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L-carnosine and its therapeutic uses

from Patrick Linder

What exactly is carnosine?

Carnosine, also known as beta-alanyl-L-histidine, is synthesized in the body from L-histidine and beta-alanine and is therefore referred to as a dipeptide (chemical compound of two amino acid residues).

Since carnosine plays a central role in protecting the human brain, it is often referred to as Neuropeptid and is increasingly used for diseases such as Parkinson's and Alzheimer's, but also autism.

The component beta-alanine is a non-essential amino acid that not only participates in carnosine synthesis in the body, but also plays an important role in glucose metabolism and energy production. Beta-alanine also serves as a building block for proteins.

Carnosine occurs naturally in healthy muscles, the heart, brain, liver, kidneys, and other tissues. Muscle contains approximately 20 μmol/g dry weight.

It can only be absorbed through animal food. Pork, for example, contains approximately 250-350 mg/100g. Red meat, poultry, and mackerel contain i.d.R. between 70 and 200 mg L-carnosine per 100 grams. The more carnosine meat contains, the longer its shelf life, as carnosine, as a powerful antioxidant, prevents it from becoming rancid.

Its concentration decreases with advancing age.

High doses of carnosine are necessary for a therapeutic effect because the body naturally breaks down carnosine through the enzyme carnosinase. The bioavailability of pure L-carnosine from dietary supplements is >= 70% when taken orally.

Most absorption occurs in the small intestine. Carnosine is transported from the blood to the muscles, brain, and other tissues. Human plasma does not contain measurable amounts of carnosine, so a possible deficiency cannot be detected by a blood test.

Possible risk groups for deficiency

A carnosine deficiency can be the result of an alanine deficiency. A beta-alanine deficiency occurs u.a. occurs in a very one-sided and protein-poor diet. Vegetarians and vegans are most at risk, as carnosine and alanine are not found in plant-based foods.

Since carnosine acts as an antioxidant and also compensates for a deficiency of other antioxidants such as vitamin E, a deficiency is more frequently observed in cases of chronic stress, autoimmune diseases, heavy metal pollution, etc.

What are the effects of L-carnosine?

