Gum Arabic Fibers Decreased Inflammatory Markers and Disease Severity Score among Rheumatoid Arthritis Patients, Phase II Trial

Ebtihal Kamal, Lamis AbdelGadir Kaddam, Maha Dahawi, Montaser Osman, Mohammed Abdelraman Salih, Alnour Alagib, Amal Saeed, Ebtihal Kamal, Lamis AbdelGadir Kaddam, Maha Dahawi, Montaser Osman, Mohammed Abdelraman Salih, Alnour Alagib, Amal Saeed

Abstract

Background: Rheumatoid arthritis (RA) is autoimmune inflammatory disease that attacks the synovium of the joints. Both TNFa and interleukin-1 play crucial roles in the pathogenesis of RA. Gum Arabic (GA) is gummy exudates from Acacia senegal tree. Gum Arabic fermentation by colonic bacteria increases serum butyrate concentrations, so it is considered as prebiotic agent. Gum Arabic (GA) has anti-inflammatory activity through its derivative butyrate. To the best of our knowledge, this is the first study conducted to investigate GA intake on inflammatory markers among RA patients.

Patients and methods: This is clinical trial phase II in which 40 patients were enrolled aged 18 to 70 years. Patients received 30g/day GA for 12 weeks. TNF α, ESR, and complete blood count were measured and DAS-28 was calculated before and after regular GA consumption. Study was approved by the Ethical committee of National Medicines and Poisons Board.

Results: This study showed significant decrease in level of serum TNF α (p value 0.05) [95% CI, 0.65 -16.5], ESR (p value 0.011) [95% CI, 2.6 -18.89], and number of swollen and tender joints in RA patients after 12 weeks of GA intake which reflected as significant decrease in disease severity score DAS 28 P.V:0.00 [95% CI, 1.25 -1.99]. On the other hand, GA had trivial change in blood indices.

Conclusion: Gum Arabic has favorable immune modulator effect on rheumatoid arthritis. It can be utilized in clinical practice as adjuvant therapy.

Trial registration: This trial was registered with ClinicalTrials.gov Identifier: NCT02804581 Registered at 19 June 2016, prospective registration.

Figures

Figure 1
Figure 1
Participant flowchart.
Figure 2
Figure 2
Effect of Gum Arabic intake on TNF level (P.V=0.05). indicates significant difference from baseline.
Figure 3
Figure 3
Effect of Gum Arabic intake on ESR Level (P.V=0.011). indicates significant difference from baseline.

