Summary

The pro-inflammatory leukotrienes (LT’s), generated by the 5-lipoxygenase (5-LO) enzyme, are heavily involved in the pathogenesis of inflammatory and resorptive bone diseases.1 No 5-LO inhibiting drugs are currently approved for bone diseases. The few synthetic LT antagonists that might be given as an off label medication have significant potential side effects.

However, from the gum resin of the boswellia tree the acetyl-11-keto-beta-boswellic acid, AKBA, a very potent, natural, 5-LO and leukotriene inhibitor, can be extracted. 2, 3 Numerous studies show its usefulness in resorptive and inflammatory diseases. 44, 45

Recently, a novel boswellia formula, std. to 90% AKBA has become available.* It shows increased clinical effectiveness over the older, lesser purified preparations and avoids some of their pitfalls. AKBA Plus ™ is rapidly becoming a Gold Standard boswellia formulation with wide applicability in nutritional programs for both bone and other chronic diseases.*   

5-Lipoxygenase and Leukotrienes in resorptive and inflammatory bone diseases
               
Multiple chemical mediators are constitutively produced from rheumatoid synovium resulting in joint destruction. These include arachidonic acid metabolites such as prostaglandins and leukotrienes, vasoactive amines, kinins, endothelins, complement fragments, reactive oxygens, neutral proteinases and cytokines. 4

The involvement of prostaglandins and thromboxanes in the pathophysiology of bone diseases, especially arthritis, is well known. These inflammatory mediators are the target of both synthetic drugs such as Celebrex, Vioxx, ibuprofen, etc. as well as natural substances like curcuminoids, and others.
               
Awareness of the role played by the pro- inflammatory metabolism of arachidonic acid into its leukotrienes (LT’s), via the 5-lipoxygenase pathway, however, is lagging behind. And yet the crucial position of the LT’s in causing the final pathological picture is becoming increasingly evident.
               
In an excellent recent review, Hikiji et. al. 5 point out this lack of appreciation for the biologic action of 5-lipoxygenase (5-LO) and LT’s in the bone remodeling of arthritis, osteoporosis, osteoarthritis and periodontitis.

The expression of 5- lipoxygenase (5-LO) and the 5-lipoxygenase activating protein (FLAP) genes in osteoarthritis and RA synoviocytes was studied at the transcriptional level. mRNA for both genes was detectable. The expression of 5-LOX and FLAP mRNA led to the synthesis of 5-LO metabolites. Consequently, it was concluded that these 5-LO products participate in inflammatory processes leading to joint destruction in RA. 6

In another study collagen-induced arthritis in DBA/1 mice was used as an experimental model of human rheumatoid arthritis. In the FLAP deficient DBA/1 mice the severity of collagen-induced arthritis was substantially reduced when compared with wild- type or heterozygous animals. This was not due to an immunosuppressive effect, because anti-collagen antibody levels were similar in wild-type and FLAP-deficient mice. The data demonstrated that leukotrienes play an essential role in both the acute and chronic inflammatory arthritis response. 7

The LT’s produce a veritable “misery” in the bony and cartilaginous tissues. 8, 9

Among the LT’s, LTB4 is the most important mediator of inflammatory pain.10, 61

Injecting LTB4 into a rat paw results in a prolonged neutrophil dependent hyperalgesic reaction associated with a marked lowering of the pain threshold.11

Several reports have demonstrated that LTB4 production is stimulated in inflammatory bone-resorptive diseases. This is true especially in rheumatoid arthritis56, but also to a lesser extent in osteoarthritis and periodontitis.57  
    
LTB4 and cysteinyl LTs increase osteoclastic bone resorption in vitro and in vivo by increasing the number and/or activity of osteoclasts.12  

On the other hand, LTB4 partially inhibits the proliferation of primary osteoblasts13

