Spirulina platensis versus silymarin in the treatment of chronic hepatitis C virus infection. A pilot randomized, comparative clinical trial

BMC Gastroenterology

Amel Salem²  Mostafa Yakoot¹ 

[1] Green Clinic and Research Centre, Alexandria 21121, Egypt;Mabarrah Clinics, Alexandria, Egypt

关键词: Safety and Efficacy;    Silymarin;    Cyanobacteria;    Spirulina platensis;    Chronic HCV;   

Others  :  1113104
DOI  :  10.1186/1471-230X-12-32

 received in 2011-07-03, accepted in 2012-04-12,  发布年份 2012

【 摘 要 】

Background

Spirulina platensis, a cynobacterium used frequently as a dietary supplement had been found to exhibit many immune-stimulating and antiviral activities. It had been found to activate macrophages, NK cells, T cells, B cells, and to stimulate the production of Interferon gamma (IFN-γ) and other cytokines. Natural substances isolated from Spirulina platensis had been found to be potent inhibitors against several enveloped viruses by blocking viral absorption/penetration and some replication stages of progeny viruses after penetration into cells. We aimed to study whether this dietary supplement possesses any therapeutically feasible activity worthy of further larger controlled clinical evaluation.

Methods

Sixty six patients with chronic hepatitis C virus infection and eligible for inclusion had been randomized to either Spirulina or Silymarin treated groups for a period of six months treatment.

The two groups were followed up and blindly compared for early (after 3 months) and end of 6 months treatment virological response. The effects of both treatments on each of alanine aminotransferase (ALT), Chronic Liver Disease Questionnaire scores (CLDQ), Arizona Sexual Experience Scale scores (ASEX) and the occurrence of any attributable adverse events were also compared.

Results

Among the 30 patients who had been treated with Spirulina and completed the 6 months protocol, 4 patients (13.3%) had a complete end of treatment virological response and 2 patients (6.7%) had a partial end of treatment response defined as significant decrease of virus load of at least 2-logs₁₀. Though the proportion of responders in Spirulina group was greater than in the Silymarin group, the difference was not statistically significant at the end of both 6 months (p = 0.12) and 3 months treatment (p = 0.22) by Exact test. Alanine aminotransferase as well as CLDQ and ASEX scores were found to be more significantly improved in Spirulina than in Silymarin treated group.

Conclusions

Our results could suggest a therapeutically feasible potential for Spirulina platensis in chronic HCV patients, worthy to conduct a larger sized and longer study to confirm these safety and efficacy encouraging results.

