Free Carnitine Levels Research Articles

Nutritional status and extended metabolic screening in Egyptian children with uncomplicated type 1 diabetes

Nutritional status assessment, including amino acids, carnitine, and acylcarnitine profile, is an important component of diabetes care management, influencing growth and metabolic regulation. A designed case–control research included 100 Egyptian participants (50 T1DM and 50 healthy controls) aged 6 to 18 years old. The participants' nutritional status was assessed using the Body Mass Index (BMI) Z-score. Extended metabolic screening (EMS) was performed using a high-performance liquid chromatography-electrospray ionization-mass spectroscopy system to evaluate the levels of 14 amino acids, free carnitine, and 27 carnitine esters. T1DM children had considerably lower anthropometric Z-scores than the control group, with 16% undernutrition and 32% short stature. Total aromatic amino acids, phenylalanine, phenylalanine/tyrosine ratio, proline, arginine, leucine, isoleucine, free carnitine, and carnitine esters levels were considerably lower in the diabetic group, suggesting an altered amino acid and carnitine metabolism in type 1 diabetes. BMI Z-score showed a significant positive correlation with Leucine, Isoleucine, Phenylalanine, Citrulline, Tyrosine, Arginine, Proline, free carnitine, and some carnitine esters (Acetylcarnitine, Hydroxy-Isovalerylcarnitine, Hexanoylcarnitine, Methylglutarylcarnitine, Dodecanoylcarnitine, Tetradecanoylcarnitine, and Hexadecanoylcarnitine). HbA1c% had a significant negative correlation with Total aromatic amino acids, Branched-chain amino acid/Total aromatic amino acids ratio, Glutamic Acid, Citrulline, Tyrosine, Arginine, Proline, and certain carnitine esters (Propionylcarnitine, Methylglutarylcarnitine, Decanoylcarnitine, Octadecanoylcarnitine and Octadecenoylcarnitine), suggest that dysregulated amino acid and carnitine metabolism may be negatively affect the glycaemic control in children with TIDM. In conclusion, regular nutritional assessments including EMS of T1DM patients are critical in terms of diet quality and protein content for improved growth and glycemic management.

Incorporating Next-Generation Sequencing as a Second-Tier Test for Primary Carnitine Deficiency.

Newborn screening (NBS) for primary carnitine deficiency (PCD) has poor performance. This study aimed to evaluate the feasibility of incorporating next-generation sequencing (NGS) as a second-tier PCD test. Between March and December 2020, 60,070 newborns were screened for inherited metabolic disorders. Newborns with free carnitine (C0) levels below 8.5 μmol/L were selected for second-tier genetic testing. In total, 130 (0.22%) newborns with low C0 levels underwent second-tier genetic testing, 87 (66.92%) had positive genetic testing results, and 30 (23.08%) carried pathogenic variants of the SLC22A5 gene. Six newborns were diagnosed with PCD. The incidence of PCD was approximately 1 in 1:10,012 newborns. The PPV reached 20% after combining with second-tier NGS. Of the eight variants identified in patients with PCD, the three most common variants were c.760C>T (p.Arg254*), c.51C>G (p.Phe17Leu), and c.1400C>G (p.Ser467Cys). The C0 levels of patients with PCD were significantly lower than those of PCD carriers (p = 0.0026) and PCD-negative individuals (p = 0.0005). Our results showed that the PPV reached 20% after combining with second-tier NGS. The MS/MS-based NBS and second-tier NGS combination can effectively reduce the false-positive rate and detect PCD in patients.