Erosive synovitis is critically reliant on the generation of leukotrienes, and more specifically on leukotriene B4 (LTB4), for disease induction as well as perpetuation. Pursuing the cellular source for this mediator it was found, via reconstitution experiments, that mast cells are a dispensable source of leukotrienes, whereas arthritis susceptibility can be restored to leukotriene-deficient mice by intravenous administration of wild-type neutrophils. These experiments demonstrate a non-redundant role for LTB4 in inflammatory arthritis and define a neutrophil mediator involved in orchestrating the synovial eruption. Yet again the conclusion was that in rheumatoid arthritis, primarily neutrophils produce LTB4’s and in turn respond to them. 14

The levels of LTB4 are higher in the synovial fluid from rheumatoid arthritis patients than from osteoarthritis patients. In addition, LTB4 levels are significantly correlated with the number of leukocytic cells and the concentrations of rheumatoid factor and immune complexes that exist in the synovial fluid from rheumatoid arthritis patients. LTB4 and LTC4 are produced in synovial tissues, but not in the chondrocytes of osteoarthritis patients. 15, 58, 59

LTB4’s seem to be involved in inflammatory joint diseases irrespective of the causative factor of the inflammation.

In a study of arthritis secondary to Lyme’s disease the potential role of LTB4 and cysteinyl leukotrienes was evaluated. The LTB4 levels in synovial fluid were significantly increased in patients with Lyme arthritis when compared to the control subjects. 16

Arthritis is a frequent complication of pustular psoriasis. However, the mechanism of onset of this arthritis still remains unclear.  A study was conducted to determine whether leukotriene LTB4 or LTC4 is one of the proinflammatory mediators that possibly enhance exacerbation of the arthritic lesions. The synovium of the knee joints showed histopathologic evidence of polymorphonuclear leukocyte (PMN) invasion, edema and dilatation of small vessels showing similarity to a histologic reaction in the skin lesions. The immunoreactive (i-) LTB4 and i-LTC4 in the samples significantly exceeded the amount measured in osteoarthritis patients used as the controls. Thus, i-LTB4 and i-LTC4 appear to be generated in the arthritis lesions of pustular psoriasis, the former attracting PMNs to the joints and the latter causing exudation of synovial fluid. 17

Endogenous synthesis of cysteinyl leukotrienes in juvenile rheumatoid arthritis (JRA) was investigated. Cysteinyl leukotriene synthesis was assessed by measuring the excretion of leukotriene E4 (LTE4) in urine. Excretion of LTE4 into urine was significantly enhanced in children with JRA compared with that in healthy children. There was a positive correlation between LTE4 excretion and the number of affected joints. 18

LTB4 is involved in cell influx and articular incapacitation in zymosan induced arthritis. Moreover, the data suggests that IL-1 and TNF-alpha are under the control of locally produced LTB4.19   
                 
More recent work has demonstrated a direct correlation between mechanical stress and the initiation of functional changes that result in increased levels of nitric oxide and leukotrienes. 20

Besides LTB4’s, other 5-LO metabolites like 5-HETEs have also been reported to have a negative regulation on bone formation. 21, 22  

As proof for the involvement of LT’s in inflammatory joint disease, LTB4 receptor antagonists have been found to have positive therapeutic consequences in rheumatoid arthritis 7, 23.

The direct interaction between the cyclooxygenase and the lipoxygenase pathways are also becoming more transparent.
               
