter leukocyte telomere length (LTL) show decreased levels of LAC, increased BMI, and a history of specific types of childhood trauma; and that ii) these multidimensional factors spanning mitochondrial metabolism, cellular aging, metabolic function, and childhood trauma provide more detailed signatures to predict longitudinal changes in depression severity in response to pioglitazone than individual factors. The findings of multidimensional signatures involved in the pathophysiology of depression and their role in predicting treatment outcomes provide a starting point for the development of a mechanistic framework linking biological networks and environmental factors to clinical outcomes in pursuit of personalized medicine strategies to effectively treat MDD.

Excessive consumption of nutrients, as well as obesity, leads to an inflammatory process, especially in adipose tissue. This inflammation reaches the systemic level and, subsequently, the central nervous system (CNS), which can lead to oxidative stress and mitochondrial dysfunction, resulting in brain damage. Thus, adequate treatment for obesity is necessary, including lifestyle changes (diet adequation and physical activity) and pharmacotherapy. However, these drugs can adversely affect the individual's health. In this sense, searching for new therapeutic alternatives for reestablishing metabolic homeostasis is necessary. L-carnitine (LC) and acetyl-L-carnitine (LAC) have neuroprotective effects against oxidative stress and mitochondrial dysfunction in several conditions, including obesity. Therefore, this study aimed to conduct a narrative review of the literature on the effect of LC and LAC on brain damage caused by obesity, in particular, on mitochondrial dysfunction and oxidative stress. Overall, these findings highlight that LC and LAC may be a promising treatment for recovering REDOX status and mitochondrial dysfunction in the CNS in obesity. Future work should focus on better elucidating the molecular mechanisms behind this treatment. [ABSTRACT FROM AUTHOR]

Intergenerational trauma increases lifetime susceptibility to depression and other psychiatric disorders. Whether intergenerational trauma transmission is a consequence of in-utero neurodevelopmental disruptions versus early-life mother-infant interaction is unknown. Here, we demonstrate that trauma exposure during pregnancy induces in mouse offspring social deficits and depressive-like behavior. Normal pups raised by traumatized mothers exhibited similar behavioral deficits to those induced in pups raised by their biological traumatized mothers. Good caregiving by normal mothers did not reverse prenatal trauma-induced behaviors, indicating a two-hit stress mechanism comprising both in-utero abnormalities and early-life poor parenting. The behavioral deficits were associated with profound changes in the brain metabotranscriptome. Striking increases in the mitochondrial hypoxia marker and epigenetic modifier 2-hydroxyglutaric acid in the brains of neonates and adults exposed prenatally to trauma indicated mitochondrial dysfunction and epigenetic mechanisms. Bioinformatic analyses revealed stress- and hypoxia-response metabolic pathways in the neonates, which produced long-lasting alterations in mitochondrial energy metabolism and epigenetic processes (DNA and chromatin modifications). Most strikingly, early pharmacological interventions with acetyl-L-carnitine (ALCAR) supplementation produced long-lasting protection against intergenerational trauma-induced depression.

