These are my favorite newsletters — discussing a new formula. It’s fun, not just because of the subject matter, which is definitely interesting, but also because I don’t have to write anything new — just grab it from the twelve months of research that went into the Barron Report related to the project and drop it in down below. I hope you enjoy it too.

Who is this for?

Joint pain is an interesting animal. Everyone has it at some point. For many people, it’s only an occasional problem — easily taken care of by a single aspirin or some Ben Gay (or by some Essential Relief^™ for that matter). For others, though, it’s a chronic problem, reducing them to a lifetime of dependency on high doses of NSAIDS or prescription drugs.

Over the years, I’ve formulated and recommended a number of products for pain. Years ago, before they were all the rage, I recommended Glucosamine and Chondroitin sulfate. Also, over the years, I’ve recommended CMO (cetyl myristoleate), MSM, Fish oil, Boswellia, and Proteolytic Enzymes, among others.

Why so many things?

Because no one solution works for everyone!

That’s so important, I’m going to repeat it one more time. No one solution works for everyone!

I don’t care what advertising statements you’ve read or how hard someone has tried to sell you a magic bullet, no one formula works for everyone. Each person is unique. Their bodies are different. And the causes of joint pain and cartilage destruction are varied.

If Glucosamine and Chondroitin already work for you, then this report is not for you (necessarily). If CMO does the trick, same thing. If you’re happy with Proteolytic Enzymes or Essential Relief^™, this probably is not for you (most likely). But if they haven’t worked, or if you still suffer from chronic pain, and the only help you’ve been able to find is from daily doses of aspirin or prescription drugs, or if you’re concerned about more than just the pain issue and are looking to prevent further degradation of your joints, then read on.

Over the past twelve months, I have been working on a formula that incorporates some extraordinary new research on natural pain relievers — 3 substances that not only relieve pain, swelling, and stiffness, but that when used in combination can also help rebuild damaged joints and tissue.

This formula offers a three pronged approach to systemically relieving chronic joint pain and inflammation.

1. It incorporates ASU to increase aggrecan levels, thereby helping to repair and rebuild damaged cartilage in the weight bearing joints.
2. It makes use of the unique ability of the undenatured type II chicken collagen found in UC-II™ to train the body’s immune system to stop attacking joint cartilage.
3. And it makes use of ginger’s ability to directly reduce pain and inflammation.

1. Avocado Soy Unsaponifiables (ASU)

In order to understand what ASUs are (apologies to Arizona State University) and how they work, we need to make a minor detour and talk about aggrecan. In fact, this discussion should help tie together some of the supplements that you may already be familiar with. Aggrecan is the acronym for a small bio-chemical molecule called, oxymoronically, the large aggregating chondroitin sulfate proteoglycan. Specifically, an aggrecan molecule consists of a protein backbone which is attached to up to 150 chondroitin sulfate chains and 60 keratan sulfate chains. Aggrecan is abundant in the human body and represents up to 10% of the dry weight of cartilage — keeping in mind that’s quite substantial since articular cartilage (the cartilage found at the end of long bones) contains up to 75% water. As many as 100 of these aggrecan monomers will then interact with hyaluronic acid molecules to form a single massive chain called an aggregate, which is a key component of joint cartilage.

Aggrecan plays a crucial role in the functioning of articular cartilage (the cartilage found in joints), primarily working to maintain high levels of hydration in the cartilage — thereby keeping the cartilage healthy and functional. As a side note, it is the presence in aggrecan of large numbers of chondroitin sulfate chains that is primarily responsible for the osmotic pressure that results in articular cartilage being 75% water.

When at rest, such as sitting down and watching TV, the osmotic swelling in the articular cartilage is at a maximum. However, when walking or standing, the weight of the body is transferred to the articular cartilage found at the ends of the long bones. At this point, your weight compresses the cartilage, literally squeezing water out of it. This continues until the osmotic swelling generates a force equal to the compressive force on the cartilage generated by your weight. When you sit down again (reducing the load), the compressive force is removed, and the cartilage once again swells to its full extent. The more aggrecan present, the better able your body is to perform this function. Note: the reason people supplement with chondroitin sulfate and glucosamine sulfate is actually to increase aggrecan levels. They are components of aggrecan, and it is aggrecan that lies at the core of cartilage health. But as it turns out, there may be a more efficient way to increase aggrecan levels.

