Beneficial effects of folic acid on inflammatory markers in the patients with metabolic syndrome: Meta-analysis and meta-regression of data from 511 participants in 10 randomized controlled trials

References

• Ain, Q. U., M. Sarfraz, G. K. Prasesti, T. I. Dewi, and N. F. Kurniati. 2021. Confounders in identification and analysis of inflammatory biomarkers in cardiovascular diseases. Biomolecules 11 (10):1464. doi: 10.3390/biom11101464.
   PubMed Web of Science ®Google Scholar
• Alberti, K. G. M. M., R. H. Eckel, S. M. Grundy, P. Z. Zimmet, J. I. Cleeman, K. A. Donato, J.-C. Fruchart, W. P. T. James, C. M. Loria, S. C. Smith, International Association for the Study of Obesity, et al. 2009. Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120 (16):1640–5. doi: 10.1161/CIRCULATIONAHA.109.192644.
   PubMed Web of Science ®Google Scholar
• Bagherieh, M., A. Kheirollahi, F. Zamani-Garmsiri, S. Emamgholipour, and R. Meshkani. 2021. Folic acid ameliorates palmitate-induced inflammation through decreasing homocysteine and inhibiting NF-κB pathway in HepG2 cells. Archives of Physiology and Biochemistry:1–8. doi: 10.1080/13813455.2021.1878539.
   PubMed Web of Science ®Google Scholar
• Bahmani, F., M. Karamali, H. Shakeri, and Z. Asemi. 2014. The effects of folate supplementation on inflammatory factors and biomarkers of oxidative stress in overweight and obese women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled clinical trial. Clinical Endocrinology 81 (4):582–7. doi: 10.1111/cen.12451.
   PubMed Web of Science ®Google Scholar
• Bastard, J. P., C. Jardel, E. Bruckert, H. Vidal, and B. Hainque. 2000. Variations in plasma soluble tumour necrosis factor receptors after diet-induced weight loss in obesity. Diabetes, Obesity & Metabolism 2 (5):323–5. doi: 10.1046/j.1463-1326.2000.00090.x.
   PubMed Web of Science ®Google Scholar
• Bastard, J. P., C. Jardel, E. Bruckert, P. Blondy, J. Capeau, M. Laville, H. Vidal, and B. Hainque. 2000. Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. The Journal of Clinical Endocrinology and Metabolism 85 (9):3338–42. doi: 10.1210/jcem.85.9.6839.
   PubMed Web of Science ®Google Scholar
• Battineni, G., G. G. Sagaro, N. Chintalapudi, F. Amenta, D. Tomassoni, and S. K. Tayebati. 2021. Impact of obesity-induced inflammation on cardiovascular diseases (CVD). International Journal of Molecular Sciences 22 (9):4798. doi: 10.3390/ijms22094798.
   PubMed Web of Science ®Google Scholar
• Benito, P., J. Caballero, J. Moreno, C. Gutiérrez-Alcántara, C. Muñoz, G. Rojo, S. Garcia, and F. C. Soriguer. 2006. Effects of milk enriched with omega-3 fatty acid, oleic acid and folic acid in patients with metabolic syndrome. Clinical Nutrition (Edinburgh, Scotland) 25 (4):581–7. doi: 10.1016/j.clnu.2005.12.006.
   PubMed Web of Science ®Google Scholar
• Bleie, Ø., A. G. Semb, H. Grundt, J. E. Nordrehaug, S. E. Vollset, P. M. Ueland, D. W. T. Nilsen, A. M. Bakken, H. Refsum, O. K. Nygård, et al. 2007. Homocysteine-lowering therapy does not affect inflammatory markers of atherosclerosis in patients with stable coronary artery disease. Journal of Internal Medicine 262 (2):244–53. doi: 10.1111/j.1365-2796.2007.01810.x.
   PubMed Web of Science ®Google Scholar
• Budoff, M. J., N. Ahmadi, K. M. Gul, S. T. Liu, F. R. Flores, J. Tiano, J. Takasu, E. Miller, and S. Tsimikas. 2009. Aged garlic extract supplemented with B vitamins, folic acid and L-arginine retards the progression of subclinical atherosclerosis: A randomized clinical trial. Preventive Medicine 49 (2-3):101–7. doi: 10.1016/j.ypmed.2009.06.018.
