아세틸-L-카르니틴

Acetyl-L-carnitine Slows the Progression from Prefrailty to Frailty in Older Subjects: A Randomized Interventional Clinical Trial.

1. Curr Pharm Des. 2022;28(38):3158-3166. doi: 10.2174/1381612828666220830092815. Acetyl-L-carnitine Slows the Progression from Prefrailty to Frailty in Older Subjects: A Randomized Interventional Clinical Trial. Malaguarnera G(1), Catania VE(2), Bertino G(3), Chisari LM(1), Castorina M(4), Bonf

Cyclosporine exacerbates ketamine toxicity in zebrafish: Mechanistic studies on drug-drug interaction.

2. J Appl Toxicol. 2017 Dec;37(12):1438-1447. doi: 10.1002/jat.3488. Epub 2017 Jun 1. Cyclosporine exacerbates ketamine toxicity in zebrafish: Mechanistic studies on drug-drug interaction. Robinson BL(1), Dumas M(1), Ali SF(1), Paule MG(1), Gu Q(1), Kanungo J(1). Author information: (1)Division

Repositioning of antibiotic levofloxacin as a mitochondrial biogenesis inhibitor to target breast cancer.

3. Biochem Biophys Res Commun. 2016 Mar 18;471(4):639-45. doi: 10.1016/j.bbrc.2016.02.072. Epub 2016 Feb 18. Repositioning of antibiotic levofloxacin as a mitochondrial biogenesis inhibitor to target breast cancer. Yu M(1), Li R(2), Zhang J(3). Author information: (1)Galactophore Department, Ji

Distinct effects of ketamine and acetyl L-carnitine on the dopamine system in zebrafish.

4. Neurotoxicol Teratol. 2016 Mar-Apr;54:52-60. doi: 10.1016/j.ntt.2016.02.004. Epub 2016 Feb 16. Distinct effects of ketamine and acetyl L-carnitine on the dopamine system in zebrafish. Robinson BL(1), Dumas M(1), Cuevas E(1), Gu Q(1), Paule MG(1), Ali SF(1), Kanungo J(2). Author information:

Prevention of paclitaxel-evoked painful peripheral neuropathy by acetyl-L-carnitine: effects on axonal mitochondria, sensory nerve fiber terminal arbors, and cutaneous Langerhans cells.

5. Exp Neurol. 2008 Mar;210(1):229-37. doi: 10.1016/j.expneurol.2007.11.001. Epub 2007 Nov 17. Prevention of paclitaxel-evoked painful peripheral neuropathy by acetyl-L-carnitine: effects on axonal mitochondria, sensory nerve fiber terminal arbors, and cutaneous Langerhans cells. Jin HW(1), Fla

Acetyl-L-carnitine requires phospholipase C-IP3 pathway activation to induce antinociception.

6. Neuropharmacology. 2004 Aug;47(2):286-94. doi: 10.1016/j.neuropharm.2004.03.016. Acetyl-L-carnitine requires phospholipase C-IP3 pathway activation to induce antinociception. Galeotti N(1), Bartolini A, Calvani M, Nicolai R, Ghelardini C. Author information: (1)Department of Pharmacology, Uni

Repeated acetyl-l-carnitine administration increases phospho-Thr34 DARPP-32 levels and antagonizes cocaine-induced increase in Cdk5 and phospho-Thr75 DARPP-32 levels in rat striatum.

7. Eur J Neurosci. 2004 Mar;19(6):1609-20. doi: 10.1111/j.1460-9568.2004.03230.x. Repeated acetyl-l-carnitine administration increases phospho-Thr34 DARPP-32 levels and antagonizes cocaine-induced increase in Cdk5 and phospho-Thr75 DARPP-32 levels in rat striatum. Scheggi S(1), Rauggi R, Nanni G

Acetyl-L-carnitine cytoprotection against 1-methyl-4-phenylpyridinium toxicity in neuroblastoma cells.

8. Biochem Pharmacol. 2003 Jul 15;66(2):297-306. doi: 10.1016/s0006-2952(03)00261-2. Acetyl-L-carnitine cytoprotection against 1-methyl-4-phenylpyridinium toxicity in neuroblastoma cells. Mazzio E(1), Yoon KJ, Soliman KF. Author information: (1)College of Pharmacy and Pharmaceutical Sciences, F

Carnitine for fatigue in multiple sclerosis.

9. Cochrane Database Syst Rev. 2010 Feb 17;(2):CD007280. doi: 10.1002/14651858.CD007280.pub2. Carnitine for fatigue in multiple sclerosis. Tejani AM(1), Wasdell M, Spiwak R, Rowell G, Nathwani S. Author information: (1)Clinical Research and Drug Information, Fraser Health Authority, 3935 Kincaid

Low Bioavailability and High TMAO Production: Novel Insights Into Acetylcarnitine and Carnitine Metabolism.

1. Mol Nutr Food Res. 2025 Dec;69(24):e70316. doi: 10.1002/mnfr.70316. Epub 2025 Nov 16. Low Bioavailability and High TMAO Production: Novel Insights Into Acetylcarnitine and Carnitine Metabolism. Krims-Davis K(1)(2), Ozola M(1), Razzivina V(1)(2), Gukalova B(1)(2), Konrade I(2)(3), Dambrova M(1)(2), Liepinsh E(1)(2). Author information: (1)Latvian Institute of Organic Synthesis, Riga, Latvia. (2)Riga Stradiņš University, Riga, Latvia. (3)Riga East Clinical Hospital, Riga, Latvia. The food supplement acetylcarnitine is marketed for use in neurological support; however, research on its bioavailability and metabolic fate has been limited. This study investigated the absorption, metabolism, and excretion of acetylcarnitine compared with those of carnitine. Healthy volunteers received either carnitine or an acetylcarnitine supplement (0.5 or 1.5 g). Plasma and urine samples were collected at baseline and at multiple time points (1-48 h) post intake and analyzed using LC‒MS/MS. Both carnitine and acetylcarnitine exhibited low intestinal absorption and renal reabsorption. The peak plasma concentrations increased over the baseline values by 48% (acetylcarnitine) and 43% (carnitine) following a 1.5 g dose. However, the increase in area under the curve (ΔAUC) from acetylcarnitine was 7.7-fold lower than that from carnitine. Elevated plasma levels of carnitine and acetylcarnitine led to a 5-fold increase in clearance, and a substantial portion of the supplements were excreted via urine. The acetylcarnitine supplement was mostly eliminated in the form of carnitine. Approximately 90% of both supplements were metabolized to TMAO, reaching 50 µM in plasma-levels previously found to be associated with adverse health outcomes. Acetylcarnitine has significantly lower bioavailability than carnitine. The intake of both supplements resulted in substantial TMAO production, raising potential health concerns. © 2025 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH. DOI: 10.1002/mnfr.70316 PMCID: PMC12700042 PMID: 41243468 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Efficacy Of Combined Nutritional And Pharmacological Interventions In PCOS: A Six Month Randomized Controlled Trial.