References

    1. Tobón G. J., Youinou P., Saraux A. The environment, geo-epidemiology, and autoimmune disease: rheumatoid arthritis. Journal of Autoimmunity. 2010;35(1):10–14. doi: 10.1016/j.jaut.2009.12.009.
    1. McInnes I. B., Schett G. The pathogenesis of rheumatoid arthritis. The New England Journal of Medicine. 2011;365(23):2205–2219. doi: 10.1056/NEJMra1004965.
    1. van Boekel M. A. M., Vossenaar E. R., van den Hoogen F. H. J., van Venrooij W. J. Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. Arthritis Research & Therapy. 2002;4(2):87–93. doi: 10.1186/ar395.
    1. Kvale D., Brandtzaeg P. Constitutive and cytokine induced expression of HLA molecules, secretory component, and intercellular adhesion molecule-1 is modulated by butyrate in the colonic epithelial cell line HT-29. Gut. 1995;36(5):737–742. doi: 10.1136/gut.36.5.737.
    1. Lührs H., Gerke T., Schauber J., et al. Cytokine-activated degradation of inhibitory κB protein α is inhibited by the short-chain fatty acid butyrate. International Journal of Colorectal Disease. 2001;16(4):195–201. doi: 10.1007/s003840100295.
    1. Segain J. P., Galmiche J. P., Raingeard de La Bletiere D., et al. Butyrate inhibits inflammatory responses through NFκB inhibition: implications for Crohn's disease. Gut. 2000;47(3):397–403. doi: 10.1136/gut.47.3.397.
    1. Zapolska-Downar D., Siennicka A., Kaczmarczyk M., Kołodziej B., Naruszewicz M. Butyrate inhibits cytokine-induced VCAM-1 and ICAM-1 expression in cultured endothelial cells: the role of NF-κB and PPARα. The Journal of Nutritional Biochemistry. 2004;15(4):220–228. doi: 10.1016/j.jnutbio.2003.11.008.
    1. Nancey S., Bienvenu J., Coffin B., Andre F., Descos L., Flourié B. Butyrate strongly inhibits in vitro stimulated release of cytokines in blood. Digestive Diseases and Sciences. 2002;47(4):921–928. doi: 10.1023/A:1014781109498.
    1. Säemann M. D., Böhmig G. A., Osterreicher C. H., et al. Anti-inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL-12 and up-regulation of IL-10 production. The FASEB Journal. 2000;14(15):2380–2382. doi: 10.1096/fj.00-0359fje.
    1. Cavaglieri C. R., Nishiyama A., Fernandes L. C., Curi R., Miles E. A., Calder P. C. Differential effects of short-chain fatty acids on proliferation and production of pro- and anti-inflammatory cytokines by cultured lymphocytes. Life Sciences. 2003;73(13):1683–1690. doi: 10.1016/S0024-3205(03)00490-9.
    1. Fukae J., Amasaki Y., Yamashita Y., et al. Butyrate suppresses tumor necrosis factor α production by regulating specific messenger RNA degradation mediated through a cis-acting AU-rich element. Arthritis & Rheumatology. 2005;52(9):2697–2707. doi: 10.1002/art.21258.
    1. Inan M. S., Rasoulpour R. J., Yin L., Hubbard A. K., Rosenberg D. W., Giardina C. The luminal short-chain fatty acid butyrate modulates NF-κB activity in a human colonic epithelial cell line. Gastroenterology. 2000;118(4):724–734. doi: 10.1016/S0016-5085(00)70142-9.
    1. Xuan N. T., Shumilina E., Nasir O., Bobbala D., Götz F., Lang F. Stimulation of mouse dendritic cells by Gum Arabic. Cellular Physiology and Biochemistry. 2010;25(6):641–648. doi: 10.1159/000315083.
    1. Millard A. L., Mertes P. M., Ittelet D., Villard F., Jeannesson P., Bernard J. Butyrate affects differentiation, maturation and function of human monocyte-derived dendritic cells and macrophages. Clinical & Experimental Immunology. 2002;130(2):245–255. doi: 10.1046/j.0009-9104.2002.01977.x.
    1. Nasir O., Umbach A. T., Rexhepaj R., et al. Effects of gum arabic (Acacia senegal) on renal function in diabetic mice. Kidney and Blood Pressure Research. 2012;35(5):365–372. doi: 10.1159/000336359.
    1. Nasir O., Artunc F., Wang K., et al. Downregulation of mouse intestinal Na-coupled glucose transporter SGLT1 by Gum arabic (Acacia Senegal) Cellular Physiology and Biochemistry. 2010;25(2-3):203–210. doi: 10.1159/000276554.
    1. Ali B. H., Beegam S., Al-Lawati I., Waly M. I., Al za'abi M., Nemmar A. Comparative efficacy of three brands of gum acacia on adenine-Induced chronic renal failure in rats. Physiological Research. 2013;62(1):47–56.
    1. Ali B. H., Al-Husseni I., Beegam S., et al. Effect of gum arabic on oxidative stress and inflammation in adenine-induced chronic renal failure in rats. PLoS ONE. 2013;8(2) doi: 10.1371/journal.pone.0055242.e55242
    1. Ushida K., Hatanaka H., Inoue R., Tsukahara T., Phillips G. O. Effect of long term ingestion of gum arabic on the adipose tissues of female mice. Food Hydrocolloids. 2011;25(5):1344–1349. doi: 10.1016/j.foodhyd.2010.12.010.
    1. Gamal El-din A. M., Mostafa A. M., Al-Shabanah O. A., Al-Bekairi A. M., Nagi M. N. Protective effect of arabic gum against acetaminophen-induced hepatotoxicity in mice. Pharmacological Research. 2003;48(6):631–635. doi: 10.1016/S1043-6618(03)00226-3.
    1. Bays A., Wahl E., Daikh D. I., Yazdany J., Schmajuk G. Implementation of disease activity measurement for rheumatoid arthritis patients in an academic rheumatology clinic. BMC Health Services Research. 2016;16(1)
    1. Ciurtin C., Wyszynski K., Clarke R., Mouyis M., Manson J., Marra G. Ultrasound-detected subclinical inflammation was better reflected by the disease activity score (DAS-28) in patients with suspicion of inflammatory arthritis compared to established rheumatoid arthritis. Clinical Rheumatology. 2016;35(10):2411–2419. doi: 10.1007/s10067-016-3326-6.
    1. Anderson J., Caplan L., Yazdany J., et al. Rheumatoid arthritis disease activity measures: American college of rheumatology recommendations for use in clinical practice. Arthritis Care & Research. 2012;64(5):640–647. doi: 10.1002/acr.21649.
    1. Matsumoto N., Riley S., Fraser D., et al. Butyrate modulates TGF-β1 generation and function: Potential renal benefit for Acacia(sen) SUPERGUM™ (gum arabic)? Kidney International. 2006;69(2):257–265. doi: 10.1038/sj.ki.5000028.
    1. Oliver J. E., Silman A. J. Risk factors for the development of rheumatoid arthritis. Scandinavian Journal of Rheumatology. 2006;35(3):169–174. doi: 10.1080/03009740600718080.
    1. Tanaka Y. Current concepts in the management of rheumatoid arthritis. Korean Journal of Internal Medicine. 2016;31(2):210–218. doi: 10.3904/kjim.2015.137.
    1. Kaddam L., FdleAlmula I., Eisawi O. A., et al. Gum Arabic as fetal hemoglobin inducing agent in sickle cell anemia; in vivo study. BMC Hematology. 2015;15(1)
    1. Dover G. J., Brusilow S., Charache S. Induction of fetal hemoglobin production in subjects with sickle cell anemia by oral sodium phenylbutyrate. Blood. 1994;84(1):339–343.
    1. Ross A. H., Eastwood M. A., Brydon W. G., Anderson J. R., Anderson D. M. A study of the effects of dietary gum arabic in humans. American Journal of Clinical Nutrition. 1983;37(3):368–375. doi: 10.1093/ajcn/37.3.368.
    1. Kang Y., Cai Y., Zhang X., Kong X., Su J. Altered gut microbiota in RA: implications for treatment. Zeitschrift für Rheumatologie. 2017;76(5):451–457. doi: 10.1007/s00393-016-0237-5.
    1. Hu Y., Sparks J. A., Malspeis S., et al. Long-term dietary quality and risk of developing rheumatoid arthritis in women. Annals of the Rheumatic Diseases. 2017;76(8):1357–1364. doi: 10.1136/annrheumdis-2016-210431.
    1. Berube L. T., Kiely M., Yazici Y., Woolf K. Diet quality of individuals with rheumatoid arthritis using the healthy eating index (HEI)-2010. Nutrition and Health. 2017;23(1):17–24. doi: 10.1177/0260106016688223.
    1. Khanna S., Jaiswal K. S., Gupta B. Managing rheumatoid arthritis with dietary interventions. Frontiers in Nutrition. 2017;4 doi: 10.3389/fnut.2017.00052.

Source: PubMed

3
S'abonner