Be Smart— Take Enzymes

Combined with the flavonoid rutin, certain digestive 
enzymes are as good as a widely prescribed NSAID 

Crime doesn’t pay—as well as politics. 
— Anonymous

© Willaume

Kids, are you interested in a career in crime? It’s exciting, you know—gunfights, car chases, and all that—and the pay can be great (if somewhat erratic). Of course, you don’t want to be leaving your fingerprints all over the place, because the cops will just try to use them against you to make it look as though you’re some kind of criminal.

So here’s what you do: go to Hawaii (hey, great plan already!) and get a job in the pineapple fields. Spend a few decades of backbreaking work cutting pineapples (Ananas comosus—crooks should know their botany), and then begin stealing jewels, robbing banks, bribing politicians, etc. You’ll have no worries, because your fingerprints will have been almost obliterated by the bromelain in the millions of pineapples you handled. It’s true!

Bromelain—An Appetite for Proteins

Bromelain is the name given to a group of enzymes found in pineapples (they’re found mostly in the stems, which are edible but not that tasty). Most of these enzymes are proteases, or proteolytic enzymes. In case you missed that biochemistry class, this means that they catalyze the degradation of proteins to their constituent amino acids—in other words, protein digestion. (All enzymes are themselves proteins, by the way, so here we have proteins attacking and destroying other proteins.)

Bromelain is widely used as a meat tenderizer. It may slowly eat your fingerprints, but if you take it as a nutritional supplement, don’t worry—it will not eat you from the inside out. On the contrary, it has therapeutic properties, notably as an anti-inflammatory and analgesic (pain reliever), as we will see.

Bromelain—Not About to Be Eaten Itself

Speaking of eating, bromelain is known to aid in digestion. For this to be possible, bromelain must, of course, survive the hostile environment of the gastrointestinal tract. That’s a highly unusual property in proteins, most of which are decomposed to amino acids under the assault of stomach acid and of digestive enzymes in the stomach and duodenum (the uppermost portion of the small intestine). This is why, e.g., a drug such as insulin cannot be taken orally—it’s a protein.

There are exceptions to this rule, however, notably the digestive enzymes, which are largely immune to the acid and to each other. But can such proteins—including at least some of the ones that constitute bromelain—be absorbed from the gut into the general circulation? Apparently some can. It has also been speculated that some unabsorbed enzymes might even exert biological activity throughout the body from within the intestines, by means of chemical signal cascades that they initiate there.

A Natural Triple Play

Bromelain’s biological activity as an anti-inflammatory and analgesic agent is best known when it’s used in combination with two other substances:

  • Trypsin is a proteolytic (digestive) enzyme produced in the duodenum from an inactive precursor secreted by the pancreas. The same description applies to a closely related enzyme called chymotrypsin. These two enzymes, both of which evolved from a common ancestral protein (that’s right—proteins evolve too), are complementary in their actions, and both also have therapeutically useful anti-inflammatory properties.

  • Rutin (aka rutoside) is a flavonoid obtained mainly from buckwheat. It’s formed by the combination of quercetin (a flavonol) and rutinose (a disaccharide), and its biological effects are attributed primarily to its antioxidant activity. Rutin is used therapeutically as an anti-inflammatory and anti-edema agent, particularly in the treatment of chronic venous insufficiency, which is responsible for varicose veins and hemorrhoids.

The combination of bromelain (90 mg), trypsin (48 mg), and rutin (100 mg), informally called ERC (for enzyme-rutin combination), has been used in several clinical trials for relief of the pain of osteoarthritis (OA) of the knees and hips. Alleviating the inflammation associated with OA is a good way to alleviate the pain, which can range from merely annoying to crippling.

Let’s Shoot for . . . Noninferiority!

The drugs most commonly prescribed for OA are NSAIDs (nonsteroidal anti-inflammatory drugs), such as aspirin, ibuprofen, and naproxen (acetaminophen is nonsteroidal, but it’s not anti-inflammatory, so it’s not an NSAID). These drugs do reduce inflammation and pain, but they’re also notorious for their severe long-term side effects—mainly peptic ulcers and upper gastrointestinal perforation and bleeding. That’s the price one can pay, and it’s often not worth it.

One of the NSAIDs most widely prescribed for OA (and for a variety of other conditions, such as acute injury and painful menstruation) is diclofenac, which is actually one of the better-tolerated of the dozens of NSAIDs on the market. The objective of some of the studies with ERC was to establish the “noninferiority” of this natural formulation compared with diclofenac.

No, that doesn’t mean that the researchers had little faith in the product’s value or that they were just a bunch of slackers who couldn’t be bothered to try harder. In clinical trials of therapeutic agents, a study designed to demonstrate noninferiority vis-à-vis a well-established drug of indisputable efficacy is perfectly respectable, especially when there may be hidden benefits of the agent in question, such as a lower risk of adverse side effects.

Enzyme-Rutin Combo Works Well in Pakistan . . .

In one randomized, double-blind study, researchers in Pakistan tested for the noninferiority of ERC versus diclofenac (for which the 50-mg dose was chosen so as to preserve efficacy but minimize the risk of adverse effects).1 They recruited 103 patients (average age 57) with OA of the knee who were experiencing acute pain. ERC was taken as one tablet thrice daily, and diclofenac as one tablet twice daily, for 6 weeks. One group received active ERC and a diclofenac placebo, while the other group received active diclofenac and an ERC placebo (this is called the double dummy technique, and you can make up your own joke about it). Both agents were enteric-coated so that the tablets would survive the stomach and not disintegrate until they reached the duodenum.

