The influence of a chronic L‐carnitine administration on the plasma metabolome of male Fischer 344 rats*

Weinert, Christoph H.; Empl, Michael T.; Krüger, Ralf; Frommherz, Lara; Egert, Björn; Steinberg, Pablo; Kulling, Sabine E.

doi:10.1002/mnfr.201600651

Cited by 17 publications

(19 citation statements)

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“…Treatment of male Fischer 344 rats by L-carnitine in drinking water for 1 year induced tenfold higher TMAO plasma concentration when compared to the control (2.5 vs. 25.0 μM) [36]. Despite that fact, no atherosclerotic lesions in the colon and aorta [32] or drastic changes in the overall plasma metabolome [36] have been noted. Moreover, under normal dietary conditions, TMAO does not increase plasma cholesterol or act as a proatherogenic molecule in mice [35].…”

Section: Discussion/conclusionmentioning

confidence: 97%

“…While the studies show the ability of TMAO to promote atherosclerosis [10,11,17,18,30,31], there are numerous contrasting results [19,[32][33][34][35][36]. Treatment of male Fischer 344 rats by L-carnitine in drinking water for 1 year induced tenfold higher TMAO plasma concentration when compared to the control (2.5 vs. 25.0 μM) [36].…”

Section: Discussion/conclusionmentioning

confidence: 99%

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L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

et al. 2018

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Background: L-carnitine can be metabolized to trimethylamine N-oxide (TMAO), a molecule that promotes atherogenesis through its interaction with macrophages and lipid metabolism. Objective: The aim of the present study was to assess whether L-carnitine supplementation may promote changes in selected serum biomarkers of atherosclerosis. Methods: Before the start, in the mid-point and after completing the 24-weeks supplementation protocol, fasting blood samples were taken from the antecubital vein. Plasma free L-carnitine and TMAO were determined by the UPLC/MS/MS method. Serum proteins were determined by the enzyme immunoassay method using commercially available kits. Total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides have been determined using standard automatic analyzer. Results: L-carnitine supplementation elevated fasting plasma carnitine in the mid-point of our study and it remained increased until the end of supplementation period. Moreover, it induced tenfold increase in plasma TMAO concentration but did not affect serum C-reactive protein, interleukin-6, tumour necrosis factor-α, L-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 or lipid profile markers. Conclusion: We demonstrated that although oral L-carnitine supplementation significantly increased plasma TMAO concentration, no lipid profile changes or other markers of adverse cardiovascular events were detected in healthy aged women over the period of 24 weeks.

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Section: Discussion/conclusionmentioning

confidence: 97%

Section: Discussion/conclusionmentioning

confidence: 99%

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

et al. 2018

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“…The disadvantages are that: i) it is time consuming; ii) it can be an additional source of error during sample preparation; iii) it excludes the possibility to change the normalization later on; and iv) it might cause low abundance metabolites to fall below their detection limit. Normalization on creatine content should only be considered if the study population consists of only men or only women, but not both ( Box ) . If reference data for preanalytical normalization are missing, post‐analytical normalization is required.…”

Section: Sample Characteristics and Preanalytical Processingmentioning

confidence: 99%

Nutrimetabolomics: An Integrative Action for Metabolomic Analyses in Human Nutritional Studies

Ulaszewska

Weinert

Trimigno

et al. 2018

Molecular Nutrition Food Res

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195

156

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The life sciences are currently being transformed by an unprecedented wave of developments in molecular analysis, which include important advances in instrumental analysis as well as biocomputing. In light of the central role played by metabolism in nutrition, metabolomics is rapidly being established as a key analytical tool in human nutritional studies. Consequently, an increasing number of nutritionists integrate metabolomics into their study designs. Within this dynamic landscape, the potential of nutritional metabolomics (nutrimetabolomics) to be translated into a science, which can impact on health policies, still needs to be realized. A key element to reach this goal is the ability of the research community to join, to collectively make the best use of the potential offered by nutritional metabolomics. This article, therefore, provides a methodological description of nutritional metabolomics that reflects on the state-of-the-art techniques used in the laboratories of the Food Biomarker Alliance (funded by the European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL)) as well as points of reflections to harmonize this field. It is not intended to be exhaustive but rather to present a pragmatic guidance on metabolomic methodologies, providing readers with useful "tips and tricks" along the analytical workflow.

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“…fruit‐derived proline‐betaines . Glycine‐betaine is often analyzed in combination with other nitrogen‐containing compounds such as choline, N,N ‐dimethylglycine (DMG), trimethylamine (TMA) or TMAO . Quantification of methylated arginine compounds such as ADMA is established in a clinical context .…”

Section: Introductionmentioning

confidence: 99%

Targeted ultra‐performance liquid chromatography/tandem mass spectrometric quantification of methylated amines and selected amino acids in biofluids

Roggensack

Merz

Dick

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale Methylated amino compounds and basic amino acids are important analyte classes with high relevance in nutrition, physical activity and physiology. Reliable and easy quantification methods covering a variety of metabolites in body fluids are a prerequisite for efficient investigations in the field of food and nutrition. Methods Targeted ultra‐performance liquid chromatography/tandem mass spectrometric (UHPLC/MS) analysis was performed using HILIC separation and timed ESI‐MRM detection, combined with a short sample preparation. Calibration in urine and blood plasma was achieved by matrix‐matched standards, isotope‐labelled internal standards and standard addition. The method was fully validated and the performance was evaluated using a subset from the Karlsruhe Metabolomics and Nutrition (KarMeN) study. Results Within this method, a total of 30 compounds could be quantified simultaneously in a short run of 9 min in both body fluids. This covers a variety of free amino compounds which are present in very different concentrations. The method is easy, precise and robust, and has a broad working range. As a proof of principle, literature‐based associations of certain metabolites with dietary intake of respective foods were clearly confirmed in the KarMeN subset. Conclusions Overall, the method turned out to be well suited for application in nutrition studies, as shown for the example of food intake biomarkers in KarMeN. Application to a variety of questions such as food‐related effects or physical activity will support future studies in the context of nutrition and health.

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The influence of a chronic L‐carnitine administration on the plasma metabolome of male Fischer 344 rats*

Abstract: Although L-carnitine supplementation did not cause large changes in the plasma metabolome, a higher risk for cardiovascular disease due to chronically elevated TMAO plasma concentrations cannot be excluded.

Cited by 17 publications

References 58 publications

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

Nutrimetabolomics: An Integrative Action for Metabolomic Analyses in Human Nutritional Studies

Targeted ultra‐performance liquid chromatography/tandem mass spectrometric quantification of methylated amines and selected amino acids in biofluids

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