Secondary carnitine deficiency during refeeding in severely malnourished patients with eating disorders: a retrospective cohort study

BackgroundSecondary carnitine deficiency in patients with anorexia nervosa has been rarely reported. This study aimed to investigate the occurrence of carnitine deficiency in severely malnourished patients with eating disorders during refeeding and assess its potential adverse effects on treatment outcomes.MethodIn a cohort study of 56 female inpatients with eating disorders at a single hospital from March 2010 to December 2020, we measured plasma free carnitine (FC) levels and compared to those of a healthy control group (n = 35). The patients were categorized into three groups based on FC levels: FC deficiency (FC< 20 µmol/L), FC pre-deficiency (20 µmol/L ≤ FC< 36 µmol/L), and FC normal (36 µmol/L ≤ FC).ResultsUpon admission, the patients had a median age of 26 years (interquartile range [IQR]: 21–35) and a median body mass index (BMI) of 13.8 kg/m2 (IQR: 12.8–14.8). Carnitine deficiency or pre-deficiency was identified in 57% of the patients. Hypocarnitinemia was associated with a decline in hemoglobin levels during refeeding (odds ratio [OR]: 0.445; 95% confidence interval [CI]: 0.214–0.926, p = 0.03), BMI at admission (OR: 0.478; 95% CI: 0.217–0.874, p = 0.014), and moderate or greater hepatic impairment at admission (OR: 6.385; 95% CI: 1.170–40.833, p = 0.032).ConclusionsHypocarnitinemia, particularly in cases of severe undernutrition (BMI< 13 kg/m2 at admission) was observed in severely malnourished patients with eating disorders during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment at admission was considered a potential indicator of hypocarnitinemia. Although hypocarnitinemia was not associated with any apparent adverse events other than anemia during refeeding, the possibility that carnitine deficiency may be a risk factor for more serious complications during sudden increases in energy requirements associated with changes in physical status cannot be denied. Further research on the clinical significance of hypocarnitinemia in severely malnourished patients with eating disorders is warranted.

Importance of L-carnitine as Biochemical Marker for Semen Quality Preservation after Cryopreservation in Stallions

Background: The aim of this work is to study the significance of carnitine fractions and NO metabolites for the assessment of spermatozoa resistance to cryopreservation, for which purpose these parameters were investigated in seminal plasma of animals divided according to the indices of spermatozoa of stallions subjected to cryopreservation. Methods: There were 18 breeding stallions with an average age of 11.28±5.46 years, all 18 were of Arabian breed. Using cluster analysis of indicators of semen quality, animals were identified into two groups: with high and low sperm resistance to cryopreservation-thawing. We assessed standard quality parameters in fresh and cryopreserved sperm, as well as carnitine and its fractions and NO metabolites in stallions’ seminal plasma, steroid hormones level and carnitine fractions in blood serum. Data were analyzed using JASP. Differences at p less than 0.05 were considered statistically significant. Result: Seminal plasma obtained from animals from the cluster with low motility after cryopreservation-thawing was characterized by a lower concentration of nitric oxide metabolites in 1,79 time (p=0.0415) and free carnitine in 1,64 time (p=0.0349). Positive moderate strength correlation were established between the level of seminal plasma free carnitine and the percentage of live spermatozoa after sperm cryopreservation-thawing.

Effect of carnitine supplementation on energy utilization in patients with type 2 diabetes and long-term tube feeding: A CARE-compliant case report

Introduction: Carnitine is essential for the energy utilization of long-chain fatty acids. However, the effects of carnitine supplementation on patients undergoing tube feeding remain unclear, and some enteral formula products do not contain carnitine. In order to gain insights into the role of carnitine supplementation on energy utilization in patients with long-term tube feeding, we observed the changes in respiratory quotient (RQ) of patients before and after the addition of carnitine due to the renewal of an enteral formula product. Case presentation: We observed 6 patients who continued tube feeding with the same enteral formula product scheduled for renewal. All 6 participants had diabetes, and indirect calorimetry data were available for 4 patients. Participants were observed for 3 months after switching to the new formulation. After the switching, a carnitine supplementation of 120 to 180 mg/day was provided, depending on the intake amount. One month after switching, blood free carnitine and total carnitine levels in all 6 patients increased from below the lower limit to within the range of the Japanese reference standard. In 3 of the 4 patients for whom indirect calorimetry was possible, the fasting RQ at baseline was &gt;0.90, suggesting impaired lipid utilization. The mean fasting RQ significantly decreased 2 months after the switch. The 1- and 2-hour postprandial RQ also showed a significant decrease after switching. Conclusion: Carnitine supplementation of enteral formulas may be important for normal energy utilization of lipids in patients receiving long-term tube feeding. An evaluation using randomized controlled trials with a larger number of patients is required.

