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1.
Influence of Besifovir Dipivoxil Maleate Combined with L-Carnitine on Hepatic Steatosis in Patients with Chronic Hepatitis B.
Jung, YW, Kim, M, Kim, BK, Park, JY, Kim, DY, Ahn, SH, Han, KH, Kim, SU
Journal of Korean medical science. 2020;(17):e104
Abstract
BACKGROUND Besifovir dipivoxil maleate (BSV) with L-carnitine is the first-line antiviral agent for chronic hepatitis B (CHB) infection. We investigated whether BSV combined with L-carnitine improves hepatic steatosis (HS). METHODS Treatment-naïve patients with CHB who were initiated on antiviral therapy (AVT) were enrolled. The magnitude of HS was assessed using hepatic steatosis index (HSI), and HS improvement was defined as a ≥ 10% reduction in the HSI score from the baseline. RESULTS The mean age of the study patients was 56 years with a male predominance (n = 178, 64.7%). The mean body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count were 23.5 kg/m², 49.6 IU/L, 49.0 IU/L, and 191.3 × 10⁹/L, respectively. The mean HSI and fibrosis (FIB)-4 index were 32.6 and 0.5, respectively. After 6 months of AVT, platelet count (mean, 191.3→167.0 × 10⁹/L), fasting glucose (mean, 113.1→105.9 mg/dL), AST (mean, 49.6→28.0 IU/L), ALT (mean, 49.0→33.9 IU/L), and total cholesterol (mean, 170.0→162.1 mg/dL) levels significantly decreased (all P < 0.05). In the BSV group, AST (mean, 95.2→30.2 IU/L) and ALT (mean, 81.1→31.1 IU/L) levels significantly reduced (all P < 0.05), whereas HSI and FIB-4 index were maintained (all P > 0.05). In the univariate analysis, age, BMI, diabetes, cirrhosis, fasting glucose level, and ALT were significantly associated with HS improvement (all P < 0.05). CONCLUSION BSV with L-carnitine did not show any improvement of HS in patients with CHB. Further prospective randomized controlled studies are needed to validate the potential beneficial effects of BSV with L-carnitine in CHB infection.
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2.
Beneficial effects of l-carnitine supplementation for weight management in overweight and obese adults: An updated systematic review and dose-response meta-analysis of randomized controlled trials.
Askarpour, M, Hadi, A, Miraghajani, M, Symonds, ME, Sheikhi, A, Ghaedi, E
Pharmacological research. 2020;:104554
Abstract
Despite preclinical studies demonstrating the efficacy of l-carnitine supplementation for weight management, findings in clinical setting are contradictory. Electronic bibliographical databases were systematically searched up to February 2019 with no limitation in language, including Scopus, PubMed, ISI Web of Science and Cochrane Library. Clinical trials registry platform were also searched. All randomized controlled trials (RCTs) which reported an effect of l-carnitine supplementation on obesity-related indices were included. Weighted mean difference (WMD) was estimated using a random-effect model (DerSimonian-Laird method). Eventually 43 eligible RCTs were included for quantitative analysis. Meta-analysis results revealed that l-carnitine supplementation significantly decreased weight (WMD: -1.129 kg, 95 % CI: -1.590, -0.669; I2: 63.4), body mass index (BMI) (WMD: -0.359 kg/m2, 95 % CI: -0.552, -0.167; I2: 85.2) and fat mass (WMD: -1.158 kg, 95 % CI: -1.763, -0.554, I2: 15.5). However, l-carnitine supplementation did not change body fat percentage (WMD: -0.874 %, 95 % CI: -1.890, 0.142, I2: 98.2) or waist circumference (WMD: -0.883 mg/dl, 95 % CI: -1.770, 0.004, I2: 74.8). l-Carnitine supplementation changed weight (r = -0.98) and BMI (r = -0.67) in a non-linear fashion based on carnitine dosage and BMI according to trial duration (r = -0.04). Interestingly subgroup analysis revealed that l-carnitine showed anti-obesity effects only in overweight and obese subjects; l-carnitine decreased weight, and BMI alone when combined with other lifestyle modifications. Anthropometric indexes were not changed following l-carnitine supplementation among patients' undergoing hemodialysis. Our study revealed that l-carnitine supplementation might have a positive effects in achieving an improved body weight and BMI especially in overweight and obese subjects.
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3.
