Inflammation and Enzymes


Enzymes – Natural, Effective Anti-Inflammatories

For practitioners, pain can be a difficult symptom to address. It is a complex and subjective experience, influenced by a variety of factors. Clients experiencing pain, either because of injury, migraine, food intolerance, illness, autoimmunity, or other conditions, can struggle to wean themselves off harmful medications due to the intense emotional and physical stress the pain is causing.

One of the most common pain relief options is NSAIDs (Non-Steroidal Anti-Inflammatory Drugs).

A growing body of evidence links NSAID use to harmful cardiovascular events such as heart failure, atrial fibrillation, stroke and heart attack – leading clients and practitioners to seek alternative methods for pain reduction. Increasingly, evidence shows that protease enzymes can effectively reduce pain, without the side effects of over-the-counter pain medication.

Systemic enzymes

Systemic enzyme therapy involves supplementing with proteolytic enzymes for a general whole-system reduction in inflammation. Numerous clinical trials and meta-analyses of oral combination therapy, conclude that it is equal to and frequently outperforms anti-inflammatories for reducing pain. These studies considered the effects of protease enzymes and bromelain on osteoarthritis, muscle injury, bone degeneration and rheumatic disease.

Fruit proteases such as Bromelain, Papain and Nattokinase offer additional benefits; with clinical trials linking these enzymes to AMPK activation, inhibition of inflammatory process, swelling reduction and reduction of physical discomfort in a range of inflammatory pathologies.

Proteolytic enzymes also have few negative outcomes and combine well with most other medications.

So what is it that enzymes do that are so effective in resolving all forms of inflammation?

Protease Enzymes

Protease enzymes, often referred to simply as proteases, play a crucial role in the breakdown of proteins.  They are essential for a wide range of biological processes and functions such as digestion, cellular regeneration protein turnover, blood clotting, immune response, tissue repair and regeneration and hormone activation.

Serine proteases include enzymes like trypsin and chymotrypsin which are part of the digestive process. These enzymes also enter the bloodstream through the small intestine, where they play a systemic role in inflammation resolution via their interaction with regulatory anti-inflammatory cytokines.

Cytokine Regulation

Nutrition professionals will already be familiar with the importance of ratios in health. Omega 3, 6, 9 and sodium, potassium and chloride are two well-known and understood examples of ratios that profoundly impact health outcomes. Cytokine balance is no different.

Cytokines play a central role in all inflammation and protease enzymes facilitate this process, by activating alpha 2 macro globulins. Cytokines themselves, exist within a balance of inflammation and resolution. They also influence immune responses, cell proliferation, and differentiation. Cytokines release damage-associated molecular patterns and uncontrolled, can activate inflammatory cell death – leading to further cytokine secretion.

In a healthy body, the biological system is well equipped with inherent control mechanisms – the progression and duration of inflammatory responses in injury, infection and autoimmunity to ensure they are regulated and resolved.

Cytokine dysregulation can result in continued inflammation, leading to pathological diseases. Continued activation of Tumour necrosis factor and interleukin 1 – two pro-inflammatory cytokines associated with osteo and rheumatoid arthritis, colitis and the development of atherosclerotic plaques, are just two examples.

Alpha 2-macroglobulin

Alpha-2-macroglobulin has little clinical value, yet clinical trials find, that facilitating its activation via protease supplementation, results in significant reduction in pain and inflammation. Protease enzymes are facilitating a very natural inflammation and pain reduction. How?

Alpha-2-macroglobulin is a large protein found in blood plasma and other bodily fluids. It is known for its regulatory role, particularly in inhibiting proteases that can damage tissues and cause inflammation.  In acute phase inflammation, such as tissue injury, bacterial or viral infection – alpha-2-macrogobulin is released, where it gets to work on inhibiting circulating proteins.

This action helps limit the spread of protease-mediated damage and inflammation in the body. Alpha-2-macroglobulin’s ability to neutralise a wide range of proteases makes it an important player in maintaining tissue integrity and controlling inflammation.

While α2-macroglobulin provides important protective functions, some pathogens have evolved to evade this trapping mechanism and exploit proteases for their own benefit.

Some proteases, however are anti-inflammatory.

In chronic inflammation, the continuing inhibition of proteases by alpha 2 macroglobulin allows an ongoing and unresolved release of cytokines to the injured, inflamed or infected area, resulting in a continuous cycle of cytokine (inflammatory) release.  It inhibits the action of endogenous serine proteases that would lead to the resolution of inflammation and regulates thrombotic, fibrinolytic and kinin cascade activation pathways.

Activating alpha-2-macroglobulin via protease supplementation converts the protein into a cytokine magnet. Circulating cytokines and other inflammatory proteins attach themselves and become inactivated. Inflammation, pain and swelling is reduced.

This process of activating alpha-2-macroglobulin with protease supplementation has been repeatedly tested in clinical trials. These conclude, potent anti-inflammatory effects that exceed the pain relief of NSAIDs, in a dose-dependent, repeatable manner, with the added benefit of an excellent safety and tolerability profile.

Natural protease secretion can be affected by many factors, including diet, hormonal regulation, nutritional status, pancreatic health, age, stress, medications, gastrointestinal disorders, genetics, and environmental factors.

Natural decline or deficiency in serine protease circulation can be corrected by protease supplementation.

Top of Form

What the clinical trials say

Studies on oral enzyme therapy consistently show comparable and often superior efficacy in pain reduction, with an improved safety profile and no adverse or side effects in athletes’ osteoarthritis, rheumatic illness, and muscle injury.

In a meta-analysis of raw patient data from six randomised trials across 774 patients with knee osteoarthritis, oral enzyme therapy made of protease enzymes and bromelain was compared with an over-the-counter NSAID. Researchers concluded that oral enzyme therapy had comparable clinical efficacy to NSAIDs and a more favourable safety profile – a similar conclusion drawn from comparable studies on hip osteoarthritis, muscle soreness and injury in athletes and rheumatic illness.

Warning – Interactions and adverse incidences

Studies on rodents show the median lethal dose of Nattokinase enzyme is 20,000 units. In human terms, an equivalent dosage far exceeds the amounts found in OTC Nattokinase. It does have an additive effect on the cholesterol-lowering of statins, indicating clients on statins that are also using Nattokinase should be closely monitored and titrated gently.

Some protease enzymes can have a mild blood thinning effect, so clients on medications such as Warfarin should avoid systemic protease supplementation.

When applied topically, Papain is a protease enzyme that can produce a rash, and inhalation is considered harmful. It should only be taken when encapsulated.

Protease enzymes should not be used with any client with an active stomach ulcer.

Vegan or Animal Enzymes

Many commercially available supplementary enzymes are derived from pancreatic porcine sources and are unsuitable for vegetarians or vegans. In tests, vegan enzymes were found to have equivalent protein-digesting activity, activate at a faster rate and be less likely to inactivate when exposed to stomach acid when compared to animal-based enzymes.

Enzyme units

When selecting a supplementary enzyme, practitioners will get more reliable results when choosing a product that labels the enzyme in ‘active units’.  Active Units measure how efficiently an enzyme catalyses a specific chemical reaction. Enzyme activity is critical because it reflects the enzyme’s ability to convert substrates into products.