Safely Manage Joint Inflammation: Curcumin

The standard of care for the arthritic patient is prescription drugs with a long list of side effects.1-3 These drugs do nothing to stop the bone and joint destruction caused by osteoarthritis or rheumatoid arthritis.4,5 Beyond that, the patient must learn to live with their crippling pain and limited mobility.

Fortunately, help is readily available. A highly specialized complex of curcumin known as BCM-95® fights the joint-damaging effects of arthritis by attacking multiple inflammatory targets at once.

A team of internationally recognized scientists has published an impressive clinical trial of this superior-absorbing curcumin complex that most Life Extension® members have used for the past several years. The study subjects were rheumatoid arthritis patients who suffered from sky-high levels of inflammation that affected not only their joints but other vital tissues as well.5

In this 2012 study, curcumin beat out the standard arthritis drug diclofenac on most measures of effectiveness.5 Curcumin was free of any of the side effects that so often accompany drug therapy.

The study also showed this superior-absorbing curcumin directly attacked the source of the problem—inflammation— rather than simply masking pain and other symptoms.5

Applying Curcumin's Multitargeted Benefits To Arthritis

Curcumin is derived from the bright yellow Indian spice turmeric and has been used by traditional medicine for almost four thousand years.6 Curcumin is well-established in the medical literature as a powerful anti-inflammatory ingredient.5 Unlike pharmaceuticals, curcumin acts through multiple pathways and on numerous targets to limit the inflammatory response that underlies both rheumatoid and osteoarthritis (See table 1 at bottom of this page).6

Scientists now universally recognize that multi-targeted therapies like curcumin are vastly superior to the typical single-targeted mechanisms of conventional drug treatments.6,7 Curcumin is a potent antioxidant, and also boosts natural antioxidant systems inside your cells.8 Curcumin can also enhance other natural detoxifying machinery in your liver.8 By slowing naturally occurring cell death in joint tissue, curcumin can help preserve supple, youthful joints.9-12

But where curcumin really shines is in directly suppressing the inflammation that underlies not only rheumatoid arthritis, but also most of the chronic diseases of aging that afflict all of us sooner or later.13 One recent report showed that curcumin can reduce all of the inflammation-promoting molecular targets for which the FDA currently approves single-targeted (and often dangerous) pharmaceuticals.7

Curcumin's ability to safely quash inflammation in such a broad-spectrum manner makes it a compelling topic among anti-aging researchers. It is being studied for its potential benefits in a number of inflammation based diseases such as Alzheimer's, cardiovascular disease, cancer, multiple sclerosis, and diabetes.5,13 To explore curcumin's therapeutic potential for rheumatoid arthritis, one of the most inflammatory diseases known, a distinguished team of international researchers decided to examine the benefits of curcumin. Based in the US at Baylor University Medical Center and in India at the Nirmala Medical Centre, the team's members represent some of the most advanced thinkers in the field.

Curcumin's Effectiveness Against Rheumatoid Arthritis

The researchers enrolled 45 people with active rheumatoid arthritis during a flare-up of the disease.5 That strategy allowed the researchers to test curcumin's effects at the peak of the inflammatory response. Each of the 45 patients was randomly assigned to one of three study groups. Group 1 was the curcumin-only group. Each patient in this group received 500 mg/day of the superior-absorbing curcumin .5,14,15 Group 2 received the curcumin formulation in addition to 50 mg/day of the non-steroidal anti-inflammatory drug diclofenac sodium. Group 3 received only diclofenac. All patients took their assigned drug regimen for 8 weeks.

Throughout the study, the patients were evaluated using a standard rheumatoid arthritis disease activity score.5 In addition, blood tests were done at the beginning and the end of the treatment period, to determine the patients' overall degree of inflammatory responses. Patients also assessed their own pain levels on a 0-10 scale. Finally, the researchers tracked the number of patients who achieved improvements of 20%, 50%, or 70% in tenderness or swollen joints by the end of the study.

The results were compelling, and demonstrated the practical advantages of curcumin over the standard drug treatment.

Curcumin-treated patients hurt less. All patients in the study experienced significant improvements in their disease activity scores by the end of the study.5 Patients in the curcumin-only group showed improvement of 44.5%; improvement was 44.4% in the curcumin plus diclofenac group, and 42.1% in the diclofenac-only group. (Patients' self-measured pain scores showed a greater difference in favor of the curcumin-only group, which had a mean 60% reduction in pain scores; the curcumin-plus-diclofenac group's mean reduction was 56%; and that of the diclofenac-only group was 50%.)