According to a recent review osteoarthritis can be divided into two categories depending on the levels of prostaglandins E2 (PGE2) and LTB4’s expressed. The starting point is that prostaglandins and leukotriene B4 have been shown to regulate proinflammatory cytokine and interstitial collagenase synthesis in human osteoarthritis synovial membrane explants. Human osteoarthritis osteoblasts produce variable levels of prostaglandin E2 and leukotriene B4 compared with normal osteoblasts. Prostaglandin E2 levels can distinguish two types of patients with osteoarthritis: osteoblasts from one group produce low levels of prostaglandin E2 and interleukin-6, and the other shows an increase in production. In contrast, osteoarthritis osteoblasts that produce high levels of prostaglandin E2 produce low levels of leukotriene B4 and vice versa. This observation could be explained by the selective metabolism of arachidonic acid via the 5-lipoxygenase or cyclooxygenase pathways in osteoarthritis osteoblasts. 51

More recent clinical observations are emerging showing the value of dual 5-LO and COX inhibitors in the treatment of osteoarthritis. In an animal model, Licofelone, a new experimental anti-inflammatory drug with such a dual inhibitory activity, prevented abnormal subchondral bone cell metabolism in experimental dog osteoarthritis. 60

Licofelone clinical studies demonstrated pain relief as well as even a mild disease modifying trend. As far as side effects were concerned there was a trend towards a reduction in overall gastrointestinal adverse effects as compared to naproxen. Gastrointestinal adverse effects were similar in patients treated with celecoxib and licofelone. Non-gastrointestinal events, (namely worsening of peripheral edema with celecoxib and the incidence of aggravated hypertension with naproxen) while present, were reduced in the licofelone groups. The drug has not been presented to the FDA for approval as a treatment of OA.

5-Lipoxygenase and Leukotrienes in Osteoporosis

A causative involvement of 5-LO, LTB4 and other arachidonic acid derived eicosanoids in osteoporosis is becoming more apparent. Again, among the 5-LO generated LT’s especially LTB4 seems to activate osteoclasts and cause surface erosion. 62

Bone resorption requires cooperation between osteoclasts and mononuclear accessory cells. 5-LO metabolites have been shown to stimulate the process of resorbing calcified matrices. 63 

Various animal models using experimental inhibition of 5-LO have prevented loss of bone mass in rodents, with a concomitant increase of femur and humerus volume, density, femur calcium levels and ash weight. 64, 65

The natural inhibition of 5-LO and LT’s by Boswellic acids (BA’s), especially the AKBA fraction
               
Sadly, it is little known that a potent natural inhibitor of the 5-lipoxygenase enzyme is available. 24, 25
               
Principally among the many extractive fractions of the gum resin of frankincense, Boswellia serrata, is the 5-LO inhibitor fraction AKBA, acetyl-11-keto-beta-boswellia acid. 2 Boswellia as such has been known for centuries to be a potent anti-inflammatory agent. Studies have proven its efficacy not only in joint diseases but also in asthma, allergies and environmental sensitivities, and various forms of cancers. 3 (Of interest are the newer findings regarding the anti-neoplastic properties of AKBA in prostate, pancreas, bladder and breast cancers). 26-28

Significantly, considering the pervasive role of LTB4 in bone diseases, AKBA was found to specifically inhibit production of LTB4 in a dose dependent manner and with a very low IC50 of 1.5 μM.

AKBA was proven to have a three times more potent inhibition of LT’s synthesis then the unpurified boswellic acids. 29

Initially, it was thought that AKBA inhibits only the 5-lipoxygenase enzyme pathway and consequently the leukotriene biosynthesis. However, experimental evidence now shows that AKBA inhibits COX-1 product formation as well in a concentration-dependent manner. The inhibitory effect of AKBA is reversible, and increased levels of arachidonic acid (AA) as substrate for COX-1 impair the efficacy. In contrast, COX-2 was less efficiently inhibited by BAs as compared to COX-1. 47

We now know that AKBA exerts its anti-inflammatory effects by a multitude of mechanisms: non-redox inhibition of the 5-LO;  impairing leukocyte infiltration; nearly complete suppression of the complement pathway; inhibition of mast cell degranulation, NFκB pathway, matrix metalloproteinases and adhesion receptors, IL-2 and IL-1β,  human leukocyte elastase,  topoisomerase I and II and  the activity of P-glycoprotein in leukemia cell lines; suppression of macrophage NO production, thus lessening the risk of anaphylaxis, and suppression of TNFα induction, as well as suppression of the P-selectin up-regulation; and more. 30-34

The role of AKBA in arthritic bone diseases

Early reports nearly 38 years ago provided the first experimental proof that boswellia extracts had analgesic properties. 35, 36

Later reports in animal models consistently showed that Boswellia serrata extracts (BE’s) had significant anti-inflammatory effects.
               
