Skip to main content Skip to main navigation menu Skip to site footer
Published: 2022-10-28

Nutrological and metabolic approaches to the action of the some special micronutrients in heart failure and metabolic syndrome: a systematic review

Costa Rica Hospital Foundation - Vitale Clinic, Costa Rica, MS, Brazil
Costa Rica Hospital Foundation - Vitale Clinic, Costa Rica, MS, Brazil
Dietary therapy Nutrology Magnesium Vitamin D Coenzyme Q10 Heart Failure Metabolic syndrome


Introduction: In the heart disease scenario, heart failure (HF) is the leading cause of hospitalizations in the United States in patients over 65 years of age, and there is evidence that this pathology affects 26 million people worldwide. Dietary guidance for patients with HF has focused on sodium restriction and fluid intake, but diet quality is often poor in HF patients and can contribute to morbidity and mortality. Restrictive diets can lead to inadequate intake of macro and micronutrients by patients with HF, highlighting deficiencies in calcium, magnesium, coenzyme Q10, zinc, iron, thiamine, vitamins D, E, and K, and folate. Objective: Through a systematic literature review, the main nutrological approaches to the action of the micronutrients magnesium, coenzyme Q10, and vitamin D in heart failure and metabolic syndrome were evidenced. Methods: The present study followed a concise systematic review model (PRISMA). The literary search process was carried out from August 2022 to September 2022 and was developed based on Scopus, PubMed, Science Direct, Scielo, and Google Scholar, using scientific articles from 1998 to 2022. The low quality of evidence was attributed to reports of cases, editorials, and brief communications, according to the GRADE instrument. The risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: The total of 136 studies were found for eligibility analysis, and then 75 of the 84 total studies were selected for this systematic review. According to the GRADE instrument, most studies showed homogeneity in their results, with I2 =98.7% >50%. The Funnel Plot showed a symmetrical behavior, not suggesting a significant risk of bias in studies with smaller sample sizes. Studies have shown that magnesium deficiency or changes in its metabolism are related to the pathophysiology of heart failure, hypertension, arrhythmias, preeclampsia, insulin resistance, and diabetes. Vitamin D plays an important role in innate and adaptive immune responses, cell cycle, and metabolic processes, evidenced by the reported relationship between its deficiency and the prevalence of immunity-mediated disorders, cancer, and cardiometabolic diseases. The VDR results in β cells, endothelium, cardiac myocytes, and renin production suggesting a role for vitamin D in these diseases. Coenzyme Q10 is part of the electron transport chain and is found in large concentrations in the mitochondrial, especially in the muscles, brain, and heart. Clinical studies have shown that pathologies such as acute myocardial infarction, arterial hypertension, and myopathies induced by statins, physical fatigue inherent in physical exercise, male infertility, preeclampsia, Parkinson's disease, periodontal disease, and migraine had low plasma concentrations of coenzyme Q10.


Metrics Loading ...


  1. Fernandes ADF, Fernandes GC, Mazza MR, Knijnik LM, Fernandes GS, Vilela AT, Badiye A, Chaparro SV. A 10-Year Trend Analysis of Heart Failure in the Less Developed Brazil. Arq Bras Cardiol. 2020 Feb;114(2):222-231. doi: 10.36660/abc.20180321.
  2. Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statis-tics–2021 update: a report from the American Heart Association. Circula-tion. 2021;143:e254–e743.
  3. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063. Epub 2022 Apr 1. Erratum in: Circulation. 2022 May 3;145(18):e1033. Erratum in: Circulation. 2022 Sep 27;146(13):e185.
  4. Vest AR, Chan M, Deswal A, Givertz MM, Lekavich C, Lennie T, Litwin SE, Parsly L, Rodgers JE, Rich MW, Schulze PC, Slader A, Desai A. Nutrition, Obesity, and Cachexia in Patients With Heart Failure: A Consensus Statement from the Heart Failure Society of America Scientific Statements Committee. J Card Fail. 2019 May;25(5):380-400. doi: 10.1016/j.cardfail.2019.03.007.
