Increased Trimethylamine N-Oxide Is Not Associated with Oxidative Stress Markers in Healthy Aged Women

Abstract

Increased plasma trimethylamine N-oxide (TMAO) levels have been associated with cardiovascular diseases (CVD). L-carnitine induces TMAO elevation in human blood, and thus, it has been suggested as developing atherosclerosis. The aim of this study was to determine the relation between selected markers of oxidative stress and plasma TMAO concentration induced by L-carnitine supplementation for 24 weeks in healthy aged women. Twenty aged women were supplemented during 24 weeks with either 1500 mg L-carnitine-L-tartrate (n=11) or isonitrogenous placebo (n=9) per day. Fasting blood samples were taken from antecubital vein. L-carnitine supplementation induced an increase in TMAO, but not in γ-butyrobetaine (GBB). Moreover, there were no significant changes in serum ox-LDL, myeloperoxidase, protein carbonyls, homocysteine, and uric acid concentrations due to supplementation. Significant reduction in white blood cell counts has been observed following 24-week supplementation, but not attributable to L-carnitine. Our results in healthy aged women indicated no relation between TMAO and any determined marker of oxidative stress over the period of 24 weeks. At the same time, plasma GBB levels were not affected by L-carnitine supplementation. Further clinical studies of plasma GBB level as a prognostic marker are needed.

The bright and the dark sides of L-carnitine supplementation: a systematic review

“…In two studied groups of healthy aged woman, LC supplementation alone [ 16 , 17 ], or in combination with L-leucine [ 18 ], induced an increase of fasting plasma TMAO levels. However, higher TMAO was not associated with determined inflammatory [ 16 ] nor oxidative stress [ 17 ] markers. Moreover, despite elevated TMAO, LC supplementation together with resistance training induced positive changes in mitochondrial DNA methylation of platelets [ 18 ].…”

“…Although the optimal dose of LC supplementation for myocardial infarction is 3 g/day in terms of all-cause mortality [ 90 ], even lower LC intake elevates fasting plasma TMAO [ 16 – 18 , 58 , 59 ], which is ten-fold higher than control after 3 months of supplementation [ 16 , 17 ]. It is worthy to mention that Bakalov et al [ 91 ] analyzing European Medicine Agency database of suspected adverse drug reaction, noticed 143 cases regarding LC.…”

Organic Cation Transporters in Human Physiology, Pharmacology, and Toxicology

“…In the context of primary systemic carnitine deficiency, oral supplementation of carnitine leads to elevated plasma concentrations of TMAO [ 178 , 179 , 180 , 181 ], whereas little information is available on long-term effects on the heart in this patient subset [ 132 ]. Several studies have questioned the cardiotoxic effects of TMAO in humans in conjunction with carnitine supplementation [ 176 , 177 , 182 , 183 ] and this rather hot topic in cardiovascular health has been extensively reviewed and discussed in recent years [ 184 , 185 , 186 , 187 ]. Inducing atherosclerosis in mice usually requires an ApoE -/- or Ldlr -/- genotype, also with or without high-fat diet [ 188 , 189 ].…”

Mitochondrial DNA copy number and trimethylamine levels in the blood: new insights on cardiovascular disease biomarkers

“…Several hypotheses have linked the TMAO to the development of atherosclerosis and CVD risk via promotion of platelet hyper-reactivity (Zhu et al, 2016), proinflammatory changes in the artery wall (Seldin et al, 2016), enhanced macrophage cholesterol accumulation and foam cell formation (Wang et al, 2011), increased levels of proinflammatory monocytes (Haghikia et al, 2018). Nevertheless, contrasting evidence on the association of TMAO and CVD emerged (Bordoni et al, 2020c; Collins et al, 2016; Jia et al, 2020; Landfald et al, 2017; Olek et al, 2019; Samulak et al, 2019), and a clear mechanistic explanation of this association is still missing.…”