Does saffron supplementation have favorable effects on liver function indicators? A systematic review and meta-analysis of randomized controlled trials

References

• Abdullaev, F. I. 2002. Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.). Experimental Biology and Medicine (Maywood, N.J.) 227 (1):20–5. doi: 10.1177/153537020222700104.
   PubMed Web of Science ®Google Scholar
• Abedimanesh, N.,. S. Z. Bathaie, S. Abedimanesh, B. Motlagh, A. Separham, and A. Ostadrahimi. 2017. Saffron and crocin improved appetite, dietary intakes and body composition in patients with coronary artery disease. Journal of Cardiovascular and Thoracic Research 9 (4):200–8. doi: 10.15171/jcvtr.2017.35.
   PubMed Web of Science ®Google Scholar
• ALMODóVAR, P., D. Briskey, A. Rao, M. Prodanov, and A. M. Inarejos-GARCíA. 2020. 2020. Bioaccessibility and pharmacokinetics of a commercial saffron (Crocus sativus L.) extract. Evidence-Based Complementary and Alternative Medicine 2020:1–8. doi: 10.1155/2020/1575730.
   Web of Science ®Google Scholar
• Amin, A., A. A. Hamza, K. Bajbouj, S. S. Ashraf, and S. Daoud. 2011. Saffron: A potential candidate for a novel anticancer drug against hepatocellular carcinoma. Hepatology (Baltimore, Md.) 54 (3):857–67. doi: 10.1002/hep.24433.
   PubMed Web of Science ®Google Scholar
• Asbaghi, O., M. Sadeghian, O. Sadeghi, S. Rigi, S. C. Tan, A. Shokri, and S. M. Mousavi. 2021. Effects of saffron (Crocus sativus L.) supplementation on inflammatory biomarkers: A systematic review and meta-analysis. Phytotherapy Research. 35 (1):20–32. doi: 10.1002/ptr.6748.
   PubMed Web of Science ®Google Scholar
• Ashktorab, H., A. Soleimani, G. Singh, A. Amr, S. Tabtabaei, G. Latella, U. Stein, S. Akhondzadeh, N. Solanki, M. C. Gondré-Lewis, et al. 2019. Saffron: The golden spice with therapeutic properties on digestive diseases. Nutrients 11 (5):943., doi: 10.3390/nu11050943.
   Web of Science ®Google Scholar
• Asrani, S. K., H. Devarbhavi, J. Eaton, and P. S. Kamath. 2019. Burden of liver diseases in the world. Journal of Hepatology 70 (1):151–71. doi: 10.1016/j.jhep.2018.09.014.
   PubMed Web of Science ®Google Scholar
• Bandegi, A. R., A. Rashidy-Pour, A. A. Vafaei, and B. Ghadrdoost. 2014. Protective effects of Crocus sativus L. extract and crocin against chronic-stress induced oxidative damage of brain, liver and kidneys in rats. Advanced Pharmaceutical Bulletin 4:493.
   PubMedGoogle Scholar
• Bhattacharjee, B.,. S. Vijayasarathy, P. Karunakar, and J. Chatterjee. 2012. Comparative reverse screening approach to identify potential anti-neoplastic targets of saffron functional components and binding mode. Asian Pacific Journal of Cancer Prevention : APJCP 13 (11):5605–11. doi: 10.7314/apjcp.2012.13.11.5605.
   PubMedGoogle Scholar
• Bhatti, I. U., F. U. Rehman, M. A. Khan, and S. K. Marwat. 2009. Effect of prophetic medicine Kalonji (Nigella sativa L.) on lipid profile of human beings: An in vivo approach. World Applied Sciences Journal 6:1053–7.
   Google Scholar
• Borenstein, M., L. Hedges, J. Higgins, and H. Rothstein. 2009. References. Wiley online library.
   Google Scholar
• Borenstein, M., L. V. Hedges, J. P. Higgins, and H. R. Rothstein. 2011. Introduction to meta-analysis. Chichester, U.K.: John Wiley & Sons.
   Google Scholar
• Chen, Y., T. Yang, J. Huang, X. Tian, C. Zhao, L. Cai, L. Feng, and H. Zhang. 2010. Comparative evaluation of the antioxidant capacity of crocetin and crocin in vivo. Chinese Pharmacological Bulletin 26:248–51.
