In the minds of many, inflammation often is associated with the pain and swelling that occurs after trauma, whether from a sports injury or a wound. However, scientists are beginning to realize that inflammation may actually be the cause behind a surprising number of conditions including Alzheimer’s, cardiovascular disease, hypertension, diabetes/insulin resistance, multiple sclerosis, cancer and depression. Even weight gain is now associated with inflammation. In fact, any condition with a modifier of “itis” at the end of the word (dermatitis, bursitis, colitis, sinusitis, etc.) is linked to inflammation.
Inflammation is an essential process. Without it, wounds would not heal. However, when inflammation continues unchecked a process that was designed to help the body heal actually becomes highly destructive. Various factors encountered in our modern day lifestyles, including poor diet, stress, lack of sleep and exercise, contribute to the ongoing inflammation that can lead to a number of diseases. Inflammation also accelerates premature aging and can sabotage the pursuit of healthy aging.
Cardiovascular Disease
When anything threatens the body’s health—from disease-causing germs to the buildup of fatty plaque in the walls of a heart vessel—the immune system sends in wave after wave of cells to swarm and destroy the invader. Scientists now theorize that when plaque deposits build up on the walls of arteries, it causes macrophages to perceive the plaque deposit to be a foreign invader, and therefore attempt to eliminate the cholesterol deposit. In the blood vessels, layers of these immune cells pile up, creating lesions that become increasingly unstable and may eventually break free, inducing a heart attack. This link between inflammation and blood vessel health may explain why half of all people who have heart attacks don’t have high cholesterol.
Scientists now realize that inflammation plays an important part in the development of cardiovascular disease and that C-reactive protein (CRP), a measure of inflammation, is a predictor of heart disease.1
Insulin Resistance, Diabetes and Weight Gain
Scientists suspected a link between inflammation, insulin resistance and diabetes as far back as the early 1900s, when they gave diabetes patients aspirin-like compounds known as salicylates and found that these anti-inflammatory compounds reduced blood sugar levels. However, the high doses necessary to produce an effect caused ringing in the ears, headaches and dizziness.2-3 Recently, researchers have achieved these same effects. However, the use of high doses of aspirin are associated with a greater incidence of gastrointestinal bleeding.
The same researchers have established an equally strong link between inflammation, insulin resistance and obesity. Fat cells (adipocytes) are known to produce inflammatory cytokines, proteins that play a key role in inflammation. Consequently, the researchers used a breed of mice with fat cells that produce a high level of inflammatory compounds. The animals with these fat cells became insulin resistant and developed diabetes. The researchers concluded that they could trigger the development of diabetes simply by inducing inflammation in the animals.4
Depression and Alzheimer’s
Scientists now believe that chronic inflammation is involved in the development of major depression that precedes Alzheimer’s disease. Chronic inflammatory changes that are suspected to be a common feature of depression could predispose depressed patients to neurodegenerative changes in later life. In support of this theory, clinical evidence shows that depression commonly precedes Alzheimer’s disease and may be an early manifestation of dementia before cognitive decline becomes apparent. Evidence indicates that chronic low-grade inflammation changes brain structure in a way similar to that seen in Alzheimer’s disease and other dementias. Neuronal loss, for example, is a common feature of major depression and dementia. Scientists have hypothesized that the activation of macrophages in the blood and brain release pro-inflammatory cytokines, which encourages the progress from depression to dementia. Such cytokines stimulate a cascade of inflammatory changes and excessive secretion of cortisol.5
Hypertension
C-reactive protein (CRP), a marker of systemic low-grade inflammation, is frequently elevated in essential hypertension. In one study of 36 subjects with essential hypertension, 36 subjects with white coat hypertension (blood pressure that rises only in the doctor’s office), and 36 subjects without hypertension, CRP levels were significantly higher in the essential hypertensive and white-coat hypertensive groups than in the group with normal blood pressure. It was also higher in the essential hypertensive group than in the white-coat hypertensive group.6
Joint Health
Inflammation is perhaps best known for its destructive effects on bone and joint health and for the role it plays in arthritis. The cyclooxygenase-2 (COX-2) enzyme is known to produce pro-inflammatory prostaglandins, which ultimately result in the destruction of cartilage.7
Cancer
Various forms of cancer are now believed to either have their origin in the inflammatory process or to be worsened by inflammation. In lung cancer, inflammatory signals can promote resistance to apoptosis, the process by which the body rids itself of cancer cells. Inflammation also promotes the multiplication of cancer cells as well as their invasiveness and their ability to spread throughout the body. Inflammation suppresses the immune system and triggers the secretion of factors that enhance angiogenesis, the development of new blood vessels that feed cancer cells. Lung cancer develops in a host environment in which the inflammatory response has become unbalanced, promoting tumor progression. It is thought that inflammation has a similar tumor-promoting effect in other forms of cancer as well.8
Natural Approaches to Reduce Inflammation
One of the most important natural tools we have in the fight against inflammation are proteolytic enzymes such as papain, bromelain, serrapeptase, amylase, and lipase as well as the bioflavonoids rutin and amla. When the body cannot resolve inflammation, blood flow diminishes, adjacent tissue becomes involved, and disease progresses. Proteolytic enzymes actually digest and deactivate inflammatory compounds that block normal healing. Proteolytic enzymes also help dissolve circulating immune complexes, which build a “wall” of fibrin around traumatic injuries creating a barrier for healing nutrients. Protein-digesting enzymes increase the assimilation of the fibrin that blocks blood and lymph vessels and causes swelling. In this way, immune responses can be resolved before irreversible damage occurs to internal organs or cartilage. Furthermore, proteolytic enzymes promote the regeneration of cartilage.