SCOT Deficiency Mimicking Sepsis: An Unusual Cause of Increased Anion Gap Metabolic Acidosis

Introduction: Succinyl-CoA:3-oxoacid CoA transferase (SCOT, EC 2.8.3.5) deficiency is a rare autosomal recessive inborn error of metabolism (IEM). We report here an infant admitted to intensive care unit with the diagnosis of sepsis. Case Presentation: A five-month-old female patient was admitted to the intensive care unit with lethargy and respiratory distress. She had severe high anion gap metabolic acidosis. The IEM was screened by plasma amino acid analysis, showing no abnormalities, and by acylcarnitine analysis, showing low-normal levels of free carnitine. Urine organic acid analysis revealed massive ketonuria and elevated levels of dicarboxylic acids. Fatty acid oxidation disorder-targeted gene panel revealed a homozygous splice site variant (c.78+1_78+6 del) in the OXCT1 gene. Discussion and Conclusion: SCOT deficiency should be considered when massive ketosis is detected in increased anion gap metabolic acidosis with sepsis-like manifestation. Supportive therapy should be initiated quickly to prevent irreversible neurological damage.

Plasma Free Amino Acid and Carnitine Levels in Pregnant Women with Hydatidiform Mole: A Case-Controlled Study

Background: To determine plasma free amino acid (FAA) and carnitine levels in pregnant women with hydatidiform mole (HM). Materials and Methods: Twenty-three pregnant women with HM, and 24 healthy pregnant wo-men as controls were enrolled in the study. FAA and carnitine concentrations were measured in plasma using liquid chromatography/tandem mass spectrometry (LC-MS). Results: The levels of alanine, arginine, and valine from the 14 amino acids examined were signif-icantly lower in the HM group than in the healthy group (p = 0.019, p = 0.009, and p = 0.03, respec-tively). In addition, several carnitines, C8DC, C16:1, and C18, of the 27 carnitines examined were significantly higher in the HM group than in the control group (p = 0.021, p = 0.03, and p = 0.021, respectively). Conclusions: This study demonstrated that a decrease in some plasma FAAs and an increase in some plasma carnitine levels might be effective in the pathogenesis of HM.

Clinical characteristics and genetic analysis of six children with carnitine palmitoyltransferase 2 deficiency.

To investigate the clinical characteristic and genetic variants of children with carnitine palmitoyltransferase 2 (CPT2) deficiency. The clinical and genetic data of 6 children with CPT2 deficiency were retrospectively analyzed. The blood acylcarnitines and genetic variants were detected with tandem mass spectrometry and whole-exon gene sequencing, respectively. There were 4 males and 2 females with a mean age of 32 months (15 d-9 years) at diagnosis. One case was asymptomatic and with normal laboratory test results, 2 had delayed onset, and 3 were of infantile type. Three cases were diagnosed at neonatal screening, and 3 cases presented with clinical manifestations of fever, muscle weakness, and increased muscle enzymes. Five children presented with decreased free carnitine and elevated levels of palmitoyl and octadecenoyl carnitines. CPT2 gene variants were detected at 8 loci in 6 children (4 harboring biallelic mutations and 2 harboring single locus mutations), including 3 known variants (p.R631C, p.T589M, and p.D255G) and 5 newly reported variants (p.F352L, p.R498L, p.F434S, p.A515P, and c.153-2A>G). It was predicted by PolyPhen2 and SIFT software that c.153-2A>G and p.F352L were suspected pathogenic variants, while p.R498L, p.F434S and p.A515P were variants of unknown clinical significance. The clinical phenotypes of CPT2 deficiency are diverse. An early diagnosis can be facilitated by neonatal blood tandem mass spectrometry screening and genetic testing, and most patients have good prognosis after a timely diagnosis and treatment.

