L-Carnitine

L-Carnitine, in brief. Fat is the densest fuel a cell can burn, but the long-chain fatty acids that make up most of it cannot cross into the mitochondria, where the burning happens, on their own. L-carnitine is the carrier that gets them in. It is a small, water-soluble molecule, not a peptide, made in animal tissues from a modified form of the amino acid lysine and also taken in from food. Enzymes attach a fatty acid to carnitine on the outside of the mitochondrion, a transporter swaps it across the inner membrane, and a second enzyme hands the fatty acid over for beta-oxidation inside. Carnitine then goes back out for the next load. It also works in reverse, carrying surplus fuel fragments out of mitochondria so they do not pile up. Almost all of it sits in heart and skeletal muscle, the tissues that burn the most fat. NextGenPeps supplies L-Carnitine as a 600 mg research material for laboratory use only.

What does L-Carnitine do?

It carries fat into the mitochondria so it can be burned. Without carnitine, long-chain fatty acids stay in the cytosol, because they cannot cross the inner mitochondrial membrane unaided.[1,2] That single job explains most of what carnitine is studied for: tissues that run on fat, such as heart and skeletal muscle, hold almost all of it.[2]

In practice that means three things:

• Fuel import. It moves long-chain fatty acids into the mitochondrial matrix for beta-oxidation and ATP production.[1,2]

• Fuel export. It carries excess acyl groups out of mitochondria as acylcarnitines, which relieves overload when fuel supply outruns the cell's ability to burn it.[3,4]

• A fuel switch. By buffering the acetyl and acyl pool it helps mitochondria move between burning fat and burning glucose; obese rats short of carnitine lost that flexibility and regained it with supplementation.[4]

NextGenPeps supplies L-Carnitine for in vitro research and approved animal studies only. It is not sold as a drug, supplement or diagnostic.

How does L-Carnitine work?

Through a three-step relay across two membranes, known as the carnitine shuttle (Figure 1). On the outer mitochondrial membrane, carnitine palmitoyltransferase 1 (CPT1) swaps the coenzyme A on a fatty acyl-CoA for carnitine, making an acylcarnitine. Carnitine-acylcarnitine translocase (CACT) then carries that acylcarnitine across the inner membrane in exchange for a free carnitine. On the matrix side, CPT2 swaps carnitine back for coenzyme A, releasing the fatty acyl-CoA for beta-oxidation and freeing the carnitine to return.[2]

The CPT1 step is the control point for the whole pathway. It is inhibited by malonyl-CoA, the first intermediate in fat synthesis, so a cell that is building fat automatically stops importing it for burning.[2] Cells take carnitine up from their surroundings through a high-affinity transporter, OCTN2, which the kidney also uses to hold on to it.[1]

Figure 1. The carnitine shuttle. Carnitine is attached by CPT1, carried across the inner membrane by CACT, and removed again by CPT2 so the fatty acid can enter beta-oxidation. Based on LIPID MAPS and Longo et al.[1,2]

What did L-Carnitine do in animal studies?

In obese and diabetic rodents it raised energy expenditure and improved glucose handling, usually without changing body weight. Results on weight itself are mixed, and one well-known mouse study found a downside through gut bacteria.

Obese diabetic mice. When genetically obese, diabetic mice were fed chow containing 0.5% L-carnitine, insulin-stimulated energy expenditure rose from 172 to 210 kJ per kg fat-free mass per hour, and the daily respiratory exchange ratio rose from 0.886 to 0.914 (p<0.01), a shift toward burning more carbohydrate. Plasma acetylcarnitine rose 2.3-fold and made up 86% of the circulating acylcarnitine pool. Insulin-stimulated glucose disposal improved in these mice and in normal mice on a high-fat diet, while body weight and food intake did not change (Figure 2).[3]

Figure 2. Energy expenditure and acetylcarnitine in obese diabetic mice. Mice fed chow with 0.5% L-carnitine burned about 22% more energy under insulin stimulation than unsupplemented controls, and carried 2.3 times as much acetylcarnitine in plasma, with no change in body weight. Data from Power et al., Diabetologia 2007.[3]