    • Carnosine works synergistically with other antioxidants such as vitamins E and C, zinc, selenium, etc., reducing their consumption. For example, people with mild vitamin E deficiency (a large portion of the population suffers from vitamin E deficiency, as demonstrated by worldwide epidemiological studies) consume more carnosine than normal.
    • Many antioxidants, such as vitamins C and E, aim to prevent free radicals from penetrating tissue, but have no effect once this initial protective layer has been breached. Carnosine is not only effective in prevention, but also actively acts after free radicals have reacted to form other dangerous compounds such as lipid peroxides and secondary products.
    • For example, a highly reactive lipid peroxidation end product, malondialdehyde (MDA), is blocked by carnosine. MDA can damage lipids, enzymes, and DNA and plays a role in atherosclerosis, joint inflammation, cataracts, and general aging.
    • By interacting with aldehydic lipid oxidation products, carnosine protects our tissues from oxidation, as aldehydes can form adducts with DNA, proteins, enzymes and lipoproteins, leading to harmful changes in their biological activity (cf. Burcham et al. 2002).
  • sport
    • Carnosine can balance the acid-base ratio in muscle cells and thus delay muscle fatigue [cf. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257613/During intense physical activity, lactic acid and other metabolic products can accumulate, leading to a decrease in levels and accelerating muscle fatigue. Carnosine can regulate the acid-base balance in muscles and thus delay fatigue, which can lead to improved performance during training or competition.
    • Carnosine may also aid in post-workout recovery as it acts as an antioxidant, helping to reduce oxidative stress and support the regeneration of muscle tissue [cf. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300828/].
    • In sports and bodybuilding, carnosine is also involved in the detoxification process of reactive aldehydes from lipid peroxidation, which are produced in skeletal muscles during physical exertion. Therefore, carnosine protects skeletal muscles from injury.
    • Carnosine has been administered to Russian athletes and swimmers for years and provides remarkable benefits in the areas of energy and endurance. As early as 1953, the Russian scientist S.ESeverin found that carnosine effectively buffers lactic acid produced by working muscles, and that taking carnosine increased muscle contractility and endurance. When carnosine is depleted, lactic acid accumulates in the muscles, the pH drops, and the muscles become fatigued. When carnosine is added, the muscles recover almost immediately and contract as if they had never been fatigued. This is known as the 'Severin Phenomenon.'
  • Longevity/Anti-Aging
    • There is some research suggesting that L-carnosine may have anti-aging properties beyond its antioxidant cell-protective abilities. It is thought to play a role in Regulation of telomere length plays [cf. https://pubmed.ncbi.nlm.nih.gov/15474517/Telomeres are the protective ends of DNA strands in chromosomes and shorten with each cell division. A longer telomere is associated with a longer cell lifespan.
    • Extending the lifespan of cells by preventing glycation
      • One of the most important effects of carnosine is its anti-glycation effect (see Aldini et al. 2002a, 2002b and Yeargans and Seidler 2003). Glycation refers to the binding of a protein to a glucose molecule, which alters the protein structure and reduces its biological activity. The result is so-called "advanced glycation end products" (AGEs), which are recognized as a major factor in the aging process.
      • Once AGEs are formed, they interact with neighboring proteins to form pathological cross-links that harden the tissue. Diabetics produce excessive amounts of AGEs earlier than non-diabetics, which, for example, can lead to the arteries of diabetics becoming i.d.R. are hardened.
      • Another consequence of AGEs is a 50-fold increase in the formation of free radicals, which v.a. arteries, the lens and the retina of the eyes, the peripheral nerves and the kidneys attack. Cataract can therefore also form due to glycation.
      • Carnosine counteracts glycation and may also play a role in the removal of glycated proteinBy combining carnosine with denatured molecules (“carnosinylation”), AGEs are marked for cellular removal.
    • Preventing the carbonylation of proteins
      • As we age, proteins tend to undergo destructive changes due to oxidation, glycation, and carbonylation. During carbonylation, carbonyl groups attach to protein molecules, causing them to split during proteolysis.
      • This protein denaturation and protein breakdown is not only heavily involved in the aging process, but also in well-known signs such as skin aging, cataracts and nerve degeneration (d.h. memory loss and dementia).
      • Carnosine reacts with the carbonyl group to form an inactive protein-carbonyl-carnosine adduct, thereby protecting the proteins and reversing denaturation.
  • Brain/neuroprotective effects
    • There is also some evidence that carnosine may have a positive effect on brain health. It is believed that the substance has neuroprotective properties and may protect against neurodegenerative diseases such as Alzheimer's and Parkinson's [see]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627134/ and https://pubmed.ncbi.nlm.nih.gov/17522447/].
    • Chelation of copper and zinc (cf. Miller and O'Dowd 2000, Chez 2003): Copper and zinc are released during normal synaptic activity. However, in slightly acidic environments, which are characteristic of Alzheimer's disease, they are reduced to their ionic forms and thus toxic to the nervous system. Carnosine naturally protects against copper-zinc toxicity in the brain by chelating the two metals. Copper-zinc chelators dissolve the drusen of Alzheimer's disease. Carnosine also prevents the cross-linking of amyloid beta in Alzheimer's disease drusen.
    • Carbonylation of phospholipids is harmful v.a. the central and peripheral nervous system and leads to memory problems and other cognitive impairments. Because carnosine counteracts the carbonylation of phospholipids, it is considered an important neuroprotector.
  • Detoxification of heavy metals
    • Carnosine plays a role in the body’s detoxification phase II, d.h. in the chelation of heavy metals (cf. Miller and O'Dowd 2000, Chez 2003). After the metals have been rendered reactive in Phase I, chelation in Phase II allows the body to excrete them via the kidneys.
    • Carnosine has the ability to chelate pro-oxidant metals such as copper, zinc and toxic heavy metals (lead, mercury, cadmium, nickel).
    • Organic mercury is included in most vaccines as an antimicrobial preservative. Carnosine can chelate organic mercury (thiomersal or thimerosal).
  • autism: A double-blind study from the USA in 2002 demonstrated significant effects of carnosine on autistic children (see https://pubmed.ncbi.nlm.nih.gov/12585724/): Thirty-one children with autism spectrum disorders were studied in an 8-week double-blind placebo study to determine whether 800 mg of L-carnosine daily compared to placebo would result in observable changes based on the Gilliam Autism Rating Scale. After 8 weeks of L-carnosine, the children showed statistically significant improvements; children receiving placebo showed no statistically significant changes. Although the mechanism of action of L-carnosine is not yet well understood, it may improve neurological function, possibly in the enterorhinal or temporal cortex.

  • Gastric mucosa/stomach ulcersSeveral recent studies show that a combination of zinc and carnosine can protect the gastric mucosa from various irritants and is effective as an antiulcer agent (Odashima et al. 2002). For example, carnosine reduces platelet clotting in patients with abnormal clotting tendencies and increases clotting in patients with reduced blood clotting.

  • Hemolytic anemia: Carnosine has protective effects on blood cell membranes, prolonging their survival, as well as cell membrane stabilizing effects, thereby protecting against chemically induced hemolytic anemia.

Side effects

Since carnosine is a natural compound that occurs in the body, it is i.d.R. very well tolerated and has a low risk of side effects.

Very high doses can cause mild gastrointestinal discomfort such as nausea, abdominal pain or diarrhea.

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