L-Carnitine

What is L-carnitine?

L-carnitine (L-carnitine) is a natural, non-protein amino acid. Originally isolated in 1905 from the meat, and the Latin word for meat / flesh – carnis, e source of its name.

In the human body the main effect of carnitine between cell membranes, helping the implementation of a mechanism for energy production. To the fullest extent this happens in bodies where energy production using large amounts of fatty acids. These are mainly the muscles and heart.

In the body, 99% of L-carnitine is found in the intracellular space and the main body of which is stored are skeletal muscle. The next concentration of L-carnitine organ is the liver.

In recent years, the amino acid is examined as part of the solutions to combat metabolic syndrome because of the good results that showed improvement in insulin sensitivity.

How obtain such L-carnitine?

Like most amino acids, L-carnitine is found in foods that we eat. Mostly in animal products, including meat is the richest source. In a much lesser extent L-carnitine can be found in milk, and plant foods in quantities are practically negligible.

Although by food sourcing about 75% of total L-carnitine per day, the remaining 25% body synthesizes alone. An exception are vegetarians who Food- managed to obtain only 10% and synthesize the remaining 90%.

Biositnezat occurs in the brain, kidney and liver with the help of two essential amino acids – lysine and methionine. While skeletal muscles are the largest storehouse of L-carnitine, they have the ability to synthesize the amino acid.

Two enzymes involved in a number of chemical reactions, are highly dependent on the presence of vitamin C to his deficit may significantly impair biositeza of L-Carnitine.

The amino acid exists in the body in two forms – L-carnitine and the acetylated form acetyl carnitine-L-(Acetyl-L-Carnitine / ALCAR / alkaryl). Alkaryl was obtained when L-carnitine contact dedicating an acetyl group from acetyl-coenzyme A (Acetyl-CoA).

Absorption, metabolism and elimination

L-carnitine   including alkaryl, is absorbed in the first part of the small intestine, mainly through sodium-dependent transporter OCTN2.

The utilization of L-carnitine from the diet is much more effective than when administered as a dietary supplement. The absorption of food is in the range of 54-87%, whereas orally administered nutritional supplement of any form of carnitine in the range of 14-18%.

It is assumed that this difference is due to the body’s ability to utilize lower doses of L-carnitine better. It is estimated that a 70 kg human sourced dietary between 20 and 200 mg L-carnitine per day, while the concentration in the food additives starting from 500 mg up to a dose, a total amount of about 2-3 grams of the day.

And despite the difference in rates as assimilation through a nutritional supplement can be provided much more L-carnitine than through food.

Assimilation also depends to a large extent already existing L-carnitine in the body. In the case of deficiency and low levels of carnitine, assimilation in the intestines is significantly increased.

This occurs while taking L-carnitine in vegetarians and vegans, which would normally occur much lower levels of the amino acid in the body and are risking group of deficit. Scientific studies show that about 10% higher digestibility of L-carnitine in people with low levels compared to people with normal levels.

Serum levels of L-carnitine in the range of 23-73 μmol / L, and those of the acetylated form – 3-14 μmol / L.

Upon oral administration of 2 g L-carnitine, acetyl-L-carnitine or propionyl-L-carnitine (Propionyl-L-Carnitine / PLC) observed peak serum concentration Cmax of L-carnitine (84.7 +/- 25.2 umol / L / h), followed by alkaryl (12.9 +/- 5.5) and PLC (5.08 +/- 3.08). The peak occurs about three hours after dosing.

After entering the blood carnitine is directed to the appropriate cells where it is needed. Unfortunately, the body is unable to store large quantities and regularly carnitine supplementation did not increase the stocks in the tissues, such effect was observed in the intake of other substances such as creatine example.

Researches have shown that following a single dose of 500 mg intravenously injected alkaryl, the majority of the amino acid is hydrolyzed and blood levels returned to baseline within about 12 hours.