Trial Registration

WHO Clinical Trial Registration ID: ACTRN12610000958088

http://apps.who.int/trialsearch/trial.aspx?trialid=ACTRN12610000958088 webcite

【 授权许可】

   
2012 Yakoot and Salem; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]World Health Organization: Hepatitis C. Factsheet No 164 (updated Oct 2000). [http://www.who.int/mediacentre/factsheets/en/] webcite (accessed 3 Feb 2008)
• [2]Patel K, Muir AJ, McHutchison JG: Diagnosis and treatment of chronic hepatitis C infection. BMJ 2006, 332(7548):1013-7.
• [3]Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease: Center for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep 1998, 47:1-39.
• [4]Sievert W, Altraif I, Razavi HA, Abdo A, Ahmed EA, Alomair A, et al.: A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt. Liver Int 2011, 31(2):61-80.
• [5]Hepatitis C: Global prevalence. Wkly Epidemiol Rec 1997, 72:341-344.
• [6]Management of hepatitis C: NIH Consens State Sci Statements. 2002, 19(3):1-46.
• [7]Thevenot T, Regimbeau C, Ratziu V, Leroy V, Opolon P, Poynard T: Meta-analysis of interferon randomized trials in the treatment of viral hepatitis C in naïve patients. Viral Hepat 1999, 8:4862.
• [8]Camma C, Licata A, Cabibbo G, Latteri F, Craxi A: Treatment of hepatitis C: critical appraisal of the evidence. Expert Opin Pharmacother 2005, 6:399-408.
• [9]Manns MP, Wedemeyer H, Cornberg M: Treating viral hepatitis C: efficacy, side effects, and complications. Gut 2006, 55:1350-1359.
• [10]Kamal SM, Nasser IA: Hepatitis C genotype 4: what we know and what we don't yet know. Hepatology 2008, 47:1371-83.
• [11]Zeuzem S, Hultcrantz R, Bourliere M: Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol 2004, 40:993-999.
• [12]Moucari R, Ripault MP, Oules V, et al.: High predictive value of early viral kinetics in retreatment with peginterferon and ribavirin of chronic hepatitis C patients non-responders to standard combination therapy. J Hepatol 2007, 46:596-604.
• [13]Koretz RL: Interferon in wonderland. Gastroenterology 1998, 115:1027-29.
• [14]Stickel F, Schuppan D: Herbal medicine in the treatment of liver diseases. Dig Liver Dis 2007, 39(4):293-304.
• [15]Batey RG, Bensoussan A, Fan YY, Bollipo S, Hossain MA: Preliminary report of a randomized, double-blind placebo-controlled trial of a Chinese herbal medicine preparation CH-100 in the treatment of chronic hepatitis C. J Gastroenterol Hepatol 1998, 3(3):244-7.
• [16]Wu C, et al.: Thirty-three patients with hepatitis C treated by chinese traditional medicine syndrome differentiation. Chinese Journal of Integrated Traditional and Western Medicine for Liver Diseases 1994, 4:44-45.
• [17]Cohen MR: Herbal and complementary and alternative medicine therapies for liver disease. A focus on Chinese traditional medicine in hepatitis C virus. Clin Liver Dis 2001, 5(2):461-78. vii
• [18]Suzuki H, et al.: Effects of glycyrrhizin on biochemical tests in patients with chronic hepatitis double blind trial. Journal of Asian Medicine 1984, 26:423-38.
• [19]Kay RA: Microalgae as food and supplement. In Critical Rev Food Sci Nutr. CRC Press, USA; 1991:555-73.
• [20]Karkos PD, Leong SC, Karkos CD, Sivaji N, Assimakopoulos DA: Spirulina in Clinical Practice: Evidence-Based Human Applications. Evid Based Complement Alternat Med 2008. doi:10.1093/ecam/nen058. PubMed Central PMCID: PMC3136577
• [21]Salazar M, Chamorro GA, Salazar S, Steele CE: Effect of Spirulina maxima consumption on reproduction and peri- and postnatal development in rats. Food Chem Toxicol 1996, 34(4):353-359.
• [22]Chamorro G, Salazar S, Castillo L: Reproductive and peri- postnatal evaluation of Spirulina maxima in mice. J Appl Phycol 1997, 9:107-12.
• [23]Salazar M, Martinez E, Madrigal E, Ruiz LE, Chamorro GA: Subchronic toxicity study in mice fed Spirulina. J Ethnopharmacol 1998, 62:235-41.
