Among the many ways to help sustain joint structure and function …

Boswellia Synergy
Combats Osteoarthritis

And does so quickly … substantial relief is gained in as little as five days
By Will Block

The piano’s thumpin’,
The dancers are bumpin’,
This here spot is more than hot
In fact, the joint is jumpin’.

— Fats Waller

I n the human body, osteoarthritis (OA) is the most common joint disorder. It causes pain, swelling, and reduced motion. According to the Center for Disease Control and Prevention, an estimated 50 million adults in the United States recently reported being told by a doctor that they have some form of arthritis, of which OA is the most common.1

LEM1201ligament150.jpg
(click on thumbnail for full sized image)
While there are over 100 different forms of arthritis, OA is a degenerative joint disease that is characterized by mechanical abnormalities involving degradation of joints, including articular cartilage (the connective tissue that covers the ends of bones in joints) and subchondral bone (the bone just below the cartilage). In the most rudimentary sense, OA is caused by joint “wear and tear.” A joint is where two or more bones meet and make contact. Joints have co-evolved with bones to allow for movement and provide for mechanical support. To understand what can happen to joints, you must grasp their structure and function.

Structure and Function Collaborations

Structure varies in accordance with how the bones are connected to each other. Essentially there are three classifications: Fibrous joint, when the connection is characterized by dense connective tissue that is rich in collagen fibers; cartilaginous joint, when the bones are joined by cartilage; and synovial joint, when bones are not directly joined, but instead mediated by a synovial cavity containing a spongy lubricating fluid.

Function varies by the degree of mobility allowable: Synarthrosis, where there is little or no mobility (e.g., fibrous joints such as skull sutures); amphiarthrosis, where there is slight mobility (most of these are cartilaginous joints, e.g., vertebrae); diarthrosis, where a variety of movements is permitted (all diarthrosis joints are synovial joints, e.g., knee, elbow, shoulder, hip, etc.).

Meet-Ups Portent Wear-Downs

In the joint type that typically concerns us the most, between each of the bone “meet-ups” is a material known as cartilage, a firm, rubbery tissue that cushions your bones at the joints, which along with synovial fluid allows the bones to glide over one another. The problem is that cartilage can break down and wear away, especially with excessive use and especially with age. The breakdown particles diminish the synovial glide and can also affect the subchondral bone, which becomes thicker as the cartilage wears down. Excessive use may result from heavy-duty exercise or even too much dancing or jumpin’ and as a consequence—as bones rub together too much—pain, swelling, and stiffness can ensue.

Around the joint, bone spurs or extra bone may form. This can put strain on the ligaments (fibrous tissue that connects bones to other bones) and muscles (connected to bones by tendons) which can become weaker and stiffer. The symptoms of OA usually make their first appearance in middle age, and by the time of 70 years, almost everyone suffers some of the symptoms. Before age 55, there is an equal distribution of OA in men and women, but after it becomes more common in women.

Beyond Wear and Tear

In addition to “wear and tear” and long-term overuse (at work or in sports), there are other factors that can also lead to OA, including genetic predisposition, overweight or obesity (especially with regards to the risk of OA in the hip, knee, ankle, and foot joints), and fractures (or other joint injuries) which can lead to OA later in life. Then there are medical conditions that can lead to OA including: bleeding disorders in the joint, such as hemophilia; and disorders blocking the blood supply near a joint, leading to avascular necrosis. Then there are other kinds of arthritis, including rheumatoid arthritis, chronic gout, and pseudogout. But of all the joint problems or arthritic diseases, OA is the most common, characterized by articular cartilage degradation. This may include an accompanying periarticular bone response, an erosion of surrounding bones.


Cartilage can break down and wear
away, especially with excessive use
and especially with age.


Lack of Disease-Modifying Drugs

OA affected nearly 27 million people in the USA in 2006, and that total is projected to increase to 67 million by 2030.2 That’s an amazing increase, and at an annual cost to society in medical care and wage loss that is expected to reach nearly $100 billion dollars by 2020.3 Yet, according to at least one pronouncement, there is no disease-modifying drug therapy for OA.2 Current pharmaceutical recommendations for managing OA focus on relieving pain and stiffness and improving physical function with the use of nonopioid analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) including cyclo-oxygenase II inhibitors. However, while these drugs can reduce both pain and inflammation quite effectively, the long term use of NSAIDs has been found to associate with enhanced risk for gastrointestinal bleeding, hypertension, congestive heart failure, and renal insufficiency, among other adverse effects. Moreover, because of the high incidence of adverse events associated with both nonselective and cyclo-oxygenase II selective NSAID therapy, effective and safer alternative treatments for OA are badly needed.

Enter Boswellia, an Ancient Medicinal Plant

In India, the ancient herb Boswellia serrata (also known as Salai guggal in Ayurvedic medicine)—a medicinal plant belonging to the Burseraceae family—has long been known for its anti-inflammatory, anti-arthritic, and analgesic activity. In fact, the first reference to Boswellia dates back to 600 BCE or earlier when the paired pillars of Ayurvedic medicine were written, Both of these, the Suśruta Saṃhitā and the Caraka Saṃhitā, praise the resin of the Boswellia serrata for its anti-rheumatoid arthritis qualities.