   PubMed Web of Science ®Google Scholar
• Chambers, J. C., P. M. Ueland, O. A. Obeid, J. Wrigley, H. Refsum, and J. S. Kooner. 2000. Improved vascular endothelial function after oral B vitamins: An effect mediated through reduced concentrations of free plasma homocysteine. Circulation 102 (20):2479–83. doi: 10.1161/01.CIR.102.20.2479.
   PubMed Web of Science ®Google Scholar
• Cialdella-Kam, L., D. Nieman, A. Knab, R. Shanely, M. Meaney, F. Jin, W. Sha, and S. Ghosh. 2016. A mixed flavonoid-fish oil supplement induces immune-enhancing and anti-inflammatory transcriptomic changes in adult obese and overweight women-A randomized controlled trial. Nutrients 8 (5):277. doi: 10.3390/nu8050277.
   PubMed Web of Science ®Google Scholar
• Danesh, J., P. Whincup, M. Walker, L. Lennon, A. Thomson, P. Appleby, J. R. Gallimore, and M. B. Pepys. 2000. Low grade inflammation and coronary heart disease: Prospective study and updated meta-analyses. BMJ (Clinical Research ed.) 321 (7255):199–204. doi: 10.1136/bmj.321.7255.199.
   PubMed Web of Science ®Google Scholar
• Dunlay, S. M., S. A. Weston, M. M. Redfield, J. M. Killian, and V. L. Roger. 2008. Tumor necrosis factor-alpha and mortality in heart failure: A community study. Circulation 118 (6):625–31. doi: 10.1161/CIRCULATIONAHA.107.759191.
   PubMed Web of Science ®Google Scholar
• Engeli, S., M. Feldpausch, K. Gorzelniak, F. Hartwig, U. Heintze, J. Janke, M. Möhlig, A. F. H. Pfeiffer, F. C. Luft, A. M. Sharma, et al. 2003. Association between adiponectin and mediators of inflammation in obese women. Diabetes 52 (4):942–7. doi: 10.2337/diabetes.52.4.942.
   PubMed Web of Science ®Google Scholar
• Espinola-Klein, C., T. Gori, S. Blankenberg, and T. Munzel. 2011. Inflammatory markers and cardiovascular risk in the metabolic syndrome. Frontiers in Bioscience (Landmark Edition) 16 (5):1663–74. doi: 10.2741/3812.
   PubMedGoogle Scholar
• Fasshauer, M., and R. Paschke. 2003. Regulation of adipocytokines and insulin resistance. Diabetologia 46 (12):1594–603. doi: 10.1007/s00125-003-1228-z.
   PubMed Web of Science ®Google Scholar
• Fatahi, S., M. Pezeshki, S. M. Mousavi, A. Teymouri, J. Rahmani, H. Kord Varkaneh, and E. Ghaedi. 2019. Effects of folic acid supplementation on C-reactive protein: A systematic review and meta-analysis of randomized controlled trials. Nutrition, Metabolism, and Cardiovascular Diseases: NMCD 29 (5):432–9. doi: 10.1016/j.numecd.2018.11.006.
   PubMed Web of Science ®Google Scholar
• Feng, D., Y. Zhou, M. Xia, and J. Ma. 2011. Folic acid inhibits lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages by suppressing MAPKs and NF-κB activation. Inflammation Research: Official Journal of the European Histamine Research Society. [et al.] 60 (9):817–22. doi: 10.1007/s00011-011-0337-2.
   PubMed Web of Science ®Google Scholar
• Fuentes, G. C., O. Castañer, J. Warnberg, I. Subirana, P. Buil-Cosiales, J. Salas-Salvadó, D. Corella, L. Serra-Majem, D. Romaguera, R. Estruch, et al. 2020. Prospective association of physical activity and inflammatory biomarkers in older adults from the PREDIMED-Plus study with overweight or obesity and metabolic syndrome. Clinical Nutrition (Edinburgh, Scotland) 39 (10):3092–8. doi: 10.1016/j.clnu.2020.01.015.
   PubMed Web of Science ®Google Scholar
• Henning, S. M., M. E. Swendseid, B. T. Ivandic, and F. Liao. 1997. Vitamins C, E and A and heme oxygenase in rats fed methyl/folate-deficient diets. Free Radical Biology and Medicine 23 (6):936–42. doi: 10.1016/S0891-5849(97)00097-X.
