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Possible therapeutic use of selected amino acids

of Patrick Linder

In this blog post we would like to introduce you to the current 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 formed in the liver, kidneys and brain from the amino acids lysine and methionine (with vitamins C, B6 and niacin and iron as cofactors). However, 98% of it is stored 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 be not sufficient to cover the needs: the body's own synthesis of carnitine, for example, is reduced. gradually with age.

  • A further acetyl group has been added to acetyl-L-carnitine (cannot be produced by the body) 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 quicker effectiveness than L-carnitine.

  • L-carnitine plays an important role in energy production. of fat utilization: As a receptor molecule, L-carnitine ensures 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 (cf. Löster 2003).

  • For example, a study from the University of Cantania in Italy administered acetyl-L-carnitine to test subjects who suffered from symptoms of fatigue: The acetyl-L-carnitine could help improve the lipid metabolism of the mitochondria, making it easier and more efficient To produce energy (Source: https://www.ncbi.nlm.nih.gov/pubmed/17658628)

  • Fat burning: It has been shown in several in vivo studies on healthy people that L-carnitine administration in humans increases 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 approx. 100.000 times per day and pumps up to 10.000 liters of blood. Due to this high energy requirement, the heart is the body organ richest in L-carnitine. It requires L-carnitine to obtain 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: increase in 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.
    • Heart attack profile and follow-up treatment (acute): L-carnitine can reduce the size of the necrotic area on the heart in the event of a heart attack and thus reduce the severity of a heart attack and increase the chances of survival (cf. Spagnoli, Lancet 1982).
  • Influence on 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, neuroprotective effect and could therefore be used for the 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 (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 the toxic metabolites for excretion via the kidneys

  • Diabetes mellitus: L-carnitine is able to lower LDL cholesterol levels and the triglyceride concentration 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 helps prevent or can help 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 need for their enormous metabolic performance. 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, can be found in various brain regions (v.a in the cerebral cortex, hippocampus and hypothalamus) and others.a important for memory, thinking and movement. 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 doses have increased the amount of ejaculate and ensured that the 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 because the process of implantation of fertilized eggs in the uterus is membrane and energy dependent. L-carnitine increased the fertilization rate in sows and reduced the rate of natural abortions.

  • L-carnitine in pregnancy and infants:
    • Pregnancy always produces a secondary L-carnitine deficiency. Already from the 12th. During the week of pregnancy, 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, an adequate 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 therefore rely on breast milk as a source of L-carnitine. Shortly after birth, significant weight loss often occurs, especially in premature babies, which can be reduced by giving L-carnitine to pregnant and breastfeeding mothers (cf. Strack 1960). The addition of L-carnitine in baby food such as:b Follow-on milk is regulated by law, according to which infant formula must contain at least 1.8 µmol/100 kJ of L-carnitine (cf. Directive 91/321/EEC).

 

Possible indications for carnitine supplementation

  • Aging (lower endogenous carnitine synthesis)
  • Low carnitine intake with food (vegetarian, vegan diet)
  • Chronic fatigue (including cancer, multiple sclerosis, celiac disease, older 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 disorders
  • Fibromyalgia
  • Tumor cachexia
  • Hyperthyroidism
  • Sport (improvement of endurance)
  • COPD (to improve exercise capacity)
  • Hepatic encephalopathy, liver cirrhosis
  • Nonalcoholic fatty liver disease and steatohepatitis
  • Kidney failure/kidney dialysis
  • HIV infection
  • Vascular dementia, Alzheimer's disease (in the early stages)
  • 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 the case of hyperthyroidism (hyperthyroidism, Graves' disease, Hashimoto's hyperthyroidism, etc.), (Acetyl)-L-carnitine can be used.
  • Bipolar disorder (individual cases of mania or psychosis have been described following supplementation with acetyl-L-carnitine).

 

Sources:

 

 

 

L-Arginine Base

 

  • L-Arginine is a semi-essential amino acid - i.e.H 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 formed in the cells of the vessel walls from L-arginine (with the help of the enzyme NO synthase) . NO has a vasodilating effect and therefore lowers blood pressure.
    • In a study with pregnant women at high risk of gestational hypertension, the preventive use of arginine together with antioxidant vitamins reduced the likelihood of hypertension, for example. significantly reduced.

    • L-arginine is therefore often used for the accompanying treatment of diseases with vascular narrowing, such as: Arteriosclerosis or Sudden hearing loss. In addition, NO, as a messenger substance in the brain, is responsible for memory function.

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

    • CAVE: in diseases that lead to severe chronic inflammation, arginine should not be supplemented, as the inflammation will cause i.dR 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 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 growth. The body also needs arginine to produce creatine for muscle regeneration. In bodybuilding it is used as a so-called “pump supplement”. The expansion of the veins in the active muscle is intended to promote strength development on the one hand and, on the other hand, the regeneration of the muscle after strain.
    • In a study from the University of Exeter (UE), scientists found that L-arginine can increase athletic performance by 20% and improve racing 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 caused by arginine administration, because sugar and fats are produced in the “power plants” of our cells burned. The animals had a lower fat content and lower fat levels in their blood.
    • In women after menopause, arginine was able to reduce the decrease in muscle strength. A trial in Duchenne muscular dystrophy also shows improved preservation of muscle tissue. For this reason, use on bedridden patients or astronauts is also being discussed.

  • Strengthening immune system: The macrophages produce NO to kill bacteria. In addition, arginine is required for cell division and maturation of white blood cells. Arginine thereby improves acquired and innate immunity.

