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The significant role of carnitine and fatty acids during pregnancy, lactation and perinatal period. Nutritional support in specific groups of pregnant women.
Manta-Vogli, PD, Schulpis, KH, Dotsikas, Y, Loukas, YL
Clinical nutrition (Edinburgh, Scotland). 2020;(8):2337-2346
Abstract
BACKGROUND & AIMS Pregnancy is characterized by a complexity of metabolic processes that may impact fetal health and development. Women's nutrition during pregnancy and lactation is considered important for both mother and infant. This review aims to investigate the significant role of fatty acids and carnitine during pregnancy and lactation in specific groups of pregnant and lactating women. METHODS The literature was reviewed using relevant data bases (e.g. Pubmed, Scopus, Science Direct) and relevant articles were selected to provide information and data for the text and associated Tables. RESULTS Dynamic features especially of plasma carnitine profile during pregnancy and lactation, indicate an extraordinarily active participation of carnitine in the intermediary metabolism both in pregnant woman and in neonate and may also have implications for health and disease later in life. Maternal diets rich in trans and saturated fatty acids can lead to impairments in the metabolism and development of the offspring, whereas the consumption of long chain-polyunsaturated fatty acids during pregnancy plays a beneficial physiologic and metabolic role in the health of offspring. CONCLUSIONS Pregnant women who are underweight, overweight or obese, with gestational diabetes mellitus or diabetes mellitus and those who choose vegan/vegetarian diets or are coming from socially disadvantaged areas, should be nutritionally supported to achieve a higher quality diet during pregnancy and/or lactation.
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SLC22A5 (OCTN2) Carnitine Transporter-Indispensable for Cell Metabolism, a Jekyll and Hyde of Human Cancer.
Juraszek, B, Nałęcz, KA
Molecules (Basel, Switzerland). 2019;(1)
Abstract
Oxidation of fatty acids uses l-carnitine to transport acyl moieties to mitochondria in a so-called carnitine shuttle. The process of β-oxidation also takes place in cancer cells. The majority of carnitine comes from the diet and is transported to the cell by ubiquitously expressed organic cation transporter novel family member 2 (OCTN2)/solute carrier family 22 member 5 (SLC22A5). The expression of SLC22A5 is regulated by transcription factors peroxisome proliferator-activated receptors (PPARs) and estrogen receptor. Transporter delivery to the cell surface, as well as transport activity are controlled by OCTN2 interaction with other proteins, such as PDZ-domain containing proteins, protein phosphatase PP2A, caveolin-1, protein kinase C. SLC22A5 expression is altered in many types of cancer, giving an advantage to some of them by supplying carnitine for β-oxidation, thus providing an alternative to glucose source of energy for growth and proliferation. On the other hand, SLC22A5 can also transport several chemotherapeutics used in clinics, leading to cancer cell death.
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The neural stem cell/carnitine malnutrition hypothesis: new prospects for effective reduction of autism risk?
Bankaitis, VA, Xie, Z
The Journal of biological chemistry. 2019;(50):19424-19435
Abstract
Autism spectrum disorders (ASDs) are developmental neuropsychiatric disorders with heterogeneous etiologies. As the incidence of these disorders is rising, such disorders represent a major human health problem with escalating social cost. Although recent years witnessed advances in our understanding of the genetic basis of some dysmorphic ASDs, little progress has been made in translating the improved understanding into effective strategies for ASD management or minimization of general ASD risk. Here we explore the idea, described in terms of the neural stem cell (NSC)/carnitine malnutrition hypothesis, that an unappreciated risk factor for ASD is diminished capacity for carnitine-dependent long-chain fatty acid β-oxidation in neural stem cells of the developing mammalian brain. The basic premise is that fetal carnitine status is a significant metabolic component in determining NSC vulnerability to derangements in their self-renewal program and, therefore, to fetal ASD risk. As fetal carnitine status exhibits a genetic component that relates to de novo carnitine biosynthesis and is sensitive to environmental and behavioral factors that affect maternal circulating carnitine levels, to which the fetus is exposed, we propose that reduced carnitine availability during gestation is a common risk factor that lurks beneath the genetically complex ASD horizon. One major prediction of the NSC/carnitine malnutrition hypothesis is that a significant component of ASD risk might be effectively managed from a public policy perspective by implementing a carnitine surveillance and dietary supplementation strategy for women planning pregnancies and for women in their first trimester of pregnancy. We argue that this prediction deserves serious clinical interrogation.
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A review of micronutrients in sepsis: the role of thiamine, l-carnitine, vitamin C, selenium and vitamin D.