Aged and obese rats. Rats kept on a high-fat diet for 12 months, along with old and genetically diabetic animals, had lower whole-body carnitine. Their muscle mitochondria oxidized fat incompletely and switched poorly to pyruvate. Eight weeks of oral carnitine reversed those mitochondrial defects, increased acetylcarnitine efflux and urinary excretion, and improved glucose tolerance.[4]

High-fat-fed mice and body weight. In C57BL/6J mice on a high-fat diet for 12 weeks, 0.5% dietary L-carnitine lowered body weight, abdominal fat and serum leptin and raised liver CPT1 activity.[5] A 2022 dose study found that 0.5% to 4% L-carnitine reduced weight gain, visceral fat and glucose intolerance in high-fat-fed mice.[6] The 2007 mouse study above, by contrast, found no weight change.[3]

Carnitine deficiency. The juvenile visceral steatosis (jvs) mouse lacks a working OCTN2 transporter.[8] Only 28% of jvs pups were alive at day 28 against 100% of normal pups, with hypoglycemia from day 21; on a carnitine-rich diet, hypoglycemia was absent at day 28.[10] Adult jvs mice develop an enlarged heart, and carnitine given from one month of age significantly suppressed that hypertrophy.[9]

Gut bacteria and TMAO. In mice, gut bacteria convert dietary L-carnitine to trimethylamine (TMA), which the liver oxidizes to TMAO. Carnitine-fed mice had plasma TMAO of 114 µM against 17 µM on chow (Figure 3). In atherosclerosis-prone Apoe-knockout mice, carnitine in the drinking water roughly doubled aortic root plaque, and suppressing gut bacteria with antibiotics completely blocked that increase.[7]

Figure 3. TMAO and TMA in carnitine-fed mice. Gut bacteria turned dietary carnitine into TMA and TMAO, raising plasma TMAO about sevenfold. Data from Koeth et al., Nature Medicine 2013.[7]

L-Carnitine vs acetyl-L-carnitine

They are the same carrier, with and without an acetyl group. Acetyl-L-carnitine is L-carnitine with an acetyl group attached at the 3-hydroxyl, the same position where fatty acids are attached in the shuttle.[2] It is also the main form carnitine takes after a load: in carnitine-fed mice acetylcarnitine was 86% of the plasma acylcarnitine pool and 88% of the skeletal muscle pool.[3]

• L-carnitine: C7H15NO3, 161.20 g/mol; the free carrier used by CPT1, CACT and CPT2.[11]

• Acetyl-L-carnitine: C9H17NO4, about 203.2 g/mol (calculated); the acetyl ester, formed when mitochondria export surplus two-carbon units.[3,4]

• For research design: the two are not interchangeable doses of one compound. Studies should state which form, and whether results are reported as free carnitine, acetylcarnitine or total carnitine.

What is L-Carnitine made of?

L-carnitine is a small quaternary ammonium compound: a four-carbon butanoic acid backbone with a hydroxyl group on carbon 3 and a trimethylammonium group on carbon 4. Its systematic name is (R)-3-hydroxy-4-(trimethylammonio)butanoate, and because it carries both a positive and a negative charge it exists as an inner salt.[2,11] It is not a peptide and contains no peptide bonds.

In animal cells it is built from trimethyllysine, released when proteins that contain it are broken down, by way of butyrobetaine.[2]

L-Carnitine at a glance

• Compound: L-carnitine (levocarnitine)

• Class: Quaternary ammonium compound; amino acid derivative, not a peptide

• Structure: (R)-3-hydroxy-4-(trimethylammonio)butanoate, inner salt[11]

• Molecular formula: C7H15NO3[11]

• Molecular weight: 161.20 g/mol[11]

• Strength: 600 mg per vial

• Identity and purity: Every lot is tested by independent labs and the certificate of analysis is published in the NextGenPeps COA library.