Effect of parenteral L-carnitine in hospitalized patients with moderate to severe COVID-19: A randomized double-blind clinical trial

Introduction: Pro-inflammatory responses have an important role in developing coronavirus disease 2019 (COVID-19). L-carnitine (LC) has been known to possess anti-inflammatory, anticoagulant, and antiviral effects. So, we aimed to evaluate the efficacy of LC in hospitalized patients with moderate-to-severe COVID-19. Methods: This double-blind, placebo-controlled, randomized clinical trial was conducted on hospitalized patients with moderate to severe COVID-19. The patients were randomized (1:1) to receive LC (n = 50) at a dose of 20 mg/kg or matching placebo (n = 51) from normal saline once daily for 14 days or until hospitalization and standard care. The primary outcome was hospital mortality and disease severity according to the World Health Organization's clinical progression scale. We also assessed the free carnitine level at baseline and the end of the study. C-reactive protein (CRP), ferritin, D-dimer, lactate dehydrogenase (LDH), and improvement of respiratory conditions were chosen as secondary outcomes Results: From 104 patients who met the inclusion criteria, 101 individuals’ data were analyzed. The LC group showed a significant reduction in LDH levels (P = 0.003), although CRP, ferritin, and D-dimer levels did not significantly differ from the placebo group. Also, no significant difference was observed in disease severity, oxygenation status, hospital mortality, or hospital stay between the two groups. Additionally, there was no increase in serum-free carnitine levels in the LC group (P &gt; 0.05 for all). Conclusion: The results of the current study did not support the superiority of LC over placebo in improving oxygenation, decreasing mortality, and hospital stay, as well as CRP, ferritin, and D-dimer in moderate to severe COVID-19 patients. Trial Registration: IRCT20170609034406N10; https://en.irct.ir/trial/60306.

Abnormal biochemical indicators of neonatal inherited metabolic disease in carriers

BackgroundTraditional biochemical screening for neonatal inherited metabolic diseases has high false-positive rates and low positive predictive values, which are not conducive to early diagnosis and increase parents’ anxiety. This study analysed the relationship between gene variant carriers and their biochemical indicators in traditional biochemical screening, aiming to find explanations for false positives in newborns.ResultsThis retrospective study included 962 newborns. Newborns underwent traditional biochemical screening at birth using blood staining and genomic sequencing of their stored blood staining using the NeoSeq Pro panel, which was able to detect 154 pathogenic genes and 86 diseases. A total of 632 newborns were carriers of gene variants. 56% of congenital hypothyroidism carriers had higher thyroid-stimulating hormone levels than normal newborns. Abnormal biochemical indices were detected in 71% of carriers of organic acid metabolic diseases, 69% of carriers of amino acid metabolic diseases, and 85% of carriers of fatty acid β oxidation disorders. In carriers associated with organic acid metabolic diseases, the propionylcarnitine (C3), C3/acetylcarnitine (C2), and methylmalonylcarnitine (C4DC) + 3-hydroxyisovalerylcarnitine (C5OH) levels were higher than those in non-carriers (C3: 4.12 vs. 1.66 µmol/L; C3/C2: 0.15 vs. 0.09; C4DC + C5OH: 0.22 vs. 0.19 µmol/L). In carriers associated with amino acid metabolic diseases, phenylalanine levels were higher than those in non-carriers (68.00 vs. 52.05 µmol/L). For carriers of fatty acid β oxidation disorders, butyrylcarnitine levels were higher than those in non-carriers (0.31 vs. 0.21 µmol/L), while the free carnitine levels were lower than those in non-carriers (14.65 vs. 21.87 µmol/L). There was a higher occurrence of carriers among newborns who received false-positive results for amino acid metabolic diseases compared to those who received negative results (15.52% vs. 6.71%). Similarly, there was a higher occurrence of carriers among newborns who received false-positive results for fatty acid β oxidation disorders compared to those who received negative results (28.30% vs. 7.29%).ConclusionsThis study showed that the carriers comprised a large number of newborns. Carriers had abnormal biochemical indicators compared with non-carriers, which could explain the false-positive rate for newborns using traditional newborn biochemical screening, especially in amino acid metabolic and fatty acid β oxidation disorders.

