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Are we only "half treating" our patients?

It is well established by now that most chronic illnesses include 2 major inflammatory pathways in their pathogenesis: the cyclooxygenase (COX) mediated and the lipoxygenase (5-LO) dependent one. While the former is widely known, and inhibited by the well popularized NSAID's (like Celebrex, Vioxx (!)), etc, the second one is virtually ignored in the current management of disease syndromes. The failure to address this pathway is the possible cause for many a therapeutic failure and lack of complete resolution of the complaints. 1

The bottom line is that the patient is only "half treated" and half satisfied.

Lipoxygenase and inflammation

The 5-LO enzyme works on the arachidonate substrate to produce the "misery" of the leukotrienes. They in turn are abundantly involved in over 35 chronic conditions including: asthma, allergies, colitis, arthritis, gastric disorders (promote ulcer formation, stimulate acid secretion, etc), scleroderma, pain, neurological diseases, and so on. 2, 3

Pharmacological inhibition of the 5-LO

Many 5-LO inhibiting experimental drugs had to be abandoned due to unacceptable side effects - death of animal subjects! Even those that made it to market carry warnings of hepatotoxicity (Zileuton) or have been associated with an increase in abnormal mental behavior (Singulair).

Advances in nutritional therapy: AKBA 90™

The premier natural 5-LO inhibitor is the herbal ingredient AKBA, acetyl-11-keto-beta-boswellia acid, the most active component of the frankincense, Boswellia serrata. 4 Studies have proven its efficacy in arthritis 5, 6, colitis 7, 8, allergies and environmental sensitivities. 9 More recent studies have confirmed the analgesic properties of boswellia extracts, both as stand alone solutions as well as synergistic enhancers of pain relief when given in conjunction with COX inhibitors, opioids and other NSAID's. 10, 11 The success of boswellia extracts is all the more surprising since only poorly standardized products have been available on the general market. The component AKBA is recognized as the active anti- inflammatory principle in the boswellia and yet by far most of the formulas have only 1-3% AKBA concentration. Fortunately the AKBA Plus™ supplement is now available with a boswellia concentration of over 90% AKBA! The enhanced efficacy of this new formula is considerable.

Dosage and Administration:

To be fully effective, however, the correct dosage needs to be administered. What do scientific studies tells us in this respect? In a human study the plasma level of AKBA was 0.1µM after oral intake of 4x786mg unpurified B. serrata extract. 12 AKBA was found to have an IC50 =1.5µM-8µM and inhibition of the complement pathway occurred only at concentrations of >50 µM. 13 Apoptosis of various cancer cell lines could be achieved with an AKBA concentration >10 µΜ. 14 Pharmacokinetic studies were done on AKBA 15-17 in order to begin elucidating the optimal dosing. In one study, 12 healthy volunteers were given a one time dose of 333mg of a boswellia extract containing 2% AKBA. The plasma levels were assessed prior to and hourly after drug administration. The peak plasma levels were reached at 4.5 ± 0.55 hours. The elimination time was 4.5 ± 0.55 hours suggesting that the drug should be given at an interval of approx. 6 hours. Interestingly at six hours post drug the maximal plasma levels of AKBA of the 12 subjects were: 1.56; 1.41; 1.84; 2.18; 1.75; 2.73; 2.39; 1.79; 1.20; 0.99; 0.86; 3.18 (x 10-3 µM/ml) meaning that no more then 50% of the subjects reached the 1.5µM concentration that all the other studies demonstrated is the minimum needed for an effective inhibitory concentration.

What is then a desirable range for an oral dose of AKBA?

Based on the available data, a daily intake of at least 150 mg of pure AKBA would be needed in order to be in the minimally effective concentration range of 2µM. Due to its high concentration (54 mg AKBA pure/capsule) the target dosage can be reached effortlessly with AKBA Plus™. 1 to 3 caps daily are sufficient in most patients although occasionally higher amounts are needed and can be safely given. To accomplish the same with a product std. to 2-3% AKBA concentration, 12 to 18 capsules daily would have to be given. Clinically sufficient time must be given for a steady state to be reached and best results to occur. AKBA Plus™ is best given with a meal for maximal absorption-although the product can be safely ingested on an empty stomach. In the current formula fenugreek and Bioperine® have been added for additional absorptive benefits.

Clinical Cases:

In over 1 million dosages dispensed, clinical successes could be seen where previously therapeutic failure had been noted. Giving appropriate dosages has had a dramatically positive effect on the speed and degree of recovery of patients in many outpatient offices. Cases are reported where young adults with asthma taking 2-3 capsules AKBA Plus™ daily were completely symptom free. After stopping the AKBA several inhalers had to be resumed. They improved again when AKBA was resumed. Arthritis patients for whom no conventional program had sufficed became completely asymptomatic after several weeks of AKBA Plus™. Several patients with ulcerative colitis significantly improved by going from >14 bowel movements/ day to 2 BM's daily.