One important way in which proteolytic enzymes exert a strong anti-inflammatory effect is through their ability to influence the expression of nuclear factor-kappa B (NF-kappaB), a key modulator in inflammation-induced cancers as well as pulmonary, autoimmune, skin, neurodegenerative, and cardiovascular disorders. When NF-kappaB is activated, it often increases proliferation, resistance to chemotherapy, and progression of various cancers. NF-kappaB increases the expression of more than 400 different gene products linked with inflammation, cancer cell survival, proliferation, invasion, and angiogenesis.9-10
The pineapple-derived enzyme bromelain has been found to inactivate NF-kappaB as well as significantly inhibit the expression of the pro-inflammatory Cox-2 enzyme. Scientists have noted that this may be the reason why bromelain has inhibited tumors in a number of animal studies.11-12
Other proteolytic enzymes such as serrapeptase and papain have been shown to produce similar anti-inflammatory effects. Serrapeptase is known to act rapidly on localized inflammation and has been studied for its anti-inflammatory effects in patients with carpal tunnel syndrome and other inflammatory disorders.13-14
Bromelain and papain have both been shown to increase levels of IL-6, thereby enhancing wound healing and tissue regeneration.15
Under clinical conditions, papain produced therapeutic effects in patients with inflammatory disorders in the genitals, intestines, liver, and eyes.16 Another study on a papain blend conducted at Wayne State University in Detroit found that nearly 70 percent of athletes treated with the enzyme supplement showed a better than expected recovery, while only 20 percent of the non-supplemented group showed a better than expected recovery.17
The combination of these enzymes produces a synergistic effect that can reduce the inflammation responsible for the decline of many areas of our health. In one double-blind, placebo-controlled trial using a combination of bromelain, serrapeptase, papain, lipase and amylase, all derived from vegetarian sources, the proteolytic enzymes significantly improved most of the major symptoms associated with joint problems. Patients experienced greatly reduced fatigue, soreness and discomfort while using the proteolytic enzymes.18 (Figure 1)
In another trial, more than 100 patients who underwent recent trauma were included in the study. The patients had inflammation caused by ophthalmologic surgery, orthodontic procedures (tooth extraction, cavities), sports injuries (muscle tears, tendonitis, rotator cuff injury, sprains, etc.) and orthopedic injury such as sciatica. In these patients, the combination of proteolytic enzymes proved to have excellent anti-inflammatory, analgesic and antioxidant properties without any side effects.19
When scientists induced inflammation in rodents, a similar effect was achieved with a combination of proteolytic enzymes. Difference in the swelling of the rat paws was measured at 1 hour, 2 hours, 3 hours and 24 hours. Groups given different doses of combined proteolytic enzymes were then compared with the control group. In animals given 100 mg/kg or 200 mg/kg of a proteolytic enzyme mixture, the swelling was inhibited by 50 percent or more after 3 hours.20 (Figure 2)
Non-Animal vs. Animal Derived
Non-animal-derived enzyme blends possess an unusually high stability and activity under a broader range of pH conditions than animal enzyme blends. Thus, they are likely to be more effective. For example, some non-animal proteolytic enzyme formulations are stable and active at pHs 2 through 12, while pancreatin has digestive activity only in an alkaline medium.
Conclusion
Although the results of inflammation are often obvious when we cut our finger or sprain our ankle, a more silent and potentially lethal form of inflammation may be at work inside our bodies. This chronic inflammation may be responsible for a variety of conditions, including heart disease, hypertension, diabetes, weight gain, cancer, arthritis, depression and Alzheimer’s. Proteolytic enzymes provide one way to help control inflammation and strengthen our health.
References:
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18. Unpublished research conducted by Dr. Mihir Patki. Study completed March 2003.
19. Unpublished research conducted by Dr. Meghna Bharti. Study completed March 2003.
20. Unpublished research conducted by Dr. SL Bodhankar. Study completed in Nov. 2002.