The effect of kefir-spirulina on glycemic status and antioxidant activity in hyperglycemia rats


  • Nur Laela Diponegoro University, Faculty of Medicine, Department of Nutrition Science, Jl. Prof. Soedarto S.H. 50275, Semarang, Indonesia, Tel.: +62 081324381073
  • Anang Mohamad Legowo Anang Mohamad Legowo, M.Sc., Ph.D. Diponegoro University, Faculty of Animal and Agricultural Sciences, Food Technology Department, Jl. Prof. Soedarto S.H 50275, Semarang, Indonesia, Tel.: +62 08156503627
  • Faizah Fulyani Diponegoro University, Faculty of Medicine, Department of Medical Biology and Biochemistry, Jl. Prof. Soedarto S.H 50275, Semarang, Indonesia, Tel.: +62 08112880027



kefir, spirulina, antioxidant, hyperglycemia, SOD


Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia. It is caused by impaired insulin secretion or by insulin receptor insensitivity. DM and its complications are often related to increases in the level of oxidative stress. Spirulina is a nutrient-dense food that contains an abundance of antioxidant compounds. In combination with kefir, it may serve as both a nutrient-rich diet and an antioxidant agent that can prevent complications of diabetes. This study aims to investigate the nutritional content of kefir-spirulina and its effect on glycemic status and antioxidant activity in streptozotocin-nicotinamide (STZ-NA) induced diabetic rats. A total of 30 male Sprague Dawley rats were divided into five groups: normal control (K1), diabetic control (K2), pioglitazone treatment (K3), kefir combined with 1% spirulina treatment (P1), and kefir combined with 2% spirulina treatment (P2). All rats were induced by STZ-NA, except for the normal control. Before and after the 28 days of intervention, blood samples were taken and analyzed for fasting plasma glucose, postprandial glucose, and SOD activity. The nutritional content, ethanol content, and total antioxidant capacity of kefir-spirulina were also analyzed. The diabetic rats that were fed with kefir-spirulina (P1 and P2) had a significant decrease in both fasting and postprandial plasma glucose (p <0.001) compared to the diabetic control rats. The decrease of plasma glucose in K2 is comparable to the control rats treated with the diabetic drug pioglitazone (K3). The activity of SOD in diabetic rats fed in P1 and P2 were higher (p <0.001) than in untreated diabetic rats (K2). The IC50 of kefir-spirulina was 42 – 43 ppm. It was concluded that kefir combined with spirulina has high nutrition and antioxidant capacity, which is proven to be capable of controlling glycemic status and enhancing antioxidant status in a diabetic rat model.


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ADA. 2018. Glycemic Targets: Standards of Medical Care in Diabetes-2018. Diabetes Care, vol. 41, p. S55-S64.

Afifah, D. N., Rahma, A., Nuryandari, S. S., Alviche, L., Hartono, P. I., Kurniawati, D. M., Wijayanti, H. S., Fitranti, D. Y., Purwanti, R. 2019. Nutrition Content, Protein Quality, and Antioxidant Activity of Varius Tempeh Gembus Preparations. Journal of Food and Nutrition Research, vol. 7, no. 8, p. 605-612.

Aissaoui, O., Amiali, M., Bouzid, N., Belkacemi, K., Bitam, A. 2017. Effect of Spirulina platensis ingestion on the abnormal biochemical and oxidative stress parameters in the pancreas and liver of alloxan-induced diabetic rats. Pharmaceutical Biology, vol. 55, no. 1, p. 1304-1312.

Alsayadi, M., Jawfi, Y. A., Belarbi, M., Soualem-Mami, Z., Merzouk, H., Sari, D. C., Sabri, F., Ghalim, M. 2014. Evaluation of Anti-Hyperglycemic and Anti-Hyperlipidemic Activities of Water Kefir as Probiotic on Streptozotocin-Induced Diabetic Wistar Rats. Journal of Diabetes Mellitus, vol. 4, no. 2, p. 85-95.

