Carnitine: what it is and what used for

Carnitine it is a non-protein amino acid (that is, it does not form Protein), and it is the compound responsible for the transport of long-chain fatty acids in the cellular units of energy production: the mitochondria.
Since it can be synthesized from the essential amino acid lysine, many nutritionists and researchers believe it should not be considered a vitamin; for others, however, given that niacin can be synthesized starting from the essential amino acid tryptophan, it can be considered as such.

Carnitine was isolated from meat extracts in 1905, but its chemical structure was not defined until 1932.
However, despite extensive studies conducted in the 1930s, the role of carnitine remained a mystery until about 50 years after its discovery.
In 1952 a group of researchers discovered that carnitine was a growth factor for Tenebrio molitor, and was also called vitamin Bt.
When it was discovered that other species of organisms were dependent on carnitine, they began to reexamine its role in the organism. , and it came to light that this molecule was essential in breaking down fat for energy.

Its importance, in fact, lies in the fundamental role it plays in the transport of fatty acids in the mitochondria.
Since the carrier molecule of fatty acids, namely acyl-CoA, cannot cross the cell membrane, a carnitine deficiency causes a reduction in the concentration of fatty acids in the mitochondria and, consequently, a reduced production of energy.

The fatty acids must in fact be transferred from the CoA to the carnitine. The acyl-camitin molecule transports the fatty acid to the mitochondrial surface of the inner mitochondrial membrane where it releases it to be transformed into energy.

Carnitine performs many other physiological functions, including the conversion of keto acids to branched-chain amino acids (valine, Ieucine and isoleucine) _, which is extremely important during fasting and exercise.

Food sources of carnitine

Meat and dairy products are the main dietary sources of carnitine. In general, the redder the meat, the higher its carnitine content. Cereals, nuts and vegetables contain little or are completely free of it. Preliminary studies indicate that an average daily diet contains about 5 to 100 mg ⁵.
However, the vast majority is synthesized by our body from the essential amino acid lysine with the help of another essential amino acid (i.e. methionine), three vitamins (vitamin C, niacin and vitamin B6) and iron. Deficiency in any of these nutrients clearly produces carnitine deficiency.

The final stage of carnitine synthesis occurs only in some “target” organs: in the liver, kidneys and brain. This is because the butyrobetaine hydroxylase enzyme , necessary for the final reaction, is present only in these tissues. This enzyme is largely responsible for controlling the synthesis of carnitine, heart muscle, skeletal muscle tissue and many other tissues.

Specific Protein for carnitine transport have been identified in the heart, skeletal muscle tissue, liver and kidneys, and facilitate the transfer of carnitine from blood to cells via carrier-mediated transport mechanisms. This active transport mechanism allows tissues to concentrate carnitine at levels even 10 times higher than those found in plasma.

In children, the activity of the enzyme of the final stage of carnitine synthesis is only 12% of the normal average for adults. From 2 and a half years of age, activity is 30% of the average adult one, which is only fully reached around the age of 15. These data underline the importance of carnitine contained in breast milk in infant nutrition: the initial concentration of carnitine in newborns directly depends on that present in the mother's organism.

The concentration in the umbilical and fetal cord blood is higher than that of the maternal blood, which indicates that the placenta is actively working to concentrate carnitine in the fetus, the synthesis of which is not yet completely efficient. Breast-fed infants have the best chance of achieving optimal carnitine concentrations because the bioavailability of carnitine obtained from breast milk is significantly greater than that of milk-based infant formulas. The administration of carnitine in premature babies has two important purposes: weight gain and growth.

In pregnant women, if a reduced synthesis of carnitine is suspected, it may be necessary to resort to supplements, in order to ensure an adequate concentration in both the fetus and the mother's tissues.

Signs and symptoms of deficiency

The first cases of carnitine deficiency in humans have been described as early as 1973.
It has always been thought that it was possible to synthesize the necessary quantity of carnitine, ingest it sufficiently with food or satisfy the need simply by a combination of these two. modality.

In fact, carnitine deficiencies are classified into two main groups: systemic (in the whole body) deficiency of carnitine and myopathic deficiency (in the muscles).
Diagnosis of systemic deficiency can be made using serum or urine samples, while the myopathic requires skeletal muscle tissue biopsy.

Carnitine deficiency: consequences

• Deficiency in iron, ascorbic acid, pyridoxine and niacin;
• Genetic defect of carnitine biosynthesis;
• Insufficient intestinal absorption of carnitine;
• Liver or kidney disorders resulting in reduced carnitine synthesis;
• Increase in metabolic losses of carnitine due to catabolism, reduced reabsorption in the renal tubule or genetic defect;
• Defective transport of carnitine from synthetic tissues to tissues of maximum use;
• Increased need for carnitine due to a high-fat diet, metabolic stress or disease.

In adults, compensation mechanisms seem to be activated that allow an adaptation that appears in fasting, in diabetes, in diets rich in fat and in other situations of secondary carnitine deficiency.

It appears that children are unable to adapt to low carnitine levels as well as adults. Several cases of deficiency have in fact been reported in children whose clinical picture resembled that of Reye's syndrome: acute cerebral edema associated with impaired liver function due to the accumulation of fat.
The clinical picture of secondary carnitine deficiency in children includes:

• loss of muscle tone;
• slowdown in growth;
• recurrent infections;
• cerebral edema, hypoglycemia and heart disorders.

Effects and benefits

Carnitine supplements can improve the utilization of fat as an energy source and have a positive effect in treating those many conditions in which there is impaired lipid utilization and energy production. In general, we can summarize the real benefits of carnitine supplementation as follows:

• Improves cognitive abilities and slows brain decline;
• Relieves chronic fatigue symptoms;
• Improves cardiovascular health (it is also used in patients with cardiovascular diseases);
• Improves insulin sensitivity;
• Preserves the functions of the mitochondrion in case of chronic stress or old age;

Reduces post-workout damage by reducing oxidative stress markers.