The levels of L-carnitine in the blood are kept within limits and using a very efficient process of reabsorption in the kidney. The degree of absorption back quickly adapt according to the levels of carnitine in the blood. Accordingly, an increase in the blood levels after intravenous or oral administration, the kidneys begin to eliminate more L-carnitine, instead of it back into the blood.

 

Physiological functions

Although in the beginning to not realize how important is L-carnitine for the work of the body in the 50 years of the 20th century, a number of studies conducted by and with the help of Irving Fritz reveal esentsialnostta amino acid in the production of energy in cells .

Carnitine plays an important role, to fatty acids can be used for energy.

To use the fatty acids they need to go through a process called beta-oxidation in the cell mitochondria.

Structurally mitochondria is divided into two compartments by means of outer and inner mitochondrial wall. L-carnitine plays a role in both places, with the aid of two enzymes called Carnitine Palmitoyltransferases. They are respectively CPT1 and CPT2.

In the outer mitochondrial wall, L-carnitine works by using CPT1, and in the inner wall – by using the CPT2.

The process of beta-oxidation happens in vatremembrannoto space. The problem is that long-chain fatty acids alone can not cross the inner membrane.

With the help of CPT1 and CPT2, L-carnitine has been associated with long-chain fatty acids and serve as a shuttle for carrying in their vatremembrannoto space.

After reach vatremembrannoto area, CPT2 divides the molecule of the component parts. Then the long-chain fatty acids can pass the beta-oxidation, while remaining free L-carnitine can fulfill his second important role in energy metabolism.

With the help of the enzyme carnitine acetyltransferase (CAT), L-carnitine in vatremembrannoto space can be converted to acetyl-L-carnitine. Subsequently alkaryl may give its acetyl group to take part in the Krebs cycle for energy production.

The need for L-carnitine for the use of fat for energy is particularly evident well in the conduct of research in which the reduction of the levels of L-carnitine in muscles by 85% resulting in 75% reduction in the levels of oxidation of palmitate, which is a marker energy production by beta-oxidation.

 

Deficiency of L-carnitine

Deficit was not observed in healthy people. Even vegans who are risking group of deficit and have much lower levels of carnitine, rarely suffer health consequences as a result of a deficit.

Deficiency of L-carnitine, however, exist in certain medical and genetic disorders and is divided into two types:

Primary systemic deficiency of L-carnitine

Primary systemic deficiency (TWI) is a rare autosomal recessive disorder of fatty acid oxidation. The disease results in much more difficult absorption of L-carnitine from the cell, accompanied by a defective process of reuptake in the kidney. Both together lead to systemic depletion of the levels of L-carnitine in the body, reaching up to below 10% of normal levels.

PSD meets every 1-5 out of 10 000 people, and most often occurs between 1 and 7 years old.

In PSD prejudice three main organs :

  • heart muscle – leading to progressive cardiomyopathy;
  • central nervous system – leading to hipoketonna hypoglycemic encephalopathy;
  • skeletal muscles – leading to myopathy.

When PSD adoption of L-carnitine in the injectable or oral form is life saving.

A secondary deficiency of L-carnitine

The secondary deficiency of L-carnitine (VD) is much more common compared with TWI, although not meeting good statistics on the number of diseases.

The secondary deficiency results in increased excretion of L-carnitine via urine. Unlike the primary, cause of the presence of a secondary deficiency is associated with other health diseases, such as liver or kidney.

VD can be caused by a defect in the metabolism of fatty acids, and taking certain medications, such as pivampicillin or valproic acid. Some therapeutic methods, such as hemodialysis, also significantly reduce the levels of L-carnitine, the drop may reach 60%.

Proven and potential health benefits in humans

L-carnitine and acetyl-L-carnitine are subjected to many studies in various fields of human health.

Metabolic syndrome

Research with people with normal and overweight, and people with diabetes showed significant effect on insulin sensitivity and glucose uptake by cells. 1,2,3,4

Glucose utilization is improved by stimulating AMPK.