In recent years, Boswellia has gained a lot of attention. Its gum resin contains boswellic acids and among these acids are β-boswellic acid, keto-β-boswellic acid, and acetyl-11-keto-β-boswellic acid (AKBA) and other active compounds. AKBA, perhaps the most active component of Boswellia, has been demonstrated to be a potent inhibitor of 5-lipoxygenase, a key enzyme in the biosynthesis of leukotrienes from arachidonic acid in the cellular inflammatory cascade.4


Of all the joint problems, osteoarthritis is
the most common, characterized by
articular cartilage degradation.


Advanced Boswellia Extract with 30% AKBA

One advanced extract of B. serrata, enriched to 30% AKBA (5-Loxin), has been shown through gene chip analysis to potently inhibit tumor necrosis factor alpha (TNF-α). Moreover, this Boswellia extract prevented the TNF-α-induced expression of matrix metalloproteinases (MMPs). One of these, MMP-3, is a cartilage degrading enzyme. The 5-Loxin extract also prevented adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) from increasing inflammation.

Furthermore, cell-based in vitro studies suggest that 5-Loxin can inhibit pro-inflammatory cytokines such as TNF-α and interleukin-1α. In one inflammation model, treatment with the 5-Loxin yielded significant improvement in paw inflammation in rats. It also exhibited significant anti-arthritic efficacy in another study with rats, while demonstrating high levels of safety, 2,000 to 3,000 times higher than the human equivalence dose. The 5-Loxin Boswellia extract was found to be non-genotoxic.

A Gene-Expression Study with the 30% AKBA Extract

One mechanism by which TNF-α can cause inflammation is by potently inducing the expression of adhesion molecules such as VCAM-1. In a study conducted only a few years ago, researchers set out to test the genetic basis of the anti-inflammatory effects of 5-Loxin in a system of TNF-α-induced gene expression in human microvascular endothelial cells (HMEC).5

The first whole genome screen for TNF-α-inducible genes in HMEC found that TNF-α acutely induced 522 genes and downregulated 141 genes in nine out of nine pairwise comparisons. Of the 522 genes induced by TNF-α in HMEC, 113 genes were clearly sensitive to the 5-Loxin Boswellia extract treatment. These TNF-α-induced genes have been found to be directly related to inflammation, cell adhesion, and proteolysis. The 5-Loxin prevented the TNF-α-induced expression of MMPs and also prevented the inducible expression of mediators of apoptosis.


Aflapin exhibited better inhibition of
5-lipoxygenase activity and MMP-3
than the 5-Loxin extract.


Most importantly, TNF-α-inducible expression of VCAM-1 and ICAM-1 were observed to be sensitive to the enriched extract. In fact, while TNF-α potently induced VCAM-1 gene expression, the 5-Loxin Boswellia extract completely prevented it. This result confirmed microarray findings and built a compelling case for the anti-inflammatory property of 5-Loxin. The aforementioned induced-rat-paw inflammation, which demonstrated a significant anti-inflammatory property of 5-Loxin, was consistent with the in vitro findings that were observed.

Aflapin More Effective than 5-Loxin

In a recent study, a novel synergistic Boswellic composition (Aflapin) derived from Boswellia serrata gum resin was found to be significantly better as an anti-inflammatory agent compared to the Boswellia extracts presently available in the market. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the comparative efficacy and tolerability of the 5-Loxin extract compared to Aflapin in the treatment of OA of the knee.6 Sixty OA subjects were included in the study and divide into three groups of 20. The first group received 100 mg of the 5-Loxin extract, the second group 100 mg of the Aflapin, and the third group a placebo. All groups took their respective doses daily for 90 days.

Each patient was evaluated for pain and physical functions by using the standard tools at the beginning (day 0), and at days 7, 30, 60 and 90. A battery of serum, urine and hematological biochemical measurements were taken. At the end, 57 subjects completed the study and both test materials conferred clinically and statistically significant improvements in pain scores and physical function scores in OA subjects.

Of interest, significant improvements in pain score and functional ability were recorded as early as 7 days after initiation of the study in the treatment group supplemented with Aflapin, but not for the 5-Loxin extract. Also, Aflapin exhibited better efficacy compared to the 5-Loxin extract. Both were judged to be safe for human consumption.

Better Bioavailability for Aflapin

Following up on this, an animal study was undertaken by many of the same researchers.7 In this study, the dose-dependent efficacy of the two Boswellia extracts were assessed against pain, joint stiffness, mobility and the cartilage degrading enzyme MMP-3 in OA rats. It was thought that the poor bioavailability of AKBA following oral administration might limit the anti-inflammatory efficacy of the 5-Loxin extract compared to Aflapin. It was suspected that Aflapin would demonstrate better bioavailability due to inclusion of a non-volatile oil portion of B. serrata gum resin.