In an animal model study Boswellia extracts displayed marked anti-inflammatory activity in carrageenan induced edema in rats and mice and dextran caused edema in rats. It was equally effective in adrenalectomised rats. In formaldehyde and adjuvant arthritis, BE’s produced prominent anti-arthritic activity but no significant effect was observed in cotton pellet-induced granuloma test. They inhibited an inflammation induced increase in serum transaminase levels and leucocyte counts. The gestation period or parturition time in pregnant rats or onset time of castor oil-induced diarrhea was unaffected and no significant effect was seen on cardiovascular, respiratory and central nervous system functions. No ulcerogenic effects were found in the rat stomach. The oral and intraperitoneal LD50 was greater than 2 g/Kg in mice and rats. 37
               
A next study revealed the synergistic effect of boswellic acid mixture (BA) and glucosamine for anti-inflammatory and anti-arthritic activities in rats. Two experiments were conducted looking at the acute anti-inflammatory activity in carrageenan induced edema and looking at the chronic anti-arthritic activity in Mycobacterium-induced arthritis. Five groups of animals were studied: the vehicle control, positive control (ibuprofen 100 mg/kg), boswellic acids (250 mg/kg), glucosamine (250 mg/kg) and a combination of boswellic acids (125 mg/kg) and glucosamine (125 mg/kg). BA when administered at 250 mg/kg in rats significantly inhibited carrageenan-induced paw edema and Mycobacterium-induced developing arthritis. In comparison to boswellic acids, glucosamine when administered at 250 mg/kg showed a mild effect in carrageenan-induced edema and moderate inhibition of paw swelling against developing arthritis. Although the combination of boswellic acids and glucosamine did not affect the acute inflammation to a greater extent, a significant chronic anti-arthritic activity was observed. The conclusion drawn was that a synergistic effect occurred in chronic inflammatory conditions when both boswellia and glucosamine were administered simultaneously. 38

The therapeutic effect of various boswellic acid formulations was extensively investigated in
adjuvant induced arthritic rats in relation to urinary excretion of connective tissue metabolites like hydroxyproline, hexosamine and uronic acid. Compared to controls, the arthritic animals showed an increase in the excretion of these metabolites in urine. The elevated levels of urinary hydroxyproline, hexosamine and uronic acid in the arthritic animals were found to be slightly decreased in the acute phase and significantly decreased in the chronic phase of the disease following the administration of boswellic acids. The results of the investigation indicated that both these anti-inflammatory resin extracts could offer a protective action against changes induced by adjuvant induced arthritis. 39
               
The effect of BA’s on lysosomal stability was studied by determining the activity of beta-glucuronidase, a typical lysosomal enzyme, in various sub-cellular fractions and its release from the lysosome-rich fraction. Adjuvant arthritic animals showed a significant increase in the beta-glucuronidase activity in sub-cellular fractions. The increased rate of the release of beta-glucuronidase from lysosome-rich fraction clearly suggested that arthritic syndrome caused decreased stability of the lysosomes. Administration of boswellic acids to arthritic animals was found to increase the lysosomal stability by inhibiting the rate of release from lysosome-rich fractions and reducing beta-glucuronidase activity in various sub-cellular fractions. 40