Curcumin-treated patients' joints were less swollen and tender. The curcumin-only group had the largest number of patients experiencing 20%, 50%, or 70% reductions in overall joint swelling and tenderness (93%, 73%, and 33%, respectively).5 Curcumin-induced measurable changes on blood tests of inflammation. These impressive improvements in joint pain and swelling were matched by changes in blood markers of inflammation. For scientists, these improvements in the patients' blood markers of inflammation are exciting proof that curcumin is hitting its multiple targets and quelling the inflammatory process.

For example, the curcumin-only and curcumin-plus-diclofenac groups saw reductions of 11.2 and 13.3% in the erythrocyte sedimentation rate test, a measure of inflammation; the diclofenac-only group had just an 8.3% reduction. Still more dramatic results were seen on the more sensitive C-reactive-protein (CRP) measurement that is capable of detecting systemic inflammation; the curcumin-only group had a 52% reduction in CRP, the curcumin-plus-diclofenac group had a 26.9% CRP reduction, and the diclofenac-only group had a 1.5% increase in CRP.5 Curcumin-treated patients had no side effects. While patients in the groups receiving diclofenac experienced drug-related adverse events, those in the curcumin-only group had none at all.

In summary, this study was the first to demonstrate that curcumin is superior to a standard anti-inflammatory drug for use in rheumatoid arthritis. It also showed that adding the standard drug did little to enhance the effect of curcumin acting alone; indeed, on many of the study's measures, curcumin alone outperformed the drug/curcumin combination.5 Let's now look at the special characteristics of the curcumin formulation that was used in this study. Those characteristics not only explain this study's success, but they also open the door to similar improvements in other inflammatory diseases for which curcumin holds promise.

WHAT YOU NEED TO KNOW: Control Joint Inflammation with Curcumin

Rheumatoid arthritis, a highly inflammatory condition, is the second most-common form of arthritis. Standard treatments for rheumatoid arthritis do little to change the underlying inflammatory causes of the disease; instead, they simply mask the symptoms while joint destruction continues. The more effective "biological agents" available today are not only costly but potentially dangerous in their wide array of side effects. Curcumin, a natural spice-derived nutraceutical, has shown promise in reducing inflammation in a host of conditions, but its usefulness has been limited by its low bioavailability in humans. A new form of curcumin, BCM-95®, has been developed with nearly 7 times the bioavailability of standard curcumin; it also remains at active levels in the blood for nearly twice as long. A clinical trial of BCM-95® in patients with active rheumatoid arthritis demonstrated superiority on most measures to a standard anti-inflammatory drug. Curcumin, and BCM-95® in particular, may hold hope for sufferers of osteoarthritis as well and may also be active in preventing other inflammatory conditions such as cancer and the consequences of obesity.

Enhanced Bioavailability

Despite its clear ability to reduce markers of inflammation in laboratory studies, development of curcumin as a human nutraceutical has been hampered by one major obstacle. Curcumin in its natural state is not well absorbed from the human intestinal tract. In addition, it appears to be rapidly broken down both in the intestine and after absorption into the bloodstream.14,16,17

That has meant the need to deliver very large doses of the supplement, doses so large that in some cases people have balked at the size and number of capsules required to achieve a good effect.14,18,19 Doses as high as 12,000 mg (that's 12 grams, more than a third of an ounce) have been used in efforts to get significant amounts of curcumin into the bloodstream.18 At such high doses, even curcumin can produce uncomfortable symptoms such as abdominal fullness and bloating, though no true toxicity has been demonstrated.19

To improve effectiveness and reduce the dose size required, researchers in the rheumatoid arthritis study made use of a specialized curcumin complex that has increased bioavailability. Bioavailability is a measure of how much of a given dose of a drug or nutrient makes it into the bloodstream for delivery to target tissues.

Researchers showed in 2008 that curcumin's bioavailability could be enhanced through a very simple expedient process.14 Curcumin is first extracted from the turmeric root. Next, it is highly purified, and then reconstituted with certain other components of the original turmeric plant. Those constituents are thought to increase intestinal absorption and also reduce natural breakdown of curcumin in the body. The reconstituted curcumin mixture used by most Life Extension members today is called BCM-95®.14

Clinical studies of BCM-95® in human volunteers have shown that its bioavailability is nearly seven times greater than that of a standard extract of curcumin.14,15 BCM-95® was also more than six times as bioavailable as a leading mixture of curcumin with two other natural products, lecithin and piperine.14 BCM-95® is not only better absorbed than standard curcumin, it achieves significant blood levels and remains in the blood longer (See figure 1 above).15 This means that your body can reap the beneficial effects of curcumin for considerably longer. This advantage applies not only to rheumatoid arthritis, but to other conditions for which curcumin may be indicated.

