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Possible therapeutic use of selected amino acids

of Patrick Linder

In this blog post we would like to share with you the current  Present the study situation on the possible therapeutic use of the amino acids acetyl-L-carnitine, L-arginine base, L-methionine, L-tryptophan and L-lysine.

acetyl-L-carnitine

  • L-carnitine is produced in the liver, kidneys and brain formed from the amino acids lysine and methionine (with the vitamin  C, B6 and niacin as well as iron as cofactors). However, it is stored 98% in the heart and muscles (cf. Rebouche 1991), where it provides energy from fatty acids.

  • Carnitine and acetyl-L-carnitine are semi-essential amino acids. The body's own synthesis may not be sufficient to cover the need: for example, the body's own synthesis of carnitine gradually decreases with age.

  • Acetyl-L-carnitine (cannot be produced by the body itself) has been given another acetyl group and can therefore  Cross the blood-brain barrier (a natural barrier that separates the bloodstream from the central nervous system). Acetyl-L-carnitine has a very high bioavailability and therefore faster effectiveness than L-carnitine.

  • L-carnitine plays a important role in energy production  or the  fat utilization: L-carnitine acts as a receptor molecule for the transport of (activated) long-chain fatty acids into the mitochondria (the “power plants” of our cells) to generate energy through fatty acid oxidation (beta-oxidation). This is because long-chain fatty acids can only be transported through the mitochondrial membranes into the mitochondria when bound to L-carnitine (cf. Löster 2003).

  • For example, a study by the University of Cantania in Italy administered acetyl-L-carnitine to subjects suffering from fatigue:  acetyl-L-carnitine  could help to  improve mitochondrial fat metabolism  and thus produce energy easily and efficiently (Source: https://www.ncbi.nlm.nih.gov/pubmed/17658628)

  • fat burning: It has been shown in several in vivo studies on healthy humans that L-carnitine supplements increase the burning of long-chain fatty acids by 37%. However, this has nothing to do with losing weight, as this requires changing several nutritional parameters.

  • Cardiovascular diseases: The heart muscle beats around 100,000 times a day and pumps up to 10,000 liters of blood. Due to this high energy requirement, the heart is the organ in the body that is richest in L-carnitine. It needs L-carnitine to extract energy from fatty acids and to protect fat cells from the toxic effects of long-chain acetyl-CoA compounds. Many heart diseases are associated with a reduced concentration of L-carnitine in the heart.
    • Angina Pectoris: Exercise capacity increases, pain relief is achieved
    • Heart muscle weakness: increasing the performance of the heart muscle
    • Increased blood lipid levels: lowering of triglycerides, lowering of Lp(a), counteracts atherosclerosis
    • Cardiac arrhythmias: L-carnitine counteracts cardiac arrhythmias by protecting the heart cells from long-chain acyl-CoA compounds that promote arrhythmias.
    • Myocardial infarction prophylaxis and follow-up treatment (acute): L-carnitine can reduce the size of the necrotic area of ​​the heart during a heart attack and thus reduce the severity of a heart attack and increase the chances of survival (cf. Spagnoli, Lancet 1982).
  • influencing the blood lipid levels (Influence on the insulin sensitivity of the cells)
  • Acetyl-L-carnitine protects the mitochondria from free radicals and harmful metabolic products and stimulates the synthesis of proteins and membrane phospholipids. It therefore has a membrane-stabilizing, antioxidant and neuroprotective effect and could therefore contribute to prophylaxis of degenerative neurological diseases
  • immune system: Immune cells contain a lot of L-carnitine and the L-carnitine requirement of these cells increases sharply during an acute infection. L-carnitine is considered a natural immune stimulator because it is needed by immune cells for their energy production (ATP production). In studies, L-carnitine was able to increase lymphocyte proliferation and activity, increase the phagocytosis activity of granulocytes and monocytes and increase the activity of natural killer cells (NK) (Sources: Uhlenbruck, G.; van Mil, A.: Immunobiological and other aspects of membrane modulation by L-carnitine. 1993; DeSimone, C. et al: Vitamins and immunity: influence of L-carnitine on the immune system. Acta Vitaminol Enzymol (1982) 4:135-140)

  • detoxification function: Liver metabolism of toxic substances: L-carnitine as a transport molecule ("biocarrier") of the toxic metabolites for excretion via the kidney

  • Diabetes mellitus: L-carnitine is able to lower LDL cholesterol levels and triglyceride concentrations in the blood, which in turn reduces oxidative stress and regulates blood sugar levels. The reduction in free fatty acids increases the effect of the body's own insulin and reduces insulin resistance, which can help prevent or improve diabetes.
  • Liver diseases: Liver: Liver cells contain up to 20,000 mitochondria, in which L-carnitine is needed to generate the large amounts of energy that the liver cells require for their enormous metabolic output. Acetyl-L-carnitine supports liver detoxification and improves glucose metabolism by counteracting insulin resistance.

