Nonsteroidal anti-inflammatory drugs (NSAIDs) are typically used to alleviate osteoarthritis pain. Unfortunately, long-term use of NSAIDs can precipitate stomach ulcers, indigestion, and increase the risk of heart attacks, strokes, and heart-related deaths. Studies have demonstrated that among commonly used NSAIDs, diclofenac poses the most risk when it comes to heart issues compared to some of the other NSAIDs. This 2015 study features 150 adults with moderate-to-severe osteoarthritis of the knee demonstrated and compared a proteolytic enzyme combination to diclofenac.
This study was a double-blind, placebo-controlled trial in which 150 adults with knee osteoarthritis were randomized to 150mg diclofenac, an enzyme combination (Wobenzyme), or placebo. In this study, pain scores improved in both the diclofenac and the enzyme group compared to placebo. The biggest differentiator between diclofenac and the natural enzyme group was in adverse events and the use of the rescue medication (paracetamol). The number of rescue medications used in the enzyme group was less than placebo, whereas there was no difference between the diclofenac and placebo groups.  Adverse events were similar in the enzyme and placebo groups, while adverse events were twice as high in the diclofenac group compared to the enzyme group.
The studied enzyme formula is delivered as enteric coated tablets. In 6 tablets there is: 288mg trypsin, 540mg bromelain, and 600mg rutin, and bioflavonoids. Study participants were given two tablets three times daily that were consumed on an empty stomach between meals.
This study is in line with previous studies showing that orally taken proteolytic enzymes have anti-inflammatory properties and can reduce joint pain. Studies have also shown that enzyme combinations can enhance mobility and recovery following sports injuries. Certainly a key advantage of proteolytic enzymes over NSAIDs is that enzymes can be used safely over a long-term period.
Bolten WW, Glade MJ, Raum S, Ritz BW. The safety and efficacy of an enzyme combination in managing knee osteoarthritis pain in adults: a randomized, double-blind, placebo-controlled trial. Arthritis. 2015;2015.

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