Bottom line: maintaining high levels of aggrecan is essential for optimizing joint health. (As a side note, aggrecan plays a major role in brain and spinal cord development and function too.)

A French Discovery

Several years ago, researchers from the University Hospital in Liege, Belgium reported in the August 2003 issue of The Journal of Rheumatology that a phytosterol/sterolin extract concentrated from the oils found tightly bound to avocado and soybean fibers could significantly boost production of aggrecan, thereby helping slow down and even repair some of the damage caused by osteoarthritis — in as little as nine days.

It should be noted that although eating avocado and soybean oil separately does indeed enhance aggrecan production (somewhat); it is only these special compounds found in ASU extract (made up of one-third avocado and two-thirds soybean unsaponifiables) that restore aggrecan synthesis blocked by the inflammation-causing compound interleukin-1-beta. In addition, ASUs also reduce levels of several other inflammatory factors such as MMP-3 production. In other words, ASU is not the same as avocado and soy oil. It is specially extracted from the fiber of avocados and soy. The problem is that before extraction, the ASUs are so tightly bound to the fiber, that they are mostly unusable by the human body.

ASU has been sold in Europe in a purified form for several years now as a prescription drug. As such, it has a number of studies supporting its effectiveness. For example, in a double-blind trial, 260 individuals with arthritis of the knee were given either a placebo or purified ASU at 300 or 600 mg daily. The results over 3 months showed that use of ASU significantly improved arthritis symptoms when compared to a placebo.

What It Means

If you’ve tried Chondroitin sulfate, Glucosamine sulfate, MSM, CMO, whatever, and none of them have worked for you, then ASUs offer an exciting alternative.

Note Well

One thing to keep in mind is that most tests with ASU have been run with purified versions of ASU. But the non prescription versions available to the general public are only about 30% phytosterols and sterolins by content. That means when used in a supplement, you will want to use 1000 mg a day as opposed to the 300 mg cited in the tests. Most ASU supplements do not make this distinction. It should also be noted that some people do not “feel” anything when using ASUs, nevertheless, they may still be benefiting. Since ASUs can slow, and in many cases even reverse, cartilage degeneration, improvement may be happening even if pain persists.

2. UC-II™ Undenatured Chicken Collagen

Although ASU works directly to build and repair joint cartilage, it doesn’t address a major aspect of the problem (in fact few things address this particular aspect). A key component of most joint destruction (sometimes an initial cause as in rheumatoid arthritis and sometimes a secondary factor triggered by an initial trauma to the tissue as in osteoarthritis) is when the immune system goes out of control and starts attacking the cartilage. In other words, once a person starts down the road of joint pain, either early on or later in the process, at some point the immune system usually “goes wrong” and becomes a factor in the gradual destruction of joint tissue. Literally, the immune system reprograms itself to treat joint tissue as a foreign invader and “eat it up.” Re-reprogramming the immune system through the use of immunomodulators is often an essential step in stopping and reversing this damage.

In the past, I have recommended several immunomudulators including CMO (cetyl myristoleate) and L-Carnosine, but UC-II seems to represent a choice uniquely suited to dealing with joint and cartilage problems. Although this discussion ultimately applies to all forms of joint damage, for the moment, let’s focus our attention specifically on rheumatoid arthritis.

Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a common autoimmune disease in which killer T-cells of the body’s own immune system (most likely triggered by invading bacteria) reprogram themselves to attack joint cartilage, resulting in inflammation and joint destruction. The current treatment strategies of suppressing immunity and inflammation offer only limited success. “Oral tolerance,” on the other hand, is a long-recognized mechanism for inducing immune tolerance — that is, suppressing a misdirected immune response. But rather than suppressing the entire immune system, oral tolerance targets specific immune cells responsible for tissue damage. Inducing the immune system to tolerate joint cartilage, rather than identifying it as a “foreign” substance, requires a specific sequence of events to take place within that part of the immune system found in the gastrointestinal tract lining. Studies have shown that small doses of undenatured type II collagen can indeed trigger this particular sequence of events, thereby deactivating killer T-cell attacks of joint cartilage in humans. Other studies have demonstrated that the undenatured type II chicken collagen found in UC-II retains its activity when exposed to human digestive fluids, which is not necessarily true of other sources. Time-dose measurements by ELISA immuno-assay of UC-II activity have shown that it retains approximately 50% activity even after as long as 90 minutes after exposure to digestive juices.