  • acetyl-L-carnitine increases the production of the neurotransmitter acetylcholine: Cholinergic nerve cells, which use acetylcholine to transmit stimuli, are found in various regions of the brain (especially in the cerebral cortex, hippocampus and hypothalamus) and are important for memory, thinking and movement, among other things. Acetyl-L-carnitine could therefore improve concentration, memory and mood and help with inner restlessness.

  • Sperm / Fertility: Sperm are the cells richest in L-carnitine. In animal experiments, carnitine supplements have increased the amount of ejaculate and ensured that sperm cells are activated, their mobility and endurance improve, their number increases and thus male fertility improves. Female fertility has also been increased in animal experiments, as the process of implantation of fertilized eggs in the uterus is membrane and energy dependent. In sows, the fertilization rate was increased by L-carnitine and the rate of natural abortions was reduced.

  • L-carnitine in pregnancy and infants:
    • Pregnancy always causes a secondary L-carnitine deficiency. From the 12th week of pregnancy onwards, the L-carnitine content in the blood decreases significantly (cf. Schoderbeck 1995). The reason is the increased energy requirement and the increased metabolism during pregnancy.In addition, iron deficiency during pregnancy often limits L-carnitine production.
    • In addition, a sufficient supply of L-carnitine supports the rapid development of lung and heart functions in the embryo (cf. Lohninger 1990).
    • After birth, the body's own synthesis of L-carnitine is initially barely developed. Newborns are therefore dependent on breast milk as a source of L-carnitine. Shortly after birth, particularly premature babies often experience significant weight loss, which can be reduced by giving L-carnitine to pregnant and breastfeeding mothers (see Strack 1960). The addition of L-carnitine to baby food such as follow-on milk is regulated by law, according to which infant formula must contain at least 1.8 µmol/100 kJ of L-carnitine (see Directive 91/321/EEC).

Possible indications for carnitine supplementation

  • aging (lower endogenous carnitine synthesis)
  • Low carnitine intake through food (vegetarian, vegan diet)
  • Chronic fatigue (including cancer, multiple sclerosis, celiac disease, old age, chronic fatigue syndrome, hepatitis C)
  • Depression in Seniors
  • Age-related deterioration of cognitive abilities, dementia
  • Cardiovascular diseases (intermittent claudication, angina pectoris, myocardial infarction, congestive heart failure, myocarditis, ventricular extrasystoles, cardiomyopathy, hypertension, stroke, Raynaud's syndrome)
  • Diabetes mellitus, obesity, metabolic syndrome
  • neuropathy (diabetes, chemotherapy, HIV medication)
  • Age-related macular degeneration
  • fertility problems
  • fibromyalgia
  • tumor cachexia
  • hyperthyroidism
  • Sport (improving endurance)
  • COPD (to improve exercise tolerance)
  • Hepatic encephalopathy, liver cirrhosis
  • Nonalcoholic fatty liver disease and steatohepatitis
  • kidney failure/kidney dialysis
  • HIV infection
  • Vascular dementia, Alzheimer's disease (early stage)
  • tuberculosis
  • prevention of prostate cancer
  • Chronic pain due to sciatica or carpal tunnel syndrome (preferably take PEA in addition to acetyl-L-carnitine)

Contraindications for carnitine supplementation

  • Not recommended for hypothyroidism (hypothyroidism); carnitine inhibits the activity of the thyroid hormone. In cases of hyperthyroidism (overactive thyroid, Graves' disease, Hashimoto's hyperfunction, etc.), (acetyl)-L-carnitine can be used.
  • Bipolar disorder (isolated cases of mania or psychosis have been described after supplementation with acetyl-L-carnitine).

Sources:

L-Arginine Base

  • L-arginine is a semi-essential amino acid – that is, it can be produced by the body itself, but not in sufficient quantities and only by consuming other essential amino acids.

  • nitric oxide (NO) is produced in the cells of the vessel walls from L-arginine (with the help of the enzyme NO synthase) educated. NO has a vasodilating effect and therefore lowers blood pressure.
    • In a study with pregnant women at high risk for gestational hypertension, the preventive intake of arginine together with antioxidant vitamins significantly reduced the likelihood of hypertension, for example.

    • L-arginine is therefore often used to accompanying treatment of diseases with vasoconstrictions used, such as arteriosclerosis or sudden hearing lossIn addition, NO acts as a neurotransmitter in the brain and is responsible for memory function.