  5. Tangvoraphonkchai K, Davenport A. Magnesium and Cardiovascular Disease. Adv Chronic Kidney Dis. 2018 May;25(3):251-260. doi: 10.1053/j.ackd.2018.02.010. PMID: 29793664.
  6. Shrimanker I, Bhattarai S. Electrolytes. 2021 Jul 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 31082167.
  7. Kikuchi K, Tanaka H, Gima M, Kashiwagi Y, Shida H, Kawamura Y, Hasebe N. [Abnormalities of magnesium (Mg) metabolism and therapeutic significance of Mg administration in patients with metabolic syndrome, type 2 diabetes, heart failure and chronic hemodialysis]. Clin Calcium. 2012 Aug;22(8):1217-26. Japanese. PMID: 22846358.
  8. Voultsos P, Bazmpani MA, Papanastasiou CA, Papadopoulos CE, Efthimiadis G, Karvounis H, Kalogeropoulos AP, Karamitsos TD. Magnesium disorders and prognosis in heart failure: A systematic review. Cardiol Rev. 2021 May 12. doi: 10.1097/CRD.0000000000000397. Epub ahead of print. PMID: 34001688.
  9. Liu M, Dudley SC Jr. Magnesium, Oxidative Stress, Inflammation, and Cardiovascular Disease. Antioxidants (Basel). 2020 Sep 23;9(10):907. doi: 10.3390/antiox9100907. PMID: 32977544; PMCID: PMC7598282.
  10. Peter J. Joris, Jogchum Plat, Stephan JL, Bakker, Ronald P. Mensink. Effects of long-term magnesium supplementation on endothelial function and cardiometabolic risk markers: A randomized controlled trial in overweight/obese adults. Scientific Reports 2017, 7: 106.
  11. Baker WL. Treating arrhythmias with adjunctive magnesium: identifying future research directions. Eur Heart J Cardiovasc Pharmacother. 2017; 1;3(2):108117.
  12. Yu L, Li H, Wang SX. Serum Magnesium and Mortality in Maintenance Hemodialysis Patients. Blood Purif. 2017;43(13): 3136.
  13. Amorim AG, Tirapegui J. Aspectos atuais da relação entre exercício físico, estresse oxidativo e magnésio. Rev Nutr, 2008; 21(5):563-75.
  14. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999;69(5):842–56.
  15. Schuch NJ, Garcia VC, Martini LA. Vitamin D and endocrine diseases. Arq Bras Endocrinol Metab 2009;53(5):625–33.
  16. Tóth Š, Šajty M, Pekárová T, Mughees A, Štefanič P, Katz M, Spišáková K, Pella J, Pella D. Addition of omega-3 fatty acid and coenzyme Q10 to statin therapy in patients with combined dyslipidemia. J Basic Clin Physiol Pharmacol. 2017.
  17. Kumar A, Kaur H, Devi P, Mohan V. Role of coenzyme Q10 (CoQ10) in cardiac disease, hypertension and Meniere-like syndrome. Pharmacology & Therapeutics, 2010, 124: 259-268.Baaij JHF, Hoenderop JGJ, Bindels RJM. Regulation of magnesium balance: lessons learned from human genetic disease. Clin Kidney J, 2012; 5(1):i15-i24.
  18. Blanchard A, Vargas-Poussou R. Désordres de la magnésémie. Nephrol Ther, 2012; 8(6):482-91.
  19. Elin RJ. Assessment of magnesium status for diagnosis and therapy. Magnes Res, 2010; 23(4):194-8.
  20. Hata A, Doi Y, Ninomiya T, Mukai N, Hirakawa Y, Hata J, et al. Magnesium intake decreases Type 2 diabetes risk through the improvement of insulin resistance and inflammation: the Hisayama Study. Diabet Med, 2013; 30(12):1487-94.