2. Naunyn Schmiedebergs Arch Pharmacol. 2026 Feb;399(3):3461-3476. doi: 10.1007/s00210-025-04626-6. Epub 2025 Sep 30. Efficacy Of Combined Nutritional And Pharmacological Interventions In PCOS: A Six Month Randomized Controlled Trial. Zahra M(1), Shah M(2), Iqbal F(1), Zubair T(3), Habib R(4), Zulfiqar F(5). Author information: (1)Department of Physiology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan. (2)Department of Physiology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan. mohsin.ibms@kmu.edu.pk. (3)Department of Medicine, Gajju Khan Medical College, Swabi, Pakistan. (4)Department of Gynecology and Obstetrics, DHQ Hospital, Mardan, Pakistan. (5)Department of Public Health, Khyber Girls Medical College, Peshawar, Pakistan. Polycystic ovary syndrome is a complex heterogenous reproductive endocrine disorder affecting mainly reproductive age women worldwide. The syndrome primarily is associated with hyperandrogenism, hyperinsulinemia, menstrual irregularity, infertility, hormonal dysregulation and obesity. Here, we examined the effects of Acetyl-L-Carnitine, L-Arginine, CoQ10, (Carnitine + Arginine + CoQ10) and Metformin, alone and in combination, on PCOS management. The trial included 63 females diagnosed with PCOS. The participants were treated with either Carnitine + Arginine + CoQ10 alone (nutraceutical group) or in combination with metformin (combination group) for six months. The outcome measures included demographic, anthropometric, clinical, endocrine, metabolic, quality of Life and stress response of the participants. Over 24 weeks, both treatment regimens improved metabolic, hormonal, and psychological outcomes in women with PCOS. Repeated-measures ANCOVA showed significant group × time interactions for BMI (p < .001, η2 = .220), waist circumference (p < .001, η2 = .314), and hip circumference (p < .001, η2 = .428), favoring the combination group. Hormonal responses varied: DHEAS (p = .045, η2 = .082), FAI (p < .001, η2 = .223), testosterone (p = .004, η2 = .113), and prolactin (p = .032, η2 = .072) declined more in the combination group, whereas LH decreased more in the nutraceutical group (p < .001, η2 = .231). Quality of life improved significantly in both arms, with greater gains in the combination group (p = .037, η2 = .071). Oxidative stress (MDA) also declined significantly in both groups (p = .003), with larger numerical reductions in the combination arm (- 22% vs - 6%), though between-group differences were not significant (p = .329). Both nutraceutical and combination therapies led to significant improvements in metabolic, hormonal, and psychological outcomes in women with PCOS over 24 weeks. Repeated-measures ANCOVA confirmed greater reductions in BMI, waist and hip circumference, DHEAS, FAI, testosterone, and prolactin, as well as superior quality-of-life gains with combination therapy. Nutraceutical therapy exerted stronger effects on LH suppression, while oxidative stress (MDA) decreased significantly in both groups without between-group differences. These findings highlight the potential of nutraceuticals as a non-pharmacological option and underscore the added benefits of metformin co-administration for patients with pronounced hyperandrogenism and central adiposity. Trial Registration: clinicalTrial.gov NCT05653895. Registered March 1, 2022. © 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. DOI: 10.1007/s00210-025-04626-6 PMID: 41026176 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Human Ethics and Consent to Participate declarations: All participants in this study were informed about the research objectives, potential risks, and benefits of the research. Written informed consent was obtained from each participant before to their inclusion in the study. The study was conducted in accordance with the ethical guidelines outlined in the Declaration of Helsinki, and ethical approval was obtained from the Khyber Medical University ethics committee. (Approval No. DIR/KMU-EB/IA/000838). Participants were assured of confidentiality, and their data were used solely for research purposes. They had the right to withdraw from the study at any stage without any consequences. Institutional Review Board Statement: This study was performed in line with the principles of the Declaration of Helsinki. Ethical approval was obtained from ethical committee of Khyber and its Advanced Study and Research Board (Approval No. DIR/KMU-AS&RB/IA/001202). Written informed consent was obtained from all participants, and the trial was registered under ClinicalTrials.gov (NCT05653895). Competing interests: The authors declare no competing interests.

A prospective randomized controlled trial of antioxidants in human IVF and embryo culture media.