In yet another study boswellic acids (BA’s) demonstrated dose-related anti-inflammatory activity (AIA) in acute tests of carrageenan-, histamine- and dextran-induced edema in rats and mice. They elicited inhibitory action on acetic acid induced vascular permeability in mice. Marked AIA was observed in chronic models of adjuvant-induced polyarthritis and formaldehyde arthritis in rats and bovine serum albumin-induced arthritis in rabbits. It produced significant protective effects in sodium urate gouty arthritis in dogs. BA’s reduced exudate volume and inhibited leucocyte migration in carrageenan-induced pleurisy in rats. BA’s additionally elicited antipyretic activity in rats and rabbits. 41
               
The effect of boswellic acids on bovine serum albumin (BSA)-induced arthritis in rabbits was studied. Oral administration of boswellic acids (25, 50 and 100 mg/kg/day) significantly reduced the population of leucocytes in a BSA-injected knee and changed the electrophoretic pattern of the synovial fluid proteins. The local injection of boswellic acids (5, 10 and 20 mg) into the knee 15 min prior to BSA challenge also significantly reduced the infiltration of leucocytes into the knee joint, reduced the infiltration of leucocytes into the pleural cavity and inhibited the migration of PMN in vitro. The leucocyte-inhibitory activity of boswellic acids was not due to its cytotoxic effect. The boswellic acids did not show any detergent or surfactant properties.48
               
Boswellic acids (BA’s) were shown to exhibit anti-inflammatory properties through inhibition of complement. In adjuvant-induced arthritis and carrageenan-induced paw edema in rats, BA’s were found to possess significant anti-inflammatory and complement-inhibitory activities. The intraperitoneal injection of BA (100 mg/kg twice a day), before and after FCA challenge and thereafter repeated for several days, significantly reduced foot pad thickness of experimental animal models and simultaneously also reduced complement activity. It also showed marked reduction in complement levels and inflammatory effects on carrageenan-induced paw edema in rats when injected intraperitoneally (100 mg/kg twice a day). 49
                       
The dried gum resin of Boswellia carterii (BC), has been used in a random, blinded study to observe the anti-arthritic effects and compare them to vehicle control in a Lewis rat adjuvant arthritis model (n = 8/group). Arthritis was induced by injecting CFA subcutaneously into the base of the tail, and the boswellia extract was administered orally for 10 consecutive days beginning on day 16 after the injection. Arthritic scores, paw edema, and the local tissue pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) were assessed. Toxicity and adverse effects of the extract were evaluated. At 0.90 g/kg per day, BC significantly decreased arthritic scores between days 20 and 25 and reduced paw edema on days 18, 20 and 22 compared to control. It also significantly suppressed local tissue TNF-α and IL-1β. The data showed that BC extract has significant anti-arthritic and anti-inflammation effects and suggest that these effects may be mediated via the suppression of pro-inflammatory cytokines. 42
               
Endothelial cells are critical elements in the pathophysiology of inflammation. Tumor necrosis factor (TNF) α potently induces inflammatory responses in endothelial cells. Recently the genetic basis of the anti-inflammatory effects of Boswellia extract (BE) was examined in a system of TNFα-induced gene expression in human microvascular endothelial cells (HMECs). Of the 522 genes induced by TNFα in HMECs, 113 genes were sensitive to BE. BE prevented the TNFα-induced expression of matrix metalloproteinases (MMPs). In the current work, the effects of BE on TNFα-inducible MMP expression in HMECs were tested. To evaluate the significance of AKBA effects of BE’s containing either 3% or 30% (5-Loxin®) AKBA were compared. Pretreatment of HMECs for 2 days with BE’s potently prevented TNFα-induced expression and activity of MMP-3, MMP-10, and MMP-12. In vivo, BE’s protected against experimental arthritis. In all experiments, both in vitro and in vivo, BE’s with 30% AKBA were more effective than BE’s of 3% AKBA.  50
               