Simple Summary: Pancreatic cancer is a significant problem worldwide. Most cancers are diagnosed at an advanced stage. Limited knowledge of the pathogenesis of pancreatic tumors results in limited diagnostic and therapeutic possibilities. Using metabolome analysis, we identified unique metabolite profiles specific not only for pancreatic ductal adenocarcinoma (PDAC) but also for neuroendocrine pancreatic tumor (PNET), which may be helpful to understand the pathogenesis of pancreatic diseases. Additionally, we discovered that disturbed metabolites, mainly acetylcarnitine C2, serotonin, and glycerophospholipid PC aa C34:1, have potential to be used as biomarkers for diagnosing and monitoring the progression of pancreatic tumors. Serum-circulating metabolites can be easily monitored without invasive procedures; they show the current condition of clinical patients and therefore help with pharmacological treatments or dietary strategies. Background: Pancreatic cancer is the most common pancreatic solid malignancy with an aggressive clinical course and low survival rate. There are a limited number of reliable prognostic biomarkers and a need to understand the pathogenesis of pancreatic tumors; neuroendocrine (PNET) and pancreatic ductal adenocarcinomas (PDAC) encouraged us to analyze the serum metabolome of pancreatic tumors and disturbances in the metabolism of PDAC and PNET. Methods: Using the AbsoluteIDQ® p180 kit (Biocrates Life Sciences AG, Innsbruck, Austria) with liquid chromatography–mass spectrometry (LC-MS), we identified changes in metabolite profiles and disrupted metabolic pathways serum of NET and PDAC patients. Results: The concentration of six metabolites showed statistically significant differences between the control group and PDAC patients (p.adj < 0.05). Glutamine (Gln), acetylcarnitine (C2), and citrulline (Cit) presented a lower concentration in the serum of PDAC patients, while phosphatidylcholine aa C32:0 (PC aa C32:0), sphingomyelin C26:1 (SM C26:1), and glutamic acid (Glu) achieved higher concentrations compared to serum samples from healthy individuals. Five of the tested metabolites: C2 (FC = 8.67), and serotonin (FC = 2.68) reached higher concentration values in the PNET serum samples compared to PDAC, while phosphatidylcholine aa C34:1 (PC aa C34:1) (FC = −1.46 (0.68)) had a higher concentration in the PDAC samples. The area under the curves (AUC) of the receiver operating characteristic (ROC) curves presented diagnostic power to discriminate pancreatic tumor patients, which were highest for acylcarnitines: C2 with AUC = 0.93, serotonin with AUC = 0.85, and PC aa C34:1 with AUC = 0.86. Conclusions: The observations presented provide better insight into the metabolism of pancreatic tumors, and improve the diagnosis and classification of tumors. Serum-circulating metabolites can be easily monitored without invasive procedures and show the present clinical patients' condition, helping with pharmacological treatment or dietary strategies. [ABSTRACT FROM AUTHOR]

Mitochondrial health declines with age, and older patients can demonstrate dysfunction in mitochondrial-rich tissues, such as cardiac and skeletal muscle. Aged mitochondria may make older adults more susceptible to adverse drug reactions (ADRs). We assessed mitochondrial metabolic function by measuring two metabolites, l-carnitine and acetylcarnitine, to determine their effectiveness as candidate clinical biomarkers for age-related, drug-induced alterations in mitochondrial metabolism. To study age- and medication-related changes in mitochondrial metabolism, we administered the FDA-approved mitochondriotropic drug, clofazimine (CFZ), or vehicle for 8 weeks to young (4-week-old) and old (61-week-old) male C57BL/6J mice. At the end of treatment, whole blood and cardiac and skeletal muscle were analyzed for l-carnitine, acetylcarnitine, and CFZ levels; muscle function was measured via a treadmill test. No differences were found in blood or cardiac carnitine levels of CFZ-treated mice, but CFZ-treated mice displayed lost body mass and alterations in endurance and levels of skeletal muscle mitochondrial metabolites. These findings demonstrate the age-related susceptibility of the skeletal muscle to mitochondria drug toxicity. Since drug-induced alterations in mitochondrial metabolism in skeletal muscle were not reflected in the blood by l-carnitine or acetylcarnitine levels, drug-induced catabolism and changes in muscle function appear more relevant to stratifying individuals at increased risk for ADRs. [ABSTRACT FROM AUTHOR]

Purpose: Acetylcarnitine can be assessed in vivo using proton MRS (1H‐MRS) with long TEs and this has been previously applied successfully in muscle. The aim of this study was to evaluate a 1H‐MRS technique for liver acetylcarnitine quantification in healthy humans before and after l‐carnitine supplementation. Method: Baseline acetylcarnitine levels were quantified using a STEAM sequence with prolonged TE in 15 healthy adults. Using STEAM with four different TEs was evaluated in phantoms. To assess reproducibility of the measurements, five of the participants had repeated 1H‐MRS without receiving l‐carnitine supplementation. To determine if liver acetylcarnitine could be changed after l‐carnitine supplementation, acetylcarnitine was quantified 2 h after intravenous l‐carnitine supplementation (50 mg/kg body weight) in the other 10 participants. Hepatic lipids were also quantified from the 1H‐MRS spectra. Results: There was good separation between the acetylcarnitine and fat in the phantoms using TE = 100 ms. Hepatic acetylcarnitine levels were reproducible (coefficient of reproducibility = 0.049%) and there was a significant (p < 0.001) increase in the relative abundance after a single supplementation of l‐carnitine. Hepatic allylic, methyl, and methylene peaks were not altered by l‐carnitine supplementation in healthy volunteers. Conclusion: Our results demonstrate that our 1H‐MRS technique could be used to measure acetylcarnitine in the liver and detect changes following intravenous supplementation in healthy adults despite the presence of lipids. Our techniques should be explored further in the study of fatty liver disease, where acetylcarnitine is suggested to be altered due to hepatic inflexibilities. [ABSTRACT FROM AUTHOR]

