SERRATIOPEPTIDASE: An agent of inflammation control and pain management

By M. Mamadou, PhD, 2013

Serratiopeptidase is a proteolytic enzyme produced by bacteria of the Serratia species. Several strains have been shown to produce serratiopeptidase (Miyata, K., et al., 1970; Miyata, K., et al., 1971; McQuade and Crewther, 1969; Lyerly and Kreger, 1981; Aiyappa and Harris, 1976; Decedue, C., et al., 1979).

These bacteria are found in the intestine of the silkworm. The role of this enzyme in the silkworm is to help breakdown (hydrolyze) the cocoon so the moth can ultimately get out. The cocoon is basically made up of the silk protein.

Since its discovery, serratiopeptidase has been the focus of many studies dealing with its biochemical characteristics, its health benefits in the human body and effective and safe methods to produce it in controlled environments.

Today, the enzyme is produced according to specifications compatible with human consumption as a dietary supplement and as directed by various regulations of safety and GMP (good manufacturing practices).

As any enzyme used as a dietary supplement, serrapeptidase is completely purified from any other molecules. Only the purified molecule under its active molecular form is used.

The enzyme serratiopeptidase is also called by other names including serralysin, serrapeptidase, Serratia E-15, and serrapeptase. There are several variants or isoforms of this enzyme isolated from various strains of Serratia.

For instance, Matsumoto et al., (1984) have characterized four different proteases from Serratia marcescens. These four proteases were different in many biochemical characteristics. One of the proteases has an optimum activity at pH 5, whereas the other proteases, in the same culture, identified by the same authors have a wider range of optimal pH from 5 to 9. In terms of dietary supplementation, all these proteases, whether used singly or as a blend in a formulation, could provide benefits.

These variations in pH optima may explain why some serrapeptidase enzymes require enteric coating to survive the stomach acid, whereas others do not appear to be considerably affected by the acid. For instance, an enzyme with optimum pH activity of 5 may well be able to sustain a relatively lower pH before the acid content in the stomach acid gets higher resulting in much lower pH.

Another specific property of serratiopeptidase in its ability to impart systemic benefits is the fact that it could be absorbed in the blood circulation when taken orally (Moriya et al., 1994; Miyata, K., 1980; Miyaka et al., 1981). Some of these studies indicated that the enzyme is absorbed and “escorted” by alpha 2- macroglobulin. This binding to alpha 2- macroglobulin in the blood circulation explains why the enzyme does not elicit allergic or other forms of immune reactions when taken.

The dietary supplement application of serratiopeptidase is based on its proteolytic effect on fibrin as blood clot controlling agent as well as its action on damaged and denatured proteins and cell debris. As early as 1967, Yamasaki et al., have shown that serratiopeptidase has the ability to control inflammation. Further studies since then have proven the relevant and beneficial application of using serratiopeptidase in many health challenge conditions.

In order to understand the critical role and benefits of serratiopeptidase and various other proteolytic enzymes, it is important to review the biological fundamentals of any health challenge.

As a result of the impact of any injurious agent (physical trauma, microbial infection, excess or insufficient metabolite, temperature or pH changes, cancer- inducing agents, excess blood sugar, etc.), the body first action is to mount a set of defensive reactions. These reactions are collectively called inflammation. More specifically, inflammation is defined as an early response by the body to control the effect of an injurious agent and to further neutralize its effect on the body, and ultimately restore homeostasis.

The initial signs of any injury-induced inflammatory response are:

- redness: due to increased blood flow in the area impacted

- swelling: due to increased vascular permeability to allow inflammatory mediator molecules and cells to move from the blood into the adjacent area that is injured: this is an initial defense mechanism

- heat: due to increased temperature to enhance the rates of the various biochemical reactions including enzyme reactions.

- pain: due to the increased physical and chemical stimuli from the three factors above. More specifically, as a result of the swelling, there is increased pressure on the sensory nerve endings resulting in pain sensation.