   Google Scholar
• Dehghan, F., F. Hajiaghaalipour, A. Yusof, S. Muniandy, S. A. Hosseini, S. Heydari, L. Z. A. Salim, and M. A. Azarbayjani. 2016. Saffron with resistance exercise improves diabetic parameters through the GLUT4/AMPK pathway in-vitro and in-vivo. Scientific Reports 6 (1):25139. doi: 10.1038/srep25139.
   PubMed Web of Science ®Google Scholar
• Dersimonian, R., and R. Kacker. 2007. Random-effects model for meta-analysis of clinical trials: An update. Contemporary Clinical Trials 28 (2):105–14. doi: 10.1016/j.cct.2006.04.004.
   PubMed Web of Science ®Google Scholar
• Dufour, D. R., J. A. Lott, F. S. Nolte, D. R. Gretch, R. S. Koff, and L. B. Seeff. 2000. National Academy of Clinical Biochemistry Standards of Laboratory Practice: Laboratory Guidelines for Screening, Diagnosis and Monitoring of Hepatic Injury. Retrieved August, 30, 2003.
   Google Scholar
• Ebrahimi, F., N. Aryaeian, N. Pahlavani, D. Abbasi, A. F. Hosseini, S. Fallah, N. Moradi, and I. Heydari. 2019. The effect of saffron (Crocus sativus L.) supplementation on blood pressure, and renal and liver function in patients with type 2 diabetes mellitus: A double-blinded, randomized clinical trial. Avicenna Journal of Phytomedicine 9:322.
   PubMed Web of Science ®Google Scholar
• Fan, J., and I. Gijbels. 1996. Local polynomial modelling and its applications: monographs on statistics and applied probability. Vol. 66. USA: CRC Press.
   Google Scholar
• Farahmand, S. K., F. Samini, M. Samini, and S. Samarghandian. 2013. Safranal ameliorates antioxidant enzymes and suppresses lipid peroxidation and nitric oxide formation in aged male rat liver. Biogerontology 14 (1):63–71. doi: 10.1007/s10522-012-9409-0.
   PubMed Web of Science ®Google Scholar
• Feher, J., and G. Lengyel. 2012. Silymarin in the prevention and treatment of liver diseases and primary liver cancer. Current Pharmaceutical Biotechnology 13 (1):210–7. doi: 10.2174/138920112798868818.
   PubMed Web of Science ®Google Scholar
• Fitzmaurice, C., D. Dicker, A. Pain, H. Hamavid, M. Moradi-Lakeh, M. F. MacIntyre, C. Allen, G. Hansen, R. Woodbrook, C. Wolfe, et al. 2015. The Global Burden of Cancer 2013. JAMA Oncology 1 (4):505–27., doi: 10.1001/jamaoncol.2015.0735.
   PubMed Web of Science ®Google Scholar
• Hemmati, M.,. S. Asghari, E. Zohoori, and M. Karamian. 2015. Hypoglycemic effects of three Iranian edible plants; jujube, barberry and saffron: Correlation with serum adiponectin level. Pakistan Journal of Pharmaceutical Sciences 28 (6):2095–9.
   PubMed Web of Science ®Google Scholar
• Higgins, J. P., D. G. Altman, P. C. GøTZSCHE, P. Juni, D. Moher, A. D. Oxman, J. Savović, K. F. Schulz, L. Weeks, and J. A. Sterne. 2011. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343 (oct18 2):d5928–d5928. doi: 10.1136/bmj.d5928.
   PubMed Web of Science ®Google Scholar
• Hosseinzadeh, H., and H. Sadeghnia. 2007. Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: Involvement of GABAergic and opioids systems. Phytomedicine 14 (4):256–62. doi: 10.1016/j.phymed.2006.03.007.
   PubMed Web of Science ®Google Scholar
• Hosseinzadeh, H.,. F. Shamsaie, and S. Mehri. 2009. Antioxidant activity of aqueous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituents, crocin and safranal. Pharmacognosy Magazine 5:419.
   Web of Science ®Google Scholar
• Hozo, S. P., B. Djulbegovic, and I. Hozo. 2005. Estimating the mean and variance from the median, range, and the size of a sample. BMC Medical Research Methodology 5 (1):13. doi: 10.1186/1471-2288-5-13.
   PubMedGoogle Scholar
• Imenshahidi, M.,. H. Hosseinzadeh, and Y. Javadpour. 2010. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytotherapy Research : PTR 24 (7):990–4. doi: 10.1002/ptr.3044.