3. Hum Reprod. 2025 Nov 1;40(11):2088-2100. doi: 10.1093/humrep/deaf183. A prospective randomized controlled trial of antioxidants in human IVF and embryo culture media. Kelley RL(1), Lee YSL(1), Agresta F(1), Pehrsson NG(2), Stevens JM(1), Huang A(1), Sgroi J(1), Rozen G(1)(3), Polyakov A(1)(4), Hale L(1), Lew R(1), Stern C(1), Toledo M(1), Cattrall F(1), Gardner DK(1)(5). Author information: (1)Melbourne IVF, East Melbourne, VIC, Australia. (2)Statistiska Konsultgruppen, Göteborg, Sweden. (3)Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC, Australia. (4)Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia. (5)School of BioSciences, University of Melbourne, Parkville, VIC, Australia. STUDY QUESTION: Does the addition of three antioxidants to culture media during gamete collection, insemination, and embryo culture increase the clinical pregnancy rate from fresh blastocyst transfers? SUMMARY ANSWER: The clinical pregnancy rate from fresh blastocyst transfers was not increased by the addition of antioxidants to IVF and embryo culture media. WHAT IS KNOWN ALREADY: Addition of antioxidants to media is beneficial in mouse IVF, embryo culture, and cryopreservation. Prospective clinical trials of sibling human oocytes found an improvement in embryo quality and increased pregnancy rates from frozen blastocyst transfers in older patients. STUDY DESIGN, SIZE, DURATION: Single-centre, prospective randomized controlled trial, superiority study comparing media with or without the addition of antioxidants from January 2019 to November 2021. A total of 1482 patients were randomized before egg collection. Patients and their doctors were blinded to the treatment group. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients undergoing IVF/ICSI cycles and intending to undergo a fresh transfer of a single blastocyst were recruited. Exclusion criteria were previous participation in the study, use of cryopreserved oocytes/embryos, artificial oocyte activation, freeze-all cycle, or extraction of sperm from testicular biopsy. Seven hundred thirty-nine patients were randomized to control media and 743 patients to media containing the 'A3' antioxidant combination of acetyl-L-carnitine, α-lipoic acid, and N-acetyl-L-cysteine (treatment group). MAIN RESULTS AND THE ROLE OF CHANCE: The clinical pregnancy rate per randomized patient per cycle from fresh embryo transfer was not different between the control and antioxidant media (26.1% vs 22.9%; P > 0.05; RR 0.88 (95% CI 0.73-1.05)). In the Per Protocol population, which excludes patients with protocol violations or without a fresh transfer due to freeze-all or no embryo available, there was also no difference in between the control and antioxidant media in clinical pregnancy rate (36.7% vs 33.2%; P > 0.05; RR 0.90 (95% CI 0.76-1.07)) and live birth rate (32.4% vs 29.5%, P > 0.05). In the Intention-to-Treat population, antioxidant media produced a significant increase in the fertilization rate from 59.2 ± 26.3% to 64.5 ± 25.4% (P < 0.001) compared to control media. Blastocyst development rate per fertilized oocyte was not affected by antioxidant media, but the higher fertilization rate resulted in more fertilized oocytes per patient and therefore more blastocysts utilized per patient in the antioxidant group compared to the control (2.70 ± 2.59 vs 3.09 ± 2.96, P < 0.01). The increase in fertilization rate was observed in a subgroup analysis of ICSI cycles (57.9 ± 27.2% vs 68.3 ± 24.7%, P < 0.0001), and a decrease in the number of cycles with failed fertilization from 8.0 to 3.7% with antioxidant media (P < 0.01). In contrast, there was no effect of antioxidant media on fertilization rate in cycles with IVF insemination. LIMITATIONS, REASONS FOR CAUTION: This was a single-centre study, so the effects of antioxidant media in clinics with different protocols are unknown. Patient oxidative stress, which may be influenced by inflammation, diet, smoking status, antioxidant supplement consumption, and other lifestyle factors, was not accounted for. Any potential effect of renewing the antioxidants in the media during culture was not examined. WIDER IMPLICATIONS OF THE FINDINGS: Addition of antioxidants to culture media did not affect pregnancy rates from fresh single embryo transfers. An increase in fertilization rate was observed, which resulted in more blastocysts available for transfer and cryopreservation. There was no effect of antioxidants on blastocyst development rate or grade. Further studies are needed to validate the observed effect of antioxidants on fertilization rate following ICSI. STUDY FUNDING/COMPETING INTEREST(S): Culture media and an independent statistician were funded by Vitrolife AB. R.L.K has received travel funding and a speaker's honorarium from Vitrolife. D.K.G. has received research grants from Vitrolife at the University of Melbourne. N.-G.P. has received consulting fees from Vitrolife for work related to the study. All other authors have nothing to declare. TRIAL REGISTRATION NUMBER: ACTRN12618001479291. TRIAL REGISTRATION DATE: 4 September 2018. DATE OF FIRST PATIENT’S ENROLMENT: 28 January 2019. © The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. DOI: 10.1093/humrep/deaf183 PMID: 40973967 [Indexed for MEDLINE]

l-Carnitine and Alpha-Lipoic Acid Fail to Improve Anaerobic and Aerobic Performance in Trained Cyclists Despite a Reduction in Blood Lactate Concentration.

4. Nutrients. 2025 Jul 4;17(13):2227. doi: 10.3390/nu17132227. l-Carnitine and Alpha-Lipoic Acid Fail to Improve Anaerobic and Aerobic Performance in Trained Cyclists Despite a Reduction in Blood Lactate Concentration. de Rozas A(1), Pérez-Díaz JJ(1), Muros JJ(2), Sánchez-Muñoz C(1), Rufían-Henares JÁ(3), Zabala M(1), Salas-Montoro JA(1). Author information: (1)Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, 18071 Granada, Spain. (2)Department of Didactics of Body Expression, University of Granada, 18071 Granada, Spain. (3)Department of Nutrition and Food Sciences, Institute of Nutrition and Food Sciences, Biomedical Research Center, University of Granada, 18071 Granada, Spain. Background/Objectives: This study aimed to evaluate the effects of four weeks of combined Acetyl-l-Carnitine and alpha-lipoic acid (ALA) supplementation on anaerobic and aerobic performance and fatigue resistance in trained cyclists, hypothesizing improvements in maximal aerobic power (MAP), Wingate test performance, and reduced lactate accumulation. Methods: In a double-blind, randomized trial, 41 male trained cyclists (age: 36 ± 12 years; MAP: 4.35 ± 0.60 W·kg-1) were assigned to a supplement group (SUP, n = 19; 1200 mg/day Acetyl-l-Carnitine, 300 mg/day ALA, 1.1 mg Vitamin B1, 2.5 µg Vitamin B12) or placebo group (PLA, n = 22) for four weeks. Performance was assessed pre- and post-intervention via counter-movement jumps (CMJs), Wingate tests (WG1, WG2), and a graded exercise test (GXT). Blood lactate ([La-]) was measured post-Wingate. A three-way mixed ANOVA analyzed Wingate performance (session, order, and group), and a two-way ANOVA assessed MAP and fatigue effects. Results: MAP increased by 3.4% (314 ± 32 W to 324 ± 37 W; p = 0.005) with no group interaction (p = 0.457). Wingate peak power showed main effects for order (p < 0.001) and session (p = 0.011) but no group interaction (p = 0.676). SUP reduced [La-] by 1.5 mmol·L-1 post-WG2 in POST (p = 0.049). No significant group differences were found for CMJ or fatigue metrics. Conclusions: Four weeks of Acetyl-l-Carnitine and ALA supplementation did not enhance aerobic or anaerobic performance in trained cyclists, despite reducing blood lactate after high-intensity exercise, suggesting no ergogenic benefits. DOI: 10.3390/nu17132227 PMCID: PMC12252364 PMID: 40647331 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Impact of Dietary Supplements on Clinical Outcomes and Quality of Life in Patients with Breast Cancer: A Systematic Review.