What is UC-II?

Most type II chicken collagen sold in dietary supplements is denatured, or hydrolyzed, which is another way of saying that the chemicals and high-heat used to process and refine it have changed its molecular configuration. An undenatured extract is made using little or no heat and limited processing. It is usually extracted using pepsin with just enough processing to concentrate the collagen and make it soluble. Denatured or hydrolyzed extracts, on the other hand, typically use high heat, acids, and enzymes to make the protein molecules more soluble; but these methods fundamentally alter the structure of the protein. Denatured proteins are often called hydrolyzed proteins — thus denatured collagen is often called hydrolyzed collagen. This does not make it useless. Hydrolzyed type II chicken collagen still has value as a source of some of the components of aggrecan, including collagen itself, hyaluronic acid, chondrotin sulfate, and glucosamine. But to receive this benefit you need to consume it in large amounts, as much as 3-10 grams a day. But more importantly, one significant thing does change in the process of denaturing. When denatured, type II chicken collagen loses its immunomodulating ability. Type II collagen must be in its native (undenatured) form to be effective in this capacity.

UC-II is extracted from chicken sternum cartilage using a patented, low-temperature process that ensures the undenatured biological activity of the type II collagen even when exposed to digestive juices for 90 minutes or more. As mentioned earlier, undenatured collagen administered orally works with the immune system to promote healthy joints by a process called oral tolerization. This process helps the body to differentiate between foreign invaders, such as bacteria, and elements that are good for the body, such as nutrients. The process of oral tolerization takes place in the small intestine where food is absorbed. Through a complex process, lymphoid tissue in the mucosal lining of the small intestine screens incoming compounds and serves as a “switch,” turning the body’s immune response on or off to foreign substances, depending upon what that substance is. In the case of undenatured type II chicken collagen, small amounts (typically around 10 milligrams) taken orally have been shown to correct a faulty immune response specifically targeted at the type II collagen present in bone joint cartilage — in effect, modulating the body’s immune response so it works correctly once again. At a cost of over $17,000 per kilogram of active ingredient, UC-II is undoubtedly the single most expensive ingredient I have ever used in a formula. Fortunately, it only takes 10 mg a day of its active ingredient for maximum effect. (In fact, it loses effectiveness if too much is used, losing all effectiveness at levels over 20 mg a day). But cost aside, the fact that it specifically addresses the problem of the immune system destroying the body’s own cartilage mandates its inclusion in the formula.

Studies

There have been a number of studies conducted with UC-II on both animals and humans, including research at the Harvard University Medical school — all of which have shown that the undenatured type II chicken collagen found in UC-II effectively reprograms the immune system to promote healthy joints and increase joint mobility and flexibility.

In a pilot clinical study, for example, 5 older women (58-78 years old) suffering from significant joint pain were given undenatured type II chicken collagen (10 mg/day) for 42 days. Improvements in pain reduction and joint flexibility were reported, along with reduced morning stiffness. In another study, researchers at Harvard Medical School found that six of ten rheumatoid arthritis patients taking undenatured type II collagen for three months showed substantial improvement, while one patient recovered completely. In addition, there were no side effects. And finally, in a 90-day, double-blind, placebo-controlled, follow-up study on patients with severe rheumatoid arthritis, Harvard scientists found that 28 patients taking undenatured type II collagen showed significant improvement compared to the placebo group, while four patients recovered completely.

An Important Note

When we talk about a 10 mg dose, we’re talking about 10 mg of active glycosylated undenatured type II chicken collagen. But there are no readily available pure sources of this component. Standard hydrolyzed chicken collagen, as explained earlier, has virtually none. And most sources of undenatured collagen offer it in the range of 10-25% concentrations. In UC-II, for example, active glycosylated undenatured type II chicken collagen comprises 25% of the whole. That means it takes 40 mg a day of UC-II to get 10 mg of active undenatured collagen. I have noticed that several of the supplement providers who are using UC-II in their formulas have mistakenly used 10 mg of UC-II itself. That means they are only providing 2.5 mg of active undenatured collagen. Given the cost, I can see why, but from your perspective, you want a full 10 mg, which requires 40 mg a day of UC-II — or more from other sources.

What It Means

For anyone suffering from progressive cartilage damage (which ultimately means anyone suffering from rheumatoid arthritis or long term osteoarthritis), reprogramming the immune system with undenatured type II chicken collagen as found in UC-II is an essential component of his or her joint repair regimen.