Early detection and accurate monitoring of chronic kidney disease (CKD) could improve care and retard progression to end-stage renal disease. Here, using untargeted metabolomics in 2155 participants including patients with stage 1-5 CKD and healthy controls, we identify five metabolites, including 5-methoxytryptophan (5-MTP), whose levels strongly correlate with clinical markers of kidney disease. 5-MTP levels decrease with progression of CKD, and in mouse kidneys after unilateral ureteral obstruction (UUO). Treatment with 5-MTP ameliorates renal interstitial fibrosis, inhibits IκB/NF-κB signaling, and enhances Keap1/Nrf2 signaling in mice with UUO or ischemia/reperfusion injury, as well as in cultured human kidney cells. Overexpression of tryptophan hydroxylase-1 (TPH-1), an enzyme involved in 5-MTP synthesis, reduces renal injury by attenuating renal inflammation and fibrosis, whereas TPH-1 deficiency exacerbates renal injury and fibrosis by activating NF-κB and inhibiting Nrf2 pathways. Together, our results suggest that TPH-1 may serve as a target in the treatment of CKD.

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The article highlights a study on the protective effects of nicotine and O-acetyl-L-carnitine against H89-induced spatial memory deficits. It discusses that the potential synergistic effects of nicotine and O-acetyl-L-carnitine in preventing protein kinase AII inhibitor (H-89)-induced spatial learning impairments.

Major depressive disorder (MDD) is one of the most common psychiatric disorders that accompany psychophysiological and mood changes. However, the pathophysiology-based disease mechanism of MDD is not yet fully understood, and diagnosis is also conducted through interviews with clinicians and patients. Diagnosis and treatment of MDD are limited due to the absence of biomarkers underlying the pathophysiological mechanisms of MDD. Although various attempts have been made to discover metabolite biomarkers for the diagnosis and treatment response of MDD, problems with sample size and consistency of results have limited clinical application. In addition, it was reported that future biomarker studies must consider exposure to antidepressants, which is the main cause of heterogeneity in depression subgroups. Therefore, the purpose of this study is to discover and validate biomarkers for the diagnosis of depression in consideration of exposure to drug treatment including antidepressants that contribute to the heterogeneity of the MDD subgroup. In the biomarker discovery and validation set, the disease group consisted of a mixture of patients exposed and unexposed to drug treatment including antidepressants for the treatment of MDD. The serum metabolites that differed between the MDD patients and the control group were profiled using mass spectrometry. The validation set including the remission group was used to verify the effectiveness as a biomarker for the diagnosis of depression and determination of remission status. The presence of different metabolites between the two groups was confirmed through serum metabolite profiling between the MDD patient group and the control group. Finally, Acetylcarnitine was selected as a biomarker. In validation, acetylcarnitine was significantly decreased in MDD and was distinguished from remission status. This study confirmed that the discovered acetylcarnitine has potential as a biomarker for diagnosing depression and determining remission status, regardless of exposure to drug treatment including antidepressants.