  21. Oost LJ, van der Heijden AAWA, Vermeulen EA, Bos C, Elders PJM, Slieker RC, Kurstjens S, van Berkel M, Hoenderop JGJ, Tack CJ, Beulens JWJ, de Baaij JHF. Serum Magnesium Is Inversely Associated With Heart Failure, Atrial Fibrillation, and Microvascular Complications in Type 2 Diabetes. Diabetes Care. 2021 Aug;44(8):1757-1765. doi: 10.2337/dc21-0236. Epub 2021 Jun 18. PMID: 34385344.
  22. Houillier P. Mechanisms and regulation of renal magnesium transport. Annu Rev Physiol, 2014; 76:411-30. Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J, 2012; 5(1):i3–i14.
  23. Fang X. et al. Dietary magnesium intake and the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality: a doseresponse meta-analysis of prospective cohort studies. BMC Med. 2016; 14, 210.
  24. Del Gobbo LC. et al. Circulating and dietary magnesium and risk of cardiovascular disease: a systematic review and meta-analysis of prospective studies. Am. J. Clin. Nutr. 2013; 98, 160–173.
  25. Joosten MM. et al. Urinary and plasma magnesium and risk of ischemic heart disease. Am. J. Clin. Nutr. 2013; 97, 1299–1306.
  26. Joris PJ, Plat J, Bakker SJ, Mensink RP. Long-term magnesium supplementation improves arterial stiffness in overweight and obese adults: results of a randomized, double-blind, placebo-controlled intervention trial. Am. J. Clin. Nutr. 2016; 103, 1260–1266.
  27. Laurent S. et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur. Heart J. 2006; 27, 2588–2605.
  28. Wilkinson IB. et al. Nitric oxide regulates local arterial distensibility in vivo. Circulation. 2002; 105, 213–217.
  29. Guerrero-Romero F. et al. Oral magnesium supplementation improves insulin sensitivity in non-diabetic subjects with insulin resistance. A double-blind placebo-controlled randomized trial. Diabetes Metab. 2004; 30, 253–258.
  30. Paolisso G. et al. Daily magnesium supplements improve glucose handling in elderly subjects. Am. J. Clin. Nutr. 1992; 55, 1161–1167.
  31. Marken PA. et al. Effects of magnesium oxide on the lipid profile of healthy volunteers. Atherosclerosis. 1989; 77, 37–42.
  32. Chacko SA. et al. Magnesium supplementation, metabolic and inflammatory markers, and global genomic and proteomic profiling: a randomized, double-blind, controlled, crossover trial in overweight individuals. Am. J. Clin. Nutr. 2011; 93, 463–473.
  33. Cosaro E. et al. Effects of magnesium supplements on blood pressure, endothelial function and metabolic parameters in healthy young men with a family history of metabolic syndrome. Nutr. Metab. Cardiovasc. Dis. 2014; 24, 1213–1220.
  34. Mortazavi M. et al. Effect of magnesium supplementation on carotid intima-media thickness and flow-mediated dilatation among hemodialysis patients: a double-blind, randomized, placebo-controlled trial. Eur. Neurol.2013; 69, 309–316.
  35. Shechter M. et al. Oral magnesium therapy improves endothelial function in patients with coronary artery disease. Circulation. 2000; 102, 2353–2358.
  36. Ellins EA, Halcox JP. Where are we heading with noninvasive clinical vascular physiology? Why and how should we assess endothelial function? Cardiol. Res. Pract 2011, 870132.
  37. Poredos P, Jezovnik MK. Testing endothelial function and its clinical relevance. J. Atheroscler. Thromb. 2013; 20, 1–8.
  38. Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007; 115, 1285–1295.
  39. Cohn JN, Quyyumi AA, Hollenberg NK, Jamerson KA. Surrogate markers for cardiovascular disease: functional markers. Circulation. 2004; 109, IV31–IV46.
  40. Beijers HJ. et al. Higher central fat mass and lower peripheral lean mass are independent determinants of endothelial dysfunction in the elderly: the Hoorn study. Atherosclerosis. 2014; 233, 310–318.