Al-Shemmari, I. G. M., Kassim Altaee, R. A. M., Hassan, A. H. 2018. Evaluation of antidiabetic and antihyperlipidemic activity of kefir in alloxan induced diabetes mellitus rat. Scientific Journal Of Medical Research, vol. 2, no. 6, p. 83-86.

AOAC. 2005. Association of Official Analytical Chemists. Arlington, Virginia, USA: Association of Official Analytical Chemists, Inc., Method Number 1, p. 24-56.

Arslan, S. 2014. A review: chemical, microbiological and nutritional characteristics of kefir. CyTA - Journal of Food, vol. 13, no. 3, p. 340-345.

Badarinath, A. V., Rao, K. M., Chetty, C. M. S., Ramkanth, S., Rajan, T. V. S., Gnanaprakash, K. 2010. A Review on In-vitro Antioxidant Methods: Comparisons, Correlations, and Considerations. International Journal of PharmTech Research, vol. 2, no. 2, p. 1276-1285.

Barengolts, E., Smith, E. D., Reutrakul, S., Tonucci, L., Anothaisintawee, T. 2019. The Effect of Probiotic Yogurt on Glycemic Control in Type 2 Diabetes or Obesity: A Meta-Analysis of Nine Randomized Controlled Trials. Nutrients, vol. 11, no. 3, 18 p.

Bellikci-Koyu, E., Sarer-Yurekli, B. P., Akyon, Y., Aydin-Kose, F., Karagozlu, C., Ozgen, A. G., Brinkmann, A., Nitsche, A., Ergunay, K., Yilmaz, E., Buyuktuncer, Z. 2019. Effects of Regular Kefir Consumption on Gut Microbiota in Patients with Metabolic Syndrome: A Parallel-Group, Randomized, Controlled Study. Nutrients, vol. 11, no. 9, 23 p.

Catalá, A. 2009. Lipid peroxidation of membrane phospholipids generates hydroxy-alkenals and oxidized phospholipids active in physiological and/or pathological conditions. Chemistry and Physics of Lipids, vol. 157, no. 1, p. 1-11.

Chandalia, M., Garg, A., Lutjohann, D., von Bergmann, K., Grundy, S. M., Brinkley, L. J. 2000. Beneficial Effects of High Dietary Fiber Intake in Patients with Type 2 Diabetes Mellitus. The New England Journal of Medicine, p. 1392-1398.

Cho, N. H., Shaw, J. E., Karuranga, S., Huang, Y., de Rocha Fernandes, J. D., Ohlrogge, A. W., Malanda, B. 2018. IDF Diabetes Atlas: Global Estimates of Diabetes Prevalence for 2017 and Projections for 2045. Diabetes Research and Clinical Practice, vol. 138, p. 271-281.

Dias, G. P., dos Santos, R. C., Carvalho, R. C., de Souza, C. G., dos Santos, A. P. F., de Andrade, D. F., d'Avila, L. A. 2020. Determination of Methanol in Gasoline and Ethanol Fuels by High-Performance Liquid Chromatography. Journal of the Brazilian Chemical Society, vol. 31, no. 5, p. 1055-1063.

El-Bashiti, T. A., Zabut, B. M., Abu Safia, F. F. 2019. Effect of Probiotic Fermented Milk (Kefir) on Some Blood Biochemical Parameters Among Newly Diagnosed Type 2 Diabetic Adult Males in Gaza Governorate. Current Research in Nutrition and Food Science, vol. 7, no. 2, p. 568-575.

Ertekin, B., Guzel-Seydim, Z. B. 2010. Effect of fat replacers on kefir quality. Journal of the. Science of Food and Agriculture, vol. 90, no. 4, p. 543-548.

FAO. 2010. Codex Standard for Fermented Milks. CODEX STAN 243-2003.p. 1-11.