5. Nutrients. 2025 Mar 11;17(6):981. doi: 10.3390/nu17060981. Impact of Dietary Supplements on Clinical Outcomes and Quality of Life in Patients with Breast Cancer: A Systematic Review. Scafuri L(1)(2), Buonerba C(1)(2), Strianese O(1), de Azambuja E(3), Palleschi M(4), Riccio V(5), Marotta V(6), Scocca C(7), Riccio G(8), Errico C(9), Arpino G(10), Di Lorenzo G(1)(2)(11). Author information: (1)Oncology Unit, "Andrea Tortora" Hospital, ASL Salerno, 84016 Pagani, Italy. (2)Associazione O.R.A. ETS-Oncology Research Assistance, 84134 Salerno, Italy. (3)Institut Jules Bordet, l'Université Libre de Bruxelles, 1070 Brussels, Belgium. (4)Medical Oncology, Breast & GYN Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy. (5)Ospedale SS Maria della Pietà, 80026 Casoria, Italy. (6)UOC Clinic of Endocrinology and Diabetology, AOU San Giovanni di Dio and Ruggi d'Aragona, 84131 Salerno, Italy. (7)Lincolnshire Pain Service Connect Health, Newcastle Upon Tyne NE12 8EU, UK. (8)Department of Medicine, University "Luigi Vanvitelli" of Naples, 80138 Naples, Italy. (9)A.O.U. Vanvitelli, Internal Medicine-San Paolo Hospital Campus (Fuorigrotta), 80142 Naples, Italy. (10)Department of Clinical Medicine and Surgery, University of Naples Federico II, 80133 Naples, Italy. (11)Department of Medicine, UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy. Background: This systematic review aimed to evaluate the efficacy and safety of dietary supplements in breast cancer patients, focusing on their impact on clinical outcomes, treatment-related side effects, and therapy adherence. Methods: Only RCTs investigating the effects of various orally administered supplements in adult breast cancer patients were included. Well-defined substances like vitamins, minerals, antioxidants, and specific herbal extracts were explored. The review excluded studies solely based on dietary interventions or non-supplemental approaches. The primary outcome assessed was quality of life. Secondary outcomes included disease-free survival, overall survival, tumor response, and biomarkers indicative of disease progression. Results: A total of 45 randomized controlled trials (RCTs) were included in this systematic review. Overall, supplementation was not associated with serious adverse events in the included trials. Vitamin D supplementation showed promise in some studies, with potential immunomodulatory and antioxidant effects, particularly when combined with other interventions. Omega-3 fatty acids and beta-glucan demonstrated potential in alleviating certain symptoms and improving quality of life. Studies on amino acids like acetyl-L-carnitine and L-arginine also yielded mixed results. Beta-glucan exhibited potential for immune-enhancing effects, while melatonin and creatine showed limited or no benefit for fatigue or muscle strength. Herbal extracts, including silymarin, curcumin, and EGCG, had varied effects. Curcumin studies presented mixed results. Silymarin showed potential for hepatoprotective effects. Conclusions: These findings highlight the potential of specific dietary supplements to improve various aspects of breast cancer care. However, the evidence is mixed across supplement types, and further research is needed to determine the most effective and safe approaches. DOI: 10.3390/nu17060981 PMCID: PMC11945011 PMID: 40290044 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest.

D-BHB supplementation before moderate-intensity exercise suppresses lipolysis and selectively blunts exercise-induced long-chain acylcarnitine increase in pilot study of patients with long-chain fatty acid oxidation disorders.

6. Mol Genet Metab. 2025 Apr;144(4):109070. doi: 10.1016/j.ymgme.2025.109070. Epub 2025 Feb 25. D-BHB supplementation before moderate-intensity exercise suppresses lipolysis and selectively blunts exercise-induced long-chain acylcarnitine increase in pilot study of patients with long-chain fatty acid oxidation disorders. Gregor AN(1), Delerive P(2), Cuenoud B(3), Monnard I(4), Redeuil K(4), Harding CO(1), Gillingham MB(5). Author information: (1)Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA. (2)Nestlé Health Science, Research and Clinical Development, Lausanne, Switzerland. (3)Nestlé Health Science, Research and Clinical Development, Lausanne, Switzerland; Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Canada. (4)Nestlé Research, Lausanne, Switzerland. (5)Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA. Electronic address: gillingm@ohsu.edu. Patients with long-chain fatty acid oxidation disorders (LC-FAOD) have impaired endogenous ketone production due to defects in the beta-oxidation pathway. We explored supplementation of exogenous D-beta-hydroxybutyrate (D-BHB) as an alternative source of energy in a randomized, double-blinded crossover pilot study. Participants ≥18 years of age with a diagnosis of LC-FAOD completed two moderate-intensity treadmill exercises following an oral supplementation of D-BHB salts or an isocaloric maltodextrin beverage. Five subjects (1 VLCADD, 2 CPT2D, 2 LCHADD), 60 % male, mean age = 33 years were enrolled. Mild to moderate GI symptoms were related to ingestion of D-BHB. Plasma D-BHB was increased after oral D-BHB compared to maltodextrin (p < .001) with an average concentration of 0.43 mM in the post-exercise period. During exercise, free fatty acids (p = .01), fold change in long-chain acylcarnitine species (LC-AC) (p ≤ .03) and systolic BP (p = .02) were lower after D-BHB compared to the maltodextrin beverage. D-BHB suppresses lipolysis and selectively blunts exercise-induced long-chain acylcarnitines. There were no differences between beverages in acetylcarnitine, blood glucose, creatine kinase, VO2, HR, RPE or respiratory exchange ratio. Consumption of the D-BHB beverage was safe and well-tolerated. Plasma D-BHB levels achieved mild ketosis and suppressed lipolysis and the associated rise in LC-AC, but fell short of stimulating the energetic effects that might have resulted in altered exercise parameters such as RER, or HR. In conclusion, our results provide a strong rationale for future studies aimed toward defining the optimal multiple-dose regimen of D-BHB per day that might improve exercise tolerance and understanding the long-term impact of treatment in LC-FAOD subjects. Copyright © 2025 Elsevier Inc. All rights reserved. DOI: 10.1016/j.ymgme.2025.109070 PMID: 40048912 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest MBG has received speaker honorarium from Ultragenyx Pharmaceutical Inc., Vitaflow, and Nutricia and received research grant/funds from Nestlé Health Science and Reneo Pharmaceutical. COH and has received research funding from Reneo Pharmaceutical and Nestle Health Science. PD and BC are full-time employees of Nestlé Health Science. IM and KR are full-time employees of Nestlé Research.

Dietary Lipid Quantity and Quality Modulate the Postprandial Metabolomic Profile in Patients with Metabolic Syndrome.