L-Carnitine's Effect on the Biomarkers of Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Choi, M, Park, S, Lee, M
Nutrients. 2020;(9)
Abstract
A systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out to assess L-carnitine supplements' influence on the biomarkers of metabolic syndrome (MetSyn). PubMed, EMBASE, Cochrane library, and CINAHL were used to collect RCT studies published prior to February 2020. RCT studies were included if they had at least one of the following biomarker outcome measurements: waist circumference (WC), blood pressure (BP), fasting blood sugar (FBS), triglyceride (TG), or high density lipoprotein-cholesterol (HDLc). Nine of twenty studies with adequate methodological quality were included in this meta-analysis. The dose of L-carnitine supplementation administered varied between 0.75 and 3 g/day for durations of 8-24 weeks. L-carnitine supplementation significantly reduced WC and systolic BP (SBP), with no significant effects on FBS, TG, and HDLc. We found that L-carnitine supplementation at a dose of more than 1 g/d significantly reduced FBS and TG and increased HDLc. In conclusion, L-carnitine supplementation is correlated with a significant reduction of WC and BP. A dose of 1-3 g/d could improve the biomarkers of MetSyn by reducing FBS and TG and increasing HDLc.
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4.
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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5.
The effect of l-carnitine supplementation on lipid profile and glycaemic control in adults with cardiovascular risk factors: A systematic review and meta-analysis of randomized controlled clinical trials.
Asadi, M, Rahimlou, M, Shishehbor, F, Mansoori, A
Clinical nutrition (Edinburgh, Scotland). 2020;(1):110-122
Abstract
BACKGROUND & AIMS Several randomized clinical trials (RCTs) have investigated the effect of l-carnitine supplementation on lipid profile and glycaemic control in adults with cardiovascular risk factors; however, the results were conflicting. Therefore, a meta-analysis was performed to assess the effect of l-carnitine on lipid profile and glycaemic control in adults with cardiovascular risk factors. METHODS We searched PubMed, Scopus, Cochrane Databases, Google Scholar, ProQuest, Web of Science and Embase for randomized, placebo-controlled human trials that investigated the effect of l-carnitine supplementation on lipid profile and glycaemic control up to April 2017. From the eligible trials, 24 articles were selected for the meta-analysis. The meta-analysis was performed in a random-effects model. Heterogeneity was determined by I2 statistics and Cochrane Q test. RESULTS The result showed significant effect of l-carnitine on TC (WMD: -13.73 [95% CI: -22.28, -5.17] mg/dL; P < 0.001), LDL-C (WMD = - 7.70 [95% CI: - 11.80, -3.61]mg/dL; p < 0.001), HDL-C (WMD = 0.82 [95% CI: 0.44, 1.21] mg/dL; P > 0.001), Lp(a) (WMD = - 7.13 [95% CI: -9.82,- 4.43]mg/dL; P < 0.001), FPG (WMD = -6.25 [95% CI: -10.35, -2.16] mg/dL; P < 0.001), HbA1C (WMD (%) = - 0.35 [95% CI: -0.65,- 0.05]; p = 0.02) and HOMA-IR (WMD (%) = - 0.94 [95% CI: -1.89, -0.00]; P = 0.05). No effect of l-carnitine was detected in TG, Apo A-I and Apo B 100 on pooled effect size. Additionally, sensitivity analysis showed l-carnitine supplementation could improve glycaemic control, particularly along with hypocaloric diet. CONCLUSION This meta-analysis showed that l-carnitine supplementation could improve lipid profile levels, particularly in doses more than 1500 mg/day. More RCTs with large sample sizes, focusing on gut microbiome profiles and dietary patterns are needed to better understand the effect of l-carnitine on patients with cardiovascular risk factors.
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6.