Farnworth, E. R. 2008. Handbook of fermented functional foods. 2nd ed. Boca Raton, USA : CRC Press. 600 p. ISBN 9780429136672.

Gedawy, A., Martinez, J., Al-Salami, H., Dass, C. R. 2018. Oral insulin delivery: existing barriers and current counter-strategies. Journal of Pharmacy and Pharmacoly, vol. 70, no. 2, p. 197-213.

Habib, M. A. B., Parvin, M. 2008. A Review on culture, production, and use of spirulina as food for humans and feeds for domestic animals and fish. FAO Fisheries and Aquaculture Circular. Food and Agriculture Organization of the United Nations, Rome 2008. 33 p.

Haddadinezhad, S., Ghazaleh, N. 2010. Relation of fasting and postprandial and plasma glucose with hemoglobinA1c in diabetics. International Journal of Diabetes in Developing Countries, vol. 30, no. 1, p. 8-10.

Hadisaputro, S., Djokomoeljanto, R. R. J., Judiono, Soesatyo, M. H. 2012. The effects of oral plain kefir supplementation on proinflammatory cytokine properties of the hyperglycemia Wistar rats induced by streptozotocin. Acta Medica Indonesiana, vol. 44, no. 2, p. 100-104.

Hendel, N., Larous, L., Belbey, L. 2016. Antioxidant activity of rosemary (Rosmarinus officinalis L.) and its in vitro inhibitory effect on Penicillium digitatum. International Food Research Journal, vol. 23, no. 4, p. 1725-1732.

Hernández-Alonso, P., Camacho-Barcia, L., Bulló, M., Salas-Salvadó, J. 2017. Nuts and Dried Fruits: An Update of Their Beneficial Effects on Type 2 Diabetes. Nutrients, vol. 9, no. 7, 34 p.

Huang, H., Liao, D., Pu, R., Cui, Y. 2018. Quantifying the effects of spirulina supplementation on plasma lipid and glucose concentrations, body weight, and blood pressure. Diabetes, Metabolic Syndrome and Obesity, vol. 11, p. 729-742.

Hulston, C. J., Churnside, A. A., Venables, M. C. 2015. Probiotic supplementation prevents high-fat, overfeeding-induced insulin resistance in human subjects. British Journal of Nutrition, vol. 113, no. 4, p. 596-602.

IBM. 2016. IBM SPSS Advanced Statistics 24. Armonk, NY: IBM Corp.

Jarouliya, U., Zacharia, A., Keservani, R. K., Prasad, G. B. K. S. 2015. Spirulina maxima and its effect on antioxidant activity in fructose induced oxidative stress with histopathological observations. Acta Facultatis Pharmaceuticae Universitatis Comenianae, vol. 62, no. 2, p. 13-19.

Judiono, Djokomoeljanto, Hadisaputro, S. 2011. Effects of clear probiotics on glycemic status, lipid peroxidation, antioxidative properties of streptozotocin induced hyperglycemia Wistar rats. Gizi Indonesia, vol. 34, no. 1, 6 p.

Karaçalı, R., Özdemİr, N., Çon, A. H. 2018. Aromatic and functional aspects of kefir produced using soya milk and Bifidobacterium species. International Journal of Dairy Technology, vol. 71, no. 4, p. 921-933.

Koru, E. 2012. Earth Food Spirulina (Arthrospira): Production and Quality standards, Food Additive, Yehia El-Samragy, IntechOpen, p. 191-202.

Kýlýc, S., Uysal, H., Akbulut, N., Kavas, G., Kesenkes, H. 1999. Chemical, microbiological and sensory changes in ripening kefirs produced from starters and grains. Ege University Journal of Agricultural Faculty, vol. 36, p.111-118.

Layam, A., Reddy, C. L. K. 2007. Antidiabetic property of spirulina. Diabetologia Croatica, vol. 35, no. 2, p. 29-33.