The effectiveness of l-carnitine in chronic liver disease remains controversial. We conducted this meta-analysis to assess the efficacy of various forms of l-carnitine in the treatment of chronic liver disease. Methods: We searched the Cochrane Library, EMBASE, KMBASE, and Medline databases for all relevant studies published until April 2022 that examined the ability of l-carnitine or its derivatives to normalize liver enzymes in patients with chronic liver disease. We performed meta-analyses of the proportion of patients with alanine aminotransferase (ALT) normalization and post-treatment serum aspartate aminotransferase (AST) and ALT levels. A random effects model was used for meta-analyses. Results: Fourteen randomized controlled trials (1217 patients) were included in this meta-analysis. The proportion of patients in whom ALT normalized was higher in the carnitine-orotate treatment group than in the control group (pooled odds ratio (OR), 95% confidence interval (CI) = 4.61 (1.48–14.39)). The proportion of patients in whom ALT normalized was also higher among those who received the carnitine-orotate complex, a combination of carnitine-orotate, biphenyl dimethyl dicarboxylate, and other minor supplementary compounds than in those who did not without significant heterogeneity (pooled OR (95% CI) = 18.88 (7.70–46.27); df = 1; p = 0.51; I2 = 0%). l-carnitine supplementation effectively lowered serum ALT levels compared to controls (pooled mean difference (95% CI) = −11.99 (−22.48 to −1.49)). Conclusions: l-carnitine supplementation significantly lowered ALT and AST levels and normalized ALT levels in patients with chronic liver disease. [ABSTRACT FROM AUTHOR]

Mitochondrial health declines with age, and older patients can demonstrate dysfunction in mitochondrial-rich tissues, such as cardiac and skeletal muscle. Aged mitochondria may make older adults more susceptible to adverse drug reactions (ADRs). We assessed mitochondrial metabolic function by measuring two metabolites, l-carnitine and acetylcarnitine, to determine their effectiveness as candidate clinical biomarkers for age-related, drug-induced alterations in mitochondrial metabolism. To study age- and medication-related changes in mitochondrial metabolism, we administered the FDA-approved mitochondriotropic drug, clofazimine (CFZ), or vehicle for 8 weeks to young (4-week-old) and old (61-week-old) male C57BL/6J mice. At the end of treatment, whole blood and cardiac and skeletal muscle were analyzed for l-carnitine, acetylcarnitine, and CFZ levels; muscle function was measured via a treadmill test. No differences were found in blood or cardiac carnitine levels of CFZ-treated mice, but CFZ-treated mice displayed lost body mass and alterations in endurance and levels of skeletal muscle mitochondrial metabolites. These findings demonstrate the age-related susceptibility of the skeletal muscle to mitochondria drug toxicity. Since drug-induced alterations in mitochondrial metabolism in skeletal muscle were not reflected in the blood by l-carnitine or acetylcarnitine levels, drug-induced catabolism and changes in muscle function appear more relevant to stratifying individuals at increased risk for ADRs.

Post-COVID syndrome is characterized by the persistence of nonspecific disabling symptoms, even several months after the resolution of the infection, with clinical characteristics similar to fibromyalgia (FM) and a prevalence of 31%. We evaluated the effectiveness of physical exercise, in association with L-acetyl-carnitine (ALC) therapy, in patients with Post-COVID syndrome, on musculoskeletal pain, dyspnea, functional capacity, quality of life, and depression. We conducted an observational case-control study on patients with Post-COVID syndrome. The patients were randomly divided into two groups: a treatment group that received rehabilitation treatment in combination with ALC 500 mg therapy; a control group that received only rehabilitation treatment. Patients were assessed at the time of recruitment (T0) and one month after the end of therapy (T1), with the administration of rating scales: NRS, Barthel Dyspnea Index (NPI), 12-Item Short Form Survey (SF-12) scale, Fibromyalgia Impact Questionnaire (FIQ), and Patient Health Questionnaire (PHQ-9). The treatment group showed statistically higher variations in pain scores, quality of life, and depression. No statistically significant differences between the two groups emerged regarding changes in dyspnea and functional capacity scores. Combining exercise with ALC is a promising and effective treatment in the management of Post-COVID syndrome, especially for musculoskeletal pain, depression, and quality of life. [ABSTRACT FROM AUTHOR]