    • NO has also been used in conventional medicine for a long time (iFv nitroglycerin / is converted very quickly into NO in the body) in heart medications for  cardiovascular diseases  used to improve blood flow to the heart, to reduce blood pressure in emergencies and in cases of severe heart failure.

    • CAUTION: Arginine should not be supplemented in the case of diseases that lead to severe chronic inflammation, as the inflammation usually produces too much NO. This leads to so-called nitrosative stress with possible oxidative damage to proteins and DNA.

  • The improved blood circulation and the release of the growth hormones prolactin and glucagon, which support both muscle building and fat loss, are reasons for the Use of L-Arginine in Sports:
    • Arginine promotes the release of growth hormone from the pituitary gland, which also regulates muscle growthIn addition, the body needs arginine to produce creatine for muscle regeneration. In bodybuilding, it is used as a so-called "pump supplement" Application. By expanding the veins in the active muscle, the development of strength is promoted on the one hand, and the regeneration of the muscle after exertion on the other.
    • In a study at the University of Exeter (UE), scientists found that L-arginine can increase athletic performance by 20% and improve race times by up to 2%.
    • In animal experiments with overweight rats and pigs, arginine had a slowing effect on weight gain, which is explained by an increase in mitochondria through arginine administration, because sugar and fats are burned in the "power plants" of our cells. The animals had a lower fat percentage and lower fat levels in the blood.
    • In women after menopause, arginine was able to reduce the decline in muscle strengthA trial on Duchenne muscular dystrophy also showed improved preservation of muscle tissue. For this reason, use in bedridden patients or astronauts is also being discussed.

  • Strengthening the immune system: Macrophages produce NO to kill bacteria. Aside from that Arginine is needed for cell division and maturation of white blood cellsArginine therefore improves both acquired and innate immunity.

  • promoting wound healing
    • Arginine provides the raw material for the production of collagen and thus provides mechanical reinforcement of the wound area.
    • In a small group of diabetics, a subcutaneous injection of arginine was able to achieve healing of leg ulcers, presumably a combined effect of blood flow, cell division and collagen production. In planned operations, the administration of arginine could therefore accelerate the healing process.

  • arginine regulates insulin secretion and is therefore often used in the treatment of diabetes: Diabetes is often associated with reduced blood levels of arginine. Intravenous administration of arginine led to an improvement in blood flow and sensitivity to  Insulin. In addition, the increased oxidative stress in the blood of diabetics was alleviated by arginine. In animal experiments, not only the  Glucose levels in the blood, but also the levels of homocysteine ​​and  blood lipids.

  • Erectile Dysfunction and Fertility
    • Since NO is formed from L-arginine in the man's corpora cavernosa, which in turn improves blood flow, regular intake of L-arginine could lead to an increased erection. While arginine provides the basic substance NO, Viagra increases the effect of NO via the messenger substance cGMP. Some studies suggest an erection-promoting effect, some against it. It could be that people with mild erectile dysfunction or a disturbed NO metabolism respond better.
    • It is possible that arginine could have a normalizing effect on fertility problems in men and women by increasing blood flow to the sexual organs. An improvement in sperm quality with the help of arginine has been shown several times. In female cows, pigs and rats, arginine reduced the rate of miscarriages and promoted the growth and development of the embryo. This is probably due to the improved blood flow to the placenta. Comprehensive studies on humans are still lacking.

  • Ammonia detoxification: Arginine ensures the detoxification of ammonia as urea in urine
  • In studies, arginine, especially in combination with  amino acid  lysine and magnesium balancing effects on anxiety disordersA study found a reduced level of the stress hormone cortisol.