It should be noted that pain is a “warning” mechanism to indicate disturbance in homeostasis. If there is pain, there is inflammation. However, there can be inflammation without pain sometimes. The lack of pain could be due to higher pain threshold or the area injured may not have sensory nerve endings in close proximity.

Another point to consider in pain sensation is that sometimes, where the pain is felt may not be where the inflammation is occurring. Irrespective of any of these situations, the inflammation must be controlled and modulated.

Additionally, as part of the inflammatory responses, there are molecules such as histamine, substance P, prostaglandins, various cytokines, etc. that play critical role in the pain sensation.

For instance there are inflammatory cytokines that promote inflammation. When they are not modulated and controlled, they perpetuate the inflammatory process. This is an important area in enzyme therapy as many studies have shown that orally administered proteolytic enzymes can specifically control these inflammatory cytokines and prevent further damage and the onset of chronic inflammation, “the silent killer” (LaMarre, et al., 1991; Heumann and Vischer, 1988; Hale and Haynes, 1992; Gebauer, et al., 1997; Desser et al., 1990; 1994; 1993; 1997).

The process of inflammation can be acute and resolved within few days or can be chronic and leading to further degenerative diseases. In the case of chronic inflammation, the body is in continuous response mode and hardly or inefficiently in a resolution, healing, or remediation mode. Consequently, the body’s resources are exhausted and opportunistic injurious agents from the outside or the inside of the body overwhelm homeostasis.

Furthermore, it is important to note that biologically, inflammation occurs all the time in the body. More specifically, in biological terms, it happens every time homeostasis is disturbed in any part of the body. Inflammation serves to alarm the body of the presence of an “injury” and through the normal and speedy response the injurious agent and its effects are removed.

Often, people talk about anti-inflammation or preventing inflammation. In fact, the proper terms should be controlling or modulating inflammation.

Inflammation is a normal process that should occur to let the body know that injury has or is occurring and needs to be taken care of. When inflammation process is completely negated, eliminated or prevented, the body’s defense mechanism may not be aware of any damage early enough to take care of it. Thus, inflammation is a normal process that must occur but it needs to be controlled and modulated!

Inflammation is not just a rash on the skin, a puncture on the body, a torn muscle, or a broken bone. It is resulting from anything that disturbs homeostasis in the body. Its response factors such as redness, swelling, heat/fever, or pain may vary in intensity and duration from case to case based on the injurious agent, the location of the injury, or other factors.

For instance, some of the additional factors that could impair inflammatory response and thus leading to poor health management response within the body include developmental issues, chronic stress, poor nutrients supply to the body, environmental pollutants, poor lifestyle habits, and many others. Normal inflammation response is the common denominator of any health challenge.

Most people are lacking a fine tuned inflammatory response system because of the factors listed above. Thus, it is very important to control inflammation so that it does not become chronic. Chronic inflammation is a “silent killer” and must be avoided! One group of biological agents that has been shown to help control inflammation is the proteolytic enzymes used as dietary supplements.

As described above, inflammation has 4 key bio-physical and chemical components. These components are processes working together to help alarm for structure/function impairment within the body and also to help the body in remedying the damage.

Because the inflammation process triggers a remediation process in the body, it should not be stopped and/or overwhelmed as in chronic inflammation. It should be controlled! That is what supplemental proteolytic enzymes do: they help control and modulate inflammation in order to enhance the healing process.

It could be noted that irrespective of the causes of the inflammation, the resulting biological conditions are:

- poor blood flow due to blood clots (fibrin), platelet aggregates

- accumulation of cell debris resulting for the damaged tissues, dead white blood cells, and other cells.

- edema resulting from the fluid and proteins moving from within the blood vessels into the tissues, and

- damaged tissues within the area affected and/or adjacent.