  • Promoting wound healing
    • Arginine provides the base material for the production of collagen and thus ensures mechanical reinforcement of the wound area.
    • Healing of leg ulcers was achieved in a small group of diabetics with a subcutaneous injection of arginine, presumably a combined effect of blood flow, cell division and collagen production. In the case of planned operations, the administration of arginine could accelerate the healing process.

  • Arginine regulates insulin secretion and is therefore often used in diabetes treatment: Diabetes is often associated with reduced blood levels of arginine. Intravenous administration of arginine resulted in improved blood flow and sensitivity to insulin. In addition, the oxidative stress in the blood, which is increased in diabetics, was alleviated by arginine. In animal experiments, not only the glucose level in the blood fell, but also the levels of homocysteine ​​and blood fats.

  • Erectile dysfunction and fertility
    • Since NO is formed from L-arginine in the men's erectile tissue, which in turn ensures better blood circulation, regular intake of L-arginine could lead to an increased erection. While arginine supplies 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 women and men 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 miscarriage rates and promoted embryo growth and development. This is probably due to the better blood flow to the placenta. Comprehensive studies on humans are still missing.

  • Ammonia detoxification: Arginine ensures the detoxification of ammonia as urea in the urine
  • In studies, arginine had balancing effects on anxiety disorders, particularly in combination with the amino acids lysine and magnesium . A study found reduced levels 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 “starting amino acid” for all (!) proteins, i.e.H All other amino acids are attached to methionine.

  • L-Methionine is the precursor anda of homocysteine, cysteine, taurine, choline and S-adenosyl-methionine (SAM). SAM in particular is involved in many metabolic processes, including:a in growth processes, the health of liver cells 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 enters the brain across the blood-brain barrier. 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 to remove heavy metals

  • Methionine has a urine acidifying effect:
    • To maintain muscle, the body needs approx. 0.5 g/day methionine. If you consume more than 1.5 g/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 and it becomes acidic.
    • This effect is exploited in the treatment of urinary tract diseases, in which an acidic pH value in the urine inhibits the attachment of bacteria to the urothelial cells and inhibits bacterial growth.
    • In addition, methionine inhibits 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 effect

  • Lowers histamine levels

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

  • Methionine helps produce the powerful antioxidant glutathione

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

 

The daily requirement for methionine
The daily requirement for methionine for adults is approximately 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 the case of liver inflammation (due to medication or alcohol abuse)


Possible signs of methionine deficiency

A lack of methionine can cause metabolic disorders. To do this you can:a include:

  • Hepatic steatosis
  • Skin and hair growth disorders
  • Increased tiredness or Lethargy
  • Depressive moods

Who is at risk of methionine deficiency?

  • Infants and young children
  • Old people
  • Competitive athlete
  • People under stress
  • Vegans (with the exception of nuts and seeds, many plant-based foods tend to be low in methionine)

 

 

 

L-Lysine

 

  • L-lysine is one of the essential amino acids - i.e.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 therefore relevant for firm skin and firm connective tissue. Since cartilage, ligaments, tendons, joints and fascia are also made of collagen, lysine or Collagen is also highly relevant for athletes.

  • Collagen and ergo lysine also influence wound healing and healing of bone fractures. Animal 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 the 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, as carnitine, as a carrier for fatty acids into the mitochondria, plays a central role in cellular energy production.
    • Since sperm and immune cells contain the most carnitine, a carnitine or Lysine deficiency also has a negative impact on fertility and immune system.

  • L-lysine has a antiviral effect and is therefore used, for example. commonly used for herpes infections. Lysine is thought to block arginine, which the herpes viruses need to multiply. For example, one study foundfound that taking 1 g of lysine daily resulted in fewer blisters forming in 26 people prone to recurrent herpes cold sores.

  • L-lysine increases intestinal calcium absorption and is therefore often used for osteoporosis. A study with 30 women (15 of them 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:
    • In a week-long study of 50 healthy people, taking 2.64 grams of lysine and L-arginine was found to reduce stress-related anxiety and levels of the stress hormone cortisol.
    • Similarly, adding 4.2 grams of lysine per kilogram of wheat flour in disadvantaged villages in Syria helped reduce the anxiety levels of men with very high levels of stress: After three months, consuming the flour enriched with the active ingredient lysine also helped, reduce cortisol levels in women.

 

For whom could supplementation generally be useful?

  • The WHO recommends a daily intake of 20-28 mg 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 often indicated for vegans.
  • Since L-lysine promotes bone growth and cell division, it is particularly important.a Adequate care is important during pregnancy and breastfeeding.
  • Since cartilage, ligaments, tendons, joints and fascia are made of collagen, which is formed from lysine, lysine is also highly relevant for athletes.

 

 

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 basics, prevention, therapy. Scientific Publishing Company mbH Stuttgart 2004
  • Hahn, A.; nutritional 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 the nerve cells no longer works properly and mood swings, sleep disorders or depressive moods can result. Unfortunately, serotonin cannot simply be taken, but can only be increased through additional L-tryptophan. (Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908021/)
  • Precursor to the hormone melatonin (the “sleep hormone”), which regulates the sensation of pain and sleep rhythms. Melatonin is produced and released more in the dark and less in the light. This happens in the pineal gland in our brain. Pathological sleep disorders are usually based on 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 lengthening 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. A low tryptophan level can lead to reduced memory performance and affect other cognitive functions. A study at the University of Bordeaux found that tryptophan improved memory in both healthy adults and adults with memory deficiencies: If there is too little tryptophan in the brain, there is a lack of neurotransmitters in the brain and the transmission of stimuli of information no longer works 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)

  • L-tryptophan can be used to produce vitamin B3 in the body

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