The Effect of L-Carnitine Supplementation on Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Yarizadh, H, Shab-Bidar, S, Zamani, B, Vanani, AN, Baharlooi, H, Djafarian, K
Journal of the American College of Nutrition. 2020;(5):457-468
Abstract
Accumulating evidence of previous experimental studies indicated that L-Carnitine positively ameliorates muscle damage. However, findings from trials vary substantially across studies. Therefore, current meta-analysis aimed to examine the effects of L-Carnitine supplementation on exercise-induced muscle damage. An electronic search of the online literature databases (Medline (PubMed), Scopus and Google Scholar) was performed up to November 2018. Either a fixed-effects model or a random-effects model (Diasorin-Liard) was used in order to estimate the effects size. Cochran's Q test and I2 tests were used to assess the heterogeneity among the studies. Funnel plot and Egger's regression test were also employed in order to assess the publication bias. Of 604 studies, seven eligible randomized controlled trials (RCTs) were included in this meta-analysis. Pooled data from seven studies showed that L-Carnitine resulted in significant improvements in muscle soreness (MS) at the five follow-up time points (0, 24, 48, 72 and 96 hours (h)) compared to placebo. Also, pooled data indicated that L-Carnitine significantly reduced creatine kinase (CK), myoglobin (Mb), and lactate dehydrogenase (LDH) levels at one follow-up period (24 h). However, no effects have been observed beyond this period. Our outcomes indicate that L-Carnitine supplementation improves delayed-onset muscle soreness (DOMS) and markers of muscle damage. Further research is needed to clarify impacts of L-Carnitine on DOMS after different types of mechanical or chemical damages.Key teaching pointsThe effect of L-Carnitine supplementation on exercise-induced muscle damage has come under scrutiny over many years.This systematic review and meta-analyses study investigated the effects of L-Carnitine supplementation on exercise-induced muscle damage.Overall, summary results indicate that L-Carnitine supplementation improves muscle soreness and markers of muscle damage (CK, LDH, and Mb).Overall, L-carnitine supplementation ameliorated muscle damage only in resistance training groups and untrained population.
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7.
A Pilot Study on the Effects of l-Carnitine and Trimethylamine-N-Oxide on Platelet Mitochondrial DNA Methylation and CVD Biomarkers in Aged Women.
Bordoni, L, Sawicka, AK, Szarmach, A, Winklewski, PJ, Olek, RA, Gabbianelli, R
International journal of molecular sciences. 2020;(3)
Abstract
l-carnitine supplementation has been used for cardiovascular health protection for a long time. Recently, trimethylamine-N-oxide (TMAO), which is an end product of l-carnitine metabolism via the activity of microbiota, has been identified as a cardiovascular disease (CVD) biomarker. The aim of this study was to assess the effect of 6 months of l-carnitine supplementation in a group of aged women engaged in a regular physical training. Platelet mitochondrial DNA methylation, an emerging and innovative biomarker, lipid profile and TMAO levels have been measured. TMAO increased after l-carnitine supplementation (before 344.3 ± 129.8 ng/mL vs. after 2216.8 ± 1869.0 ng/mL; n = 9; paired t-test, p = 0.02). No significant effects on TMAO were exerted by training alone (n = 9) or by l-leucine supplementation (n = 12). TMAO levels after 6 months of l-carnitine supplementation were associated with higher low-density lipoprotein-cholesterol (LDL-c) (Spearman Rho = 0.518, p = 0.003) and total cholesterol (TC) (Spearman Rho = 0.407, p = 0.026) levels. l-carnitine supplementation increased D-loop methylation in platelets (+6.63%; paired t-test, p = 0.005). D-loop methylation was not directly correlated to the TMAO augmentation observed in the supplemented group, but its increase inversely correlated with TC (Pearson coefficient = -0.529, p = 0.029) and LDL-c (Pearson coefficient = -0.439, p = 0.048). This evidence supports the hypothesis that the correlation between l-carnitine, TMAO and atherosclerosis might be more complex than already postulated, and the alteration of mitochondrial DNA (mtDNA) methylation in platelets could be involved in the pathogenesis of this multifactorial disease.
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8.
Efficacy and Safety of the Combination of Superoxide Dismutase, Alpha Lipoic Acid, Vitamin B12, and Carnitine for 12 Months in Patients with Diabetic Neuropathy.
Didangelos, T, Karlafti, E, Kotzakioulafi, E, Kontoninas, Z, Margaritidis, C, Giannoulaki, P, Kantartzis, K
Nutrients. 2020;(11)
Abstract
AIM: To investigate the efficacy of Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine, and Vitamin B12 (B12) in one tablet in Diabetic Neuropathy (DN). PATIENTS-METHODS In this prospective, double-blind, placebo-controlled study, 85 patients with Diabetes Mellitus Type 2 (DMT2) were randomly assigned, either to receive the combination of four elements (active group, n = 43), or placebo (n = 42) for 12 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured the vibration perception threshold (BIO), and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Pain (PS) and quality of life (QL) questionnaires were administered. RESULTS At follow-up, BIO, MNSIQ, QL, PAIN, and SNCV, SNAP, and B12 levels had significantly improved inactive group (p <0.001, p <0.001, p <0.001, p <0.001, p = 0.027, p = 0.031, and p <0.001 respectively), whereas the inplacebo group MCR (mean circular resultant) and PAIN deteriorated (p <0.001, p <0.001). The changes in MNSIQ, QL, SNCV, BIO, and PAIN differed significantly between groups (p <0.001, p <0.001, p = 0.031, p <0.001, and p <0.001 respectively). CONCLUSIONS The combination of the four elements in one tablet for 12 months in patients with DMT2 improved all indices of peripheral neuropathy, including SNAP and SNCV, pain, and Quality of Life perception, except CARTs and MNSIE.