7. Nutrients. 2024 Dec 11;16(24):4267. doi: 10.3390/nu16244267. Dietary Lipid Quantity and Quality Modulate the Postprandial Metabolomic Profile in Patients with Metabolic Syndrome. Mora-Ortiz M(1)(2)(3)(4), Yubero-Serrano EM(1)(2)(3)(4)(5), Priego-Capote F(6)(7), Gutierrez-Mariscal FM(1)(2)(3)(4), Alcala-Diaz JF(1)(2)(3)(4), Torres-Peña JD(1)(2)(3)(4), Arenas de-Larriva AP(1)(2)(3)(4), Delgado-Lista J(1)(2)(3)(4), Perez-Martinez P(1)(2)(3)(4), Roche HM(8)(9), López-Miranda J(1)(2)(3)(4). Author information: (1)Lipids and Atherosclerosis Unit, Internal Medicine Unit, Reina Sofia University Hospital, 14004 Cordoba, Spain. (2)Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain. (3)Department of Medical and Surgical Sciences, Universidad de Córdoba, 14071 Cordoba, Spain. (4)CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain. (5)Department of Food and Health, Instituto de la Grasa, Spanish National Research Council (CSIC), 28006 Seville, Spain. (6)Departamento de Química Analítica y Nanoquímica, Edificio Marie Curie (anexo), Universidad de Córdoba, 14071 Cordoba, Spain. (7)CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain. (8)Nutrigenomics Research Group, University College Dublin Conway Institute, School of Public Health, University College Dublin, D04 V1W8 Dublin, Ireland. (9)Institute for Global Food Security, Queen's University Belfast, Belfast BT7 1NN, UK. The literature on the postprandial metabolic changes in individuals with Metabolic Syndrome (MetS) remains limited, despite the fact that postprandial states represent the most common physiological condition in Western societies. BACKGROUND/OBJECTIVES: The objective of this study was to investigate the plasma metabolomics profile in both fasting and postprandial states following a high-fat challenge in individuals with MetS who consumed diets with varying quantities and qualities of dietary fat over 12 weeks. METHODS: Seventy-five patients with MetS (28 males and 47 females) from the Spanish LIPGENE cohort were included in the study. MetS patients were randomly stratified to follow one of four dietary interventions (isoenergetic diets) for a 12-week long-term study. The four diets were high in saturated fatty acids and high in monounsaturated fatty acids (HSFA and HMUFA), low-fat high-complex carbohydrates (LFHCC), and LFHCC supplemented with n-3. The metabolomics analysis of plasma samples was carried out using Liquid Chromatography Time-of-Flight Mass Spectrometry (LC-TOF/MS). RESULTS: We observed a decrease in inflammation biomarkers, including acetylcarnitine and L-carnitine during the fasting state and hexanoyl-L-carnitine and isobutyryl-L-carnitine during the postprandial period, mediated by the replacement of HSFA with HMUFA. Additionally, antioxidant compounds such as 4-hydroxybenzaldehyde and L-valine were expressed at higher levels after consumption of the HMUFA diet compared to the HSFA diet. HSFA also presented altered levels of phosphatidylcholine, a metabolite previously linked with insulin resistance. CONCLUSIONS: These findings suggest that replacing HSFA with HMUFA may reduce inflammation and improve antioxidant profiles, supporting the potential for tailored dietary interventions in individuals with MetS. DOI: 10.3390/nu16244267 PMCID: PMC11677668 PMID: 39770889 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Nutraceutical interventions for erectile dysfunction: a systematic review and network meta-analysis.

8. J Sex Med. 2024 Oct 31;21(11):1054-1063. doi: 10.1093/jsxmed/qdae123. Nutraceutical interventions for erectile dysfunction: a systematic review and network meta-analysis. Barbonetti A(1), Tienforti D(1), Antolini F(1), Spagnolo L(1), Cavallo F(2), Di Pasquale AB(3), Maggi M(4)(5)(6), Corona G(7). Author information: (1)Andrology Unit, Department of Clinical Medicine, Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, 67100, Italy. (2)Graduate School of Integrated Psychotherapy, Bergamo, 24121, Italy. (3)Urology Unit, Department of Urology, ASL 1 Abruzzo, "S. Salvatore" Hospital, L'Aquila, 67100, Italy. (4)Andrology, Women's Endocrinology and Gender Incongruence Unit, Mario Serio Department of Experimental and Clinical Biomedical Sciences, University of Florence, Careggi Teaching Hospital, Florence, 50134, Italy. (5)Istituto Nazionale Biostrutture e Biosistemi, Rome, 00136, Italy. (6)Endocrinology Unit, Mario Serio Department of Experimental and Clinical Biomedical Sciences, University of Florence, Careggi Teaching Hospital, Florence, 50134, Italy. (7)Endocrinology Unit, Azienda Ausl Bologna, Bologna, 40133, Italy. BACKGROUND: Although nutraceutical-based treatments are often offered for erectile dysfunction (ED), their efficacy remains doubtful, and the choice of one substance over the other is challenged by the dearth of head-to-head comparative studies. AIM: We aimed to compare the efficacy of available nutraceutical interventions, alone or in combination with phosphodiesterase type 5 inhibitors (PDE5i), in improving erectile function in men with ED through a network meta-analysis (NMA), which incorporates direct and indirect evidence into one model thus generating a hierarchy of effectiveness. METHODS: PubMed, Scopus, Web of Sciences, and Cochrane Library databases were searched for randomized placebo-controlled trials (RCTs) assessing the effect of any nutraceutical regimen in improving erectile function when compared to each other, placebo, and/or PDE5i in men with ED. Data were included in a random-effects NMA, where efficacy of treatments was ranked by surface under the cumulative ranking curve (SUCRA). Two NMAs were also conducted separately for organic and non-organic ED. Reciprocal comparisons between all treatments were analyzed by league tables. OUTCOMES: The main outcome was the standardized mean difference in the score of the International Index of Erectile Function (IIEF)-5 or IIEF-6. RESULTS: Fifteen RCTs provided information on 1000 men with ED. In the overall NMA, compared to placebo, the combination propionyl L-carnitine (PLC) + acetyl L-carnitine (ALC) + Sildenafil was associated with the highest SUCRA (97%) in improving erectile function score, followed by L-Arginine + Tadalafil (84%), Sildenafil (79%), Tadalafil (72%), and L-Arginine (52%). No other treatment regimen showed efficacy with statistical significance. In patients with organic ED, the efficacy of Sildenafil and Tadalafil was significantly improved by PLC + ALC and L-Arginine, respectively. On the contrary, in non-organic ED, nutraceuticals did not improve the therapeutic performance of daily Tadalafil. CLINICAL IMPLICATIONS: This NMA contributes valuable insights into the potential of nutraceutical interventions for ED. STRENGTHS AND LIMITATIONS: We employed strict inclusion criteria related to study design and diagnostic tool, ensuring the assumption of transitivity and the consistency of the analysis. CONCLUSION: Against a background of general ineffectiveness of most nutraceutical interventions, L-Arginine and the mix PLC + ALC appeared to be of some usefulness in improving erectile function, especially in combination with PDE5i in organic ED. © The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. DOI: 10.1093/jsxmed/qdae123 PMID: 39279185 [Indexed for MEDLINE]

Antioxidant treatment for oligoasthenoteratozoospermia and varicocele: a DBPC trial to evaluate the impact of age and body mass index.