For improving insulin sensitivity helps reduce the amount of acyl and acetyl groups in the cell whose accumulation has been shown to lead to a decrease in insulin sensitivity.

The reduction of these groups can be done by putting them outside the cell, followed by excretion through the urine. A possible mechanism is the introduction of these groups into the mitochondria where they can be used during beta-oxidation.

Reduction of symptoms of Alzheimer’s

Carnitine, especially alkaryl at doses of about 3 grams per day, has been studied in a number of scientific experiments to improve the mental capacity and delay in cognitive function in elderly people suffering from Alzheimer’s disease.

While half of the studies show good and statistically significant positive results, unfortunately the rest of the studies found no difference between the groups of people.

However, it should be noted that even when observing the positive results potency them is not high enough to be able alkaryl be recommended as a single agent to combat the disease, but it can be a good option to supplement medication.

Attention deficit hyperactivity disorder

Currently there are two well-conducted studies.

In 2002 the German team of scientists found significant improvement of symptoms in children diagnosed with ADHD, ranging between 20 and 65% for different players.

A study from 2007 involving 112 children observed different results depending on the type ADHD. Not observed improvement in ADHD of mixed type, but those present at the disease from inattentive type (inattentive type).

In both studies using doses in the range of 3-4 grams per day alkaryl.

Blood Pressure

Several studies have shown a considerable potential of L-carnitine in combating hypertension.

In one study, the combination of 1 g of acetyl L-carnitine, and 400 mg of alpha-lipoic acid leads to about 10 units of decline in systolic blood pressure in people over 55 years old diagnosed with ischemic heart disease.

Similar results were seen in younger people suffering from high blood pressure. There has been significant improvement in insulin sensitivity.

Intermittent claudication

Propionyl-L-carnitine showed significant positive results in people suffering from intermittent claudication. Continued use of this form at a dose of 2-3 grams daily, repeatedly showed improved symptoms and increased the distances that can be traveled by patients.

The standard form of L-carnitine also showed good results in this respect, but weaker compared to propionyl-L-carnitine. It is possible to align the results if the dose of the standard form be increased.

Secondary prevention in people had a heart attack

People had a heart attack probably would also benefit from taking a standard dose of 3-4 grams of L-carnitine a day.

No little research that showed a significant reduction in mortality in the groups receiving L-carnitine. There is also reducing the side effects caused by heart attacks.

Meta-analysis of 2013 conducted by DiNicolantonio JJ and his team consisting of 13 well-conducted research confirms the benefits of taking L-carnitine of people had a heart attack.

Not absent and researches that do occur positives but also not observed negative ones.

Prevention of deficiency in people undergoing hemodialysis

Haemodialysis often leads to a deficiency of certain substances. L-carnitine is one of them and this can lead to deterioration of existing or appearance of new side effects of this type of treatment.

That is why the intake of L-carnitine in people on dialysis to be endorsed and recommended by the Food and Drug Administration in the United States (US FDA)

 

L-carnitine and its role in sport

Carnitine is still one of the best selling nutritional supplements to support weight loss and improve athletic performance.

Still L-carnitine is the first thing that pops into the minds of almost all who decide to download a few extra kilos and reduce subcutaneous fat.

Carnitine is often used to improve endurance and reduce fatigue during workouts with aerobic predominant character.

Unfortunately carnitine also remains one of the substances most controversial scientific data behind when it comes to confirm its effectiveness in this context.

These contradictions can be seen well in the analysis of Eric P Brass from 2000.

It selected 17 scientific experiments earliest conducted in 1985 and the last in 1996 .. All studies tracked the effects of taking standard doses of L-carnitine (3-4 g) training on various parameters.

Tracked markers such as maximum volume administered oxygen (VO2 max), lactate accumulation, respiratory quotient (RQ) and others.

