based on Reviews

Possible therapeutic use of selected amino acids

from 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 meet these needs: 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 an additional 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) for energy production through fatty acid oxidation (beta-oxidation). Long-chain fatty acids can only be transported through the mitochondrial membranes into the mitochondria when bound to L-carnitine (see 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 lipid metabolism and thus produce energy easily and efficiently (Source: https://www.ncbi.nlm.nih.gov/pubmed/17658628)

  • Fat burning: Several in vivo studies on healthy humans have shown that L-carnitine supplementation increases the burning of long-chain fatty acids by 37%. However, this has nothing to do with losing weight, as several nutritional parameters need to be changed.

  • Cardiovascular diseases: The heart muscle beats approximately 100,000 times per day, pumping up to 10,000 liters of blood. Due to this high energy demand, the heart is the body's richest organ 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 reduced L-carnitine concentrations 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 triglycerides, lowering 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 in the heart during a myocardial infarction 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 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 membrane-stabilizing, antioxidant, and neuroprotective effects and could therefore contribute to Prevention of degenerative neurological diseases
  • immune systemImmune cells contain very high levels of L-carnitine, and their L-carnitine requirements increase significantly during an acute infection. L-carnitine is considered a natural immune stimulant because it is needed by immune cells for their energy production (ATP production). Studies have shown that L-carnitine can increase lymphocyte proliferation and activity, increase the phagocytic activity of granulocytes and monocytes, and increase the activity of natural killer (NK) cells (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 toxic metabolites for excretion via the kidneys

  • Diabetes mellitus: L-carnitine is able to lower LDL cholesterol 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 effectiveness of the body's insulin and reduces insulin resistance, which can contribute to the prevention or improvement of diabetes.
  • Liver diseases: Liver: Liver cells contain up to 20,000 mitochondria, which require L-carnitine to generate the large amounts of energy they require for their tremendous 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 brain regions (v.a. in cerebral cortex, hippocampus and hypothalamus) and u.a. important for memory, thinking, and movement. Acetyl-L-carnitine may therefore improve concentration, memory, and mood and help with inner restlessness.

  • Sperm/Fertility: Sperm are the cells richest in L-carnitine. In animal studies, carnitine supplements have increased the amount of ejaculate and ensured the activation of sperm cells, improved their motility and endurance, and increased their number, thus improving male fertility. Female fertility has also been increased in animal studies, as the process of implantation of fertilized eggs in the uterus is membrane- and energy-dependent. In sows, L-carnitine increased the fertilization rate and reduced the rate of natural abortions.

  • L-carnitine during pregnancy and in infants:
    • Pregnancy always causes a secondary L-carnitine deficiency. Starting as early as the 12th week of pregnancy, the L-carnitine level in the blood decreases significantly (see Schoderbeck 1995). This is caused by the increased energy demand and increased metabolism during pregnancy.In addition, iron deficiency during pregnancy often limits L-carnitine production.
    • In addition, an adequate supply of L-carnitine supports 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 poor. Newborns are therefore dependent on breast milk as a source of L-carnitine. Shortly after birth, particularly premature babies experience significant weight loss, which can be reduced by administering L-carnitine to pregnant and breastfeeding mothers (cf. Strack 1960). The addition of L-carnitine to baby food such as z.BFollow-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
  • Non-alcoholic 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 hyperthyroidism (overactive thyroid, Graves' disease, Hashimoto's hyperthyroidism, 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 – d.hIt 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 vascular walls from L-arginine (with the help of the enzyme NO synthase) educated. NO has a vasodilating and therefore blood pressure lowering effect.
    • 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 vascular constrictions used, such as arteriosclerosis or Sudden hearing loss. In addition, NO acts as a messenger substance in the brain and is responsible for memory function.

    • NO has also been used in conventional medicine for a long time (i.F.v. 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 lower blood pressure in emergencies and in cases of severe heart failure.

