| Lipoxygenase Inhibition: A Missed opportunity for | | | | If the label does not specifically state that the AKBA |
| controlling pain and inflammation | | | | content is minimum 90% you are not getting the |
| Are we only "half treating" our back and joint pains? | | | | best quality possible. |
| Back and joint pains are among the top reasons for | | | | With the right quality and dosage, however, either |
| visits to the doctor. Yet complete resolution of the | | | | taken alone or together with other therapies |
| complaint is often slow in coming or never completely | | | | symptom relief could be seen from this nutritional |
| resolved. Why? | | | | modality. Improvement in previously therapy resistant |
| There are 2 major physiologic pathways leading to | | | | back or joint pain, prolonged "holding" of chiropractic |
| inflammatory and pain responses: the cyclooxygenase | | | | adjustments and faster pain relief after injury has |
| (COX) mediated and the lipoxygenase (5-LO) | | | | been routinely noted. |
| dependent one. While the former is widely known, | | | | Safety and toxicology; |
| and inhibited by the well popularized NSAID's (like | | | | High concentration boswellia extracts are considered |
| Celebrex, Vioxx(!)), etc, the second one is virtually | | | | GRAS - generally regarded as safe. There are |
| ignored in the current management of pain | | | | practically no side effects except for an occasional |
| syndromes. Principal cause for this is the failure of | | | | report of headache. There have not been any |
| major drug companies to develop synthetic drugs | | | | reports of the intestinal distress seen with other |
| that can inhibit the 5-LO and its downstream | | | | boswellia preparations. |
| metabolites, the all important leukotrienes. To make | | | | Conclusion |
| up for the failure to deal with the 5-LO, | | | | High concentration boswellia extracts with 90% or |
| pharmaceutical solutions like corticosteroids are usually | | | | more AKBA is highly beneficial for the treatment of |
| put in place - with their well known side effects. | | | | pain syndromes ranging from back to joints and |
| The bottom line is that when only one of two | | | | other damaged soft tissues. They can help in other |
| pathways to pain is addressed the patient is only | | | | organ and neurological pain conditions due to their |
| "half treated" and half satisfied. | | | | anti- inflammatory properties. It can be given as a |
| Lipoxygenase and pain | | | | stand alone solution or in conjunction with other COX |
| The 5-LO enzyme works to produce the "misery" of | | | | inhibitors. They are considered nutritional supplements |
| the leukotrienes.1 They are abundantly involved in | | | | and should be part of a general health maintenance. |
| over 35 chronic conditions including: asthma, allergies, | | | | (These statements have not been evaluated by the |
| colitis, arthritis, gastric disorders (promote ulcer | | | | FDA. These ingredients are not intended to diagnose, |
| formation, stimulate acid secretion, etc), scleroderma, | | | | treat, cure, or prevent any disease. Never start a |
| neurological diseases, and so on. 2 | | | | new program without consulting a qualified heath care |
| More recently the involvement of the leukotrienes in | | | | professional.) |
| pain syndromes has become clear from a multitude | | | | References |
| of studies. 1 | | | | 1. Whitehouse MW, Rainsford KD. Lipoxygenase |
| 5-LO and leukotriene B4 are involved in orofacial pain | | | | inhibition: The neglected frontier for regulating chronic |
| perception and mechanical and thermal sensitivity.3-7 | | | | inflammation and pain. Inflammopharmacology. |
| Postoperative incision pain in animal models could be | | | | 2006;14( 3-4):99-102. 2. Werz O, Steinhilber D. |
| considerably reduced using experimental 5-LO | | | | Pharmacological intervention with 5-lipoxygenase: New |
| inhibitors.8 | | | | insights and novel compounds. Expert Opinion on |
| The beneficial effects of 5-LO inhibition were | | | | Therapeutic Patents. 2005;15( 5):505-519. 3. Aley KO, |
| demonstrated in the reduction of inflammatory | | | | Levine JD. Contribution of 5- and 12-lipoxygenase |
| events accompanying experimental spinal cord injury. | | | | products to mechanical hyperalgesia induced by |
| 9 | | | | prostaglandin E2 and epinephrine in the rat. |
| Several studies have identified inflammatory | | | | Experimental Brain Research. 2003;148( 4):482-487. 4. |
| mediators in disk herniation, such as leukotrienes. | | | | Amann R, Schuligoi R, Lanz I, Peskar BA. Effect of a |
| Cytokines occurring in degenerated facets have been | | | | 5-lipoxygenase inhibitor on nerve growth |
| shown to contribute to the pain of degenerative | | | | factor-induced thermal hyperalgesia in the rat. |
| lumbar disorders. 10, 11 | | | | European Journal of Pharmacology. 1996;306( |
| 5-LO has been shown to be involved in both pain | | | | 1-3):89-91. 5. Bisgaard H, Kristensen JK. Leukotriene |
| modulation and induction of opioid tolerance at the | | | | B4 produces hyperalgesia in humans. Prostaglandins. |
| spinal level. 12 5-LO metabolites are found in clinical | | | | 1985;30( 5):791-797. 6. Chichorro JG, Lorenzetti BB, |