Most studies found no beneficial effect of taking L-carnitine, but few do the opposite.

These contradictions persist and are found in more recent research conducted before last few years.

When it comes to losing weight, things get even worse. Scientific data carried out on humans or even rats in this direction are lacking almost completely.

There are two tests on rats with negative results  and three human, one of which with negative and two positive.

At this stage it can be argued emphatically that the L-carnitine improves athletic performance and body composition. It is not entirely clear if there is no result, why is missing and therefore – if there is a positive result, what is the reason.

But there is light in the tunnel and scientific work of the last decade, held by Francis B. Stephens and colleagues reveals some details and opens the way to conduct new studies.

Without going into major detail that the curious can read themselves, we will explain briefly what it is.

The work poses the hypothesis that the availability of free carnitine in the cells is the limiting factor that prevents the absorption and utilization of fatty acids for energy during exercise.

From the available research on L-carnitine has now confirmed and one major problem is that neither the oral nor venous administration (infusion lasting several hours) of L-carnitine were able to increase the levels of the amino acid into the cells.

Such a problem is not observed in test animals – rats, cats, horses and the like.

In other words, L-carnitine does not accumulate in the body, such as is obtained with the substance and the food additive creatine.

It was further confirmed that during physical activity with high intensity levels of L-carnitine in the cells significantly reduced.

Stephens team observed 65% reduction in the levels of L-carnitine in the cells in the physical activity of an intensity greater than 75% Wmax, accompanied by a 35% reduction in the oxidation of long chain fatty acids. Similar results were seen in other scientific experiments.

The team of Stephens puts on the theory that levels of absorbed and used for energy fatty acids during exercise may increase if you find a way to increase the levels of intracellular L-carnitine.

They managed to achieve this effect by using a controlled intravenous infusion of insulin in doses that cause hyperinsulinemia. There is a 15% increase in the total carnitine in skeletal muscle.

Then repeat this effect by a more practical approach – by oral intake of drinks containing 4h500 ml ’94 carbohydrates and 3 g L-carnitine.

It was on this may be due to the positive results of the aforementioned research on Co- L-carnitine and sports performance. 25 In his athletes received a dose of 1.36 g L-carnitine together 80 g carbohydrates.

Of course, this is the time to step a little more firmly and to emphasize that the intake of huge amounts of carbohydrates is definitely not suitable for everyone and even more practical approach of injecting insulin does not guarantee anything.

However, the team of Stephens puts a new foundation that in the coming years, scientists can build.

 

Dosage, possible side effects and contraindications

Generally L-carnitine is a safe substance and recommended doses has no side effects.

Standard recommended dosage is in the range of 3-4 grams L-carnitine per day, divided into 2-3 times daily administration.

Given the peculiarities in the above article, you can experiment and take doses around meals rich in carbohydrates, when insulin levels are high.

Route of administration and dose applies to all popular varieties of carnitine. It does not matter whether the product be administered in the form of a liquid, capsule, tablet, dragee or powder.

It is possible that some people high intake of L-carnitine lead to the fish odor syndrome – a strange fish odor of sweat, breath or urine.

The reason for this is the rise in the levels of substance trimethylamine in the metabolism of L-carnitine and its discharge from the body. It is safe and meets with high intake of other substances, such as trimethylglycine (TMG) and choline.

In people diagnosed with Hashimoto and decreased function of the thyroid gland, the intake of L-carnitine is contraindicated due to data showing that orally administered L-carnitine prevents the entry of thyroid hormones in the cell nucleus.

Conclusion:

L-carnitine is one of those substances. One of those supplements – well researched, but still many question marks ahead.

Clearly, carnitine has great potential and could be part of the solution of many of the diseases that struggle in the present.

Most likely you are used to connect the L-carnitine weakening and improving endurance, but as we have noted, the data at this stage are too contradictory.

However, carnitine is safe and if you feel nothing prevents to do an experiment and decide for themselves.