Sources

  • Bailey SJ et al., "Acute L-arginine supplementation reduces the O2 cost of moderate-intensity exercise and enhances high-intensity exercise tolerance." J Appl Physiol (1985). 2010 Nov;109(5):1394-403)
  • Lomonosova YN et al., "L-arginine supplementation protects exercise performance and structural integrity of muscle fibers after a single bout of eccentric exercise in rats." PLoS One. 2014 Apr 15;9(4):e94448
  • Zajac A et al., "Arginine and ornithine supplementation increases growth hormone and insulin-like growth factor-1 serum levels after heavy-resistance exercise in strength-trained athletes." J Strength Cond Res. 2010 Apr;24(4):1082-90.
  • Collier SR et al., "Growth hormone responses to varying doses of oral arginine." Growth Horm IGF Res. 2005 Apr;15(2):136-9
  • Costa KA et al., "L-arginine supplementation prevents increases in intestinal permeability and bacterial translocation in male Swiss mice subjected to physical exercise under environmental heat stress." J Nutr. 2014 Feb;144(2):218-23
  • Un O et al., "l-Arginine and tetrahydrobiopterin, but not sodium nitrite partially restored erectile dysfunction in aged rats." Aging male. 2014 Jun 5:1-8
  • Morgante G et al., "Treatment with carnitine, acetyl carnitine, L-arginine and ginseng improves sperm motility and sexual health in men with asthenopermia." Minerva Urol Nefrol. 2010 Sep;62(3):213-8
  • Orozco-Gutiérrez JJ et al., "Effect of L-arginine or L-citrulline oral supplementation on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction." Cardiol J. 2010;17(6):612-8
  • Das S, Mattson DL "Exogenous L-arginine attenuates the effects of angiotensin II on renal hemodynamics and the pressure natriuresis-diuresis relationship." Clin Exp Pharmacol Physiol. 2014 Apr;41(4):270-8
  • Rossella Marullo et al, The metabolic adaptation evoked by arginine enhances the effect of radiation in brain metastases, Science Advances (2021). DOI: 10.1126/sciadv.abg1964

L-methionine

  • L-methionine is one of the essential amino acids; i.e. it cannot be synthesized by the body itself, but must be supplied from outside

  • Methionine is the “starting amino acid” for all (!) proteins, i.e. all other amino acids are attached to methionine.

  • L-methionine is the precursor of homocysteine, cysteine, taurine, choline and S-adenosyl-methionine (SAM), among others. SAM in particular is involved in many metabolic processes, including growth processes, the health of liver cells and the formation of neurotransmitters (SAM influences the brain metabolism). Therefore, L-methionine / SAM is often used to relieve stress and also in the treatment of depression.

  • Methionine passes through the blood-brain barrier into the brain. It ensures that myelin (a special protective layer of the nerves) can be formed.

  • Methionine is a sulfur-containing amino acid and binds heavy metals such as copper, cadmium, lead, ammonia and mercury; Methionine is therefore often used in heavy metal detoxification

  • Methionine has a urine acidifying effect:
    • The body needs about 0.5 g of methionine per day to maintain muscle. If you consume more than 1.5 g per day, the body has to break down the excess. This breakdown produces sulfate, which is excreted via the kidneys. Protons are secreted into the urine, which becomes acidic.
    • This effect is seen in the treatment of urinary tract diseases in which an acidic pH value in the urine inhibits the adhesion of bacteria to the urothelial cells and inhibits bacterial growth.
    • In addition inhibits methionine formation of kidney stones, improves stone solubility and supports the effect of certain antibiotics.

  • L-methionine is an important methyl group donor and therefore plays a central role in epigenetics

  • L-methionine supports selenium effect

  • Lowers histamine levels

  • Methionine helps prevent excessive fat deposits in the liver and supports liver tissue in its renewal.

  • Methionine helps to form the powerful antioxidant glutathione

  • Keratin (the “strengthening protein”) is formed from the building block methionine, among others. As a precursor of keratin, methionine therefore ensures the regeneration and strength of hair and nails.

The daily requirement of methionine
The daily requirement of methionine for adults is about 13 mg per kilogram of body weight.


Typical groups for an increased need for methionine

  • when exposed to heavy metals
  • for allergies
  • for depression
  • in wound healing and muscle injuries
  • for urinary tract infections
  • in case of liver inflammation (due to drug or alcohol abuse)


Possible signs of methionine deficiency

A lack of methionine can lead to metabolic disorders. These can include:

  • fatty liver disease
  • skin and hair growth disorders
  • Increased fatigue or lethargy
  • Depressive moods

Who is at risk for methionine deficiency?

  • infants and toddlers
  • Old people
  • competitive athletes
  • people under stress
  • Vegans (with the exception of nuts and seeds, many plant foods are rather low in methionine)

L-lysine

  • L-lysine is one of the essential amino acids - ie it cannot be synthesized by the body itself, but must be supplied from outside

  • L-lysine is a basic amino acid

  • Lysine is in the form of hydroxylysine an important component of the structural protein collagen (building block of connective tissue) and thus relevant for firm skin and strong connective tissueSince cartilage, ligaments, tendons, joints and fascia are also made of collagen, lysine or collagen is also of great relevance for athletes.

  • Collagen and ergo lysine also influence the wound healing and healing of bone fracturesAnimal studies have shown that lysine can accelerate wound healing and shorten recovery time.