• [24]Belay A: The potential application of Spirulina (Arthrospira) as a nutritional and therapeutic supplement in Health management. JANA 2002, 5:27-48.
• [25]Hirahashi T, Matsumoto M, Hazeki K, Saeki Y, Ui M, Seya T: Activation of the human innate immune system by spirulina: augmentation of interferon production and NK cytotoxicity by oral administration of hot water extract of Spirulina platensis. Int Immunopharmacol 2002, 2:423-34.
• [26]Pugh N, Ross SA, ElSohly HN, et al.: Isolation of three high molecular weight polysaccharide preparations with potent immunostimulatory activity from Spirulina platensis, aphanizomenon flos-aquae and Chlorella pyrenoidosa. Planta Med 2001, 8:737-42.
• [27]Blinkova LP, Gorobets OB, Baturo AP: Biological activity of Spirulina. Zh Mikrobiol Epidemiol Immunobiol 2001, 2:114-8.
• [28]Hayashi O, Katoh T, Okuwaki Y: Enhancement of antibody production in mice by dietary Spirulina platensis. J Nutr Sci Vitaminol 1994, 40(5):431-41.
• [29]Hernandez-Corona A, Nieves I, Meckes M: Antiviral activity of spirulina maxima against herpes simplex virus type 2. Antiviral Res 2002, 56(3):279-85.
• [30]Schaeffer DJ, Krylov VS: Anti-HIV activity of extracts and compounds from algae and cyanobacteria. Ecotoxicol En Spirulina Saf 2000, 45(3):208-27.
• [31]Hayashi T: Studies on evaluation of natural products for antiviral effects and their applications. Yakugaku Zasshi 2008, 128(1):61-79.
• [32]Hayashi K, Hayashi T, Kojima I: A natural sulfated polysaccharide, calcium spirulan, isolated from Spirulina platensis: in vitro and ex vivo evaluation of anti-herpes simplex virus and anti-human immunodeficiency virus activities. AIDS Res Hum Retroviruses 1996, 12(15):1463-71.
• [33]Boyd MR, Gustafson KR, McMahon JB, et al.: Antimicrob. Agents Chemother 1997, 41:1521-30.
• [34]Dey B, Lerner D, Lusso P, et al.: J Virol. 2000, 74:4562-69.
• [35]Esser MT, Mori T, Mondor I, et al.: J Virol. 1999, 73:4360-71.
• [36]Huskens D, Férir G, Vermeire K, et al.: Microvirin, a novel alpha(1,2)-mannose-specific lectin isolated from microcystis aeruginosa, has anti-HIV-1 activity comparable with that of cyanovirin-N but a much higher safety profile. J Biol Chem 2010, 285(32):24845-54.
• [37]Kehr JC, Zilliges Y, Springer A, et al.: A mannan binding lectin is involved in cell-cell attachment in a toxic strain of microcystis aeruginosa. Mol Microbiol 2006, 59(3):893-906.
• [38]Helle F, Wychowski C, Vu-Dac N, et al.: Cyanovirin-N inhibits hepatitis C virus entry by binding to envelope protein glycans. J Biol Chem 2006, 281(35):25177-83.
• [39]Balzarini J: Carbohydrate-binding agents: a potential future cornerstone for the chemotherapy of enveloped viruses? Antivir Chem Chemother 2007, 18(1):1-11.
• [40]Younossi ZM, Guyatt G, Kiwi M, Boparai N, King D: Development of a disease specific questionnaire to measure health related quality of life in patients with chronic liver disease. Gut 1999, 45:295-300.
• [41]Younossi ZM, Boparai N, McCormick M, Price LL, Guyatt G: Assessment of utilities and health-related quality of life in patients with chronic liver disease. Am J Gastroenterol 2001, 96:579-583.
• [42]McGahuey CA, Gelenberg AJ, Laukes CA, Moreno FA, Delgado PL, McKnight KM, Manber R: The Arizona Sexual Experience Scale (ASEX): reliability and validity. J Sex Marital Ther 2000, 26(1):25-40.
• [43]Băicuş C, Tănăsescu C: Chronic viral hepatitis, the treatment with spiruline for one month has no effect on the aminotransferases. Rom J Intern Med 2002, 40(1-4):89-94.
• [44]Danoff A, Khan O, Wan DW, Hurst L, Cohen D, Tenner CT, Bini EJ: Sexual dysfunction is highly prevalent among men with chronic hepatitis C virus infection and negatively impacts health-related quality of life. Am J Gastroenterol 2006, 101(6):1235-43.
• [45]Soykan A, Boztaş H, Idilman R, Ozel ET, Tüzün AE, Ozden A, Ozden A, Kumbasar H: Sexual dysfunctions in HCV patients and its correlations with psychological and biological variables. Int J Impot Res 2005, 17(2):175-9.