Background: Free carnitine (C0) and short chain acylcarnitine (SCA) blood concentrations play a significant role in fatty acid oxidation process during the first days of life. The aim of this study was to demonstrate C0 and SCA concentrations in Dried Blood Spots (DBS) of full term breastfed infants in relation to their birth weight (BW) perinatally. Methods: Breastfed full term infants (n = 12,000, 6000 males, 6000 females) with BW 2000–4000 g were divided into 4 equal groups: Group A, 2000–2500 g, B 2500–3000 g, C 3000–3500 g and D 3500–4000 g. Blood samples in the form of DBS were collected on the 3rd day of life and analyzed via a liquid chromatography tandem mass spectrometry (LC-MS/MS) protocol. Results: BW-related C0 and SCAs were found as follows: C0 was determined to be statistically significantly higher in group A (BW 2000–2500 g) in both males and females. Lower acetylcarnitine (C2) and hydroxybutyrylcarnitine (C4OH) blood concentrations were detected in group A of both sexes, whereas butyrylcarnitine (C4) concentrations were found to be lower in the same group of males only. Furthermore, high concentrations of C2 and C4OH were shown in group D (BW 3500–4000 g) in both sexes. SCA sum of means ± SD values in males and females of group A were statistically significantly lower as compared to other study groups. Conclusion: Due to the number of the samples, data from this study could be applied as neonatal screening reference values for full term breastfed newborns in relation to their birth weight.

Effective and safe treatment of patients with polymorbidity is an urgent task of modern healthcare. Of particular difficulty is the treatment of patients with cardiovascular comorbidity, which requires an integrated approach to the treatment and development of a special, so-called patient-oriented approach. Modern scientific evidence proposes the use of levocarnitine, as part of complex therapy to increase its effectiveness. So, it was shown that levocarnitine can have a beneficial effect on blood pressure in patients with hypertension, especially those who are overweight and obese. Levocarnitine is also effective in the treatment of heart failure, which has been studied in several clinical studies, which demonstrated its ability to increase the ejection fraction of the left ventricle, stroke volume of blood and other indicators. Optimization of the bioavailability of nitrogen oxide (NO) and a decrease in systemic oxidative stress while taking levocarnitine plays an important positive role in complex therapy in patients with coronary artery disease: exertional angina and post-infarction cardiosclerosis, reducing the number of anginal attacks. Since levocarnitine has powerful antioxidant effects, it also has the neuroprotective effect found in in vitro studies in animal experiments. In case of impaired renal function, due to accelerated elimination and impaired reabsorption, a deficiency of levocarnitine in the body tissues develops, and therefore the US Food and Drug Administration (US FDA) decided on the possibility of using levocarnitine in patients on hemodialysis. Thus, taking into account the positive effects of levocarnitine in a number of frequently combined diseases, it can be considered as the drug of choice in the treatment of patients with polymorbidity.

Major depressive disorder (MDD) is a primary psychiatric illness worldwide; there is a dearth of new mechanistic models for the development of better therapeutic strategies. Although we continue to discover individual biological factors, a major challenge is the identification of integrated, multidimensional traits underlying the complex heterogeneity of depression and treatment outcomes. Here, we set out to ascertain the emergence of the novel mitochondrial mediator of epigenetic function acetyl-L-carnitine (LAC) in relation to previously described individual predictors of antidepressant responses to the insulin-sensitizing agent pioglitazone. Herein, we report that i) subjects with MDD and shorter leukocyte telomere length (LTL) show decreased levels of LAC, increased BMI, and a history of specific types of childhood trauma; and that ii) these multidimensional factors spanning mitochondrial metabolism, cellular aging, metabolic function, and childhood trauma provide more detailed signatures to predict longitudinal changes in depression severity in response to pioglitazone than individual factors. The findings of multidimensional signatures involved in the pathophysiology of depression and their role in predicting treatment outcomes provide a starting point for the development of a mechanistic framework linking biological networks and environmental factors to clinical outcomes in pursuit of personalized medicine strategies to effectively treat MDD.

