<b>Revisiting </b><b>the Cardiovascular Implications of L-Carnitine Metabolism</b><b>: Evidence from Mongolian Pastoralists </b><b>and Experimental Validation</b>

As a characteristic nutrient found in red meat, L-carnitine has been proposed to increase cardiovascular risk via the trimethylamine N-oxide (TMAO) pathway. However, systematic validation of this association in populations with distinct dietary patterns remains lacking. This study presents the first comparative analysis of L-carnitine metabolic characteristics between Mongolian pastoralists (n = 50), who have a long-term dietary consumption of grass-fed beef and lamb, and urban lacto-ovo vegetarians (n = 15), complemented by animal experiments validating its biological effects. The results showed that compared with the vegetarian group, blood L-carnitine levels were significantly higher (P &lt; 0.01) while TMAO levels were significantly lower (P &lt; 0.05) in the pastoralist group. Analysis of metabolic characteristics revealed that blood L-carnitine was positively associated with HDL-C, α-linolenic acid, and EPA, and negatively associated with LDL-C and n-6 fatty acids. Molecular mechanism investigations showed significantly upregulated hepatic CYP7A1 expression (P &lt; 0.01) with no significant change in FMO3 expression, along with enhanced myocardial ATPase activity in the pastoralist group. Animal experiments confirmed that supplementation with L-carnitine derived from grass-fed beef and lamb significantly increased hepatic and cardiac L-carnitine concentrations in rats (P &lt; 0.05) and reduced TMAO levels (P &lt; 0.01), and enriched gut microbiota with anti-inflammatory species such as Faecalibacterium, while no TMAO-producing E. timonensis strains were detected. These results suggest that L-carnitine derived from grass-fed beef and lamb may circumvent TMAO formation through a unique metabolic pathway and exhibit potential benefits in improving lipid metabolism. This study provides new empirical evidence for evaluating the health effects of L-carnitine and underscores the critical role of dietary sources and host metabolic characteristics in nutritional assessment, offering important reference value for refining dietary guidelines.