   PubMed Web of Science ®Google Scholar
• Jiang, X., A. Awati, A. Agazzi, F. Vitari, A. Ferrari, H. Bento, M. Crestani, C. Domeneghini, and V. Bontempo. 2015. Effects of a blend of essential oils and an enzyme combination on nutrient digestibility, ileum histology and expression of inflammatory mediators in weaned piglets. Animal 9 (3):417–26. doi: 10.1017/S1751731114002444.
   PubMed Web of Science ®Google Scholar
• Jose Bagur, M., G. L. Alonso Salinas, A. M. Jimenez-Monreal, S. Chaouqi, S. Llorens, M. MARTíNEZ-Tome, and G. L. Alonso. 2017. Saffron: An old medicinal plant and a potential novel functional food. Molecules 23 (1):30. doi: 10.3390/molecules23010030.
   PubMed Web of Science ®Google Scholar
• Karimi, E., E. Oskoueian, R. Hendra, and H. Z. Jaafar. 2010. Evaluation of Crocus sativus L. stigma phenolic and flavonoid compounds and its antioxidant activity. Molecules (Basel, Switzerland) 15 (9):6244–56. doi: 10.3390/molecules15096244.
   PubMed Web of Science ®Google Scholar
• Khorasany, A. R., and H. Hosseinzadeh. 2016. Therapeutic effects of saffron (Crocus sativus L.) in digestive disorders: A review. Iranian Journal of Basic Medical Sciences 19:455.
   PubMed Web of Science ®Google Scholar
• Konstantopoulos, P.,. I. P. Doulamis, A. Tzani, M. L. Korou, E. Agapitos, I. S. Vlachos, V. Pergialiotis, C. Verikokos, G. Mastorakos, and N. L. Katsilambros. 2017. Metabolic effects of Crocus sativus and protective action against non-alcoholic fatty liver disease in diabetic rats. Biomedical Reports 6:513–8.
   PubMed Web of Science ®Google Scholar
• Kunutsor, S. K., T. A. Apekey, and J. Walley. 2013. Liver aminotransferases and risk of incident type 2 diabetes: A systematic review and meta-analysis. American Journal of Epidemiology 178 (2):159–71. doi: 10.1093/aje/kws469.
   PubMed Web of Science ®Google Scholar
• Liu, Z. L., L. Z. Xie, J. Zhu, G. Q. Li, S. J. Grant, and J. P. Liu. 2013. Herbal medicines for fatty liver diseases. Cochrane Database of Systematic Reviews 24 (8):CD009059.
   Web of Science ®Google Scholar
• Lozano, R., M. Naghavi, K. Foreman, S. Lim, K. Shibuya, V. Aboyans, J. Abraham, T. Adair, R. Aggarwal, S. Y. Ahn, et al. 2012. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010. The Lancet 380 (9859):2095–128., doi: 10.1016/S0140-6736(12)61728-0.
   PubMed Web of Science ®Google Scholar
• Mansoori, P., S. Akhondzadeh, F. Raisi, P. Ghaeli, A. Jamshidi, A. Nasehi, H. Sohrabi, and S. Saroukhani. 2011. A randomized, double-blind, placebo-controlled study of safety of the adjunctive saffron on sexual dysfunction induced by a selective serotonin reuptake inhibitor. Journal of Medicinal Plants 10:121–30.
   Google Scholar
• Mashmoul, M.,. A. Azlan, B. N. M. Yusof, H. Khaza'Ai, N. Mohtarrudin, and M. T. Boroushaki. 2014. Effects of saffron extract and crocin on anthropometrical, nutritional and lipid profile parameters of rats fed a high fat diet. Journal of Functional Foods 8:180–7. doi: 10.1016/j.jff.2014.03.017.
   Web of Science ®Google Scholar
• Mashmoul, M.,. A. Azlan, N. Mohtarrudin, B. N. Mohd Yusof, H. Khaza'ai, H. E. Khoo, M. Farzadnia, and M. T. Boroushaki. 2016. Protective effects of saffron extract and crocin supplementation on fatty liver tissue of high-fat diet-induced obese rats. BMC Complementary and Alternative Medicine 16 (1):401 doi: 10.1186/s12906-016-1381-9.
   PubMed Web of Science ®Google Scholar
• Milajerdi, A., S. Jazayeri, V. Bitarafan, N. Hashemzadeh, E. Shirzadi, Z. Derakhshan, M. Mahmoodi, A. Rayati, A. Djazayeri, and S. Akhondzadeh. 2017. The effect of saffron (Crocus sativus L.) hydro-alcoholic extract on liver and renal functions in type 2 diabetic patients: A double-blinded randomized and placebo control trial. Journal of Nutrition & Intermediary Metabolism 9:6–11. doi: 10.1016/j.jnim.2017.07.002.
