How L-Carnitine Works
L-carnitine primarily functions as a carrier molecule that transports long-chain fatty acids from the cytosol across the mitochondrial membranes for β-oxidation, which generates energy. 1
Primary Mechanism of Action
L-carnitine (levocarnitine) plays several critical roles in human metabolism:
Fatty Acid Transport: L-carnitine serves as the essential carrier molecule that transports long-chain fatty acids across the outer and inner mitochondrial membranes into the mitochondrial matrix where β-oxidation occurs 1, 2
Enzymatic System: This transport process is controlled by the carnitine palmitoyltransferase system, consisting of three key enzymes 1:
- Carnitine palmitoyltransferase I (CPT I)
- Carnitine palmitoyltransferase II (CPT II)
- Carnitine:acylcarnitine translocase (CACT)
Acyl Group Removal: L-carnitine promotes the excretion of excess organic or fatty acids by forming acylcarnitines, which are quickly excreted 2, 3
CoA Homeostasis: It helps maintain the balance between acyl-CoA and free CoA in mitochondria and cytosol 4, 3
Biochemical Properties
- L-carnitine is a quaternary ammonium compound derived from amino acids 1
- It is biosynthesized within the human body using L-lysine and L-methionine as substrates 1, 5
- Found in highest concentrations in energy-demanding tissues such as skeletal muscles, myocardium, liver, and adrenal glands 1
- Besides fatty acid metabolism, L-carnitine is also involved in glucose metabolism 1
Pharmacokinetics
Absorption: L-carnitine is absorbed in the small intestine via multiple transporters, with absorption mechanisms varying based on dosage 1, 6
- Bioavailability of supplemental L-carnitine is only 5-18% for oral doses of 1-6g
- Dietary L-carnitine has much higher bioavailability (up to 75%)
Distribution: After entering the bloodstream, L-carnitine is distributed to various tissues, with carrier-mediated transport ensuring high tissue-to-plasma concentration ratios in tissues dependent on fatty acid oxidation 6
Elimination: L-carnitine is primarily eliminated via urinary excretion, with 98-99% tubular reabsorption under normal conditions 6
Clinical Significance
L-carnitine's role in energy metabolism makes it particularly important in:
Primary carnitine deficiency: Characterized by low concentrations of levocarnitine in plasma, RBC, and/or tissues 2
Secondary carnitine deficiency: Can result from inborn errors of metabolism, where L-carnitine helps alleviate metabolic abnormalities by clearing toxic acylCoA compounds 2
Hemodialysis patients: L-carnitine supplementation may help reduce inflammation by lowering CRP levels 1
Exercise metabolism: During high-intensity exercise, mitochondrial fatty acid oxidation may be limited by the availability of free L-carnitine 7
Dietary Sources
L-carnitine is found predominantly in animal products 1, 4:
- Highest concentrations in red meats (beef, lamb)
- Also present in fish, poultry, and milk
- Very low amounts in vegetables, fruits, and plant oils
- Mushrooms contain more L-carnitine than plants
Healthy individuals, including strict vegetarians, typically synthesize sufficient L-carnitine without requiring supplementation 1.
Measurement and Assessment
Carnitine status can be assessed by measuring:
- Free carnitine
- Total carnitine
- Acylcarnitine levels
- Acyl-to-free carnitine ratio (normal when ≤0.25, deficiency when >0.4) 1
These measurements require specialized laboratory facilities using techniques such as tandem mass spectrometry 1.