Curcumin and Osteoarthritis

Osteoarthritis, long thought to be a purely "degenerative" disease, is now recognized to have multiple inflammatory components. Scientists are rapidly exploring curcumin's potential role in suppressing those inflammatory processes.

One of the key features of osteoarthritis is the breakdown of the slippery cartilage that lines joints, lubricating them and cushioning them from the impact of constant use.12 That cartilage breakdown is triggered by multiple pro-inflammatory signaling molecules, many of which are secreted from the membranes that line the joint.10

Studies now show that curcumin can protect this vital lubricating cartilage in several ways. Curcumin directly counteracts the effect of those inflammatory molecules, especially within cartilage cells themselves.12 In the joint-lining membranes, curcumin suppresses the growth of the inflammatory cells that are responsible for cartilage destruction.20 And curcumin even inhibits the "cartilage-eating" enzymes that carry out the destructive process itself.21,22

A pair of human studies showed that joint pain was reduced and joint function was improved, in patients taking a commercial curcumin complex that was formulated to improve absorption.23 Those studies, like the one detailed above, also demonstrated improvements in blood tests measuring inflammation.

Summary

Inflammation lies at the heart of virtually all diseases associated with aging. In fact, people with inflammatory conditions experience accelerated aging that affects every tissue and organ in their bodies.

Rheumatoid arthritis is one of the most aggressive and destructive of the inflammatory conditions that afflict humans, and it is one that has proven resistant to all but the most dangerous forms of standard medical treatment.

Curcumin has held out great hope for management of all kinds of inflammatory diseases, but its benefits have been hampered by its poor absorption and availability to inflamed tissues. A superior-absorbing curcumin formulation( BCM-95®) has up to 7 times the bioavailability of commercial products.

A clinical trial of BCM-95® among sufferers of active rheumatoid arthritis demonstrated not only that the formula was safe, but also that the effectiveness of only 500 mg a day exceeded that of a standard anti-inflammatory drug.5

Additional new studies suggest that this curcumin formula can reduce obesity-associated inflammation as well.24 Together, these findings suggest that highly bioavailable curcumin represents an entirely new chapter in the management of some of humankind's most feared diseases.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

Editor's Note

Science continues to evolve, and new research is published daily. As such, we have a more recent article on this topic: Major Advance! New Highly Bioavailable Curcumin

References

1. Gasparyan AY, Ayvazyan L, Cocco G, Kitas GD. Adverse cardiovascular effects of antirheumatic drugs: implications for clinical practice and research. Curr Pharm Des. 2012 Apr 1;18(11):1543-55.

2. Chen YF, Jobanputra P, Barton P, et al. A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness. Health Technol Assess. 2006 Nov;10(42):iii-iv, xi-xiii, 1-229.

3. Available at: http://www.medsafe.govt.nz/profs/puarticles/dmards.htm. Accessed April 9, 2012.

4. Richette P. Pharmacological therapies for osteoarthritis. Therapie. 2011 Sep-Oct;66(5):383-90.

5. Chandran B, Goel A. A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phytother Res. 2012 Mar 9.

6. Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: the Indian solid gold. Adv Exp Med Biol. 2007;595:1-75.

7. Goel A, Jhurani S, Aggarwal BB. Multi-targeted therapy by curcumin: how spicy is it? Mol Nutr Food Res. 2008 Sep;52(9):1010-30.

8. Farombi EO, Shrotriya S, Na HK, Kim SH, Surh YJ. Curcumin attenuates dimethylnitrosamine-induced liver injury in rats through Nrf2-mediated induction of heme oxygenase-1. Food Chem Toxicol. 2008 Apr;46(4):1279-87.

9. Buhrmann C, Mobasheri A, Matis U, Shakibaei M. Curcumin mediated suppression of nuclear factor-kappaB promotes chondrogenic differentiation of mesenchymal stem cells in a high-density co-culture microenvironment. Arthritis Res Ther. 2010;12(4):R127.

10. Csaki C, Mobasheri A, Shakibaei M. Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1beta-induced NF-kappaB-mediated inflammation and apoptosis. Arthritis Res Ther. 2009;11(6):R165.