   PubMed Web of Science ®Google Scholar
• Higgins, J. P. T., D. G. Altman, P. C. Gøtzsche, P. Jüni, D. Moher, A. D. Oxman, J. Savovic, K. F. Schulz, L. Weeks, J. A. C. Sterne, Cochrane Statistical Methods Group, et al. 2011. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ (Clinical Research ed.) 343:d5928. doi: 10.1136/bmj.d5928.
   PubMed Web of Science ®Google Scholar
• Jung, U. J., and M. S. Choi. 2014. Obesity and its metabolic complications: The role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. International Journal of Molecular Sciences 15 (4):6184–223. doi: 10.3390/ijms15046184.
   PubMed Web of Science ®Google Scholar
• Kaptoge, S., S. R. K. Seshasai, P. Gao, D. F. Freitag, A. S. Butterworth, A. Borglykke, E. Di Angelantonio, V. Gudnason, A. Rumley, G. D. O. Lowe, et al. 2014. Inflammatory cytokines and risk of coronary heart disease: New prospective study and updated meta-analysis. European Heart Journal 35 (9):578–89. doi: 10.1093/eurheartj/eht367.
   PubMed Web of Science ®Google Scholar
• Kern, P. A., M. Saghizadeh, J. M. Ong, R. J. Bosch, R. Deem, and R. B. Simsolo. 1995. The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. The Journal of Clinical Investigation 95 (5):2111–9. doi: 10.1172/JCI117899.
   PubMed Web of Science ®Google Scholar
• Koh, K. K. 2002. Effects of estrogen on the vascular wall: Vasomotor function and inflammation. Cardiovascular Research 55 (4):714–26. doi: 10.1016/s0008-6363(02)00487-x.
   PubMed Web of Science ®Google Scholar
• Koh, K. K., S. H. Han, and M. J. Quon. 2005. Inflammatory markers and the metabolic syndrome: Insights from therapeutic interventions. Journal of the American College of Cardiology 46 (11):1978–85. doi: 10.1016/j.jacc.2005.06.082.
   PubMed Web of Science ®Google Scholar
• Kritchevsky, S. B., M. Cesari, and M. Pahor. 2005. Inflammatory markers and cardiovascular health in older adults. Cardiovascular Research 66 (2):265–75. doi: 10.1016/j.cardiores.2004.12.026.
   PubMed Web of Science ®Google Scholar
• Liuzzo, G., L. M. Biasucci, J. R. Gallimore, R. L. Grillo, A. G. Rebuzzi, M. B. Pepys, and A. Maseri. 1994. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. The New England Journal of Medicine 331 (7):417–24. doi: 10.1056/NEJM199408183310701.
   PubMed Web of Science ®Google Scholar
• Loscalzo, J. 2006. Homocysteine trials–clear outcomes for complex reasons. The New England Journal of Medicine 354 (15):1629–32. doi: 10.1056/NEJMe068060.
   PubMed Web of Science ®Google Scholar
• Makino, E., T. Fukuyama, Y. Watanabe, R. Tajiki-Nishino, H. Tajima, A. Ohnuma-Koyama, N. Takahashi, R. Ohtsuka, and Y. Okazaki. 2019. Subacute oral administration of folic acid elicits anti-inflammatory response in a mouse model of allergic dermatitis. The Journal of Nutritional Biochemistry 67:14–9. doi: 10.1016/j.jnutbio.2019.01.009.
   PubMed Web of Science ®Google Scholar
• Moens, A. L., C. J. Vrints, M. J. Claeys, J. P. Timmermans, H. C. Champion, and D. A. Kass. 2008. Mechanisms and potential therapeutic targets for folic acid in cardiovascular disease. American Journal of Physiology. Heart and Circulatory Physiology 294 (5):H1971–1977. doi: 10.1152/ajpheart.91503.2007.
   PubMed Web of Science ®Google Scholar
• Natali, A., E. Toschi, S. Baldeweg, D. Ciociaro, S. Favilla, L. Saccà, and E. Ferrannini. 2006. Clustering of insulin resistance with vascular dysfunction and low-grade inflammation in type 2 diabetes. Diabetes 55 (4):1133–40. doi: 10.2337/diabetes.55.04.06.db05-1076.