In a study with larger animals, 29 dogs with manifestations of chronic joint and spinal disease were observed. Osteoarthritis and degenerative conditions were confirmed radiologically in 25 of 29 cases. The boswellia resin extract was administered with the regular food at a dose of 400mg/ 10 kg body weight once daily for 6 weeks. Already after two weeks of treatment, an overall efficacy of the dietary supplement was evident in 71% of 24 eligible dogs. A statistically significant reduction of severity and resolution of typical clinical signs in individual animals, such as intermittent lameness, local pain and stiff gait, were reported after 6 weeks. Effects of external factors that aggravate lameness, such as "lameness when moving" and "lameness after a long rest" diminished gradually. The authors suggest that when quality and stability of the resin extract are ensured, the standardized preparations can be recommended as an herbal dietary supplement in order to provide symptomatic support in osteoarthritic disease. 43
               
Several human clinical trials have been performed.
               
A randomized double blind placebo controlled crossover study was conducted to assess the efficacy, safety and tolerability of Boswellia serrata extract (BSE) in 30 patients with osteoarthritis of the knees. 15 patients in each group received either BSE or placebo for eight weeks. After the first intervention, washout was given and then the groups were crossed over to receive the opposite intervention for eight weeks. All patients receiving BSE treatment reported a decrease in knee pain, increased knee flexion and increased walking distance. The frequency of swelling in the knee joint was decreased. Radiologically there was no change; however the observed differences between the BSE treated and placebo group were clinically relevant and statistically significant. BSE was well tolerated by the subjects except for minor gastrointestinal complaints. 45
               
The clinical efficacy of a mixture containing Withania, Boswellia serrata extracts, curcumin and a zinc complex was evaluated in a randomized, double-blind, placebo controlled, cross-over study in patients with osteoarthritis. After a one-month single blind run-in period, 42 patients with osteoarthritis were randomly allocated to receive either a treatment with the mixture or a matching placebo for a period of three months. After a 15-day wash-out period the patients were transferred to the other treatment for a further period of three months. Clinical efficacy was evaluated every fortnight on the basis of severity of pain, morning stiffness, Ritchie articular index, joint score, disability score and grip strength. Other parameters like erythrocyte sedimentation rate and radiological examination were carried out on a monthly basis. Treatment with the mixture formulation produced a significant drop in severity of pain and disability. Radiological assessment, however, did not show any significant changes in both the groups. 46

Dosage and Administration

The currently available understanding of the boswellia components metabolism and functions helps to clarify which boswellia extracts are going to give maximum clinical benefits.
               
Since the anti-inflammatory value of the AKBA fraction is undoubtedly superior and since the other boswellic components may in fact be, under certain conditions, even counter productive to the stated therapeutic goals, knowing the AKBA standardization of a particular formula is of critical importance. 
           
Not surprisingly, the most convincing therapeutic successes were seen, both in individual doctors’ practices and in controlled studies, when sufficiently high dosages of AKBA were administered such that adequate plasma levels could be reached. The success of the work with boswellia extracts up to now is all the more surprising since only poorly AKBA standardized products have been available on the general market.
               
The relevance of the quality and quantity of the boswellia fractions in ensuring therapeutic success became evident in a study of outpatients with active RA. They were enrolled into a multicenter controlled trial and given only 9 tablets of BA’s (total 3600 mg daily) containing a non specified AKBA amount, or placebo. In that case no measurable efficacy over placebo judging by laboratory or clinical parameters could be ascertained. 44
               
AKBA Plus™ now allows for the first time that the necessary effective plasma levels can be reached to ensure a higher success rate then before. 

The boswellia extract is standardized to 90% AKBA as opposed to the commonly available 1-3% AKBA content. (Most formulas even list only a general boswellic acids concentration with no mention of the AKBA content, which obviously is inadequate.)
               
The enhanced efficacy of this new formula is considerable.

In nearly 2 million dosages dispensed clinical successes could be seen in a vast majority of patients.

Based on clinical observations and pharmacokinetic data on AKBA52, 53 the start up dosage for most adults should be a daily dose of a total of 150mg, divided in three doses.  
               