Belsky, JB, Wira, CR, Jacob, V, Sather, JE, Lee, PJ
Nutrition research reviews. 2018;(2):281-290
Abstract
Sepsis is defined as the dysregulated host response to an infection resulting in life-threatening organ dysfunction. The metabolic demand from inefficiencies in anaerobic metabolism, mitochondrial and cellular dysfunction, increased cellular turnover, and free-radical damage result in the increased focus of micronutrients in sepsis as they play a pivotal role in these processes. In the present review, we will evaluate the potential role of micronutrients in sepsis, specifically, thiamine, l-carnitine, vitamin C, Se and vitamin D. Each micronutrient will be reviewed in a similar fashion, discussing its major role in normal physiology, suspected role in sepsis, use as a biomarker, discussion of the major basic science and human studies, and conclusion statement. Based on the current available data, we conclude that thiamine may be considered in all septic patients at risk for thiamine deficiency and l-carnitine and vitamin C to those in septic shock. Clinical trials are currently underway which may provide greater insight into the role of micronutrients in sepsis and validate standard utilisation.
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Levocarnitine and vitamin B complex for the treatment of pegaspargase-induced hepatotoxicity: A case report and review of the literature.
Blackman, A, Boutin, A, Shimanovsky, A, Baker, WJ, Forcello, N
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2018;(5):393-397
Abstract
Asparaginase is a chemotherapeutic agent that is commonly used in combination with other medications for the treatment of acute lymphoblastic leukemia. An adverse effect of asparaginase includes hepatotoxicity, which can lead to severe liver failure and death. Several reports have documented successful treatment of asparaginase-induced hepatotoxicity using levocarnitine (l-carnitine) and vitamin B complex. Herein, we report a patient with acute lymphoblastic leukemia that experienced acute liver injury following pegaspargase administration. Our patient was successfully treated with l-carnitine and vitamin B complex for 8 days and achieved recovery of hepatic function. Furthermore, we review the current literature and provide a recommendation on a regimen that can be used as an option for the treatment of asparaginase-induced hepatic injury.
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The effect of L-carnitine supplementation on serum leptin concentrations: a systematic review and meta-analysis of randomized controlled trials.
Nazary-Vannani, A, Ghaedi, E, Mousavi, SM, Teymouri, A, Rahmani, J, Varkaneh, HK
Endocrine. 2018;(3):386-394
Abstract
PURPOSE The actual effects of L-carnitine administration on leptin serum level is inconsistent. In order to assess the efficacy of L-carnitine supplementation on serum leptin we conducted a meta-analysis of randomized controlled trials (RCTs). METHODS Seven studies with 325 cases and 330 controls were included. The pooled weighted mean difference (WMD) was calculated by random-effects model. The heterogeneity across studies was evaluated by using Cochrane's Q and I2 tests. In addition, we carried out the metaninf command to test the effect of each individual study on the overall result. RESULTS L-carnitine supplementation seemed to have no significant effect on serum leptin concentrations (WMD: -0.565 ng/mL; 95% CI: -2.417 to 1.287, p = 0.550). However, between-study heterogeneity was higher across all studies (I2 = 84.3%, p < 0.0001). Subgroup analysis to find the sources of heterogeneity showed that L-carnitine dosage (g) ( < 2 g: I2 = 00.0%, p = 0.408), and study population (diabetes: I2 = 46.7%, p = 0.153, and non-diabetes: I2 = 15.1%, p = 0.317) were the potential sources of heterogeneity. Besides, a more significant reduction in serum leptin concentration was observed with a daily dose of ≥ 2 mg L-carnitine (WMD: -2.742 ng/mL; 95% CI: -3.039 to -2.444, p < 0.001), in diabetic patients (WMD: -2.946 ng/mL; 95% CI: -3.254 to -2.638, p < 0.001), and with intervention duration <12 weeks (WMD: -2.772 ng/mL; 95% CI: -3.073 to -2.471, p < 0.001). CONCLUSION L-carnitine consumption does not reduce serum leptin significantly. However, a significant effect on leptin was observed in diabetic patients and patients who received doses more than 3 mg per day in the course of <12 weeks.
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Does skeletal muscle carnitine availability influence fuel selection during exercise?
Stephens, FB
The Proceedings of the Nutrition Society. 2018;(1):11-19
Abstract
Fat and carbohydrate are the major fuel sources utilised for oxidative, mitochondrial ATP resynthesis during human skeletal muscle contraction. The relative contribution of these two substrates to ATP resynthesis and total energy expenditure during exercise can vary substantially, and is predominantly determined by fuel availability and exercise intensity and duration. For example, the increased ATP demand that occurs with an increase in exercise intensity is met by increases in both fat and carbohydrate oxidation up to an intensity of approximately 60-70 % of maximal oxygen consumption. When exercise intensity increases beyond this workload, skeletal muscle carbohydrate utilisation is accelerated, which results in a reduction and inhibition of the relative and absolute contribution of fat oxidation to total energy expenditure. However, the precise mechanisms regulating muscle fuel selection and underpinning the decline in fat oxidation remain unclear. This brief review will primarily address the theory that a carbohydrate flux-mediated reduction in the availability of muscle carnitine to the mitochondrial enzyme carnitine palmitoyltransferase 1, a rate-limiting step in mitochondrial fat translocation, is a key mechanism for the decline in fat oxidation during high-intensity exercise. This is discussed in relation to recent work in this area investigating fuel metabolism at various exercise intensities and taking advantage of the discovery that skeletal muscle carnitine content can be nutritionally increased in vivo in human subjects.