9. Asian J Androl. 2024 May 1;26(3):239-244. doi: 10.4103/aja202381. Epub 2024 Feb 2. Antioxidant treatment for oligoasthenoteratozoospermia and varicocele: a DBPC trial to evaluate the impact of age and body mass index. Busetto GM(1)(2), Rodrigues BF(3), Virmani A(4), Checchia A(1)(5), Ninivaggi A(1)(2), Ricapito A(1)(2), Barbieri G(1)(2), Fischetti P(1)(2), Falagario UG(1), Annese P(2), d'Altilia N(2), Mancini V(2), Ferro M(6), Crocetto F(7), Porreca A(8), Bettocchi C(1)(2), Cormio L(1)(9), Agarwal A(10), Carrieri G(1)(2). Author information: (1)University of Foggia, Foggia 71122, Italy. (2)Department of Urology and Renal Transplantation, Policlinico of Foggia, Foggia 71122, Italy. (3)Department of Urology, Human Reproduction Section, Federal University of Sao Paulo, Sao Paulo 05403-000, Brazil. (4)Alfasigma Healthscience, Utrecht 3528 BG, The Netherlands. (5)Urology Unit, "G. Tatarella" Hospital, Cerignola 71042, Italy. (6)Urology Unit, European Institute of Oncology (IEO) IRCCS, Milan 20142, Italy. (7)University of Naples Federico II, Naples 80126, Italy. (8)Department of Oncological Urology, Veneto Institute of Oncology (IOV) IRCCS, Padua 35039, Italy. (9)Urology Unit, "L. Bonomo" Hospital, Andria 70031, Italy. (10)Global Andrology Forum, Moreland Hills, OH 44022, USA. Oxidative stress is one of the main mechanisms responsible for male infertility. Various conditions such as varicocele, obesity, advanced age, and lifestyle can lead to an increase in reactive oxygen species, causing an oxidative imbalance in the reproductive environment. Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizing the egg. Excessive reactive oxygen species can affect sperm metabolism, leading to immobility, impaired acrosome reaction, and cell death, thereby impairing reproductive success. This double-blind randomized study evaluated the effect of supplementation with L-carnitine, acetyl-L-carnitine, vitamins, and other nutrients on semen quality in 104 infertile patients with or without varicocele, while also investigating the impact of factors such as obesity and advanced age on treatment. Sperm concentration significantly increased in the supplemented group compared to the placebo group ( P = 0.0186). Total sperm count also significantly increased in the supplemented group ( P = 0.0117), as did sperm motility ( P = 0.0120). The treatment had a positive effect on patients up to 35 years of age in terms of sperm concentration ( P = 0.0352), while a body mass index (BMI) above 25 kg m -2 had a negative effect on sperm concentration ( P = 0.0110). Results were not showing a net benefit in stratifying patients in accordance with their BMI since sperm quality increase was not affected by this parameter. In conclusion, antioxidant supplementation may be beneficial for infertile patients and has a more positive effect on younger patients with a normal weight. Copyright © 2024 Copyright: © The Author(s)(2024). DOI: 10.4103/aja202381 PMCID: PMC11156455 PMID: 38305695 [Indexed for MEDLINE] Conflict of interest statement: All authors and Alfasigma HealthScience Company declared no competing interests.

Combined Rehabilitation with Alpha Lipoic Acid, Acetyl-L-Carnitine, Resveratrol, and Cholecalciferolin Discogenic Sciatica in Young People: A Randomized Clinical Trial.

10. Medicina (Kaunas). 2023 Dec 18;59(12):2197. doi: 10.3390/medicina59122197. Combined Rehabilitation with Alpha Lipoic Acid, Acetyl-L-Carnitine, Resveratrol, and Cholecalciferolin Discogenic Sciatica in Young People: A Randomized Clinical Trial. Scaturro D(1), Vitagliani F(2), Tomasello S(3), Sconza C(4), Respizzi S(4), Letizia Mauro G(1). Author information: (1)Department of Surgical, Oncological and Stomatological Disciplines, University of Palermo, 90144 Palermo, Italy. (2)Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy. (3)Faculty of Medicine and Surgery, University of Palermo, 90127 Palermo, Italy. (4)Department of Physical and Rehabilitation Medicine, Humanitas Clinical and Research Centre IRCSS, 20019 Milan, Italy. Background and Objectives: In the Western world, back pain and sciatica are among the main causes of disability and absence from work with significant personal, social, and economic costs. This prospective observational study aims to evaluate the effectiveness of a rehabilitation program combined with the administration of Alpha Lipoic Acid, Acetyl-L-Carnitine, Resveratrol, and Cholecalciferol in the treatment of sciatica due to herniated discs in young patients in terms of pain resolution, postural alterations, taking painkillers, and quality of life. Materials and Methods: A prospective observational study was conducted on 128 patients with sciatica. We divided the sample into 3 groups: the Combo group, which received a combination of rehabilitation protocol and daily therapy with 600 mg Alpha Lipoic Acid, 1000 mg Acetyl-L-Carnitine, 50 mg Resveratrol, and 800 UI Cholecalciferol for 30 days; the Reha group, which received only a rehabilitation protocol; and the Supplement group, which received only oral supplementation with 600 mg Alpha Lipoic Acid, 1000 mg Acetyl-L-Carnitine, 50 mg Resveratrol, and 800 UI Cholecalciferol. Clinical assessments were made at the time of recruitment (T0), 30 days after the start of treatment (T1), and 60 days after the end of treatment (T2). The rating scales were as follows: the Numeric Rating Scale (NRS); the Oswestry Disability Questionnaire (ODQ); and the 36-item Short Form Health Survey (SF-36). All patients also underwent an instrumental stabilometric evaluation. Results: At T1, the Combo group showed statistically superior results compared to the other groups for pain (p < 0.05), disability (p < 0.05), and quality of life (p < 0.05). At T2, the Combo group showed statistically superior results compared to the other groups only for pain (p < 0.05) and quality of life (p < 0.05). From the analysis of the stabilometric evaluation data, we only observed a statistically significant improvement at T2 in the Combo group for the average X (p < 0.05) compared to the other groups. Conclusions: The combined treatment of rehabilitation and supplements with anti-inflammatory, pain-relieving, and antioxidant action is effective in the treatment of sciatica and can be useful in improving postural stability. DOI: 10.3390/medicina59122197 PMCID: PMC10744495 PMID: 38138300 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest.

Palmitoylethanolamide and acetyl-L-carnitine act synergistically with duloxetine and pregabalin in fibromyalgia: results of a randomised controlled study.

11. Clin Exp Rheumatol. 2023 Jun;41(6):1323-1331. doi: 10.55563/clinexprheumatol/pmdzcq. Epub 2023 Jun 28. Palmitoylethanolamide and acetyl-L-carnitine act synergistically with duloxetine and pregabalin in fibromyalgia: results of a randomised controlled study. Salaffi F(1), Farah S(1), Sarzi-Puttini P(2), Di Carlo M(1). Author information: (1)Rheumatology Clinic, Università Politecnica delle Marche, Jesi, Ancona, Italy. (2)Rheumatology Unit, IRCCS Galeazzi-Sant'Ambrogio Hospital, ASST, Milan State University School of Medicine, Milan, Italy. OBJECTIVES: Fibromyalgia (FM) is characterised by a form of debilitating pain that is unresponsive to standard analgesics. The aim of this study was to evaluate the efficacy of supplementing ongoing pregabalin (PGB) and duloxetine (DLX) treatment with palmitoylethanolamide (PEA) and acetyl-L-carnitine (ALC) for 24 weeks in FM patients. METHODS: After undergoing three months of stable treatment with DLX+PGB, FM patients were randomised to continue the same treatment (Group 1) or to add PEA 600 mg b.i.d + ALC 500 mg b.i.d. (Group 2) for a further 12 weeks. Every two weeks throughout the study, cumulative disease severity was estimated using the Widespread Pain Index (WPI) as the primary outcome measure; the secondary outcomes were the fortnightly scores of the patient-completed revised Fibromyalgia Impact Questionnaire (FIQR) and the modified Fibromyalgia Assessment Status (FASmod) questionnaire. All three measures were expressed as time-integrated area under the curve (AUC) values. RESULTS: One hundred and thirty (91.5%) of the initial 142 FM patients completed the study: 68 patients in Group 1 and 62 in Group 2. Twenty-four weeks after randomisation, the Group 2 patients showed additional significant improvements in all three outcome measures. Although there was some fluctuation in both groups during the study period, the AUC values of the WPI scores steadily decreased in Group 2 (p=0.048), which also showed better outcomes in terms of the AUC values of the FIQR (p=0.033) and FASmod scores (p=0.017). CONCLUSIONS: This is the first randomised controlled study demonstrating the effectiveness of the adding on therapy of PEA+ALC to DLX+PGB in FM patients. DOI: 10.55563/clinexprheumatol/pmdzcq PMID: 37378482 [Indexed for MEDLINE]