Impact of protein and carnitine consuption on outcomes of care development of full-term newborns with critical perinatal diseases

There were studied results of the impact of increased consumption of proteins and L-carnitine in the nutrition program of full-term newborns with perinatal diseases on the results of physical development and inpatient treatment features. The purpose of the work was to study the correlations between short-term higher consumption of protein and carnitine by full-term newborns and the results of their physical development, the duration of hospital care development. The vital signs of 59 full-term newborns were studied in a randomized controlled trial in the period 2017-2020. The main critical disease of the perinatal period in newborns of both groups was found to be hypoxic-ischemic encephalopathy of a moderate degree in 86.7% and 86.2%, without a statistically significant difference. One group (n=30) received nutrition with mother's milk or formula, the second group (n=29) received similar nutrition with fortification with a protein and L-carnitine supplement during the hospital stay. At the beginning and at the end of the treatment, physical development of the newborns was studied and correlations between the obtained data were investigated. Newborns of both groups did not differ in characteristics at the beginning of the study. The proportions of the newborns' weight corresponded to the limits of the 50% percentile. The group with increased consumption of protein and carnitine, fortification group (FG) demonstrated better indicators of physical development, they regained body mass faster. Body mass of the newborns of the fortification group goup was 3966.9±439.1 g, compared to the standard nutrition (SN) group, with indicators being 3554.6±452.3 g, at p=0.003. The rate of increase in body length in FG was twice that of the SN group. Consumption of a larger dose of protein was accompanied by a shorter stay in the intensive care unit – 10.0 (8.0; 12.0) days versus 12.0 (11.0; 16.0) days, with U=235.0; p=0.002; earlier discharge from the hospital – 21.0 (19.0; 27.0) days versus 26.5 (22.0; 31.0) days, with U=267.0, p=0.01. Carnitine supplementation in the FG group led to an increase in the level of free carnitine in the blood plasma samples taken before the discharge from the hospital. The study of correlations revealed a positive correlation between the consumption of a full dose of proteins and the total increase in height (R=0.3, p&lt;0.05), the increase in body weight (R=0.3, p&lt;0.05). A negative correlation was found between the protein level and the duration of treatment in the hospital (R= -0.3, p&lt;0.05). The level of free carnitine had a positive effect on the increase in body length (R=0.51, p&lt;0.05), daily weight gain (R=0.3, p&lt;0.05). A poor increase in body length was associated with a longer duration of respiratory support: the correlation had an inverse direction R= -0.4, p&lt;0.05. Improving nutritional strategies has significant prospects for improving care development of full-term babies with critical perinatal states.

Low serum carnitine level is associated with increased urinary carnitine excretion in late pregnancy.

Carnitine is essential for fatty acid metabolism. Free carnitine (FCA) is excreted in the urine in the glomerulus, but is partly reabsorbed by a carnitine transporter. The mechanism underlying the decrease in serum carnitine level during pregnancy is unclear. To investigate whether low carnitine level is associated with increased renal excretion in pregnant women. We recruited 43 healthy pregnant and 25 non-pregnant women. Total carnitine (TCA) and FCA levels were measured using the enzymatic cycling method, and the acylcarnitine (ACA) level was calculated. Fractional excretion (FE) was calculated as carnitine clearance divided by creatinine clearance. The mean TCA, FCA, and ACA levels were lower at 12weeks of gestation in pregnant than non-pregnant women (P < .001); the levels decreased further at 36weeks, reaching 39%, 36%, and 52% of those in non-pregnant women, respectively (P < .001). The FEs were 3-4-fold higher in pregnant women than non-pregnant women. Pregnant women had a lower serum FCA/TCA ratio than non-pregnant women (0.788±0.098 vs 0.830±0.074, respectively; P < .05), whereas the urine FCA/TCA ratio was similar between the groups. Low carnitine level is associated with increased renal excretion during late pregnancy.