   PubMed Web of Science ®Google Scholar
• Padfield, G. J., J. N. Din, E. Koushiappi, N. L. Mills, S. D. Robinson, N. L. M. Cruden, A. J. Lucking, S. Chia, S. A. Harding, D. E. Newby, et al. 2013. Cardiovascular effects of tumour necrosis factor α antagonism in patients with acute myocardial infarction: A first in human study. Heart (British Cardiac Society) 99 (18):1330–5. doi: 10.1136/heartjnl-2013-303648.
   PubMed Web of Science ®Google Scholar
• Page, M. J., J. E. McKenzie, P. M. Bossuyt, I. Boutron, T. C. Hoffmann, C. D. Mulrow, L. Shamseer, J. M. Tetzlaff, E. A. Akl, S. E. Brennan, et al. 2021. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ (Clinical Research ed.) 372:n71. doi: 10.1136/bmj.n71.
   PubMed Web of Science ®Google Scholar
• Phillips, C. M., and I. J. Perry. 2013. Does inflammation determine metabolic health status in obese and nonobese adults? The Journal of Clinical Endocrinology and Metabolism 98 (10):E1610–1619. doi: 10.1210/jc.2013-2038.
   PubMed Web of Science ®Google Scholar
• Pickup, J. C., M. B. Mattock, G. D. Chusney, and D. Burt. 1997. NIDDM as a disease of the innate immune system: Association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 40 (11):1286–92. doi: 10.1007/s001250050822.
   PubMed Web of Science ®Google Scholar
• Pradhan, A. D., J. E. Manson, N. Rifai, J. E. Buring, and P. M. Ridker. 2001. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286 (3):327–34. doi: 10.1001/jama.286.3.327.
   PubMed Web of Science ®Google Scholar
• Reddy, P., D. Lent-Schochet, N. Ramakrishnan, M. McLaughlin, and I. Jialal. 2019. Metabolic syndrome is an inflammatory disorder: A conspiracy between adipose tissue and phagocytes. Clinica Chimica Acta; International Journal of Clinical Chemistry 496:35–44. doi: 10.1016/j.cca.2019.06.019.
   PubMed Web of Science ®Google Scholar
• Ridker, P. M., and M. Rane. 2021. Interleukin-6 signaling and anti-interleukin-6 therapeutics in cardiovascular disease. Circulation Research 128 (11):1728–46. doi: 10.1161/CIRCRESAHA.121.319077.
   PubMed Web of Science ®Google Scholar
• Ridker, P. M., J. E. Buring, N. R. Cook, and N. Rifai. 2003. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: An 8-year follow-up of 14 719 initially healthy American women. Circulation 107 (3):391–7. doi: 10.1161/01.CIR.0000055014.62083.05.
   PubMed Web of Science ®Google Scholar
• Ridker, P. M., N. Rifai, L. Rose, J. E. Buring, and N. R. Cook. 2002. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. The New England Journal of Medicine 347 (20):1557–65. doi: 10.1056/NEJMoa021993.
   PubMed Web of Science ®Google Scholar
• Rość, D., P. Adamczyk, J. Boinska, R. Szafkowski, I. Ponikowska, K. Stankowska, B. Góralczyk, and B. Ruszkowska-Ciastek. 2015. CRP, but not TNF-α or IL-6, decreases after weight loss in patients with morbid obesity exposed to intensive weight reduction and ­balneological treatment. Journal of Zhejiang University. Science. B 16 (5):404–11. doi: 10.1631/jzus.B1400219.
   PubMed Web of Science ®Google Scholar
• Ross, R. 1999. Atherosclerosis–an inflammatory disease. The New England Journal of Medicine 340 (2):115–26. doi: 10.1056/NEJM199901143400207.
   PubMed Web of Science ®Google Scholar
• Scheller, J., and S. Rose-John. 2006. Interleukin-6 and its receptor: From bench to bedside. Medical Microbiology and Immunology 195 (4):173–83. doi: 10.1007/s00430-006-0019-9.
   PubMed Web of Science ®Google Scholar
• Schuett, H., M. Luchtefeld, C. Grothusen, K. Grote, and B. Schieffer. 2009. How much is too much? Interleukin-6 and its signalling in atherosclerosis. Thrombosis and Haemostasis 102 (2):215–22. doi: 10.1160/TH09-05-0297.
