by Wald M, M.D.1, Honzíková M, M.D.2, Lysíková M, M.D., Ph.D.2, Masinovský Z, Ph.D.2 1Department of Surgery, 2nd Medical Faculty, Charles University, Prague, Czech Republic 2Department of Enzyme Therapy, Society of General Medicine, J.E. Purkyne Czech Medical Association, Prague, Czech Republic
  
Introduction
A large number of conditions are primarily inflammatory in nature and may be significantly complicated by the presence of secondary forms of inflammation. Regardless of whether the cause of the problem is due to bacterial, viral or auto-immune influences, the result may be an ongoing situation with significant clinical and laboratory manifestations of the inflammatory process.   
Dietary supplements designed to provide Systemic Enzyme Support (SES) can play an important role in helping to maintain normal inflammatory processes within the body and thereby help support and speed healing. This is not only beneficial for the patient, but for healthcare in general as ultimately it may help to reduce the costs associated with maintaining health.
Most healthcare professionals select treatments based on what they believe will be effective over a long period of time as well as what will bring a specific patient the fewest risks in connection with treatment. One of the major benefits of using systemic enzyme support is the relatively small amount of undesirable effects combined with good tolerance and efficacy.
Systemic enzyme support was for a long time regarded as a purely empirical treatment method. Due to the rapid development of immunology, biochemistry and molecular biology in the last few decades, systemic enzyme support has undergone significant development, as it has been shown that behind the empirically supported clinical results are a complex set of regulatory processes, which previously were unknown. Today, scientists have a better understanding with respect to the mechanisms by which Systemic Enzyme Support may be exerting it’s desired effects. Specifically, the effect of proteolytic enzymes (proteases) on the cytokine network and their action at the level of the cell membrane both in terms of cellular adhesion as well as modulation of cellular receptors has been described. One of the main pioneers in the clinical use of the systemic proteases was Professor Max Wolf, who worked in New York in the 1930s not only as a sought-after physician but also as a researcher at Fordham University. At the present time, with regard to the historically best known pharmacological and clinical effects, proteases are placed in the international ATC classification in the M09AB group – anti-inflammatory enzymes.
Systemic Enzyme Support – definition
Hydrolytic enzymes have been used widely for decades and a range of scientific publications have recently demonstrated their importance in supporting numerous areas of health. At the present time proteases are indicated for parenteral application in malfunctions of blood coagulation (urokinase), to affect fibrotic processes (hyaluronidase) or in treatment of malignant hemotological conditions (asparaginase). The aim of oral application of enzymes may be either substitution of digestive enzymes in external secretory insufficiency of the pancreas (see accompanying article: “The Importance of Good Digestion“) or use of their systemic effects (proteases). So, Systemic Enzyme Support can be defined as a modality which uses oral administration of exogenous hydrolytic (mainly proteolytic) enzymes of animal origin (trypsin, chymotrypsin) and plant origin (bromelain, papain) in the form of enteric-coated tablets for supporting healthy and normal inflammatory processes in the body. As a result, systemic enzyme support can help maintain a healthy immune system, healthy blood flow and circulation, healthy joint function, as well as help to reduce muscles pain after exercising. Systemic enzymes can exert a positive effect on rheological properties of blood as a result of their fibrinolytic properties. Data have also shown that administering systemic enzymes together with certain antibiotics is able to improve the tissue availability of the antibiotics.
Proteases

The main component of products designed for systemic enzyme support are proteolytic (i.e. protein splitting) enzymes of animal or plant origin. These are endopeptidases which hydrolyze peptide bonds in certain protein (peptide) chain locations on the basis of a more or less specific affinity to particular amino acid elements of these chains.
Trypsin is a pancreatic endopeptidase, which splits peptide bonds formed by the carboxylic group of the amino acids such as lysine or arginine. It is obtained from the pancreas of pigs by repeated refining and subsequent activation of the proenzyme trypsinogen.
Chymotrypsin is a pancreatic endopeptidase, which hydro-lytically splits peptide bonds formed by carboxylic groups of the amino acids tyrosine, phenylalanine and tryptophan. Chymotrypsin is obtained by extraction and chromatographic purification from the pancreas of cattle and subsequent activation of the proenzyme chymotrypsinogen.
Bromelain is an endopeptidase obtained from pineapples. Bromelain hydrolytically splits peptide bonds formed by the amino acids lysine, alanine, tyrosine and glycine. Bromelain is a family of individual macromolecules and is not a single enzyme.
Papain is a mixture of proteolytic enzymes separated from the fruit of the tropical Carica papaya, which is a member of the melon family. Papain splits polypeptides, particularly between the bonds of arginine, phenylalanine and lysine.
These proteases are typically combined in preparations for oral administration. The reason for these combinations is an assumption that the effects of individual enzymes will complement each other resulting in the multiplication of the final therapeutic efficacy. Another reason for these combinations is the assumption of an increase in the resorption of individual proteases by the intestinal mucous membrane when administered together with other proteases.
Most of the combined systemic enzyme support preparations currently used usually contains rutin (rutoside) in addition to two or more proteases. Rutin belongs to the group of bioflavonoids and can help to reduce the permeability of veins and capillaries.

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