The primary outcome measures were pain, joint function, and the patients’ and doctors’ subjective assessments of the patients’ condition. There were marked improvements in all three measures with both agents, and ERC was found to be as good as diclofenac—a clear demonstration of noninferiority. Surprisingly, and in contrast with other studies, the incidence of adverse side effects (none serious) was essentially the same with both agents. There were no significant differences between the two treatment groups with regard to their lab tests, but there was a tendency for the levels of certain liver enzymes to decrease with ERC (which is good) and to increase with diclofenac (not good).

In reference to ERC, the authors stated,1

Onset of efficacy may be slower, but the patients may profit from its well-known superior safety and tolerability profile. Thus ERC emerge [sic] as an alternative in the standard of care for OA, allowing more patients to be treated for longer periods without the inherent toxicities of NSAIDs.

. . . And in Germany

Two years later, German researchers published the results of a similar study—the same therapeutic agents, the same noninferiority objective, and the same double dummy protocol.2 Here, however, the patients took two ERC tablets thrice daily, and one diclofenac tablet twice daily, for 6 weeks. And the patients (90 of them, average age 52) suffered not from painful OA of the knee, but of the hip (an affliction, by the way, that shows a clear preference for postmenopausal women).*

*In their paper, the authors referred to “. . . patients with painful heap of osteoarthritis of the hip.” It takes a heap of expertise to translate German into good English (nicht wahr?), but perhaps the journal editor wasn’t, uh, hip to that fact.

In this study, the primary outcome measures were joint pain, joint stiffness, and physical function. The results were virtually the same, in all respects, as those of the Pakistani study: a clear noninferiority of ERC vs. diclofenac was established, with no significant differences in the incidence of adverse effects, and a tendency for the liver enzymes to favor ERC. The German authors made the same point as their Pakistani counterparts regarding the probable risk/benefit advantage of ERC over diclofenac in long-term use.

Bromelain Alone Works for Knee-Injury Pain

Not all studies use the enzyme-rutin combination discussed above, nor do they all focus on osteoarthritis. For example, researchers in the United Kingdom studied bromelain alone in 77 volunteers (average age 37) who suffered from a common condition: mild, acute knee pain and inflammation caused by injury.3 For 1 month, the volunteers received either 200 or 400 mg daily of bromelain in an open-label (not placebo-controlled) trial.

Bromelain treatment produced substantial improvements in measures of pain, stiffness, and physical function, as well as in the patients’ general sense of well-being. The benefits were dose-dependent: the higher dose yielded consistently better results than the lower dose. This suggests a real benefit of bromelain over and above the placebo effect, because the volunteers didn’t know they had been randomized to two different dosages.

Not Using Enzymes Might Be a Crime

Enzymes are a mystery to most folks, and that encourages all kinds of marketing claims to be made about the things they can do. Some such claims are about as credible as a politician under oath, but here we’re talking about scientific research demonstrating that bromelain, alone or in combination with other agents, works well in relieving the pain of osteoarthritis. And it’s almost certainly safer, in the long run, than NSAIDs.

Oh, about that career in crime: if you don’t fancy working in the pineapple fields to get rid of your fingerprints, do the next best thing—wear gloves.


  1. Akhtar NM, Naseer R, Farooqi AZ, Aziz W, Nazir M. Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee—a double-blind prospective randomized study. Clin Rheumatol 2004;23:410-5.
  2. Klein G, Kullich W, Schnitker J, Schwann H. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomized study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol 2006;24:25-30.
  3. Walker AF, Bundy R, Hicks SM, Middleton RW. Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults. Phytomedicine 2002;9:681-6.



Frankincense—A Gift to Your Joints

In the search for anti-inflammatory agents to combat the pain and inflammation of osteoarthritis, no source is too exotic to be investigated. One such is Boswellia serrata,a deciduous tree from the dry hills of northwestern India. It’s known in Sanskrit as gajabhakshya, which implies that elephants eat it. We don’t know whether or not elephants get arthritis, but arthritic humans who ingest an extract from the tree’s gum resin—you know it as frankincense—can benefit from it.

Indian researchers reached this conclusion after studying the effects of a B. serrataextract (BSE) on 30 patients (average age 59) with osteoarthritis of the knee.1 For 8 weeks, the patients received either 333 mg of BSE or placebo thrice daily. The study was designed as a crossover trial, in which the patients served as their own controls: 4 weeks on one agent and 4 weeks on the other, with a 1-week “washout” period in between.

Compared with placebo, BSE produced significant improvements in all three of the measures used: pain, loss of movement, and swelling. All the patients reported decreased knee pain, increased knee flexion, increased walking distance, and improved capacity for climbing stairs, kneeling, sitting cross-legged, and squatting. There was also reduced swelling in their knees. Radiographic (x-ray) measurements, however, showed no changes.

These gratifying results can now be added to the roster of benefits attributed to frankincense since ancient times, when it came into use in the Indian medical practice known as Ayurveda. Boswellia has long been prized for its anti-inflammatory and analgesic effects and has been found in modern times to be helpful for diseases as diverse as osteoarthritis, rheumatoid arthritis, inflammatory bowel disease (ulcerative colitis and Crohn’s disease), bronchial asthma, and possibly even cancer. For more on these subjects, see “Blessed Relief for Inflamed Bowels, Lungs, and Joints”(January 2002) and “Ancient Herbs Might Save Your Life” (April 2002).


  1. Kimmatkar N, Thawani V, Hingorani L, Khiyani R. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee—a randomized double-blind placebo-controlled trial. Phytomedicine 2003;10:3-7.