Li, Y., Aiello, G., Bollati, C., Bartolomei, M., Arnoldi, A., Lammi, C. 2020. Phycobiliproteins from Arthrospira Platensis (Spirulina): A New Source of Peptides with Dipeptidyl Peptidase-IV Inhibitory Activity. Nutrients, vol. 12, no. 3, 11 p.

Magalhães, K. T., de Melo Pereira, G. V., Campos, C. R., Dragone, G., Schwan, R. F. 2011. Brazilian kefir: structure, microbial communities and chemical composition. Brazilian Journal of Microbiolog, vol. 42, no. 2, p. 693-702.

Mao, D. B., Shi, C. W., Wu, J. Y., Xu, C. P. 2014. Optimization of exopolysaccharide production in submerged culture of Daedalea dickinsii and its antioxidant activity. Bioprocess and Biosystems Engineering, vol. 37, p. 1401-1409.

Matough, F. A., Budin, S. B., Hamid, Z. A., Alwahaibi, N., Mohamed, J. 2012. The role of oxidative stress and antioxidants in diabetic complication. Sultan Qaboos University Medical Journal, vol. 12, no. 1, p. 556-569. h

Molyneux, P. 2004. The use of the stable free radical Diphenylpicryl-hydrazyl (DPPH) for estimating antioxidant activity. Songklanakarin Journal of Science and Technology, vol. 26, no. 2, p. 211-219.

Moussa S. A. 2008. Oxidative stress in diabetes mellitus. Romanian Journal of Biophysics, vol. 18, no. 3, p. 225-236.

Niccolai, A., Shannon, E., Abu-Ghannam, N., Biondi, N., Rodolfi, L., Tredici, M. R. 2019. Lactic acid fermentation of Arthrospira platensis (spirulina) biomass for probiotic-based products. Journal of Applied Phycology, vol. 31, p. 1077-1083.

Nurliyani, Harmayani, E., Sunarti. 2015. Antidiabetic Potential of Kefir Combination from Goat Milk and Soy Milk in Rats Induced with Streptozotocin-Nicotinamide. Korean Journal of Food Science of Animal Resources, vol. 35, no. 6, p. 847-858.

Okechukwu, P. N., Ekeuku, S. O., Sharma, M., Nee, C. P., Chan, H. K., Mohamed, N., Froemming, G. R. A. 2019. In vivo and in vitro antidiabetic and antioxidant activity of spirulina. Pharmacognosy Magazine, vol. 15, no. 62, p. 17-29.

Omayma, A. R., EL-Sonbaty, S. M., Aziza, S. A., Aboelftouh, A. E. 2013. Effect of Probiotic Fermented Soy Milk and Gamma Radiation on Nitrosourea-Induced Mammary Carcinogenesis. Nature and Science, vol. 11, no. 11, p. 35-42.

Otles, S., Cagindi, O. 2003. Kefir: A Probiotic Dairy Composition, Nutritional and Therapeutic Aspects. Pakistan Journal of Nutrition, vol. 2, no. 2, p. 54-59.

Plessas, S., Nouska, C., Mantzourani, I., Kourkoutas, Y., Alexopoulos, A., Bezirtzoglou, E. 2017. Microbiological Exploration of Different Types of Kefir Grains. Fermentation, vol. 3, no. 1, 10 p.

Pogačić, T., Šinko, S., Zamberlin, Š., Samaržija, D. 2013. Microbiota of kefir grains. Mljekarstvo, vol. 63, no. 1, p. 3-14.

Rosa, D. D., Dias, M. M. S., Grześkowiak, Ł. M., Reis, S. A., Conceição, L. L., Peluzio, M. do C. G. 2017. Milk kefir: nutritional, microbiological and health benefits. Nutrition Research Reviews, vol. 30, no. 1, p. 82-96.

Sadeghi, S., Jalili, H., Ranaei Sadat, S. O., Sadeghi, M. 2018. Anticancer and Antibacterial Properties in Peptide Fractions from Hydrolyzed Spirulina Protein. Journal of Agriculture, Science and Techology, vol. 20, p. 673-683.

