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Carnitine, the L-β-hydroxy-&#x03B3-N-trimethylaminobutyric acid, is synthesized primarily in the liver and kidneys from lysine and methionine. Carnitine covers an important role in lipid metabolism, acting as an obligatory cofactor for β-oxidation of fatty acids by facilitating the transport of long-chain fatty acids across the mitochondrial membrane as acylcarnitine esters. Furthermore, since carnitine behaves as a shuttle for acetyl groups from inside to outside the mitochondrial membrane, it covers also a key role in glucose metabolism and assists in fuel-sensing. A reduction of the fatty acid transport inside the mitochondria results in the cytosolic accumulation of triglycerides, which is implicated in the pathogenesis of insulin resistance. Acute hyper-carnitinemia stimulates nonoxidative glucose disposal during euglycemic hyper-insulinemic clamp in healthy volunteers. Similar results were obtained in type 2 diabetic patients. The above findings were confirmed in healthy volunteers using the minimal modeling of glucose kinetics. The total end-clamp glucose tissue uptake was significantly increased by the administration of doses of acetyl-L-carnitine (ALC) from 3.8 to 5.2 mg/kg/min, without a significant dose-response effect. In conclusion, both L-carnitine and ALC are effective in improving insulin-mediated glucose disposal either in healthy subjects or in type 2 diabetic patients. Two possible mechanisms might be invoked in the metabolic effect of carnitine and its derivative: the first is a regulation of acetyl and acyl cellular trafficking for correctly meeting the energy demand; the second is a control action in the synthesis of key glycolytic and gluconeogenic enzymes. [ABSTRACT FROM AUTHOR]

L-Carnitine and acetyl-L-carnitine (ALC) are both used to improve mitochondrial function. Although it has been argued that ALC is better than L-carnitine in absorption and activity, there has been no experiment to compare the two compounds at the same dose. In the present experiment, the effects of ALC and L-carnitine on the levels of free, acyl, and total L-carnitine in plasma and brain, rat ambulatory activity, and biomarkers of oxidative stress are investigated. Aged rats (23 months old) were given ALC or L-carnitine at 0.15% in drinking water for 4 weeks. L-Carnitine and ALC were similar in elevating carnitine levels in plasma and brain. Both increased ambulatory activity similarly. However, ALC decreased the lipid peroxidation (malondialdehyde, MDA) in the old rat brain, while L-carnitine did not. ALC decreased the extent of oxidized nucleotides (oxo8dG/oxo8G) immunostaining in the hippocampal CA1 and cortex, while L-carnitine did not. ALC decreased nitrotyrosine immunostaining in the hippocampal CA1 and white matter, while L-carnitine did not. In conclusion, ALC and L-carnitine were similar in increasing ambulatory activity in old rats and elevating carnitine levels in blood and brain. However, ALC was effective, unlike L-carnitine, in decreasing oxidative damage, including MDA, oxo8dG/oxo8G, and nitrotyrosine, in old rat brain. These data suggest that ALC may be a better dietary supplement than L-carnitine. [ABSTRACT FROM AUTHOR]