| cases of herniated nucleus pulposus and experimental | | | | Zampronio AR. Involvement of bradykinin, cytokines, |
| data gathered in the study of associated radicular | | | | sympathetic amines and prostaglandins in |
| pain in animals demonstrated that 5-LO inhibition may | | | | formalin-induced orofacial nociception in rats. British |
| prove to be beneficial in such conditions.13 | | | | Journal of Pharmacology. 2004;141( 7):1175-1184. 7. |
| Pharmacological inhibition of the 5-LO | | | | Martin HA. Leukotriene B4 induced decrease in |
| While the market availability of COX inhibitors is | | | | mechanical and thermal thresholds of C-fiber |
| widespread the opposite seems to be the case with | | | | mechanonociceptors in rat hairy skin. Brain Research. |
| pharmaceuticals in the lipoxygenase class direction. | | | | 1990;509( 2):273-279. 8. Gaspar AF, Prado WA. |
| Partially this is not due to lack of trying. Promising | | | | Comparison of pre- versus post-incision administration |
| experimental drugs had to be abandoned due to | | | | of intraplantar indomethacin and MK886 in a rat model |
| unacceptable side effects - death of animal subjects! | | | | of postoperative pain. Brazilian Journal of Medical and |
| Even those that made it to market carry warnings of | | | | Biological Research. 2007;40( 8):1141-1147. 9. |
| hepatotoxicity (Zileuton) or have been associated | | | | Genovese T, Rossi A, Mazzon E, et al. Effects of |
| with an increase in abnormal mental behavior | | | | zileuton and montelukast in mouse experimental spinal |
| (Singulair). On the other hand there is a persistent | | | | cord injury. British Journal of Pharmacology. 2008;153( |
| lack of research on the part of the pharmaceutical | | | | 3):568-582. 10. Goupille P, Jayson MIV, Valat J-, |
| industry secondary to a tragic underestimation of the | | | | Freemont AJ. The role of inflammation in disk |
| potential market size. | | | | herniation-associated radiculopathy. Seminars in |
| Financial disincentives explain the lack of studies of | | | | Arthritis and Rheumatism. 1998;28( 1):60-71. 11. |
| extracts of "natural" substances which are not easily | | | | Igarashi A, Kikuchi S, Konno S, Olmarker K. |
| patentable. | | | | Inflammatory cytokines released from the facet joint |
| Advances in nutritional therapy with high | | | | tissue in degenerative lumbar spinal disorders. Spine. |
| concentration boswellia (frankincense) extracts | | | | 2004;29( 19):2091-2095. 12. Trang T, McNaull B, |
| The premier 5-LO inhibitor is the natural, herbal | | | | Quirion R, Jhamandas K. Involvement of spinal |
| ingredient AKBA, acetyl-11-keto-beta-boswellia acid, | | | | lipoxygenase metabolites in hyperalgesia and opioid |
| the most active component of the frankincense, | | | | tolerance. European Journal of Pharmacology. |
| Boswellia serrata. Boswellia as such has been known | | | | 2004;491( 1):21-30. 13. Singh VP, Patil CS, Kulkarni SK. |
| for centuries to be a potent anti-inflammatory agent. | | | | Effect of licofelone against mechanical hyperalgesia |
| Studies have proven its efficacy in arthritis, colitis, | | | | and cold allodynia in the rat model of incisional pain. |
| allergies and environmental sensitivities. 14-16 | | | | Pharmacological Reports. 2005;57( 3):380-384. 14. |
| More recent studies have confirmed the analgesic | | | | Ammon HPT. Boswellic acids in chronic inflammatory |
| properties of boswellia extracts, both as stand alone | | | | diseases. Planta Medica. 2006;72( 12):1100-1116. 15. |
| solutions as well as synergistic enhancers of pain relief | | | | Ammon HPT. Boswellic acids for the treatment of |
| when given in conjunction with COX inhibitors, opioids | | | | chronic inflammatory diseases. Medizinische |
| and other NSAID's. 17, 18 | | | | Monatsschrift fur Pharmazeuten. 2003;26( 9):309-315. |
| The success of boswellia extracts is all the more | | | | 16. Poeckel D, Werz O. Boswellic acids: Biological |
| surprising since only poorly standardized products | | | | actions and molecular targets. Current Medicinal |
| have been available on the general market. The | | | | Chemistry. 2006;13( 28):3359-3369. 17. Bishnoi M, Patil |
| component AKBA is recognized as the active anti- | | | | CS, Kumar A, Kulkarni SK. Analgesic activity of |
| inflammatory principle in the boswellia and yet by far | | | | acetyl-11-keto-beta-boswellic acid, a |
| most of the formulas have only 1-3% AKBA | | | | 5-lipoxygenase-enzyme inhibitor. Indian Journal of |
| concentration. | | | | Pharmacology. 2005;37( 4):255-256. 18. Bishnoi M, Patil |
| Fortunately high concentration boswellia extracts are | | | | CS, Kumar A, Kulkarni SK. Protective effects of |
| now available with a concentration of over 90% | | | | nimesulide (COX inhibitor), AKBA (5-LOX inhibitor), and |
| AKBA! This leads to enhanced efficacy. There are a | | | | their combination in aging-associated abnormalities in |
| number of high quality boswellia products on the | | | | mice. Methods and Findings in Experimental and Clinical |
| market. To get the best a careful reading of the | | | | Pharmacology. 2005;27( 7):465-470. |
| supplement facts on the label is necessary. | | | | |