Abstract

Background: Emerging evidence suggests that dietary one-carbon metabolism-related B-vitamins are associated with the reduced risk of cardiovascular disease (CVD) in the general population. However, only a few studies have assessed their associations in patients with type 2 diabetes (T2D). Objective: This study aimed to assess the associations between the intake of three one-carbon metabolism-related B-vitamins (folate, vitamin B6, and vitamin B12) and CVD risk in Chinese patients with T2D. Methods: A hospital-based case-control study of 419 patients with T2D and newly diagnosed CVD and 419 age- (±5 years) and sex-matched T2D-only controls was carried out in China. A validated 79-item semi-quantitative food-frequency questionnaire administered in face-to-face interviews was used to measure dietary B-vitamin intake. Conditional logistic regression was used to assess associations, which were tested by estimating odds ratios (ORs) with 95% confidence intervals (CIs). Results: Compared with the lowest quartile, the multivariable-adjusted ORs and 95% CIs for highest quartile were 0.32 (95% CI: 0.20, 0.52; p trend <0.001) for folate, 0.47 (95% CI: 0.30, 0.76; p trend = 0.002) for vitamin B6, and 1.02 (95% CI: 0.67, 1.55; p trend = 0.841) for vitamin B12. Consistent inverse associations were found for folate intake from eggs, vegetables, fruits, soy, and other foods but not for folate intake from grains. Conclusions: Findings suggest that the high consumption of folate and vitamin B6, but not that of vitamin B12, might be associated with the low risk of CVD in patients with T2D. This study suggests that dietary folate and vitamin B6 protect against CVD in patients with T2D.

