calcium diet, inflammation and oxidative stress

  • SANDEEP DAS Department of Human Physiology, Reproductive Physiology and Endocrinology Laboratory, Tripura University (A Central University), Agartala, Tripura, India.
  • DIPAYAN CHOUDHURI Department of Human Physiology, Reproductive Physiology and Endocrinology Laboratory, Tripura University (A Central University), Agartala, Tripura, India.


Objective: Emerging evidence established the role of dietary calcium in the modulation of obesity. Obesity is known to induce inflammatory and oxidative stress in adipocytes resulting in several metabolic complications. In the present study, we evaluated the role of low and high calcium diet on systemic inflammatory response and oxidative stress markers in both plasma and hepatic tissues in male rats.

Methods: A total of 30 male rats were divided into three groups and fed with control, low calcium (0.25%), and high calcium (1.0%) diet for 3 months. All the diets were isocaloric in nature. At the end of the treatment, all rats were sacrificed, followed by collection of blood and hepatic tissue for inflammatory, oxidative, antioxidant, and histological study.

Results: Rats fed with a low calcium diet showed a significant increase in the body weight gain, liver mass, plasma inflammatory markers C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. Low calcium diet significantly increased the lipid peroxidation and protein carbonylation and decreased the superoxide dismutase and glutathione peroxidase activities in both plasma and liver. High calcium diet, on the other hand, showed the reversed effect.

Conclusion: Low calcium in the diet, along with obesity, increases the systemic inflammatory response, which in turn increases oxidative stress both in blood and hepatic tissues. This might be associated with obesity-induced hepatic disorder. High calcium in diet attenuates this effect.

Keywords: Calcium, Interleukin-6, Tumor necrosis factor-α, Lipid peroxidation, Superoxide dismutase, Glutathione peroxidase