11. Henrotin Y, Clutterbuck AL, Allaway D, et al. Biological actions of curcumin on articular chondrocytes. Osteoarthritis Cartilage. 2010 Feb;18(2):141-9.

12. Shakibaei M, Schulze-Tanzil G, John T, Mobasheri A. Curcumin protects human chondrocytes from IL-l1beta-induced inhibition of collagen type II and beta1-integrin expression and activation of caspase-3: an immunomorphological study. Ann Anat. 2005 Nov;187(5-6):487-97.

13. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as "Curecumin": from kitchen to clinic. Biochem Pharmacol. 2008 Feb 15;75(4):787-809.

14. Antony B, Merina B, Iyer VS, Judy N, Lennertz K, Joyal S. A pilot cross-over study to evaluate human oral bioavailability of BCM-95CG (Biocurcumax), a novel bioenhanced preparation of curcumin. Indian J Pharm Sci. 2008 Jul-Aug;70(4):445-9.

15. Benny M, Antony B. Bioavailability of Biocurcumax (BCM-095). Spice India. 2006;September:11-15.

16. Garcea G, Berry DP, Jones DJ, et al. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev. 2005 Jan;14(1):120-5.

17. Sharma RA, McLelland HR, Hill KA, et al. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001 Jul;7(7):1894-900.

18. Lao CD, Ruffin MTt, Normolle D, et al. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med. 2006;6:10.

19. Epelbaum R, Schaffer M, Vizel B, Badmaev V, Bar-Sela G. Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer. 2010;62(8):1137-41.

20. Lev-Ari S, Strier L, Kazanov D, et al. Curcumin synergistically potentiates the growth-inhibitory and pro-apoptotic effects of celecoxib in osteoarthritis synovial adherent cells. Rheumatology (Oxford). 2006 Feb;45(2):171-7.

21. Shakibaei M, John T, Schulze-Tanzil G, Lehmann I, Mobasheri A. Suppression of NF-kappaB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: Implications for the treatment of osteoarthritis. Biochem Pharmacol. 2007 May 1;73(9):1434-45.

22. Mathy-Hartert M, Jacquemond-Collet I, Priem F, Sanchez C, Lambert C, Henrotin Y. Curcumin inhibits pro-inflammatory mediators and metalloproteinase-3 production by chondrocytes. Inflamm Res. 2009 Dec;58(12):899-908.

23. Belcaro G, Cesarone MR, Dugall M, et al. Efficacy and safety of Meriva(R), a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients. Altern Med Rev. 2010 Dec;15(4):337-44.

24. Weisberg SP, Leibel R, Tortoriello DV. Dietary curcumin significantly improves obesity-associated inflammation and diabetes in mouse models of diabesity. Endocrinology. 2008 Jul;149(7):3549-58.

25. Rahme E, Bernatsky S. NSAIDs and risk of lower gastrointestinal bleeding. Lancet. 2010 Jul 17;376(9736):146-8.

26. Catley M. Dissociated steroids. Scientific World Journal. 2007 Mar 30;7:421-30.

27. Diaz-Borjon A. Guidelines for the use of conventional and newer disease-modifying antirheumatic drugs in elderly patients with rheumatoid arthritis. Drugs Aging. 2009;26(4):273-93.

28. Agarwal SK. Biologic agents in rheumatoid arthritis: an update for managed care professionals. J Manag Care Pharm. 2011 Nov-Dec;17(9 Suppl B):S14-8.

29. Boyce EG, Halilovic J, Stan-Ugbene O. Golimumab: Review of the efficacy and tolerability of a recently approved tumor necrosis factor-alpha inhibitor. Clin Ther. 2010 Sep;32(10):1681-703.

30. Nam JL, Winthrop KL, van Vollenhoven RF, et al. Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis. 2010 Jun;69(6):976-86.

31. Singh JA, Beg S, Lopez-Olivo MA. Tocilizumab for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2011 Jan;38(1):10-20.

32. Swanson CD, Akama-Garren EH, Stein EA, et al. Inhibition of epidermal growth factor receptor tyrosine kinase ameliorates collagen-induced arthritis. J Immunol. 2012 Apr 1;188(7):3513-21.

33. Dziedziejko V, Kurzawski M, Safranow K, Chlubek D, Pawlik A. The effect of ESR1 and ESR2 gene polymorphisms on the outcome of rheumatoid arthritis treatment with leflunomide. Pharmacogenomics. 2011 Jan;12(1):41-7.

34. Hattori Y, Suzuki K, Hattori S, Kasai K. Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells. Hypertension. 2006 Jun;47(6):1183-8.