    • CAUTION: In cases of diseases that lead to severe chronic inflammation, arginine should not be supplemented, as the inflammation i.d.R. Too much NO is already being produced. 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 growth 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 goal is to promote strength development on the one hand, and muscle regeneration after exercise 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 attributed to an increase in mitochondria due to arginine administration, since sugar and fat are burned in the "power plants" of our cells. The animals had a lower fat percentage and lower fat levels in their blood.
    • In women after menopause, arginine could reduce the decline in muscle strengthLikewise, a trial in Duchenne muscular dystrophy has shown improved preservation of muscle tissue. For this reason, its 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 cells. Arginine therefore improves both acquired and innate immunity.

  • Promote 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, subcutaneous injections of arginine have been shown to promote healing of leg ulcers, presumably through a combined effect of blood flow, cell division, and collagen production. Therefore, in elective surgeries, administration of arginine may 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 in 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 L-arginine is used in the male corpus cavernosum to produce NO, which in turn improves blood flow, regular intake of L-arginine could lead to an improved erection. While arginine provides the precursor NO, Viagra enhances the effect of NO via the neurotransmitter cGMP. Some studies support an erection-promoting effect, while others disagree. It may be that individuals with mild erectile dysfunction or impaired NO metabolism respond better.
    • It is conceivable that arginine could have a normalizing effect on fertility problems in both men and women by increasing blood flow to the reproductive organs. Improvements in sperm quality with the help of arginine have been demonstrated repeatedly. In female cows, pigs, and rats, arginine reduced the rate of miscarriages and promoted embryonic growth and development. This is presumably due to improved blood flow to the placenta. Comprehensive human studies 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; d.h. it cannot be synthesized by the body itself, but must be supplied from outside

  • Methionine is the “Start amino acid” for all (!) proteins, d.h. all other amino acids are attached to methionine.

  • L-Methionine is the precursor u.a. of homocysteine, cysteine, taurine, choline, and S-adenosylmethionine (SAM). SAM, in particular, is involved in many metabolic processes, u.a. in growth processes, liver cell health, or the formation of neurotransmitters (SAM influences 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 the formation of myelin (a special protective layer of nerves).

  • 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 approximately 0.5 g of methionine per day to maintain muscle. If you consume more than 1.5 g per day, the body must break down the excess. This breakdown produces sulfate, which is excreted via the kidneys. Protons are secreted into the urine, thus acidifying it.
    • 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 bacterial growth.
    • In addition inhibits Methionine the 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 action

  • Lowers histamine levels

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

  • Methionine helps to form the powerful antioxidant glutathione

  • Keratin (the “strengthening protein”) is formed from, among other things, the building block methionine.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
  • for wound healing and muscle injuries
  • for urinary tract infections
  • in cases of liver inflammation (due to drug or alcohol abuse)


Possible signs of methionine deficiency

A deficiency of methionine can lead to metabolic disorders. u.a. belong:

  • 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 - d.h. 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 connective tissueSince cartilage, ligaments, tendons, joints and fascia are also made of collagen, lysine or collagen is also of great importance 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 in 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 infections usedLysine is thought to block arginine, which the herpes virus needs to multiply. For example, one study found that taking 1 g of lysine daily resulted in fewer blisters in 26 people prone to recurring cold sores.

  • L-Lysine increases intestinal calcium absorption and is therefore often used for osteoporosis.A 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. These values ​​are often not achieved in cases of malnutrition and certain life situations.
  • 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, v.a. in Pregnancy and breastfeeding 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 J.L., Gropper S.S., Hunt S.M. Advanced nutrition and human metabolism, 2nd ed. West Publishing, 1995
  • Hahn A., Ströhle A., Wolters M.; Nutrition - Physiological Principles, Prevention, Therapy. Scientific Publishing Company mbH Stuttgart 2004
  • Hahn, A.; Dietary Supplements; Scientific Publishing Company Ltd. 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 Stimulus transmission between nerve cells is no longer correct and mood swings, sleep disturbances or depressive moods can 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 Regulates pain perception and sleep rhythm. Melatonin is produced and released in greater quantities in darkness and less in light. This occurs 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 deficits Improves memory 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 function 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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