   PubMed Web of Science ®Google Scholar
• Solini, A., E. Santini, and E. Ferrannini. 2006. Effect of short-term folic acid supplementation on insulin sensitivity and inflammatory markers in overweight subjects. International Journal of Obesity (2005) 30 (8):1197–202. doi: 10.1038/sj.ijo.0803265.
   PubMed Web of Science ®Google Scholar
• Spoelstra-de, M. A., C. B. Brouwer, F. Terheggen, J. M. Bollen, C. D. Stehouwer, and Y. M. Smulders. 2004. No effect of folic acid on markers of endothelial dysfunction or inflammation in patients with type 2 diabetes mellitus and mild hyperhomocysteinaemia. The Netherlands Journal of Medicine 62 (7):246–53.
   PubMed Web of Science ®Google Scholar
• Stanhewicz, A. E., and W. L. Kenney. 2017. Role of folic acid in nitric oxide bioavailability and vascular endothelial function. Nutrition Reviews 75 (1):61–70. doi: 10.1093/nutrit/nuw053.
   PubMed Web of Science ®Google Scholar
• Tahir, A., P. J. Martinez, F. Ahmad, S. P. Fisher-Hoch, J. McCormick, J. L. Gay, S. Mirza, and S. U. Chaudhary. 2021. An evaluation of lipid profile and pro-inflammatory cytokines as determinants of cardiovascular disease in those with diabetes: A study on a Mexican American cohort. Scientific Reports 11 (1):2435. doi: 10.1038/s41598-021-81730-6.
   PubMed Web of Science ®Google Scholar
• Talari, H. R., M. Rafiee, A. Farrokhian, F. Raygan, F. Bahmani, M. Darooghegi Mofrad, Y. Hamidian, O. R. Tamtaji, F. Karamali, Z. Asemi, et al. 2016. The effects of folate supplementation on carotid intima-media thickness and metabolic status in patients with metabolic syndrome. Annals of Nutrition & Metabolism 69 (1):41–50. doi: 10.1159/000448295.
   PubMed Web of Science ®Google Scholar
• Title, L. M., E. Ur, K. Giddens, M. J. McQueen, and B. A. Nassar. 2006. Folic acid improves endothelial dysfunction in type 2 diabetes–an effect independent of homocysteine-lowering. Vascular Medicine (London, England) 11 (2):101–9. doi: 10.1191/1358863x06vm664oa.
   PubMed Web of Science ®Google Scholar
• Title, L. M., P. M. Cummings, K. Giddens, J. J. Genest, Jr, and B. A. Nassar. 2000. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. Journal of the American College of Cardiology 36 (3):758–65. doi: 10.1016/s0735-1097(00)00809-3.
   PubMed Web of Science ®Google Scholar
• Tuttle, H. A., G. Davis-Gorman, S. Goldman, J. G. Copeland, and P. F. McDonagh. 2004. Proinflammatory cytokines are increased in type 2 diabetic women with cardiovascular disease. Journal of Diabetes and Its Complications 18 (6):343–51. doi: 10.1016/S1056-8727(03)00088-6.
   PubMed Web of Science ®Google Scholar
• Verhaar, M. C., R. M. Wever, J. J. Kastelein, T. van Dam, H. A. Koomans, and T. J. Rabelink. 1998. 5-methyltetrahydrofolate, the active form of folic acid, restores endothelial function in familial hypercholesterolemia. Circulation 97 (3):237–41. doi: 10.1161/01.CIR.97.3.237.
   PubMed Web of Science ®Google Scholar
• Viswanathan, M., K. A. Treiman, J. Kish-Doto, J. C. Middleton, E. J. Coker-Schwimmer, and W. K. Nicholson. 2017. Folic acid supplementation for the prevention of neural tube defects: An updated evidence report and systematic review for the US preventive services task force. JAMA 317 (2):190–203. doi: 10.1001/jama.2016.19193.
   PubMed Web of Science ®Google Scholar
• Yeh, E. T. 2005. High-sensitivity C-reactive protein as a risk assessment tool for cardiovascular disease. Clinical Cardiology 28 (9):408–12. doi: 10.1002/clc.4960280905.
   PubMed Web of Science ®Google Scholar