All the above conditions contain denatured/damaged proteins that need to be removed to re-establish a normal microenvironment for healing to take place. Furthermore by removing the dead tissues and proteins and improving the blood circulation, the area could be properly re- supplied with healing molecules and nutrients.

Although the body has natural proteases to deal with such aspect of “cleaning” inflammation sites, there are many factors overtime that reduce the body’s ability to properly and timely perform the functions.

Two key factors worth mentioning here are poor diet and stress. Without adequate nutrients, the body cannot make the necessary molecules needed to help the healing process, and the risks of chronic inflammations are increased.

The other factor is stress. Cortisol which is the main stress molecule in the body stops the healing process and promotes chronic inflammation. Cortisol does so by inhibiting the production of most immune molecules as well as molecules needed to heal. It is one of the main reasons why people under chronic stress, thus high cortisol, are very susceptible to diseases and take much longer time to heal from any health challenges.

In today’s society, poor eating habits and living stress conditions are widespread: these facts undermine proper inflammation response and timely healing without adequate assistance.

As mentioned above, no matter what the cause of the inflammation, there are damaged protein molecules that need to be removed and blood flow restored adequately.

The beneficial role of serratiopeptidase and supplemental proteolytic enzymes in controlling inflammation and promoting timely healing is to hydrolyze, breakdown the various damaged protein molecules. In so doing, they restore blood circulation, clean-up the site (along with the white blood cells), and promote healing.

One question often asked is: how can serrapeptidase and other enzymes help in so many health challenges?

The simple answer is because all health challenges have a common denominator that is often overlooked. That common denominator is inflammation that is not controlled or modulated.

When an inflammatory process is not modulated, it will negatively affect the body’s overall defense system and increase the risks for other diseases and health challenges.

Serrapeptidase and other proteolytic enzymes that are proven stable and functional in the system are effective in modulating inflammatory processes. It is because of this fact that enzymes and other biological therapeutic agents are referred to as “adjunct therapeutic agents”.

In many studies (Ishira et al., 1983; Aratani, et al., 1980; Okomure et al., 1977; Neubauer, 1961), it has been shown that using serratiopeptidase and/or other proteolytic enzymes along with antibiotics or other medications, healing occurs much faster.

The main reason is because the enzymes facilitate access of the medications to the damaged sites or injurious agents such as pathogens, for instance. More specifically, by improving blood flow dynamics, removing cellular debris and other extraneous molecules, the therapeutical agents can easily reach their target sites.

In a study comparing serratiopeptidase and diclofenac, Jaday et al. (2010) induced edema in rats. The animals treated with 20 mg/kg of serratiopeptidase did as well if not better in some cases than the animals treated with diclofenac, a common and potent non-steroidal anti-inflammatory drug (NSAID).

Serrapeptidase has also been shown to help in such conditions as othorhinolaryngology, osteoarthritis, carpal tunnel syndrome, various painful conditions, bacterial infections, swelling and chronic edema in various organs or tissues, and other health challenge cases (Majima et al., 1988; Selan, et al., 1993; Panagariva, et al., 1999; Mazzone, et al., 1990; Klein, et al., 2000; Esch, et al., 1989; Kee, et al., 1989).

In all the various areas studied and/or observed in clinical settings, the role and benefits of serratiopeptidase can be summarized as enhancing blood circulation, removing cellular debris, and modulating inflammatory cytokines. Also, by resolving the edema and other pressure-inducing molecules on the sensory nerve endings, serrapeptidase and other proteolytic enzymes assist in managing pain.

In a preventative and wellness perspective, it is important to maintain a lifestyle including diet, stress management, clean living conditions, and dietary supplements such as enzymes and antioxidants to help the body manage the various inflammatory processes.

Serrapeptidase is an enzyme purified from non-pathogenic strain of serratia and produced in highly controlled GMP conditions. Its biochemistry as well as the best methods of production has been well studied. Furthermore, its use and application in the areas of human health are documented and continue to be a major aspect of inflammation and pain management protocol in many clinics around the world.


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