© 2022 The Author(s). Published by S. Karger AG, Basel

References GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1736–88. Liu S, Li Y, Zeng X, Wang H, Yin P, Wang L, et al. Burden of cardiovascular diseases in China, 1990–2016: findings from the 2016 global burden of disease study. JAMA Cardiol. 2019;4:342–52. Haffner SJ, Cassells H. Hyperglycemia as a cardiovascular risk factor. Am J Med. 2003;115(8):6S–11S. Lyon P, Strippoli V, Fang B, Cimmino L. B vitamins and One-Carbon metabolism: implications in human health and disease. Nutrients. 2020;12(9):2867. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002;325(7374):1202. Bailey LB, Gregory JF. Folate metabolism and requirements. J Nutr. 1999;129(4):779–82. Lentz SR. Mechanisms of homocysteine-induced atherothrombosis. J Thromb Haemost. 2005;3(8):1646–54. Fezeu LK, Ducros V, Guéant JL, Guilland JC, Andreeva VA, Hercberg S, et al. MTHFR 677C → T genotype modulates the effect of a 5-year supplementation with B-vitamins on homocysteine concentration: the SU.FOL.OM3 randomized controlled trial. PLoS One. 2018;13(5):e0193352. Venn BJ, Mann JI, Williams SM, Riddell LJ, Chisholm A, Harper MJ, et al. Assessment of three levels of folic acid on serum folate and plasma homocysteine: a randomised placebo-controlled double-blind dietary intervention trial. Eur J Clin Nutr. 2002;56(8):748–54. de Koning EJ, van der Zwaluw NL, van Wijngaarden JP, Sohl E, Brouwer-Brolsma EM, van Marwijk HW, et al. Effects of two-year vitamin b(12) and folic acid supplementation on depressive symptoms and quality of life in older adults with elevated homocysteine concentrations: additional results from the B-PROOF study, an RCT. Nutrients. 2016;8(11):748. Maruyama K, Eshak ES, Kinuta M, Nagao M, Cui R, Imano H, et al. Association between vitamin B group supplementation with changes in % flow-mediated dilatation and plasma homocysteine levels: a randomized controlled trial. J Clin Biochem Nutr. 2019;64(3):243–9. Christen WG, Cook NR, Van Denburgh M, Zaharris E, Albert CM, Manson JE. Effect of combined treatment with folic acid, vitamin b(6), and vitamin b(12) on plasma biomarkers of inflammation and endothelial dysfunction in women. J Am Heart Assoc. 2018;7(11):e008517. Brouwer IA, van Dusseldorp M, West CE, Meyboom S, Thomas CMG, Duran M, et al. Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial. J Nutr. 1999;129(6):1135–9. Huang T, Ren J, Huang J, Li D. Association of homocysteine with type 2 diabetes: a meta-analysis implementing Mendelian randomization approach. BMC Genomics. 2013;14:867. Hu Y, Xu Y, Wang G. Homocysteine levels are associated with endothelial function in newly diagnosed type 2 diabetes mellitus patients. Metab Syndr Relat Disord. 2019;17(6):323–7. Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJC, Jakobs C, Bouter LM, et al. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus: a population-based study. Arterioscler Thromb Vasc Biol. 1998;18(1):133–8. Buysschaert M, Dramais AS, Wallemacq PE, Hermans MP. Hyperhomocysteinemia in type 2 diabetes: relationship to macroangiopathy, nephropathy, and insulin resistance. Diabetes Care. 2000;23(12):1816–22. Muzurović E, Kraljević I, Solak M, Dragnić S, Mikhailidis DP. Homocysteine and diabetes: role in macrovascular and microvascular complications. J Diabetes Complications. 2021;35(3):107834. Jayedi A, Zargar MS. Intake of vitamin B6, folate, and vitamin B12 and risk of coronary heart disease: a systematic review and dose-response meta-analysis of prospective cohort studies. Crit Rev Food Sci Nutr. 2019;59(16):2697–707. Wang ZM, Zhou B, Nie ZL, Gao W, Wang YS, Zhao H, et al. Folate and risk of coronary heart disease: a meta-analysis of prospective studies. Nutr Metab Cardiovasc Dis. 2012;22(10):890–9. He K, Merchant A, Rimm EB, Rosner BA, Stampfer MJ, Willett WC, et al. Folate, vitamin B6, and B12 intakes in relation to risk of stroke among men. Stroke. 2004;35(1):169–74. Wu SL, Peng LY, Chen YM, Zeng FF, Zhuo SY, Li YB, et al. Greater adherence to dietary guidelines associated with reduced risk of cardiovascular diseases in Chinese patients with type 2 diabetes. Nutrients. 2022;14(9):1713. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care.2003;26(Suppl 1):S5–20. China Society of Cardiology of Chinese Medical Association Editorial Board of Chinese Journal of Cardiology. Guideline for diagnosis and treatment of patients with ST-elevation myocardial infarction. Zhonghua Xin Xue Guan Bing Za Zhi. 2010;38(8):675–90. Chinese Society of Cardiology of Chinese Medical Association, Editorial Board of Chinese Journal of Cardiology. Guideline for diagnosis and treatment of patients with unstable angina and non-ST-segment elevation myocardial infarction. Zhonghua Xin Xue Guan Bing Za Zhi. 2007;35(4):295–304. Rao M. China Guideline for cerebrovascular disease prevention and treatment. Beijing: People's Medical Publishing House; 2007. Ainsworth BE, Haskell WL, Herrmann SD, Meckes N, Bassett DR, Tudor-Locke C, et al. Compendium of physical activities: a second update of codes and MET values. Med Sci Sports Exerc. 2011;43(8):1575–81. Whitworth JA; World Health Organization, International Society of Hypertension Writing Group. 