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Inborn Errors of Metabolism with Myopathy: Defects of Fatty Acid Oxidation and the Carnitine Shuttle System.
El-Gharbawy, A, Vockley, J
Pediatric clinics of North America. 2018;(2):317-335
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Abstract
Fatty acid oxidation disorders (FAODs) and carnitine shuttling defects are inborn errors of energy metabolism with associated mortality and morbidity due to cardiomyopathy, exercise intolerance, rhabdomyolysis, and liver disease with physiologic stress. Hypoglycemia is characteristically hypoketotic. Lactic acidemia and hyperammonemia may occur during decompensation. Recurrent rhabdomyolysis is debilitating. Expanded newborn screening can detect most of these disorders, allowing early, presymptomatic treatment. Treatment includes avoiding fasting and sustained extraneous exercise and providing high-calorie hydration during illness to prevent lipolysis, and medium-chain triglyceride oil supplementation in long-chain FAODs. Carnitine supplementation may be helpful. However, conventional treatment does not prevent all symptoms.
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Sudden valproate-induced hyperammonemia managed with L-carnitine in a medically healthy bipolar patient: Essential review of the literature and case report.
Cattaneo, CI, Ressico, F, Valsesia, R, D'Innella, P, Ballabio, M, Fornaro, M
Medicine. 2017;(39):e8117
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Abstract
RATIONALE Valproic Acid is a commonly used psychiatric drug primarily used as a mood stabilizer. Mild hyperammonemia is a Valproic Acid common adverse effect. This report presents an example of treated hyperammonemia on Valproic acid therapy managed with L-carnitine administration in BD patients characterized by sudden vulnerability. PATIENT CONCERNS We report the case of a 29-year-old man suffering from bipolar disorder (BD) and substance use disorder who exhibited sudden altered mental status upon admittance to the inpatient unit. The patient was started on Valproic acid with no improvement. DIAGNOSES The patient had remarkably high ammonia levels (594 μg/dL) without hepatic insufficiency, likely due to his valproate treatment. INTERVENTIONS The patient was administered lactulose, intravenous hydration, and i.v. levocarnitine supplementation 4.5 g/day. OUTCOMES The administration leads to reduction of ammonia levels to 99 μg/dL within 12 hours upon initiation of carnitine therapy and progressive restore of his mental status within 24 hours. LESSONS Resolution of hyperammonemia caused by Valproic acid therapy may be enhanced with the administration of L-carnitine. An interesting aspect of this case was how rapidly the patient responded to the carnitine therapy.
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[Correlation between serum L-carnitine concentration and neutrophil engraftment in patients treated with cord blood transplantation].
Sano, F, Kondo, T, Matsuhashi, Y, Hyo, R, Koresawa, R, Susuki, S, Hayashi, K, Tasaka, T, Wada, H, Sugihara, T
[Rinsho ketsueki] The Japanese journal of clinical hematology. 2016;(2):165-70
Abstract
In cord blood transplantation (CBT), the amount of time elapsing until hematological engraftment has effects on the transplantation results. Carnitine deficiency has been reported to cause erythropoietin refractory anemia in chronic hemodialysis patients and thrombocytopenia or leukopenia of cirrhosis, and carnitine supplementation can improve hematopoiesis in patients with hepatic or renal failure. Patients who receive CBT may suffer from carnitine deficiency, but no studies have investigated the carnitine status of such patients. Herein, we determined the concentration of free carnitine (FC) and investigated the correlation between FC and engraftment in patients who received CBT. Twenty-three patients who received CBT at our hospital during the period from April 2013 to January 2015 were enrolled in this study. One patient was excluded because of graft failure, such that 22 patients were ultimately evaluable. FC concentrations of the patients were sequentially monitored at 4 time points (before conditioning therapy, day 0, day 7, and day 14), basic laboratory data were collected, and their correlations with engraftment were analyzed. FC concentrations of the patients were generally low (before conditioning therapy: 33.1, day 0: 43.2, day 7: 38.3, and day 14: 37.8 μmol/l). Significant inverse correlations were observed between FC concentrations and the number of days required for neutrophil engraftment on day 0 and day 14 (before conditioning therapy: P=0.15, r=-0.33, day 0: P=0.04, r=-0.43, day 7: P=0.30, r=-0.23, and day 14: P=0.01, r=-0.55). These results suggest carnitine to be an important nutrient that promotes hematopoietic recovery after CBT.