The researchers found that Aflapin exhibited better inhibition of 5-lipoxygenase activity and MMP-3 than the 5-Loxin extract. Comparing the efficacy of these two extracts proved that the newer version was superior, and safe as well. Importantly, observations showed that the availability of AKBA in systemic circulation of experimental animals is increased by 51.78% in Aflapin-supplemented animals.

Early Efficacy for Novel Boswellic Composition

In a very recent 30-day, double-blind, randomized, placebo-controlled study, Aflapin was compared to the 5-Loxin extract in the management of clinical symptoms of OA of the knee.8 Sixty eligible OA subjects participated, with 30 receiving 100 mg of the 5-Loxin extract daily for 30 days, 30 receiving 100 mg of Aflapin daily for 30 days, and the remaining 30 receiving a placebo daily for 30 days.

As with the prior comparative study, each subject was evaluated for pain and physical functions by using the standard tools at the beginning, and then at days 5, 15 and 30. A series of biochemical tests in serum, urine and hematological parameters established the safety of Aflapin.


Aflapin, the new synergistic
formulation, produced significant
improvements in pain score
and functional ability in
as little as 5 days of treatment.


The observations suggest that Aflapin conferred clinically and statistically significant improvements in pain scores and physical function scores in OA subjects. In conclusion, Aflapin is a safe, fast acting and effective alternative intervention in the management of OA. The researchers found that it conferred clinically and statistically significant improvements in pain scores and physical function scores in OA subjects, and moreover, that the new synergistic formulation produced significant improvements in pain score and functional ability in as little as 5 days of treatment.

There are Other Osteoarthritis Supplements

A number of complexes have been identified and researched over the years as other effective approaches to OA, including: the glucosamines and chondroitin (see “Supplements Put the Brakes on Osteoarthritis” in the December, 2003 issue); bromelain, trypsin, and rutin (see “Enzyme-Flavonoid Mixture Fights Arthritis” in the June, 2005 issue), and turmeric (see “Turmeric Is The Spice of Life” in the November, 2004 issue. Fortunately, you don’t have to work to comprise a formulation of your own. That’s because there are already formulations that employ the latest science-based novel synergistic Boswellic compositions, such as Aflapin, as well as all the other worthy systems that have been clearly established. With a judicious choice, your joints may once again be jumpin’.

References

  1. Centers for Disease Control and Prevention (CDC).Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation --- United States, 2007-2009. MMWR Morb Mortal Wkly Rep 2010 Oct 8;59(39):1261-5.
  2. Sampson ER, Hilton MJ, Tian Y, Chen D, Schwarz EM, Mooney RA, Bukata SV, O’Keefe RJ, Awad H, Puzas JE, Rosier RN, Zuscik MJ.Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis. Sci Transl Med 2011 Sep 21;3(101):101ra93.
  3. Oliviero F, Ramonda R, Punzi L.New horizons in osteoarthritis. Swiss Med Wkly 2010 Sep 17;140:w13098. doi: 10.4414/smw.2010.13098.
  4. Sengupta K, Krishnaraju AV, Vishal AA, Mishra A, Trimurtulu G, Sarma KV, Raychaudhuri SK, Raychaudhuri SP. Comparative efficacy and tolerability of 5-Loxin and Aflapin against osteoarthritis of the knee: a double blind, randomized, placebo controlled clinical study. Int J Med Sci 2010 Nov 1;7(6):366-77.
  5. Roy S, Khanna S, Shah H, Rink C, Phillips C, Preuss H, Subbaraju GV, Trimurtulu G, Krishnaraju AV, Bagchi M, Bagchi D, Sen CK. Human genome screen to identify the genetic basis of the anti-inflammatory effects of Boswellia in microvascular endothelial cells. DNA Cell Biol 2005 Apr;24(4):244-55.
  6. Sengupta K, Krishnaraju AV, Vishal AA, Mishra A, Trimurtulu G, Sarma KV, Raychaudhuri SK, Raychaudhuri SP. Comparative efficacy and tolerability of 5-Loxin and Aflapin against osteoarthritis of the knee: a double blind, randomized, placebo controlled clinical study. Int J Med Sci 2010 Nov 1;7(6):366-77.
  7. Sengupta K, Kolla JN, Krishnaraju AV, Yalamanchili N, Rao CV, Golakoti T, Raychaudhuri S, Raychaudhuri SP. Cellular and molecular mechanisms of anti-inflammatory effect of Aflapin: a novel Boswellia serrata extract. Mol Cell Biochem 2011 Aug;354(1-2):189-97.
  8. Vishal AA, Mishra A, Raychaudhuri SP. A double blind, randomized, placebo controlled clinical study evaluates the early efficacy of Aflapin in subjects with osteoarthritis of knee. Int J Med Sci 2011;8(7):615-22.


Will Block is the publisher and editorial director of Life Enhancement magazine.

Featured Product

FREE Subscription

  • You're just getting started! We have published thousands of scientific health articles. Stay updated and maintain your health.

    It's free to your e-mail inbox and you can unsubscribe at any time.
    Loading Indicator