Pathophysiological roles of the serum acylcarnitine level and acylcarnitine/free carnitine ratio in patients with cardiovascular diseases

IntroductionL-carnitine exerts protective effects, such as maintaining mitochondrial functions and decreasing reactive oxygen species, while acylcarnitine (AC) is linked to the development of heart failure and atherosclerosis. HypothesisSerum carnitines play important pathophysiological roles in cardiovascular diseases. MethodsPre-operative biochemical data were obtained from 117 patients (71 men, average age 69.9 years) who underwent surgery for cardiovascular diseases. Measurements included pre-operative biochemical data including estimated glomerular filtration rate (eGFR), physical functions, skeletal muscle mass index (SMI) measured by bioelectrical impedance analysis, anterior thigh muscle thickness (MTh) measured by ultrasound, and routine echocardiography. Carnitine components were measured with the enzyme cycling method. Muscle wasting was diagnosed based on the Asian Working Group for Sarcopenia criteria. ResultsPlasma brain natriuretic peptide (BNP) level was correlated with serum free carnitine (FC) and AC level, and the acylcarnitine/free carnitine ratio (AC/FC). AC/FC was elevated with stage of chronic kidney disease. In multivariate analysis, log (eGFR) and log (BNP) were extracted as independent factors to define log (serum AC) (eGFR: β = 0.258, p = 0.008; BNP: β = 0.273, p = 0.011), even if corrected for age, sex and body mass index. AC/FC was negatively correlated with hand-grip strength (r = -0.387, p = 0.006), SMI (r = -0.314, p = 0.012), and anterior thigh MTh (r = -0.340, p = 0.014) in men. ConclusionsA significant association between serum AC level and AC/FC, and chronic kidney disease and heart failure exists in patients with cardiovascular diseases who have undergone cardiovascular surgery. Skeletal muscle loss and muscle wasting are also linked to the elevation of serum AC level and AC/FC.

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

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. 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. 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. 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.

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

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. 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. 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. 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.

The influence of increased protein intake and L-carnitine supply on the outcomes of term newborns in intensive therapy

We studied the possibilities of increased protein and L-carnitine supplementation in full-term newborns with perinatal diseases to improve the results of intensive care. Aim: to assess the impact of short-term increased protein consumption and L-carnitine supplementation by full-term newborns on the main indicators of treatment effectiveness in the intensive care unit. Materials and methods. To check the impact of the proposed method of feeding newborns, the life indicators of 59 full-term children, who were randomly divided into two groups, were studied. The first group (n = 30) received standard nutrition with mother’s milk or formula, the second group (n = 29) received a food product fortified with a protein supplement and a subsidy of L-carnitine during hospital stay. Results. Infants of both groups had statistically equivalent anthropometric characteristics at the beginning of the study. The proportions of infants of both sexes were within the 50 % percentile. Starting from the third week, caloric intake for the standard diet group (SG) and the enrichment group (FG), respectively, was 111.83 ± 7.19 kcal/kg/day, against 113.44 ± 5.61 kcal/kg/day, p = 0.0667. Per 1 g of protein, children in the FG group had amount of non-protein calories as 28.68 (27.50; 29.80) kcal/kg/day, compared to the indicator in the SG group of 42.37 (41.60; 38.00) kcal/kg/day, with U = 28.0000; p = 0.0001. Carnitine supplementation in the FG group led to an increase in the level of free carnitine in the last blood plasma samples, before the children were discharged home. In general, the proposed nutrition strategy was accompanied by better indicators of the physical development of children, and a statistically probable faster recovery of body weight in the fortification group. Thus, the generalized indicator of body weight of children of the SG group was 3966.90 ± 439.08 g, compared to the FG group of 3554.62 ± 452.28 g, with p = 0.0033. In general, children who consumed more protein were transferred from the intensive care unit earlier – 12.00 (11.00; 16.00) days, against 10.00 (8.00; 12.00) days, with U = 235,00; p = 0.0024; previously discharged from the hospital – 26.50 (22.00; 31.00) days, against 21.00 (19.00; 27.00) days, with U = 267.00, p = 0.0109. This strategy proved to be safe, as confirmed by normal levels of phenylalanine and urea at all stages of the examination of children. Conclusions. Short-term increased protein consumption against the background of carnitine supplementation improves the results of physical development of newborns and indicators of hospitalization and intensive care unit stay. Larger studies and catamnestic observation of children are needed.