Probio-X Relieves Symptoms of Hyperlipidemia by Regulating Patients' Gut Microbiome, Blood Lipid Metabolism, and Lifestyle Habits.

12. Microbiol Spectr. 2023 Jun 15;11(3):e0444022. doi: 10.1128/spectrum.04440-22. Epub 2023 Apr 6. Probio-X Relieves Symptoms of Hyperlipidemia by Regulating Patients' Gut Microbiome, Blood Lipid Metabolism, and Lifestyle Habits. Wang H(#)(1)(2)(3)(4)(5), Ma C(#)(1)(2), Li Y(1)(2), Zhang L(3)(4)(5), A L(1)(2), Yang C(3)(4)(5), Zhao F(3)(4)(5), Han H(1)(2), Shang D(1)(2), Yang F(1)(2), Zhang Y(1)(2), Zhang H(3)(4)(5), Sun Z(3)(4)(5), Guo R(1)(2). Author information: (1)Department of Clinical Nutrition, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia, China. (2)Inner Mongolia Key Laboratory of Nutrition and Health, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia, China. (3)Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China. (4)Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China. (5)Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China. (#)Contributed equally Hyperlipidemia is a key risk factor for cardiovascular disease, and it is associated with lipid metabolic disorders and gut microbiota dysbiosis. Here, we aimed to investigate the beneficial effects of 3-month intake of a mixed probiotic formulation in hyperlipidemic patients (n = 27 and 29 in placebo and probiotic groups, respectively). The blood lipid indexes, lipid metabolome, and fecal microbiome before and after the intervention were monitored. Our results showed that probiotic intervention could significantly decrease the serum levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol (P < 0.05), while increasing the levels of high-density lipoprotein cholesterol (P < 0.05) in patients with hyperlipidemia. Probiotic recipients showing improved blood lipid profile also exhibited significant differences in their lifestyle habits after the 3-month intervention, with an increase in daily intake of vegetable and dairy products, as well as weekly exercise time (P < 0.05). Moreover, two blood lipid metabolites (namely, acetyl-carnitine and free carnitine) significantly increased after probiotic supplementation cholesterol (P < 0.05). In addition, probiotic-driven mitigation of hyperlipidemic symptoms were accompanied by increases in beneficial bacteria like Bifidobacterium animalis subsp. lactis and Lactiplantibacillus plantarum in patients' fecal microbiota. These results supported that mixed probiotic application could regulate host gut microbiota balance, lipid metabolism, and lifestyle habits, through which hyperlipidemic symptoms could be alleviated. The findings of this study urge further research and development of probiotics into nutraceuticals for managing hyperlipidemia. IMPORTANCE The human gut microbiota have a potential effect on the lipid metabolism and are closely related to the disease hyperlipidemia. Our trial has demonstrated that 3-month intake of a mixed probiotic formulation alleviates hyperlipidemic symptoms, possibly by modulation of gut microbes and host lipid metabolism. The findings of the present study provide new insights into the treatment of hyperlipidemia, mechanisms of novel therapeutic strategies, and application of probiotics-based therapy. DOI: 10.1128/spectrum.04440-22 PMCID: PMC10269629 PMID: 37022264 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest.

Dynamic Metabolic Signatures of Choline and Carnitine across Healthy Pregnancy and in Cord Blood: Association with Maternal Dietary Protein.

13. J Nutr. 2023 Apr;153(4):999-1007. doi: 10.1016/j.tjnut.2023.02.013. Epub 2023 Feb 11. Dynamic Metabolic Signatures of Choline and Carnitine across Healthy Pregnancy and in Cord Blood: Association with Maternal Dietary Protein. Shanmuganathan M(1), Bogert M(2), Kroezen Z(1), Britz-McKibbin P(1), Atkinson SA(3). Author information: (1)Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada. (2)Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada. (3)Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada. Electronic address: satkins@mcmaster.ca. BACKGROUND: In pregnancy, choline is deemed an essential nutrient and carnitine needs are increased, but amounts remain undefined. OBJECTIVES: We aimed to measure choline and total dietary protein and dairy protein intake from food and supplements across pregnancy and the response to intake by profiling choline and carnitine metabolites across pregnancy and in cord blood. METHODS: An exploratory analysis of choline and protein intake from 3-d diet records and measures of 36 serum choline and carnitine metabolites in early (12-17 wk) and late (36-38 wk) pregnancy was conducted in participants from the Be Healthy in Pregnancy study randomized to high dairy protein+walking exercise or usual care. Metabolites were measured in fasted maternal and cord serum using multisegment injection-capillary electrophoresis-mass spectrometry. Mixed ANOVA adjusted for body mass index was performed for comparison of metabolites across pregnancy and between intervention and control. RESULTS: In 104 participants, the median (Q1, Q3) total choline intake was 347 (263, 427) mg/d in early and 322 (270, 437) mg/d in late pregnancy. Only ∼20% of participants achieved the recommended adequate intake (450 mg/d) and ∼10% consumed supplemental choline (8-200 mg/d). Serum-free choline (μmol/L) was higher in late compared with early pregnancy [12.9 (11.4, 15.1) compared with 9.68 (8.25, 10.61), P < 0.001], but choline downstream metabolites were similar across pregnancy. Serum carnitine [10.3 (9.01, 12.2) compared with 15.9 (14.1, 17.9) μmol/L, P < 0.001] and acetylcarnitine [2.35 (1.92, 2.68) compared with 3.0 (2.56, 3.59), P < 0.001] were significantly lower in late pregnancy. High cord:maternal serum metabolite ratios were found in most measured metabolites. CONCLUSIONS: Despite inadequate choline intake, serum-free choline was elevated in late pregnancy and enriched in cord blood compared with maternal serum. Serum carnitine declined in late pregnancy despite a high protein diet. The higher cord:maternal concentrations in choline and carnitine metabolites suggest active uptake in late pregnancy, reflecting the importance of these circulating metabolites in fetal development. This trial was registered at clinicaltrials.gov as NCT01689961. Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.tjnut.2023.02.013 PMID: 36780943 [Indexed for MEDLINE]

Impact of Supplementation and Nutritional Interventions on Pathogenic Processes of Mood Disorders: A Review of the Evidence.