  41. Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006; 444, 881–887.
  42. Ras RT, Streppel MT, Draijer R, Zock PL. Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis. Int. J. Cardiol.2013; 168, 344–351.
  43. Seelig M. Cardiovascular consequences of magnesium deficiency and loss: pathogenesis, prevalence and manifestations-magnesium and chloride loss in refractory potassium repletion. Am. J. Cardiol.1989; 63, 4G–21G.
  44. Turgut F. et al. Magnesium supplementation helps to improve carotid intima media thickness in patients on hemodialysis. Int. Urol. Nephrol. 2008; 40, 1075–1082.
  45. Lorenz MW. et al. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and metaanalysis. Circulation. 2007; 115, 459–467.
  46. Calder PC. et al. A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies. Br. J. Nutr. 2013, 109, S1–S34.
  47. Cunha AR, Umbelino B, Correia ML, Neves MF. Magnesium and vascular changes in hypertension. Int. J. Hypertens. 2012, 754250.
  48. Song Y, He K, Levitan EB, Manson JE, Liu S. Effects of oral magnesium supplementation on glycaemic control in Type 2 diabetes: a meta-analysis of randomized double-blind controlled trials. Diabet. Med. 2006; 23, 1050–1056.
  49. Simental-Mendia LE, Sahebkar A, Rodriguez-Moran M, Guerrero-Romero F. A systematic review and meta-analysis of randomized controlled trials on the effects of magnesium supplementation on insulin sensitivity and glucose control. Pharmacol. Res.2016; 111, 272–282.
  50. Heil W, Ehrhardt V. Reference ranges for adults and children. Pre-analytical considerations in Roche Diagnostics 9th Edition (2008).
  51. Moslehi N, Vafa M, Rahimi-Foroushani A, Golestan B. Effects of oral magnesium supplementation on inflammatory markers in middle-aged overweight women. J. Res. Med. Sci. 2012; 17, 607–614.
  52. Van Mil AC. et al. Impact of volunteer-related and methodology-related factors on the reproducibility of brachial artery flowmediated vasodilation: analysis of 672 individual repeated measurements. J. Hypertens. 2016; 34, 1738–1745.
  53. Maier JA, Malpuech-Brugère C, Zimowska W, Rayssiguier Y, Mazur A. Low magnesium promotes endothelial cell dysfunction: implications for atherosclerosis, inflammation and trombosis. Biochim. Biophys. Acta. 2004; 1689, 13–21.
  54. Maier JA. Endothelial cells and magnesium: implications in atherosclerosis. Clin. Sci. (Lond.)2012; 122, 397–407.
  55. Santulli G. MicroRNAs and Endothelial (Dys) Function. J. Cell Physiol. 2016; 231, 1638–1644 .
  56. Sorriento D. et al. Endothelial cells are able to synthesize and release catecholamines both in vitro and in vivo. Hypertension. 2012; 60, 129–136.
  57. Nesby-O'Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr 2002;76(1):187–92.
  58. Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr 2005;135(2):317–22.
  59. Hyppönen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr 2007;85(3):860–8.
  60. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008;117(4):503–11.
  61. Salehpour A, Shidfar F, Hosseinpanah F, Vafa M, Razaghi M, Hoshiarrad A, et al. Vitamin D 3 and the risk of CVD in overweight and obese women: a randomized controlled trial. Br J Nutr 2012;108(10):1866–73. S0007114512000098.
  62. Hewison M. Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin North Am 2010;39(2):365–79.
  63. Cantorna MT. Vitamin D and its role in immunology: multiple sclerosis, and inflammatory bowel disease. Prog Biophys Mol Biol 2006;92(1):60–4.