BIOCHEMICAL PROFILE OF FULL-TERM NEWBORNS WITH DIFFERENT PROTEIN SUPPLY ON THE BACKGROUND OF THE TREATMENT OF CRITICAL DISEASES OF THE PERINATAL PERIOD

Study of the effect of increased protein and L-carnitine supplementation in term neonates with critical illnesses on the biochemical profile and improvement of intensive care outcomes.&#x0D; Objective: assessment of the impact of increased L-carnitine and protein supplementation on the physical development and biochemical profile of newborns who were in a critical condition.&#x0D; Materials and methods. The life indicators of 59 full-term children, who were randomly divided into two groups, were studied. The first group (n = 30) received standard nutrition with mother's milk or formula, the second group (n = 29) received protein-fortified food and L-carnitine supplementation during the hospital stay.&#x0D; The results. Babies of both groups had statistically equivalent characteristics at the beginning of the study. Against the background of higher consumption of proteins, the number of non-protein calories per 1 g of protein in the study group was 28.68 kcal/kg/day (27.50; 29.80), against the indicator of the standard diet group of 42.37 kcal/kg/day (41 .60; 38.00), with U = 28.0000; p = 0.000001. Carnitine supplementation in the GZ group led to an increase in the level of free carnitine in the last blood plasma samples of newborns. In general, the proposed nutrition strategy was accompanied by better indicators of physical development of children. Children who consumed more protein were transferred from the intensive care unit earlier – 10.00 (8.00; 12.00) days, against 12.00 (11.00; 16.00) days, with U = 235.00; p = 0.0024; previously discharged from the hospital -21.00 (19.00; 27.00) days, against 26.50 (22.00; 31.00) days at U = 267.00, p = 0.0109. This strategy proved to be safe, as confirmed by normal levels of phenylalanine and blood biochemical indicators at all stages of the examination of children, including urea nitrogen and creatinine.&#x0D; Conclusions. Short-term increased consumption of protein against the background of carnitine supplementation improves the results of the physical development of newborns, does not lead to deviations in the biochemical profile, and is safe.

Evaluation of fatty acids and carnitine as biomarkers of PFOS exposure in biota (fish and dolphin) from Galveston Bay and the northwestern Gulf of Mexico

