Peptides

Definition of Peptides

Peptides are structural components (fragments) of proteins that form at various stages of protein metabolism when they enter the body exogenously. They are also a result of biochemical transformations of amino acids, as well as through targeted creation of bioactive substances during production. These consist of a sequence of amino acids connected by peptide bonds.

Unlike proteins and individual amino acids, which are highly valued in sports and sports medicine, particularly in Non-Medicinal Practices (NMP), the study of peptides and their potential in athletes’ NMP is just beginning. It’s important to clarify that this review does not cover medium or large peptides that interfere with hormonal exchange, are administered by injection, and essentially represent a method prohibited by WADA for increasing levels of androgens or growth hormones in athletes to enhance muscle mass and strength. While the use of large peptides (fragments of growth hormone) in clinical medicine is permissible with a proven safety and efficacy base, corresponding certification, and registration, in modern sports, it’s an illegal method banned by WADA, and its promotion could lead to undesirable consequences.

According to international definitions, a bioactive peptide is a protein fragment that, besides its nutritive properties, possesses specific biological functions (López-Barrios L. et al., 2014). The list of these functions is extensive, typically related to the course of individual diseases and pathological states. In recent years, certain peptides have been found to be effective in sports applications (details below). The general term for short peptides with specific biological properties is “regulatory peptides.” In sports nutrition, they are considered part of the group of pharmacological nutrients (Dmitriev A.V., Kalinchev A.A., 2017).

Peptide pharmacology is an independent field within experimental and clinical pharmacology that has been evolving for several decades. The latest findings in the science of peptides are regularly published in the “Journal of Peptide Science,” established and issued by the European Peptide Society. Theoretical and practical aspects of peptide use in sports are published in specialized journals on sports nutrition.

The significance and potential of peptide directions in clinical and sports nutrition are underscored by the collaboration plans developed since 2018 between the Swiss food and beverage giant Nestlé and the Irish company Nuritas. This partnership aims to create a network of bioactive peptides for various essential target areas. The collaboration is based on Nuritas’ innovative technologies, which use DNA analysis and artificial intelligence to predict, construct, and validate the chemical structures of peptides with designated properties from food sources. Nestlé’s scientific and marketing structures will subsequently finance research into the most promising molecules and promote them as finished products in the most prospective areas, primarily in the food industry and healthcare.

Sources of Regulatory Peptides in the Body

The primary source of peptides in the body is the enzymatic breakdown of proteins as they pass through the gastrointestinal tract, starting from the stomach and ending in the colon. Special additional forms used as dietary supplements include protein hydrolysates of various origins; individual peptide fractions with varying molecular weights; and complexes of peptides with other nutrients and pharmacological nutrients.

In the gastrointestinal tract, peptides of different molecular masses are formed under the influence of stomach hydrochloric acid (acid hydrolysis), enzymes in the gastric juice, the pancreas (enzymatic hydrolysis), enzymes of the microbiome in different sections of the intestine (bacterial enzymatic hydrolysis), and some other bioactive substances. Some peptides are formed directly in the body as a result of metabolic processes.

Clinical-Pharmacological Classification of Short Peptides

The classification of so-called “short” peptides used in clinical and sports medicine is based on the physicochemical profile of the peptide, the number and characteristics of amino acids in the chain, and the predominant direction of metabolic action. While some compounds are already actively used in practice and have varying levels of evidence (from highest ‘A’ to lowest ‘D’), others are considered promising due to theoretical premises and/or experimental positive results. However, this publication deems it necessary to include all available options in the classification, given the rapid development of sports nutrition as a science and part of clinical nutrition, as well as the growing interest of practicing doctors and trainers in new natural pharmacology methods. This only considers one method of introducing short peptides into the body – oral (enteral), completely excluding injection forms in accordance with the requirements of the WADA-2018 Prohibited List.

Protein hydrolysates are a combination of short, medium, and long peptides and free amino acids that combine nutritive and regulatory functions.

Peptide thymomimetics (thymalin, thymogen, vilon) are complexes of short peptides with a molecular weight ranging from 600 to 6000 Da, primarily exerting immunostimulating, anti-inflammatory, and regenerative effects.

Short ACE inhibitor peptides (angiotensin-converting enzyme) are components of dairy protein hydrolysate, such as tripeptides (valine-proline-proline – VPP, etc.), and a range of other short peptides of animal and plant origin capable of blocking ACE activity and inhibiting the conversion of angiotensin-1 to angiotensin-2, stabilizing blood pressure and other cardiovascular system indicators (Kawaguchi K. et al., 2012).

L-glutamine peptides:

• Dipeptides of L-glutamine (L-alanyl-L-glutamine, glycyl-L-glutamine) predominantly influence the integrative function of the intestine (local immunity, nutrient absorption, intestinal barrier) and muscle tissue anabolism.
• Tri- and tetrapeptides, whose structural component is the L-alanyl-L-glutamine bond (e.g., the peptide line IPH-AGAA), primarily affect skeletal muscle functions.

Dipeptides of tyrosine, cysteine, glycine (glycyl-L-tyrosine, L-alanyl-L-tyrosine, L-alanyl-L-cysteine) stabilize cellular membranes and are part of many dipeptides alongside L-glutamine (Furst P., 2000).

Glutathione and Its Analogs Glutathione, a tripeptide of γ-glutamyl-cysteinyl-glycine, is one of the most widespread intracellular peptides known for its polymodal action, participating in amino acid transport across cell membranes and in various oxidative-reductive and other cellular processes. It is one of the most commonly used peptides in sports nutrition products, despite conflicting data on its effectiveness when introduced exogenously.

Antimicrobial Peptides (AMPs) These peptides, produced by the cells of macroorganisms and the microbiome, exhibit antibacterial action (Mahlapuu M. et al., 2016). Synthesized in all living organisms either in ribosomes or outside of them, they are mainly used topically in dermatology and cosmetology due to their low stability, which also aligns with the goals of sports medicine to some extent.

Neurogenic Dipeptides The effectiveness of these peptides when ingested is determined by their ability not only to penetrate the intestinal barrier using the PEPT1 transport system but also to cross the blood-brain barrier (BBB) using the PEPT2 transport system. In Russia, neurogenic peptides include medications like Dilept and Noopept, which contain dipeptides L-prolyl-L-tyrosine and L-prolyl-L-glycine, providing the compounds with psychotropic properties (Seredenin S.B. et al., 2010; Gudasheva T.A., 2011).

Protein-Peptide Complexes In these complexes, short peptides act as catalysts for the absorption of proteins broken down into peptides and amino acids in the stomach and intestines after ingestion (synergism with the action of proteolytic enzymes) and their utilization by tissues (IPH-AGAA and SNL lines – complexes of di- and tetrapeptides).

Chelated Amino Acid Compounds These are special structural formulas of amino acids with metal ions in the form of chelates, capable of exerting the same effects as the amino acids themselves but in significantly smaller doses. They also help prevent and reduce manifestations of mineral and trace element deficiencies in the body. For example, chelated compounds of magnesium, iron, manganese, copper, etc., belong to this group. In chelated amino acid compounds, the metal cation acts as a bridge connecting the amino acids. Despite the lack of a specific peptide bond between the amino acids, they, with their specific features, function as a single complex. In this sense, chelated amino acid compounds can be included in the general classification of short peptides, which also represent a unified whole in terms of transport through the intestinal wall after ingestion and in the process of metabolism in the body’s organs and tissues.