• Appearance: Solid powder in a sealed vial. The pharmaceutical form is described as a white, crystalline, hygroscopic powder[11]

• Reconstitution: Water or aqueous buffer; readily soluble in water[11]

• Half-life: About 17.4 hours (apparent terminal) after intravenous dosing, in the prescribing information for a levocarnitine product[11]

• Regulatory status: Levocarnitine is FDA-approved by prescription (Carnitor) for primary systemic carnitine deficiency and some secondary deficiencies.[11] The NextGenPeps material is research use only

Is L-Carnitine FDA approved?

As a prescription drug, yes, for specific deficiency conditions. Levocarnitine tablets, oral solution and injection (Carnitor) are approved for primary systemic carnitine deficiency and for secondary carnitine deficiency caused by inborn errors of metabolism; the injection is also approved for carnitine deficiency in end-stage renal disease on dialysis.[11] Research-grade material is a different product: it is not manufactured to a pharmaceutical label and is not approved for any use.

What is L-Carnitine used to study?

Researchers use it whenever fatty acid supply to mitochondria, or the clearance of surplus fuel from them, is the variable of interest.

• Fatty acid oxidation. Carnitine supply and CPT1 activity are the standard levers for studying how cells import and burn long-chain fat.[1,2]

• Insulin resistance and metabolic flexibility. Rodent models of obesity and diabetes use carnitine to test whether exporting excess acyl groups restores glucose handling.[3,4]

• Diet-induced obesity. High-fat-fed mouse models track body weight, fat mass and liver lipid enzymes with and without dietary carnitine.[5,6]

• Inherited carnitine deficiency. The jvs mouse, which lacks OCTN2, models systemic carnitine deficiency, its heart enlargement and its fasting hypoglycemia.[8,9,10]

• Gut microbiome metabolism. Carnitine is a substrate for bacterial TMA production, used to study TMAO and atherosclerosis in mice.[7]

Buying L-Carnitine for research: what each vial includes

Every lot is tested by independent labs and the certificate of analysis is published in the NextGenPeps COA library.

• Documentation. The lot's certificate of analysis is published in the COA library.

• US-based fulfilment. Orders ship within 24 hours from the United States, with free US shipping on orders over $150.

• Research use only. L-Carnitine is sold strictly for in vitro and approved animal research. It is not for human or veterinary use and is not sold as a drug, supplement or diagnostic.

L-Carnitine handling, storage and analytical notes

Format. Supplied as a solid in a sealed vial and dissolved in water or aqueous buffer before use. No dosing instructions are supplied, and none should be taken from the studies above.

Storage. Keep the sealed vial cold (2 to 8 °C) and dry; L-carnitine is hygroscopic and takes up moisture from air once opened.[11] Hold solutions at 2 to 8 °C and avoid repeated freeze-thaw cycles. For comparison, the pharmaceutical label stores its tablets and solutions at controlled room temperature.[11]

Weighing. Because the powder absorbs water, mass measured after exposure to air can overstate the carnitine content. Weigh quickly or work from a stock solution of known concentration.

Measurement. Carnitine in tissue and plasma exists as free carnitine and as many acylcarnitines. Mass spectrometry profiling is the usual way to separate them, and studies should report which pool they measured.[3]

Naming. L-carnitine, levocarnitine and (R)-carnitine are the same compound. Acetyl-L-carnitine is a separate compound, the acetyl ester.

What is not established about L-Carnitine

• Weight effects. High-fat-fed mouse studies disagree: some report lower body weight and fat,[5,6] while others report better glucose handling with no change in weight.[3]

• Net cardiovascular effect. Carnitine supports heart energy supply, yet its gut-bacterial conversion to TMAO increased plaque in atherosclerosis-prone mice.[7] Which effect dominates depends on the model and the microbiome.

• Transfer between species. Most outcome data come from rodents fed carnitine in chow or drinking water. Uptake, gut metabolism and tissue levels differ between species and routes.[7,11]

• Research-grade equivalence. Research material is not equivalent to a pharmaceutical product, so quantitative work should verify its own concentration.

Research Use Only. The statements made within this website have not been evaluated by the US Food and Drug Administration. These materials are not intended to diagnose, treat, cure or prevent any disease and are not intended for human or veterinary use. Studies described on this page are reported for scientific context and are not guidance of any kind.