  64. Michos ED, Melamed ML. Vitamin D and cardiovascular disease risk. Curr Opin Clin Nutr Metab Care 2008;11(1):7–12.
  65. Vaidya A. Vitamin D and cardio-metabolic disease. Metabolism 2013;62(12):1697.
  66. Wolden-Kirk H, Overbergh L, Christesen HT, Brusgaard K, Mathieu C. Vitamin D and diabetes: its importance for beta cell and immune function. Mol Cell Endocrinol 2011;347(1): 106–20.
  67. Kim HJ, Kang CK, Park H, Lee MG. Effects of vitamin D supplementation and circuit training on indices of obesity. and insulin resistance in T2D and vitamin D deficient elderly women. J Exerc Nutr Biochem 2014;18(3):249.
  68. Chiu KC, Chu A, Go VLW, Saad MF. Hypovitaminosis D is associated with insulin resistance and β cell dysfunction. Am J Clin Nutr 2004;79(5):820–5.
  69. Norman PE, Powell JT. Vitamin D and cardiovascular disease. Circ Res 2014;114(2):379–93.
  70. Herrmann M, Sullivan DR, Veillard A, McCorquodale T, Straub IR, Scott R, et al. Serum 25-Hydroxy vitamin D: a predictor of macrovascular and microvascular complications in patients with type 2 diabetes. Diabetes Care 2014;38(3): 521–8.
  71. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest 2005;115(5):1111–9.
  72. Cani PD, Delzenne NM. Gut microflora as a target for energy and metabolic homeostasis. Curr Opin Clin Nutr Metab Care 2007;10(6):729–34.. 0b013e3282efdebb.
  73. Caricilli AM, Picardi PK, de Abreu LL, Ueno M, Prada PO, Ropelle ER, et al. Gut microbiota is a key modulator of insulin resistance in TLR 2 knockout mice. PLoS Biol 2011; 9(12):e1001212.
  74. Moraes ACF, Silva IT, Almeida-Pititto B, Ferreira SRG. Microbiota intestinal e risco cardiometabólico: mecanismos e modulação dietética. Arq Bras Endocrinol Metab 2014;58(4): 317–27.
  75. Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 1998;98(8):731–3.
  76. Calder PC, Ahluwalia N, Albers R, Bosco N, Bourdet-Sicard R, Haller D, et al. A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies. Br J Nutr 2013;109(S1):S1–S34.
  77. Almeida-Pititto B, Ribeiro-Filho FF, Bittencourt MS, Lotufo PA, Bensenor I, Ferreira SR. Usefulness of circulating E-selectin to early detection of the atherosclerotic process in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Diabetol Metab Syndr 2016;8(19).
  78. Littaru G, Langsjoen P. Coenzyme Q10 and statins: Biochemical and clinical implications. Mitochondrion, 2007, 7: S168-S174.
  79. Littaru G, Langsjoen P. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Molecular Biotechnology, 2007, 37(1):31-37. Mitochondrion, 2007, 7: S168-S174.
  80. Littaru G, Langsjoen P. Clinical aspects of coenzyme Q10: an update. Nutrition, 2010, 26(3): 250-254.
  81. Mas E, Mori T. Coenzyme Q10 and statin myalgia: What is the evidence? Current Atherosclerosis Reports. 2010, 12(6): 407-413.
  82. Pepe S, Marasco S, Haas S, Sheeran F, Krum H, Rosenfeldt F. Coenzyme Q10 in cardiovascular disease. Mitochondrion. 2007, 7(S):154-167.
  83. Prakash S, Sunitha J, Hans M. Role of coenzyme Q10 as an antioxidant and bioenergizer in periodontal diseases. Indian Journal of Pharmacology. 2010, 42(6): 334-337.
  84. Michley L, Allen J, Bradley R. Coenzyme Q10 deficience in patients with Parkinson’ disease. Journal of the Neurological Sciences. 2012, 318: 72-75.

How to Cite

Assumpção, V. P. F., & Assumpção, O. Q. (2022). Nutrological and metabolic approaches to the action of the some special micronutrients in heart failure and metabolic syndrome: a systematic review. International Journal of Nutrology, 15(3).