1. Popkin BM, Gordon-Larsen P. The nutrition transition: Worldwide obesity dynamics and their determinants. Int J Obes Relat Metab Disord 2004;28 Suppl 3:S2-9.
2. Via M. The malnutrition of obesity: Micronutrient deficiencies that promote diabetes. ISRN Endocrinol 2012;2012:103472.
3. Schrager S. Dietary calcium intake and obesity. J Am Board Fam Pract 2005;18:205-10.
4. Peixoto TC, Moura EG, de Oliveira E, Soares PN, Guarda DS, Bernardino DN, et al. Cranberry (Vaccinium macrocarpon) extract treatment improves triglyceridemia, liver cholesterol, liver steatosis, oxidative damage and corticosteronemia in rats rendered obese by high fat diet. Eur J Nutr 2018;57:1829-44.
5. Gregor MF, Hotamisligil GS. Thematic review series: Adipocyte biology. Adipocyte stress: The endoplasmic reticulum and metabolic disease. J Lipid Res 2007;48:1905-14.
6. Jo J, Gavrilova O, Pack S, Jou W, Mullen S, Sumner AE, et al. Hypertrophy and/or hyperplasia: Dynamics of adipose tissue growth. PLoS Comput Biol 2009;5:e1000324.
7. Fernández-Sánchez A, Madrigal-Santillán E, Bautista M, Esquivel-Soto J, Morales-González A, Esquivel-Chirino C, et al. Inflammation, oxidative stress, and obesity. Int J Mol Sci 2011;12:3117-32.
8. Sacerdoti D, Singh SP, Schragenheim J, Bellner L, Vanella L, Raffaele M, et al. Development of NASH in obese mice is confounded by adipose tissue increase in inflammatory NOV and oxidative stress. Int J Hepatol 2018;2018:1-14.
9. Das S, Choudhuri D. Role of low calcium and high calcium diet on adipocyte metabolism with respect to serum parathyroid hormone (PTH) levels in male Wistar rats. Indian J Physiol Pharmacol 2017;61:430-9.
10. Aslam MN, Bassis CM, Zhang L, Zaidi S, Varani J, Bergin IL, et al. Calcium reduces liver injury in mice on a high-fat diet: Alterations in microbial and bile acid profiles. PLoS One 2016;11:e0166178.
11. dos Santos LC, de Pádua Cintra I, Fisberg M, Martini LA. Calcium intake and its relationship with adiposity and insulin resistance in post-pubertal adolescents. J Hum Nutr Diet 2008;21:109-16.
12. Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121-6.
13. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974;47:469-74.
14. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70:158-69.
15. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.
16. Reznick AZ, Packer L. Oxidative damage to proteins: Spectrophotometric method for carbonyl assay. Methods Enzymol 1994;233:357-63.
17. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265-75.
18. Panchal SK, Ward L, Brown L. Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats. Eur J Nutr 2013;52:559-68.
19. Villarroel P, Villalobos E, Reyes M, Cifuentes M. Calcium, obesity, and the role of the calcium-sensing receptor. Nutr Rev 2014;72:627-37.
20. Mulder P, Morrison MC, Verschuren L, Liang W, van Bockel JH, Kooistra T, et al. Reduction of obesity-associated white adipose tissue inflammation by rosiglitazone is associated with reduced non-alcoholic fatty liver disease in LDLr-deficient mice. Sci Rep 2016;6:31542.
21. Wisse BE. The inflammatory syndrome: The role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol 2004;15:2792-800.
22. Cheung AT, Ree D, Kolls JK, Fuselier J, Coy DH, Bryer-Ash M, et al. An in vivo model for elucidation of the mechanism of tumor necrosis factor-alpha (TNF-alpha)-induced insulin resistance: Evidence for differential regulation of insulin signaling by TNF-alpha. Endocrinology 1998;139:4928-35.
23. Brass EP, Vetter WH. Interleukin-6, but not tumour necrosis factor-alpha, increases lipogenesis in rat hepatocyte primary cultures. Biochem J 1994;301 (Pt 1):193-7.
24. Sun X, Zemel MB. Calcium and 1,25-dihydroxyvitamin D3 regulation of adipokine expression. Obesity (Silver Spring) 2007;15:340-8.
25. Zemel MB, Sun X. Dietary calcium and dairy products modulate oxidative and inflammatory stress in mice and humans. J Nutr 2008;138:1047-52.
26. Huang CJ, McAllister MJ, Slusher AL, Webb HE, Mock JT, Acevedo EO, et al. Obesity-related oxidative stress: The impact of physical activity and diet manipulation. Sports Med Open 2015;1:32.
27. Noeman SA, Hamooda HE, Baalash AA. Biochemical study of oxidative stress markers in the liver, kidney and heart of high fat diet induced obesity in rats. Diabetol Metab Syndr 2011;3:17.
28. Carmiel-Haggai M, Cederbaum AI, Nieto N. A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. FASEB J 2005;19:136-8.
29. Rameshreddy P, Uddandrao VV, Brahmanaidu P, Vadivukkarasi S, Ravindarnaik R, Suresh P, et al. Obesity-alleviating potential of asiatic acid and its effects on ACC1, UCP2, and CPT1 mRNA expression in high fat diet-induced obese sprague-dawley rats. Mol Cell Biochem 2018;442:143-54.
30. Manna P, Jain SK. Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: Causes and therapeutic strategies. Metab Syndr Relat Disord 2015;13:423-44.
31. Vincent HK, Powers SK, Dirks AJ, Scarpace PJ. Mechanism for obesity-induced increase in myocardial lipid peroxidation. Int J Obes Relat Metab Disord 2001;25:378-88.
32. Abozid MM, Zein H, El-Halem AA. Effect of common carp and African catfish oils on rats fed on high-fat diet. Int J Pharm Pharm Sci 2018;10:96-101.
33. Kerner A, Avizohar O, Sella R, Bartha P, Zinder O, Markiewicz W, et al. Association between elevated liver enzymes and C-reactive protein: Possible hepatic contribution to systemic inflammation in the metabolic syndrome. Arterioscler Thromb Vasc Biol 2005;25:193-7.
34. Fronczyk A, Mol?da P, Safranow K, Piechota W, Majkowska L. Increased concentration of C-reactive protein in obese patients with Type 2 diabetes is associated with obesity and presence of diabetes but not with macrovascular and microvascular complications or glycemic control. Inflammation 2014;37:349-57.
35. Conceição EP, Moura EG, Soares PN, Ai XX, Figueiredo MS, Oliveira 0E, et al. High calcium diet improves the liver oxidative stress and microsteatosis in adult obese rats that were overfed during lactation. Food Chem Toxicol 2016;92:245-55.
36. Sapkota NK. Modifiable risk factors of prediabetes. Innovare J Med Sci 2017;5:1-2.
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