  • In addition, the amino acid L-lysine has a cardiovascular protective function, as it is also a building block of vascular collagen (our artery walls are also made of collagen)

  • L-lysine is central building block of L-carnitine (iron and vitamins C and B3 are required as cofactors)
    • Therefore, L-lysine is also relevant for our performance, since carnitine plays a central role as a carrier for fatty acids into the mitochondria. cellular energy production plays.
    • Since sperm and immune cells contain the most carnitine, a carnitine or lysine deficiency also has a negative effect on fertility and immune system out of.

  • L-Lysine has a antiviral effect and is therefore e.g. often in  herpes infectionsIt is believed that lysine blocks arginine, which the herpes viruses need to reproduce. One study, for example, found that:that daily intake of 1 g of lysine resulted in fewer blisters in 26 people who were prone to recurrent herpes cold sores.

  • L-lysine increases intestinal calcium absorption and is therefore often used for osteoporosisA study of 30 women (15 healthy, the other 15 suffering from osteoporosis) found that taking calcium and lysine reduced calcium loss in the urine.

  • L-Lysine is a accelerator of the painkiller ibuprofen
  • reduction of anxiety and the stress hormone cortisol:
    • A one-week study of 50 healthy people found that taking 2.64 grams of lysine and L-arginine reduced stress-related anxiety and levels of the stress hormone cortisol.
    • Similarly, the addition of 4.2 grams of lysine per kilogram of wheat flour in disadvantaged villages in Syria helped reduce anxiety levels in men with very high stress levels: After three months, consumption of the flour enriched with the active ingredient lysine also helped reduce cortisol levels in women.

For whom might supplementation generally be useful?

  • The WHO recommends a daily intake of 20-28 mg of lysine per kg of body weight. In cases of malnutrition and in certain life situations, these values ​​are often not achieved.
  • Since most plant-based foods are low in lysine (exceptions: legumes and soy), supplementation is vegans often displayed.
  • Since L-lysine promotes bone growth and cell division, it is particularly pregnancy and breastfeeding an adequate supply is important.
  • Since cartilage, ligaments, tendons, joints and fascia are made of collagen, which is formed from lysine, lysine is also important for sportsman of high relevance.

Sources:

  • Groff JL, Gropper SS, Hunt SM Advanced nutrition and human metabolism, 2nd ed. West Publishing, 1995
  • Hahn A., Ströhle A., Wolters M; Nutrition - Physiological principles, prevention, therapy. Wissenschaftliche Verlagsgesellschaft mbH Stuttgart 2004
  • Hahn, A.; Dietary supplements; Scientific Publishing Company mbH Stuttgart, 2006
  • M. Singh et al. Medicinal Uses of L-Lysine: Past and Future. Int. J. Res. Pharm. Sci. 2011; 2(4): 637-642
  • Protein and Amino Acid Requirements in Human Nutrition. Report of a Join Report of a Joint WHO/FAO/UNU Expert Consultation. WHO technical report series; no. 935; 2002
  • R. Civitelli et al. Dietary L-lysine and calcium metabolism in humans. Nutrition 1992; 8(6):400-5.

L-tryptophan

  • Precursor of the neurotransmitter serotonin (the “happiness hormone”), which regulates mood and appetite. If the serotonin level is permanently too low, the  Transmission of stimuli between nerve cells is no longer correct  and mood swings, sleep disorders or depressive moods can be the result. Unfortunately, serotonin can  not  simply  take, but can  only increased by additional L-tryptophan  (Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908021/)
  • Precursor of the hormone melatonin (the “sleep hormone”), which  Pain sensation and sleep rhythm are regulated.Melatonin is produced and released in greater quantities in the dark and in smaller quantities in the light. This happens in the pineal gland in our brain. Pathological sleep disorders are usually caused by low melatonin concentrations in the blood. Numerous studies have shown that tryptophan has a positive effect on sleep by shortening the time it takes to fall asleep and prolonging the REM phase (source: Bonmati-Carrion MA et al.).  Int J Mol Sci. 2014 Dec 17;15(12):23448-500. doi: 10.3390/ijms151223448)

  • Improved brain performance: Researchers have found that tryptophan has a positive effect on memory.  low tryptophan levels  can lead to reduced memory performance  and other cognitive functions. A study by the University of Bordeaux found that tryptophan in both healthy adults and adults with memory lapses  memory improved  has: Is to  If there is little tryptophan in the brain, a  Lack of neurotransmitters in the brain and the transmission of information no longer functions properly (sources: Ferracioli-Oda E, Qawasmi A, Bloch MH.  PLoS One. 2013 May 17;8(5):e63773. doi: 10.1371/journal.pone.0063773. Print 2013; http://www.tandfonline.com/doi/abs/10.3109/07853890008998828)

  • Vitamin B3 can be produced in the body from L-tryptophan

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