Studies have shown, however, that the actual AKBA dosage needed to achieve the anti–inflammatory strength of corticosteroids might be closer to 500 mg per day.54 This would be the equivalent of 9-10 capsules daily of AKBA Plus™. One patient has reported complete resolution of all symptoms only after taking 12 AKBA Plus™ capsules daily for several weeks.

(To achieve the plasma levels of these 10 AKBA Plus™ capsules approx. 30 caps of common preparations would be needed, clearly not an acceptable proposition).

Children obviously need smaller doses, for example one capsule divided in several portions. The capsules may be opened and the contents may be mixed in such carriers as apple sauce, yogurt, etc. Titrating up to larger doses as needed for best effect is well tolerated.

(For additional prescribing information please see our separate communication with dosage instructions, available from True Botanica; or register for one of our free phone teaching conferences.)
      
Ideally, in order to enhance effectiveness, AKBA Plus™ should be administered every 8 hours. This will lead to the most consistent blood levels since the half life of AKBA is about 6-7 hours.
     
The bioavailability of AKBA Plus™ is enhanced in this professional formula through the addition of Fenugreek and Bioperine®. However, giving the supplement with a slightly fatty meal will further improve absorption.

Safety and toxicology;
               
Based on the review of tolerability of nearly 2 million administered doses, AKBA Plus™ is virtually side effects free.  Isolated cases of headache after AKBA Plus™ ingestion have been noted with intake of even one single capsule. There has been no dose dependent intolerance observed. There have not been any reports of the intestinal distress seen with many other boswellia preparations. Toxicological studies also attest to the safety of this AKBA formulation. These positive safety findings distinguish AKBA Plus™ from non-purified boswellia extracts where some safety concerns remain. 55
               
AKBA Plus™ is manufactured in a GMP approved facility. The supplement is third party tested and certified.

Conclusion
 
There is convincing evidence that both the cyclooxygenase and the lipoxygenase proinflammatory pathways are involved in the pathophysiology of arthritis, osteoarthritis and other resorptive bone diseases.
               
Currently only the COX metabolites are targeted. Not to address the necessary inhibition of the 5-LO enzyme and the inhibition of the leukotriene synthesis leaves a patient essentially only “half treated” and likely with continuing symptoms.
               
Moreover, considering that suppressing the COX pathway leads to a shifting toward increased expression of the leukotrienes condemns the patient to needing an even higher amount of steroids or NSAID’s in order to manage the pain syndrome.
               
Additionally, giving an adequate amount of boswellia extracts ensures a synergistic effect which increases the effectiveness of the other therapies given.
               
Since AKBA is more than likely a dual COX and 5-LO inhibitor it is even reasonable to start a nutritional program with AKBA Plus ™ first as a stand alone and add a natural COX inhibitor such as curcumin, for example, at a later date if needed. For all these reasons- to wit because there is no arthritic joint disease that does not have a 5-LO mediated pathology- giving a quality boswellia preparation should be a “must give” consideration in the nutritional treatment of all patients with bone and joint disease.  
In order to achieve reliable results, however, adequate blood levels of the most active anti- inflammatory boswellia fraction, the AKBA, must be reached. This can easily be accomplished with highly purified and concentrated AKBA Plus ™ - arguably the most potent boswellia formula on the market.

AKBA Plus™ is positioned to become the Gold Standard supplement in its class.**         

*For more information:

The monograph: “Therapeutic Advantages of a New Pharmaceutical Grade Boswellia Extract is available to licensed physicians.
               
Please contact the company and request other professional AKBA reports on asthma, colitis, prostate disease, and detailed instructions on how to prescribe AKBA for best results.
               
A professional catalog on other AKBA containing condition specific health supplements is also available.

**These statements have not been evaluated by the FDA.  These products are not intended to diagnose, treat, cure, or prevent any disease.

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