Safety and toxicology;

AKBA Plus™ contains only ingredients "generally regarded as safe" (GRAS). It has practically no side effects. Isolated cases of headache have been noted with daily dosages more than several capsules. There have not been any reports of the intestinal distress seen with other boswellia preparations. Toxicological studies attest to the safety of this formula. AKBA Plus™ is manufactured in a GMP approved facility. The supplement is third party tested and certified.

Conclusion

AKBA Plus™ is indispensable for the treatment of pain syndromes ranging from back to joints and other damaged soft tissues. It is appropriate in other organ and neurological pain conditions due to its anti- inflammatory properties. It can be given as a stand alone solution or in conjunction with other COX inhibitors. *

For more information:

Please contact the company and request the comprehensive AKBA report, professional catalog, etc.

Other pain related products from True Botanica include: Joint Relief Plus™; Pain Relief Plus™; Curcumin Plus™; Back Relief Plus™; all exclusively distributed to licensed prescribers.

References

1. Whitehouse MW, Rainsford KD. Lipoxygenase inhibition: The neglected frontier for regulating chronic inflammation and pain. Inflammopharmacology. 2006 [cited 14 May 2008];14(3-4):99-102. 2. Rubin P, Mollison KW. Pharmacotherapy of diseases mediated by 5-lipoxygenase pathway eicosanoids. Prostaglandins and Other Lipid Mediators. 2007 [cited 14 May 2008];83(3 SPEC. ISS.):188-97. 3. Werz O, Steinhilber D. Pharmacological intervention with 5-lipoxygenase: New insights and novel compounds. Expert Opinion on Therapeutic Patents. 2005 [cited 14 May 2008];15(5):505-19. 4. Ammon HPT. Boswellic acids in chronic inflammatory diseases. Planta Medica. 2006 [cited 14 May 2008];72(12):1100-16. 5. 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 [cited 14 May 2008];10(1):3-7. 6. Singh S, Khajuria A, Taneja SC, Khajuria RK, Singh J, Qazi GN. Boswellic acids and glucosamine show synergistic effect in preclinical anti-inflammatory study in rats. Bioorganic and Medicinal Chemistry Letters. 2007 [cited 14 May 2008];17(13):3706-11. 7. Anthoni C, Laukoetter MG, Rijcken E, Vowinkel T, Mennigen R, Müller S, et al. Mechanisms underlying the anti-inflammatory actions of boswellic acid derivatives in experimental colitis. American Journal of Physiology - Gastrointestinal and Liver Physiology. 2006 [cited 14 May 2008];290(6). 8. Madisch A, Miehlke S, Eichele O, Mrwa J, Bethke B, Kuhlisch E, et al. Boswellia serrata extract for the treatment of collagenous colitis. A double-blind, randomized, placebo-controlled, multicenter trial. International Journal of Colorectal Disease. 2007 [cited 14 May 2008];22(12):1445-51. 9. Ammon HPT. Boswellic acids: Leukotriene biosynthesis inhibitors. Deutsche Apotheker Zeitung. 1997 [cited 14 May 2008];137(3):53-4. 10. Bishnoi M, Patil CS, Kumar A, Kulkarni SK. Potentiation of antinociceptive effect of NSAIDs by a specific lipooxygenase inhibitor, acetyl 11-keto-beta boswellic acid. Indian Journal of Experimental Biology. 2006 [cited 14 May 2008];44(2):128-32. 11. Bishnoi M, Patil CS, Kumar A, Kulkarni SK. Analgesic activity of acetyl-11-keto-beta-boswellic acid, a 5-lipoxygenase-enzyme inhibitor. Indian Journal of Pharmacology. 2005 [cited 14 May 2008];37(4):255-6. 12. Poeckel D, Werz O. Boswellic acids: Biological actions and molecular targets. Current Medicinal Chemistry. 2006 [cited 9 May 2008];13(28):3359-69. 13. Safayhi H, Sailer ER, Ammon HPT. 5-lipoxygenase inhibition by acetyl-11-keto-β-boswellic acid (AKBA) by a novel mechanism. Phytomedicine. 1996 [cited 14 May 2008];3(1):71-2. 14. Liu J-, Huang B, Hooi SC. Acetyl-keto-β-boswellic acid inhibits cellular proliferation through a p21-dependent pathway in colon cancer cells. British Journal of Pharmacology. 2006 [cited 14 May 2008];148(8):1099-107. 15. Shah SA, Rathod IS, Suhagia BN, Patel DA, Parmar VK, Shah BK, et al. Estimation of boswellic acids from market formulations of boswellia serrata extract and 11-keto β-boswellic acid in human plasma by high-performance thin-layer chromatography. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 2007 [cited 14 May 2008];848(2):232-8. 16. Sharma S, Thawani V, Hingorani L, Shrivastava M, Bhate VR, Khiyani R. Pharmacokinetics study of 11-keto β-boswellic acid. Phytomedicine. 2004 [cited 14 May 2008];11(2-3):255-60. 17. Sharma JN, Mohammed LA. The role of leukotrienes in the pathophysiology of inflammatory disorders: Is there a case for revisiting leukotrienes as therapeutic targets? Inflammopharmacology. 2006 [cited 14 May 2008];14(1-2):10-6.