Abstract Background Obesity in dogs is an increasing problem associated with morbidity, shortened life span and poor life quality. Overweight dogs exhibit postprandial hyperlipidaemia, highlighting the need to identify potential dysregulations in lipid metabolism. This study investigated metabolites related to lipid metabolism (i.e. acylcarnitines and taurine) and phospholipids in a feed-challenge test and aimed to identify metabolic variations in spontaneously overweight dogs. Twenty-eight healthy male Labrador Retriever dogs were included, 12 of which were classified as lean (body condition score (BCS) 4–5 on a 9-point scale) and 16 as overweight (BCS 6–8). After overnight fasting (14–17 h), fasting blood samples were collected and dogs were fed a high-fat meal followed by postprandial blood sample collection hourly for 4 h. Liquid chromatography-time of flight mass spectrometry (LC-TOFMS) was used to identify plasma metabolites and phospholipids. Multivariate models, mixed model repeated measures and linear regression analyses were used for data interpretation. Results In all dogs, propionylcarnitine, stearoylcarnitine and nine phospholipids increased in response to food intake, while vaccenylcarnitine decreased (P ≤ 0.005 for all). Overall, carnitine and acetylcarnitine signal areas in the feed-challenge test were lower in overweight dogs (P ≤ 0.004). Notably, fasting plasma acetylcarnitine was lower in overweight dogs than in lean dogs (P = 0.001) and it did not change in response to feeding. The latter finding was in contrast to the decreased acetylcarnitine signal area found in lean dogs at one hour postprandially (P 6) than in lean dogs (P

Post-COVID syndrome is characterized by the persistence of nonspecific disabling symptoms, even several months after the resolution of the infection, with clinical characteristics similar to fibromyalgia (FM) and a prevalence of 31%. We evaluated the effectiveness of physical exercise, in association with L-acetyl-carnitine (ALC) therapy, in patients with Post-COVID syndrome, on musculoskeletal pain, dyspnea, functional capacity, quality of life, and depression. We conducted an observational case-control study on patients with Post-COVID syndrome. The patients were randomly divided into two groups: a treatment group that received rehabilitation treatment in combination with ALC 500 mg therapy; a control group that received only rehabilitation treatment. Patients were assessed at the time of recruitment (T0) and one month after the end of therapy (T1), with the administration of rating scales: NRS, Barthel Dyspnea Index (NPI), 12-Item Short Form Survey (SF-12) scale, Fibromyalgia Impact Questionnaire (FIQ), and Patient Health Questionnaire (PHQ-9). The treatment group showed statistically higher variations in pain scores, quality of life, and depression. No statistically significant differences between the two groups emerged regarding changes in dyspnea and functional capacity scores. Combining exercise with ALC is a promising and effective treatment in the management of Post-COVID syndrome, especially for musculoskeletal pain, depression, and quality of life.

Chemotherapy-induced peripheral neuropathy (CIPN) is common and leads to suboptimal treatment. Acetyl-L-carnitine (ALC) is a natural compound involved in neuronal protection. Studies have suggested ALC may be effective for the prevention and treatment of CIPN.A 24-week randomized double-blind trial comparing ALC (3,000 mg per day) with placebo in women undergoing adjuvant taxane-based chemotherapy was conducted. The primary objective was to determine if ALC prevents CIPN as measured by the 11-item neurotoxicity (NTX) component of the Functional Assessment of Cancer Therapy (FACT) -Taxane scale at 12 weeks. Secondary objectives included changes in 24-week end points, functional status (FACT-Trial Outcome Index [TOI]), fatigue (Functional Assessment of Chronic Illness Therapy [FACIT] -Fatigue), and NTX grade.A total of 409 patients were evaluable (208 received ALC; 201, placebo). In a multivariate linear regression, week-12 scores were 0.9 points lower (more CIPN) with ALC than placebo (95% CI, -2.2 to 0.4; P = .17), whereas week-24 scores were 1.8 points lower with ALC (95% CI, -3.2 to -0.4; P = .01). Patients receiving ALC were more likely to have a > 5-point decrease in FACT-NTX scores (38% v 28%; P = .05), and FACT-TOI scores were 3.5 points lower with ALC (P = .03). Grade 3 to 4 neurotoxicity was more frequent in the ALC arm (eight v one). No differences between arms were observed for FACIT-Fatigue or other toxicities. Serum carnitine level increased with ALC but remained stable with placebo.There was no evidence that ALC affected CIPN at 12 weeks; however, ALC significantly increased CIPN by 24 weeks. This is the first study to our knowledge showing that a nutritional supplement increased CIPN. Patients should be discouraged from using supplements without proven efficacy.