   Google Scholar
• Mohamadpour, A. H., Z. Ayati, M. R. Parizadeh, O. Rajbai, and H. Hosseinzadeh. 2013. Safety evaluation of crocin (a constituent of saffron) tablets in healthy volunteers. Iranian Journal of Basic Medical Sciences 16 (1):39–46.
   PubMed Web of Science ®Google Scholar
• Moher, D., L. Shamseer, M. Clarke, D. Ghersi, A. Liberati, M. Petticrew, P. Shekelle, and L. A. Stewart. 2015. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic Reviews 4:1 doi: 10.1186/2046-4053-4-1.
   PubMed Web of Science ®Google Scholar
• Moravej Aleali, A., R. Amani, H. Shahbazian, F. Namjooyan, S. M. Latifi, and B. Cheraghian. 2019. The effect of hydroalcoholic Saffron (Crocus sativus L.) extract on fasting plasma glucose, HbA1c, lipid profile, liver, and renal function tests in patients with type 2 diabetes mellitus: A randomized double‐blind clinical trial. Phytotherapy Research 33 (6):1648–57. doi: 10.1002/ptr.6351.
   PubMed Web of Science ®Google Scholar
• Mousavi, B., S. Z. Bathaie, F. Fadai, Z. Ashtari, N. Ali Beigi, S. Farhang, S. Hashempour, N. Shahhamzei, and H. Heidarzadeh. 2015. Safety evaluation of saffron stigma (Crocus sativus L.) aqueous extract and crocin in patients with schizophrenia. Avicenna Journal of Phytomedicine 5 (5):413–9.
   PubMed Web of Science ®Google Scholar
• Mousavi, S. M., E. Karimi, M. Hajishafiee, A. Milajerdi, M. R. Amini, and A. Esmaillzadeh. 2020. Anti-hypertensive effects of cinnamon supplementation in adults: A systematic review and dose-response Meta-analysis of randomized controlled trials. Critical Reviews in Food Science and Nutrition 60 (18):3144–54.
   PubMed Web of Science ®Google Scholar
• Mousavi, S. M., K. Djafarian, A. Mojtahed, H. K. Varkaneh, and S. Shab-Bidar. 2018. The effect of zinc supplementation on plasma C-reactive protein concentrations: A systematic review and meta-analysis of randomized controlled trials. European Journal of Pharmacology 834:10–6. doi: 10.1016/j.ejphar.2018.07.019.
   PubMed Web of Science ®Google Scholar
• Mousavi, S. M., S. Shab-Bidar, H. Kord-Varkaneh, M. Khorshidi, and K. Djafarian. 2019b. Effect of alpha-lipoic acid supplementation on lipid profile: A systematic review and meta-analysis of controlled clinical trials. Nutrition (Burbank, Los Angeles County, Calif.) 59:121–30. doi: 10.1016/j.nut.2018.08.004.
   PubMed Web of Science ®Google Scholar
• Mousavi, S.,. A. Milajerdi, A. Sheikhi, H. Kord‐Varkaneh, C. Feinle‐Bisset, B. Larijani, and A. Esmaillzadeh. 2019a. Resveratrol supplementation significantly influences obesity measures: A systematic review and dose–response meta‐analysis of randomized controlled trials. Obesity Reviews 20 (3):487–98. doi: 10.1111/obr.12775.
   PubMed Web of Science ®Google Scholar
• Muniraman, H., D. Gardner, J. Skinner, A. Paweletz, A. Vayalakkad, Y. H. Chee, C. Clifford, S. Sanka, V. Venkatesh, A. Curley, et al. 2017. Biomarkers of hepatic injury and function in neonatal hypoxic ischemic encephalopathy and with therapeutic hypothermia. European Journal of Pediatrics 176 (10):1295–303., doi: 10.1007/s00431-017-2956-2.
   PubMed Web of Science ®Google Scholar
• Papandreou, M. A., C. D. Kanakis, M. G. Polissiou, S. Efthimiopoulos, P. Cordopatis, M. Margarity, and F. N. Lamari. 2006. Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents . J Agric Food Chem 54 (23):8762–8. doi: 10.1021/jf061932a.