Santaguida, P. L., Balion, C., Hunt, D., Morrison, K., Gerstein, H., Raina, P., Booker, L., Yazdi, H. 2005. Diagnosis, Prognosis, and Treatment of Impaired Glucose Tolerance and Impaired Fasting Glucose. AHRQ Evidence Reports/Technology Assessments, p. 1-11.

Sarkar, S. 2007. Potential of kefir as a dietetic beverage - A review. British Food Journal, vol. 109, no. 4, p. 280-290.

Schultz Johansen, J., Harris, A. K., Rychly, D. J., Ergul, A. 2005. Oxidative stress and the use of antioxidants in diabetes: Linking basic science to clinical practice. Cardiovascular Diabetology, vol. 4, 11 p.

Senthil, N., Balu, P. M., Murugesan, K. 2013. Antihyperglycemic effect of spirulina, insulin and morinda citrifolia against streptozotocin induced diabetic rats. International Journal of Current Microbiology and Applied Sciences, vol. 2, no. 10, p. 237-559.

Simova, E., Beshkova, D., Angelov, A., Hristozova, T., Frengova, G., Spasov, Z. 2002. Lactic acid bacteria and yeasts in kefir grains and kefir made from them. Journal of Industrial Microbiology and Biotechnology, vol. 28, no. 1, p. 1-6.

SOD Assay. 2019. KTv019. Kamiya Biomedical Company.

System, D. 2012. Glucose GOD FS: Application for serum and plasma. Application response.

Szkudelski, T. 2001. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiological Research, vol. 50, no. 6, p. 537-546.

Valko, M., Leibfritz, D., Moncol, J., Cronin, M. T. D., Mazur, M., Telser, J. 2007. Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry and Cell Biology, vol. 39, no. 1, p. 44-84.

Venkatakrishan, K., Chiu, H. F., Wang, C. K. 2019. Popular functional foods and herbs for the management of type-2-diabetes mellitus: A comprehensive review with special reference to clinical trial and its proposed mechanism. Journal of Functional Foods, vol 57, p. 425-438.

Wang, X., Juan, Q. F., He, Y. W., Zhuang, L., Fang, Y. Y., Wang, Y. H. 2017. Multiple effects of probiotics on different types of diabetes: a systematic review and meta-analysis of randomized, placebo-controlled trials. Journal of Pediatric Endocrinology and Metabolism, vol. 30, no. 6, p. 611-622.

Waris, G., Ahsan, H. 2006. Reactive oxygen species: Role in the development of cancer and various chronic conditions. Journal of Carcinogenesis, vol. 5, no. 14, 8 p.

Waris, G., Ahsan, H. 2006. Reactive oxygen species: Role in the development of cancer and various chronic conditions. Journal of Carcinogenesis, vol. 5, no. 14, 8 p.

Waugh, J., Keating, G. M., Plosker, G. L., Easthope, S., Robinson, D. M. 2006. Pioglitazone: A Review of its Use in Type 2 Diabetes Mellitus. Drugs, vol. 66, p. 85-109.

WHO. 1999. Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO consultation. Part 1, Diagnosis and classification of diabetes mellitus). Geneva, World Health Organization.

Wu, L. C., Ho, J. A. A., Shieh, M. C., Lu, I. W. 2005. Antioxidant and Antiproliferative Activities of Spirulina and Chlorella Water Extracts. Journal of Agricultural and Food Chemistry, vol. 53, no. 10, p. 4207-4212.

Zhang, Q., Wu, Y., Fei, X. 2016. Effect of probiotics on glucose metabolism in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials. Medicina, vol. 52, no. 1, p. 28-34.



How to Cite

Laela, N., Legowo, A. M. ., & Fulyani, F. (2021). The effect of kefir-spirulina on glycemic status and antioxidant activity in hyperglycemia rats. Potravinarstvo Slovak Journal of Food Sciences, 15, 101–110.