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003;21(11):1983–92. Joint committee issued Chinese guideline for the management of dyslipidemia in adults. 2016 Chinese guideline for the management of dyslipidemia in adults. Zhonghua Xin Xue Guan Bing Za Zhi. 2016;44(10):833–53. Zhang CX, Ho SC. Validity and reproducibility of a food frequency questionnaire among Chinese women in Guangdong province. Asia Pac J Clin Nutr. 2009;18(2):240–50. Yang Y, Wang G, Pan X. China food composition. 2nd ed. Beijing, China: Peking University Medical Press; 2009. Shu XO, Yang G, Jin F, Liu D, Kushi L, Wen W, et al. Validity and reproducibility of the food frequency questionnaire used in the Shanghai Women’s Health Study. Eur J Clin Nutr. 2004;58(1):17–23. Willett WC, Sampson L, Stampfer MJ, Rosner B, Bain C, Witschi J, et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol. 1985;122(1):51–65. Willett WC, Howe GR, Kushi LH. Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr. 1997;65(Suppl 4):1220S–8S. , O’Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet. 2010;376(9735):112–23. Chen L, Li Q, Fang X, Wang X, Min J, Wang F. Dietary intake of homocysteine metabolism-related B-Vitamins and the risk of stroke: a dose-response meta-analysis of prospective studies. Adv Nutr. 2020;11(6):1510–28. Ala OA, Akintunde AA, Ikem RT, Kolawole BA, Ala OO, Adedeji TA. Association between insulin resistance and total plasma homocysteine levels in type 2 diabetes mellitus patients in south west Nigeria. Diabetes Metab Syndr. 2017;11(Suppl 2):S803–09. Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke. 2009;40(4):1365–72. Albert CM, Cook NR, Gaziano JM, Zaharris E, MacFadyen J, Danielson E, et al. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA. 2008;299(17):2027–36. Walters GWM, Redman E, Gulsin GS, Henson J, Argyridou S, Yates T, et al. Interrelationship between micronutrients and cardiovascular structure and function in type 2 diabetes. J Nutr Sci. 2021;10:e88. Chaturvedi S, Hoffman RM, Bertino JR. Exploiting methionine restriction for cancer treatment. Biochem Pharmacol. 2018;154:170–3. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002;288(16):2015–22. Van Guelpen B, Hultdin J, Johansson I, Stegmayr B, Hallmans G, Nilsson TK, et al. Folate, vitamin B12, and risk of ischemic and hemorrhagic stroke: a prospective, nested case-referent study of plasma concentrations and dietary intake. Stroke. 2005;36(7):1426–31. Pang X, Liu J, Zhao J, Mao J, Zhang X, Feng L, et al. Homocysteine induces the expression of C-reactive protein via NMDAr-ROS-MAPK-NF-κB signal pathway in rat vascular smooth muscle cells. Atherosclerosis. 2014;236(1):73–81. Basu A, Jenkins AJ, Stoner JA, Thorpe SR, Klein RL, Lopes-Virella MF, et al. Plasma total homocysteine and carotid intima-media thickness in type 1 diabetes: a prospective study. Atherosclerosis. 2014;236:188–95. Zhang S, Bai YY, Luo LM, Xiao WK, Wu HM, Ye P. Association between serum homocysteine and arterial stiffness in elderly: a community-based study. J Geriatr Cardiol. 2014;11(1):32–8. Villa P, Perri C, Suriano R, Cucinelli F, Panunzi S, Ranieri M, et al. L-folic acid supplementation in healthy postmenopausal women: effect on homocysteine and glycolipid metabolism. J Clin Endocrinol Metab. 2005;90(8):4622–9. Kannan K, Jain SK. Effect of vitamin B6 on oxygen radicals, mitochondrial membrane potential, and lipid peroxidation in H2O2-treated U937 monocytes. Free Radic Biol Med. 2004;36(4):423–8. Zhan J, Liu YJ, Cai LB, Xu FR, Xie T, He QQ. Fruit and vegetable consumption and risk of cardiovascular disease: a meta-analysis of prospective cohort studies. Crit Rev Food Sci Nutr. 2017;57(8):1650–63. Aune D, Giovannucci E, Boffetta P, Fadnes LT, Keum N, Norat T, et al. Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-a systematic review and dose-response meta-analysis of prospective studies. Int J Epidemiol. 2017;46(3):1029–56. Bechthold A, Boeing H, Schwedhelm C, Hoffmann G, Knüppel S, Iqbal K, et al. Food groups and risk of coronary heart disease, stroke and heart failure: a systematic review and dose-response meta-analysis of prospective studies. Crit Rev Food Sci Nutr. 2019;59(7):1071–90. Park K, Son J, Jang J, Kang R, Chung HK, Lee KW, et al. Unprocessed meat consumption and incident cardiovascular diseases in Korean adults: the Korean genome and epidemiology study (KoGES). Nutrients. 2017;9(5):498. Soliman GA. Dietary cholesterol and the lack of evidence in cardiovascular disease. Nutrients. 2018;10(6):780. Larsson SC, Männistö S, Virtanen MJ, Kontto J, Albanes D, Virtamo J. Folate, vitamin B6, vitamin B12, and methionine intakes and risk of stroke subtypes in male smokers. Am J Epidemiol. 2008;167(8):954–61. Homocysteine Lowering Trialists’ Collaboration. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr. 2005;82(4):806–12. Beaton GH. Approaches to analysis of dietary data: relationship between planned analyses and choice of methodology. Am J Clin Nutr. 1994;59(Suppl 1):253S–61S. Article / Publication Details

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Received: December 14, 2021
Accepted: September 03, 2022
Published online: October 13, 2022

Number of Print Pages: 11
Number of Figures: 1
Number of Tables: 5

ISSN: 0250-6807 (Print)
eISSN: 1421-9697 (Online)

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