Forms available

Carnitine is commercially available in different forms, with the aim of improving its bioavailability, which can have slightly different effects. Below we list the main ones:

• L-carnitine or carnitine - basic, cheaper form. Slightly less bioavailable, but concentrated (as pure).
• L-carnitine tartrate (LCT) - tartaric acid salt. Better solubility and absorption.
• Propionyl-L-carnitine (PLC) - uncommon form, used mainly to improve cognitive functions or with cardiovascular problems.
• Acetyl-L-carnitine (or ALCAR) - the addition of the acetyl group improves its absorption and allows it to pass through the blood brain barrier. It acts as a substrate for the production of the neurotransmitter acetylcholine; it is recommended in case of chronic fatigue for the improvement of cognition.

It is good to always make use of the camitina in L form (left-handed), alone or linked to acetic or propionic acid.
The best form depends on the purpose: in Alzheimer's disease and to achieve an effect on brain tissue, it appears that the best form is L-acetylcarnitine; in angina the best choice could be L-propionylcarnitine as the myocardium seems to prefer it to L-acetylcarnitine.

In detail, acetylcarnitine is proving to be a real "nootropic", that is a substance capable of improving cognitive abilities. As previously pointed out, this form is in fact capable of crossing the blood brain barrier, a characteristic that allows this form of carnitine to gain various potentials. Unlike the "simple" L-carnitine, it is in fact able to increase the levels of acetylcholine in the synapses, help memory (and cognitive processes in general) and perform a stimulating and energizing action on the mind and body, both for relieve symptoms of fatigue in the elderly and to support muscle recovery in athletes. Furthermore, this molecule has interesting antioxidant activities, thanks to which it carries out an important neuroprotective action on the brain.

Bibliography

1. Bremer J, Carnitine-metabolism and function. Physiol Rev 63, 1420-1480, 1983.
2. Bamij MS, Nutritional and health implications of lysine carnitine relationship. Wld Rev Nutr Diet 44, 185-211, 1984.
3. Borum PR, Carnitine. Ann Rev Nutr 3, 233-259, 1983.
4. Carter HE, et al., Chemical studies on vitamin BT isolation and characterization as camitine. Arch Biochem Biophys 38, 405-416, 1952.
5. Scholte HR., Stinis JT, and Jennekens FGI, Low camitine levels in serum of pregnant women. NEJM 299, 1079, 1080, 1979.
6. Cederblad G, Fahraeus L, and Lindgren K, Plasma camitine and renal-carnìtine clearance during pregnancy. Am J Clin Nutr 44, 379-383, 1986.
7. Warshaw JB and Curry E. Comparison of serum camitine and ketone body concentrations in breast and in formula-fed infants. J Pediatr 97, 122-125, 1980.
8. Ardissone P, et al., The effects of treatment with L-carnìtìne of hypoglycemia in pre-term AGA infants. Cur Ther Res 38, 256-264, 1985.
9. Engel AG and Angelini C, carnitine deficiency of human skeletal muscle with associated lipid storage myopathy: A new syndrome. Science 179, 899-902, 1973.
10. Borum PR and Bennett SG, Camitine as an essential nutrient. J Am Coll Nutr 5, 177-182, 1986.
11. Gilbert EF, Carnitine deficiency. Pathology 17, 161-169, 1985.
12. Winter se, et al., Plasma camitine deficiency, clinical observation in 51 pediatric patients. AJDC 141, 660-665, 1987.
13. Glasgow AM, Eng G and Engel AG, Systemic camitine deficiency simulating recurrent Reye's syndrome. J Pediatr 96, 889-891, 1980.
14. Chapoy PR. et al., Systemic camitine deficiency: A treatable inherited lipid storage disease presenting as Reye's syndrome. NEJM 303, 1389-1394, 1980.
15. Rebouche CJ and Engel AG, Camitine metabolism and deficiency syndrome. Mayo Clin Proc 58, 533·540, 1983.
16. Siliprandi N. et al., Transport and function of L-camitine and L-propionylcarnitine: Relevance to some cardiac myopathies and cardiac ischemia. Z Cardiol 76 (Suppl. 5). 34-40, 1987.
17. Paulson DJ, et al., Protection of the ischaemic myocardium by L-propionylcamitine: Effects on the recovery of cardiac output after ischaemia and repurfusion, camitine transport, and fatty acids oxidation. Cardiovasc Res 20, 356-341, 1986.
18. Pettegrew, J., Levine, J. & McClure, R. Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression. Mol Psychiatry 5, 616–632 (2000). https://doi.org/10.1038/sj.mp.4000805
19. Chen, Ning et al. “L-carnitine for cognitive enhancement in people without cognitive impairment.” The Cochrane database of systematic reviews vol. 3,3 CD009374. 26 Mar. 2017, doi:10.1002/14651858.CD009374.pub3
20. Malaguarnera M, Gargante MP, Cristaldi E, Colonna V, Messano M, Koverech A, Neri S, Vacante M, Cammalleri L, Motta M. Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue. Arch Gerontol Geriatr. 2008 Mar-Apr; 46 (2): 181-90. doi: 10.1016 / j.archger.2007.03.012. Epub 2007 Jul 20. PMID: 17658628.
21. White HL, Scates PW. Acetyl-L-carnitine as a precursor of acetylcholine. Neurochem Res. 1990 Jun;15(6):597-601. doi: 10.1007/BF00973749. PMID: 2215852.