Perfluorooctane sulfonate (PFOS) is a ubiquitous pollutant that elicits a wide range of toxic effects in exposed biota. Coastal zones in highly urbanized or industrial areas are particularly vulnerable to PFOS pollution. At present, information is lacking on biomarkers to assess PFOS effects on aquatic wildlife. This study investigated the efficacy of l-carnitine (or carnitine) and fatty acids as biomarkers of PFOS exposure in aquatic biota. The levels of PFOS, total and free carnitine, and 24 fatty acids (measured as fatty acid methyl esters or FAMEs) were measured in the liver, and muscle or blubber, of fish and dolphins sampled from Galveston Bay and the northern Gulf of Mexico (nGoM). Overall, bottlenose dolphins (Tursiops truncatus) had the highest hepatic PFOS levels. Galveston Bay fish, gafftopsail catfish (Bagre marinus), red drum (Sciaenops ocellatus), and spotted seatrout (Cynoscion nebulosus), had hepatic PFOS levels ∼8-13× higher than nGoM pelagic fish species, red snapper (Lutjanus campechanus) and yellowfin tuna (Thunnus albacares). The multivariate analysis of PFOS liver body-burdens and biomarkers found carnitine to be a more modal biomarker of PFOS exposure than FAMEs. Significant positive correlation of hepatic PFOS levels with total carnitine was evident for biota from Galveston Bay (fish only), and a significant correlation between PFOS and total and free carnitine was evident for biota from the nGoM (fish and dolphins). Given the essential role of carnitine in mediating fatty acid β-oxidation, our results suggest carnitine to be a likely candidate biomarker of environmental PFOS exposure and indicative of potential dyslipidemia effects.

Evaluation of free and bound carnitine in young athletes

The study of the characteristics of carnitine metabolism in representatives of certain sports makes it possible to study the effect of physical loads of various nature on the body of a young athlete, and also makes it possible to assess the competitive potential and predict the tolerance of long-term and intense loads. Purpose. This study is to investigate the characteristics of carnitine metabolism in young athletes of various specializations. Material and methods. The study included athletes aged 14 to 18 who had been engaged in intense physical exercise for at least 12 hours per week forthe past 12 months or more. The control group consisted of healthy children aged 14 to 18 who were not involved in sports. In the blood serum of all study participants, the concentration of free carnitine, acetylcarnitine and acylcarnitines was determined. Based on the data obtained, ratios were calculated reflecting the activity of lipid beta-oxidation enzymes. Results. We found that the content of free carnitine in the representatives of all the studied groups was within the normal range. At the same time, the level of free carnitine in the blood of athletes involved in field hockey was significantly lower than that of athletes-swimmers and representatives of the control group (p&lt;0.001). It was also studied that, compared with athletes-swimmers and the control group, athletes-hockey players have significantly higher functional activity of carnitine palmitoyltransferase 1 (p&lt;0.05) and lipid beta-oxidation enzymes (p&lt;0.001). Conclusion. In our work we have demonstrated that athletes involved in team sports (field hockey) have a more pronounced shift towards fatty acid oxidation compared to aerobic sports (swimming). A possible reason for the identified changes may be a more significant effect of alternating aerobic and anaerobic loads on lipid metabolism compared to exclusively aerobic activity.

Newborn Screening with (C16 + C18:1)/C2 and C14/C3 for Carnitine Palmitoyltransferase II Deficiency throughout Japan Has Revealed C12/C0 as an Index of Higher Sensitivity and Specificity.

Carnitine palmitoyltransferase (CPT) II deficiency is a long-chain fatty acid oxidation disorder. It manifests as (1) a lethal neonatal form, (2) a hypoglycemic form, or (3) a myopathic form. The second form can cause sudden infant death and is more common among Japanese people than in other ethnic groups. Our study group had earlier used (C16 + C18:1)/C2 to conduct a pilot newborn screening (NBS) study, and found that the use of C14/C3 for screening yielded lower rates of false positivity; in 2018, as a result, nationwide NBS for CPT II deficiency started. In this study, we evaluated the utility of these ratios in 71 NBS-positive infants and found that the levels of both C14/C3 and (C16 + C18:1)/C2 in patients overlapped greatly with those of infants without the disease. Among the levels of acylcarnitines with various chain lengths (C18 to C2) and levels of free carnitine (C0) as well as their ratios of various patterns, C12/C0 appeared to be a promising index that could reduce false-positive results without missing true-positive cases detected by current indices. Although some cases of the myopathic form may go undetected even with C12/C0, its use will help prevent life-threatening onset of the hypoglycemic form of CPT II deficiency.