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9.
L-Carnitine Reduces Oxidative Stress and Promotes Cells Differentiation and Bone Matrix Proteins Expression in Human Osteoblast-Like Cells.
Terruzzi, I, Montesano, A, Senesi, P, Villa, I, Ferraretto, A, Bottani, M, Vacante, F, Spinello, A, Bolamperti, S, Luzi, L, et al
BioMed research international. 2019;:5678548
Abstract
Bone fragility and associated fracture risk are major problems in aging. Oxidative stress and mitochondrial dysfunction play a key role in the development of bone fragility. Mitochondrial dysfunction is closely associated with excessive production of reactive oxygen species (ROS). L-Carnitine (L-C), a fundamental cofactor in lipid metabolism, has an important antioxidant property. Several studies have shown how L-C enhances osteoblastic proliferation and activity. In the current study, we investigated the potential effects of L-C on mitochondrial activity, ROS production, and gene expression involved in osteoblastic differentiation using osteoblast-like cells (hOBs) derived from elderly patients. The effect of 5mM L-C treatment on mitochondrial activity and L-C antioxidant activity was studied by ROS production evaluation and cell-based antioxidant activity assay. The possible effects of L-C on hOBs differentiation were assessed by analyzing gene and protein expression by Real Time PCR and western blotting, respectively. L-C enhanced mitochondrial activity and improved antioxidant defense of hOBs. Furthermore, L-C increased the phosphorylation of Ca2+/calmodulin-dependent protein kinase II. Additionally, L-C induced the phosphorylation of ERK1/2 and AKT and the main kinases involved in osteoblastic differentiation and upregulated the expression of osteogenic related genes, RUNX2, osterix (OSX), bone sialoprotein (BSP), and osteopontin (OPN) as well as OPN protein synthesis, suggesting that L-C exerts a positive modulation of key osteogenic factors. In conclusion, L-C supplementation could represent a possible adjuvant in the treatment of bone fragility, counteracting oxidative phenomena and promoting bone quality maintenance.
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10.
Prevention by L-carnitine of DNA damage induced by 3-hydroxy-3-methylglutaric and 3-methylglutaric acids and experimental evidence of lipid and DNA damage in patients with 3-hydroxy-3-methylglutaric aciduria.
Delgado, CA, Balbueno Guerreiro, GB, Diaz Jacques, CE, de Moura Coelho, D, Sitta, A, Manfredini, V, Wajner, M, Vargas, CR
Archives of biochemistry and biophysics. 2019;:16-22
Abstract
3-hydroxy-3-methylglutaric aciduria (HMGA) is an inherited disorder of the leucine catabolic pathway in which occurs a deficiency of the 3-hydroxy-3-methylglutaryl-CoA lyase enzyme. Therefore, the organic acids 3-hydroxy-3-methylglutaric (HMG) and 3-methylglutaric (MGA), mainly, accumulate in tissues of affected patients. Lately, much attention has been focused on free radicals as mediators of tissue damage in human diseases, causing lipid peroxidation, protein oxidation and DNA damage. The treatment of this disease is based in a restricted protein ingest and supplementation with l-carnitine (LC), an antioxidant and detoxifying agent. In the present work, we investigated the in vitro oxidative damage to DNA induced by the accumulation of organic acids and oxidative stress parameters in vivo of patients with 3-HMG, as well as the effect of the recommended therapy. The in vitro DNA damage was analyzed by the alkaline comet assay in leukocytes incubated with HMG and MGA (1 mM, 2.5 mM and 5 mM) and co-incubated with LC (90 μM and 150 μM). The in vivo urinary 15-F2t-isoprostane levels and urinary oxidized guanine species were measured by ELISA kits in patient's urine before and after the treatment with LC. HMG and MGA induced a DNA damage index (DI) significantly higher than that of the control group. The DI was significantly reduced in the presence of LC. It was also verified a significant increase of oxidized guanine species and urinary isoprostane levels, biomarker of oxidative DNA damage and lipid peroxidation respectively, in patients before treatment. After the treatment and supplementation with LC, patients presented significantly lower levels of those biomarkers. Analyzing the data together, we can conclude that HMGA patients present oxidative lipid and DNA damage, which is induced by HMG and MGA, and the antioxidant therapy with LC can prevent that kind of injuries.