14. Nutrients. 2021 Feb 26;13(3):767. doi: 10.3390/nu13030767. Impact of Supplementation and Nutritional Interventions on Pathogenic Processes of Mood Disorders: A Review of the Evidence. Hoepner CT(1), McIntyre RS(2), Papakostas GI(3). Author information: (1)Bay Area Psychiatric, A Nursing Corporation, San Francisco, CA 94111, USA. (2)Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, ON M5T 2S8, Canada. (3)Massachusetts General Hospital, Boston, MA 02114, USA. This narrative review was conducted using searches of the PubMed/Medline and Google Scholar databases from inception to November 2019. Clinical trials and relevant articles were identified by cross-referencing major depressive disorder (and/or variants) with the following terms: folate, homocysteine, S-adenosylmethionine (SAMe), L-acetylcarnitine, alpha-lipoic acid, N-acetylcysteine, L-tryptophan, zinc, magnesium, vitamin D, omega-3 fatty acids, coenzyme Q10, and inositol. Manual reviews of references were also performed using article reference lists. Abnormal levels of folate, homocysteine, and SAMe have been shown to be associated with a higher risk of depression. Numerous studies have demonstrated antidepressant activity with L-methylfolate and SAMe supplementation in individuals with depression. Additionally, the amino acids L-acetylcarnitine, alpha-lipoic acid, N-acetylcysteine, and L-tryptophan have been implicated in the development of depression and shown to exert antidepressant effects. Other agents with evidence for improving depressive symptoms include zinc, magnesium, omega-3 fatty acids, and coenzyme Q10. Potential biases and differences in study designs within and amongst the studies and reviews selected may confound results. Augmentation of antidepressant medications with various supplements targeting nutritional and physiological factors can potentiate antidepressant effects. Medical foods, particularly L-methylfolate, and other supplements may play a role in managing depression in patients with inadequate response to antidepressant therapies. DOI: 10.3390/nu13030767 PMCID: PMC7996954 PMID: 33652997 [Indexed for MEDLINE] Conflict of interest statement: Cara T. Hoepner - Speaker bureau, advisory board, and personal fees: Eisai, Shire, and Sunovion; Advisory board and personal fees: Takeda; Speaker bureau and personal fees: Ironshore. Roger McIntyre - Personal fees: Allergan, Janssen, Lundbeck, Minerva, Neurocrine, Otsuka, Pfizer, Purdue, Shire, Sunovion, and Takeda; Grants: CIHR/GACD/Chinese National Natural Research Foundation and Stanley Medical Research Institute. George Papakostas - Consultant: Abbott Laboratories, Acadia Pharmaceuticals, Inc*, Alkermes, Inc, Alfasigma USA*, Inc, AstraZeneca PLC, Avanir Pharmaceuticals, Axsome Therapeutics*, Boston Pharmaceuticals, Inc.*, Brainsway Ltd, Bristol-Myers Squibb Company, Cala Health*, Cephalon Inc., Dey Pharma, L.P., Eli Lilly Co., Genentech, Inc*, Genomind, Inc*, GlaxoSmithKline, Evotec AG, H. Lundbeck A/S, Inflabloc Pharmaceuticals, Janssen Global Services LLC*, Jazz Pharmaceuticals, Johnson & Johnson Companies*, Methylation Sciences Inc, Mylan Inc*, Novartis Pharma AG, One Carbon Therapeutics, Inc*, Osmotica Pharmaceutical Corp.*, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer Inc., Pierre Fabre Laboratories, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Sage Therapeutics*, Shire Pharmaceuticals, Sunovion Pharmaceuticals, Taisho Pharmaceutical Co, Ltd*, Takeda Pharmaceutical Company LTD, Theracos, Inc., and Wyeth, Inc.; Honoraria (for lectures or consultancy): Abbott Laboratories, Acadia Pharmaceuticals Inc, Alkermes Inc, Alfasigma USA Inc, Asopharma America Central Y Caribe, Astra Zeneca PLC, Avanir Pharmaceuticals, Bristol-Myers Squibb Company, Brainsway Ltd, Cephalon Inc., Dey Pharma, L.P., Eli Lilly Co., Evotec AG, Forest Pharmaceuticals, GlaxoSmithKline, Inflabloc Pharmaceuticals, Grunbiotics Pty LTD, Hypera S.A., Jazz Pharmaceuticals, H. Lundbeck A/S, Medichem Pharmaceuticals, Inc, Meiji Seika Pharma Co. Ltd, Novartis Pharma AG, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer, Pharma Trade SAS, Pierre Fabre Laboratories, Ridge Diagnostics, Shire Pharmaceuticals, Sunovion Pharmaceuticals, Takeda Pharmaceutical Company LTD, Theracos, Inc., Titan Pharmaceuticals, and Wyeth Inc.; Research support (paid to hospital): AstraZeneca PLC, Bristol-Myers Squibb Company, Forest Pharmaceuticals, the National Institute of Mental Health, Neuralstem, Inc*, PAMLAB LLC, Pfizer Inc., Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Sunovion Pharmaceuticals, Tal Medical, and Theracos, Inc.; Speaker bureau (not currently): Bristol Myers Squibb Co and Pfizer, Inc. * Asterisk denotes activity undertaken on behalf of Massachusetts General Hospital.

Efficacy and Safety of the Combination of Superoxide Dismutase, Alpha Lipoic Acid, Vitamin B12, and Carnitine for 12 Months in Patients with Diabetic Neuropathy.

15. Nutrients. 2020 Oct 23;12(11):3254. doi: 10.3390/nu12113254. 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(1), Karlafti E(1), Kotzakioulafi E(1), Kontoninas Z(1), Margaritidis C(1), Giannoulaki P(2), Kantartzis K(3)(4)(5). Author information: (1)Diabetes Center, 1st Propaedeutic Department of Internal Medicine, Medical School, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece. (2)Department of Nutrition and Dietetics, University General Hospital of Thessaloniki AHEPA, 54636 Thessaloniki, Greece. (3)Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University of Tübingen, 72076 Tübingen, Germany. (4)Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, 72076 Tübingen, Germany. (5)German Center for Diabetes Research (DZD), 72076 Tübingen, Germany. 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. DOI: 10.3390/nu12113254 PMCID: PMC7690794 PMID: 33114210 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest. The providing company of the supplement had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.