3. Ginger

There are two cyclo-oxygenase (COX) enzymes present in the human body, COX-1 and COX-2. The COX-1 enzyme is found in most tissues and is necessary for a variety of important internal functions, such as protecting the stomach lining, maintaining renovascular function and platelet aggregation. The COX-2 enzyme, though, has an entirely different function. It is a necessary component of the inflammation process, which is a normal, healthy attempt by the body to heal itself. However, when inflammation gets out of control (such as in the case of arthritis or other chronic inflammatory disorders), ongoing pain and discomfort is the result. Prescription COX-2 inhibitors such as Vioxx and Celebrex have proven helpful in relieving out of control inflammation and its accompanying pain — but with notable side effects such as an increased risk of heart attacks and strokes. That’s where botanical COX-2 inhibitors such as ginger can help. Botanical COX-2 inhibitors block the action of the COX-2 enzyme in much the same way as prescription drugs do, but without the side effects.

Although it’s probably better known for its anti-nausea properties, ginger is also an effective COX-2 inhibiting anti-inflammatory herb that has historically been used for arthritis and rheumatism. In a study of patients with rheumatoid arthritis, osteoarthritis, and muscular discomfort, the majority of those who received ginger experienced, to varying degrees, relief of pain and swelling. None of the patients reported adverse effects during the period of ginger consumption, which ranged from three months to 2.5 years. Another double blind trial found ginger extract to be effective at relieving pain in people with osteoarthritis of the hip or knee. Likewise, in another double blind study, ginger was significantly more effective than a placebo in pain relief and overall improvement.

Ginger contains very potent anti-inflammatory compounds called gingerols. These substances explain why so many people with osteoarthritis or rheumatoid arthritis experience reductions in their pain levels and improvements in their mobility when they consume ginger regularly. In two clinical studies involving patients who responded to conventional drugs and those who didn’t, physicians found that 75% of arthritis patients and 100% of patients with muscular discomfort experienced relief of pain and/or swelling.

A twelve month placebo-controlled, double-blind, crossover study published in Osteoarthritis Cartilage magazine (no really, that’s its name) tracked 29 patients with painful arthritis in the knee (6 men and 23 women ranging in age from 42-85 years). By the end of the first six months, those given ginger were experiencing significantly less pain on movement and handicap than those given placebo. Pain on movement decreased from a score of 76.14 at baseline to 41.00, while handicap decreased from 73.47 to 46.08. In contrast, those who were switched from ginger to placebo experienced an increase in pain of movement (up to 82.10) and handicap (up to 80.80) from baseline. In the final phase of the study when all patients were getting ginger, pain remained low in those already taking ginger in phase 2, and decreased again in the group that had been on placebo.

Not only did participants’ subjective experiences of pain lessen, but swelling in their knees, an objective measurement of lessened inflammation, dropped significantly in those treated with ginger. The mean target knee circumference in those taking ginger dropped from 43.25cm when the study began to 39.36cm by the 12th week. When this group was switched to placebo in the second phase of the study, their knee circumferences increased, while those who had been on placebo but were now switched to ginger experienced a decrease in knee circumference. In the final phase, when both groups were given ginger, mean knee circumference continued to drop, reaching lows of 38.78 and 36.38 in the two groups.

What It Means

Ginger extract helps to relieve chronic pain by reducing inflammation.

Conclusion

This formula offers a three pronged approach to systemically relieving chronic joint pain and inflammation.

1. It incorporates ASU to increase aggrecan levels, thereby helping to repair and rebuild damaged cartilage in the weight bearing joints.
2. It makes use of the unique ability of the undenatured type II chicken collagen found in UC-II™ to train the body’s immune system to stop attacking joint cartilage.
3. And it makes use of ginger’s ability to directly reduce pain and inflammation.

As I mentioned at the top of the report, if Glucosamine and Chondroitin already work for you, then this formula may not necessarily be for you. If CMO does the trick, same thing. If you’re happy with Proteolytic Enzymes or Essential Relief^™ this most likely is not for you. But if they haven’t worked as well as you might like, or if you still suffer from chronic pain, and the only help you’ve been able to find is from daily doses of aspirin or prescription drugs, or if you’re concerned about more than just the pain itself and are looking to prevent further degradation of your joint tissue, then this formula just might be what you’re looking for.