35. Hamdy NA. Denosumab: RANKL inhibition in the management of bone loss. Drugs Today (Barc). 2008 Jan;44(1):7-21.

36. Myasoedova E, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. Is the incidence of rheumatoid arthritis rising?: results from Olmsted County, Minnesota, 1955-2007. Arthritis Rheum. 2010 Jun;62(6):1576-82.

37. Available at: http://www.cdc.gov/arthritis/basics/rheumatoid.htm. Accessed March 23, 2012.

38. Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol. 2011 Sep;23(5):471-8.

39. Leray V, Freuchet B, Le Bloc'h J, Jeusette I, Torre C, Nguyen P. Effect of citrus polyphenol- and curcumin-supplemented diet on inflammatory state in obese cats. Br J Nutr. 2011 Oct;106 Suppl 1:S198-201.

40. Lin JK, Pan MH, Lin-Shiau SY. Recent studies on the biofunctions and biotransformations of curcumin. Biofactors. 2000;13(1-4):153-8.

41. Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001 Jul-Aug;21(4B):2895-900.

42. Sharma RA, McLelland HR, Hill KA, et al. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001 Jul;7(7):1894-1900.

43. Everett PC, Meyers JA, Makkinje A, Rabbi M, Lerner A. Preclinical assessment of curcumin as a potential therapy for B-CLL. Am J Hematol. 2007 Jan;82(1):23-30.

44. Bayet-Robert M, Kwiatkowski F, Leheurteur M, et al. Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer. Cancer Biol Ther. 2010 Jan;9(1):8-14.

45. Dhillon N, Aggarwal BB, Newman RA, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008 Jul 15;14(14):4491-9.

46. Epelbaum R, Schaffer M, Vizel B, Badmaev V, Bar-Sela G. Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer. 2010;62(8):1137-41.

47. Ide H, Tokiwa S, Sakamaki K, et al. Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen. Prostate. 2010 Jul 1;70(10):1127-33.

48. Kanai M, Yoshimura K, Asada M, et al. A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol. 2011 Jul;68(1):157-64.

49. Sharma RA, Euden SA, Platton SL, et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res. 2004 Oct 15;10(20):6847-54.

50. Biswas J, Sinha D, Mukherjee S, Roy S, Siddiqi M, Roy M. Curcumin protects DNA damage in a chronically arsenic-exposed population of West Bengal. Hum Exp Toxicol. 2010 Jun;29(6):513-24.

51. Garcea G, Berry DP, Jones DJ, et al. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev. 2005 Jan;14(1):120-5.

52. Holt PR, Katz S, Kirshoff R. Curcumin therapy in inflammatory bowel disease: a pilot study. Dig Dis Sci. 2005 Nov;50(11):2191-3.

53. Dominiak K, McKinney J, Heilbrun LK, Sarkar FH. Critical need for clinical trials: an example of a pilot human intervention trial of a mixture of natural agents protecting lymphocytes against TNF-alpha induced activation of NF-kappaB. Pharm Res. 2010 Jun;27(6):1061-5.

54. He ZY, Shi CB, Wen H, Li FL, Wang BL, Wang J. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest. 2011 Mar;29(3):208-13.

55. Yu J, Zhou X, He X, Dai M, Zhang Q. Curcumin induces apoptosis involving bax/bcl-2 in human hepatoma SMMC-7721 cells. Asian Pac J Cancer Prev. 2011;12(8):1925-9.

56. Yan G, Graham K, Lanza-Jacoby S. Curcumin enhances the anticancer effects of trichostatin a in breast cancer cells. Mol Carcinog. 2012 Jan 30.

57. Singh P, Sarkar S, Umar S, Rengifo-Cam W, Singh AP, Wood TG. Insulin-like growth factors are more effective than progastrin in reversing proapoptotic effects of curcumin: critical role of p38MAPK. Am J Physiol Gastrointest Liver Physiol. 2010 Apr;298(4):G551-62.

58. Shehzad A, Khan S, Sup Lee Y. Curcumin molecular targets in obesity and obesity-related cancers. Future Oncol. 2012 Feb;8(2):179-90.

59. Wilken R, Veena MS, Wang MB, Srivatsan ES. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer. 2011;10:12.

60. Carroll RE, Benya RV, Turgeon DK, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila). 2011 Mar;4(3):354-64.

61. Cruz-Correa M, Shoskes DA, Sanchez P, et al. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2006 Aug;4(8):1035-8.