   PubMed Web of Science ®Google Scholar
• Parsi, A., M. Torkashvand, E. Hajiani, M. Rahimlou, and N. Sadeghi. 2020. The effects of crocus sativus extract on serum lipid profile and liver enzymes in patients with non-alcoholic fatty liver disease: A randomized placebo-controlled study. Obesity Medicine 17:100165. doi: 10.1016/j.obmed.2019.100165.
   Google Scholar
• Pour, F. K., N. Aryaeian, M. Mokhtare, R. S. Mirnasrollahi Parsa, L. Jannani, S. Agah, S. Fallah, and N. Moradi. 2020. The effect of saffron supplementation on some inflammatory and oxidative markers, leptin, adiponectin, and body composition in patients with nonalcoholic fatty liver disease: A double-blind randomized clinical trial . Phytotherapy Research : PTR 34 (12):3367–78. doi: 10.1002/ptr.6791.
   PubMed Web of Science ®Google Scholar
• Promrat, K., D. E. Kleiner, H. M. Niemeier, E. Jackvony, M. Kearns, J. R. Wands, J. L. Fava, and R. R. Wing. 2010. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 51 (1):121–9. doi: 10.1002/hep.23276.
   PubMed Web of Science ®Google Scholar
• Rahmani, J., A. Miri, I. Namjoo, N. Zamaninour, M. B. Maljaei, K. Zhou, R. Cerneviciute, S. M. Mousavi, H. K. Varkaneh, A. Salehisahlabadi, et al. 2019. Elevated liver enzymes and cardiovascular mortality: A systematic review and dose-response meta-analysis of more than one million participants . European Journal of Gastroenterology & Hepatology 31 (5):555–62., doi: 10.1097/MEG.0000000000001353.
   PubMed Web of Science ®Google Scholar
• Ramli, F. N., A. Abu Bakar Sajak, F. Abas, Z. A. Mat Daud, and A. Azlan. 2020. Effect of Saffron Extract and Crocin in Serum Metabolites of Induced Obesity Rats. BioMed Research International 2020:1–15. doi: 10.1155/2020/1247946.
   Web of Science ®Google Scholar
• Ruhl, C. E., and J. E. Everhart. 2009. Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population . Gastroenterology 136 (2):477–85. doi: 10.1053/j.gastro.2008.10.052.
   PubMed Web of Science ®Google Scholar
• Schmidt, M.,. G. Betti, and A. Hensel. 2007. Saffron in phytotherapy: Pharmacology and clinical uses. Wiener Medizinische Wochenschrift (1946) 157 (13-14):315–9. doi: 10.1007/s10354-007-0428-4.
   PubMedGoogle Scholar
• Sepahi, S.,. S. A. Mohajeri, S. M. Hosseini, E. Khodaverdi, N. Shoeibi, M. Namdari, and S. A. S. Tabassi. 2018. Effects of Crocin on diabetic maculopathy: A placebo-controlled randomized clinical trial. American Journal of Ophthalmology 190:89–98. doi: 10.1016/j.ajo.2018.03.007.
   PubMed Web of Science ®Google Scholar
• Serrano-DíAZ, J., A. M. SáNCHEZ, M. MARTíNEZ-Tome, P. Winterhalter, and G. L. Alonso. 2013. A contribution to nutritional studies on Crocus sativus flowers and their value as food. Journal of Food Composition and Analysis 31 (1):101–8. doi: 10.1016/j.jfca.2013.03.009.
   Web of Science ®Google Scholar
• Shamsi-Baghbanan, H., A. Sharifiyan, S. Esmaeili, and B. Minaei. 2014. Hepatoprotective herbs, avicenna viewpoint. Iranian Red Crescent Medical Journal 16 (1):e12313. doi: 10.5812/ircmj.12313.
   Web of Science ®Google Scholar
• Tung, N. H., and Y. Shoyama. 2013. New minor glycoside components from saffron. Journal of Natural Medicines 67 (3):672–6. doi: 10.1007/s11418-012-0721-4.
   PubMed Web of Science ®Google Scholar
• Xia, J., I. V. Sinelnikov, B. Han, and D. S. Wishart. 2015. MetaboAnalyst 3.0—making metabolomics more meaningful. Nucleic Acids Research 43 (W1):W251–257. doi: 10.1093/nar/gkv380.
   PubMed Web of Science ®Google Scholar
• Xiong, F., and Y.-S. Guan. 2017. Cautiously using natural medicine to treat liver problems. World Journal of Gastroenterology 23 (19):3388–95. doi: 10.3748/wjg.v23.i19.3388.
   PubMed Web of Science ®Google Scholar