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Prudent dietary pattern influences homocysteine level more than folate, vitamin B12, and docosahexaenoic acid: a structural equation model approach

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Abstract

Purpose

A structural equation model (SEM) was used to test multiple and simultaneous relationships between socio-demographic factors, dietary patterns, biochemical levels of folate, vitamin B12, docosahexaenoic acid (DHA), and its effects on homocysteine (Hcy) level.

Methods

Socio-demographic and lifestyle characteristics, blood sample, anthropometric measurements, and a food-frequency questionnaire (FFQ) were obtained from 281 individuals of ISA-Capital study (Sao Paulo, Brazil). The dietary patterns (DP) were estimated using factor analysis with principal component’s estimation based on the frequency of daily intake derived from the 38-item FFQ. The SEM considered a theoretical model where the DP were expected to be directly associated with Hcy level, and indirectly via biochemical levels of folate, vitamin B12, and DHA. The variables sex, age, ethnicity, and MTHFR C677T polymorphism were included in the model.

Results

The Prudent DP (− 0.12, p = 0.04) had a negative effect, while MTHFR C677T polymorphism (0.16, p = 0.01), age (0.22, p < 0.01), and being man (0.16, p = 0.01) had a positive effect on Hcy level. There were no indirect effects of any dietary patterns on Hcy level, neither via folate, vitamin B12, nor DHA. DHA was negatively associated with the Modern DP (− 0.12, p = 0.04) and positively associated with the Prudent DP (0.19, p < 0.01).

Conclusions

The DP mainly composed of fruits and vegetables, natural juices, potato/cassava/cooked cornmeal, fish, and chicken, which was negatively associated with the Hcy level in this population. These findings support the role of a healthy dietary pattern in health outcomes, rather than promoting specific foods or nutrients, for policy-based health promotion strategies.

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References

  1. Martí-Carvajal AJ, Solà I, Lathyris D (2015) Homocysteine-lowering interventions for preventing cardiovascular events. In: Martí-Carvajal AJ (ed) Cochrane database of systematic reviews. Wiley, Chichester, p CD006612

    Google Scholar 

  2. Refsum H, Smith AD, Ueland PM et al (2004) Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 50:3–32. https://doi.org/10.1373/clinchem.2003.021634

    Article  CAS  PubMed  Google Scholar 

  3. Kim J-M, Park K-Y, Shin D-W et al (2016) Relation of serum homocysteine levels to cerebral artery calcification and atherosclerosis. Atherosclerosis 254:200–204. https://doi.org/10.1016/j.atherosclerosis.2016.10.023

    Article  CAS  PubMed  Google Scholar 

  4. Selhub J (2008) Public health significance of elevated homocysteine. Food Nutr Bull 29:S116–S125. https://doi.org/10.1177/15648265080292S116

    Article  PubMed  Google Scholar 

  5. Refsum H, Ueland PM, Nygård O, Vollset SE (1998) Homocysteine and cardiovascular disease. Annu Rev Med 49:31–62. https://doi.org/10.1146/annurev.med.49.1.31

    Article  CAS  PubMed  Google Scholar 

  6. Selhub J, Jacques PF, Wilson PW et al (1993) Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 270:2693–2698

    Article  CAS  PubMed  Google Scholar 

  7. Jacques PF, Bostom AG, Wilson PW et al (2001) Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr 73:613–621

    Article  CAS  PubMed  Google Scholar 

  8. Selhub J (2006) The many facets of hyperhomocysteinemia: studies from the Framingham cohorts. J Nutr 136:1726S–1730S

    Article  CAS  PubMed  Google Scholar 

  9. de Benoist B (2008) Conclusions of a WHO technical consultation on folate and vitamin B12 deficiencies. Food Nutr Bull 29:S238–S244. https://doi.org/10.1177/15648265080292S129

    Article  PubMed  Google Scholar 

  10. World Health Organization (2006) Guidelines on food fortification with micronutrients. World Health Organization, Geneva, Switzerland

    Google Scholar 

  11. Li D, Mann NJ, Sinclair AJ (2006) A significant inverse relationship between concentrations of plasma homocysteine and phospholipid docosahexaenoic acid in healthy male subjects. Lipids 41:85–89

    Article  CAS  PubMed  Google Scholar 

  12. García-Alonso FJ, Jorge-Vidal V, Ros G, Periago MJ (2012) Effect of consumption of tomato juice enriched with n-3 polyunsaturated fatty acids on the lipid profile, antioxidant biomarker status, and cardiovascular disease risk in healthy women. Eur J Nutr 51:415–424. https://doi.org/10.1007/s00394-011-0225-0

    Article  CAS  PubMed  Google Scholar 

  13. Huang T, Zheng J, Chen Y et al (2011) High consumption of Ω-3 polyunsaturated fatty acids decrease plasma homocysteine: a meta-analysis of randomized, placebo-controlled trials. Nutrition 27:863–867. https://doi.org/10.1016/j.nut.2010.12.011

    Article  CAS  PubMed  Google Scholar 

  14. Huang T, Wahlqvist ML, Li D (2010) Docosahexaenoic acid decreases plasma homocysteine via regulating enzyme activity and mRNA expression involved in methionine metabolism. Nutrition 26(1):112–119. https://doi.org/10.1016/j.nut.2009.05.015

    Article  CAS  PubMed  Google Scholar 

  15. Huang T, Wahlqvist ML, Li D (2012) Effect of n-3 polyunsaturated fatty acid on gene expression of the critical enzymes involved in homocysteine metabolism. Nutr J 11:6. https://doi.org/10.1186/1475-2891-11-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. USDA Evidence Analysis Library Division (2014) A series of systematic reviews on the relationship between dietary patterns and health outcomes. United States Department of Agriculture, Virginia

    Google Scholar 

  17. Tucker KL, Selhub J, Wilson PW, Rosenberg IH (1996) Dietary intake pattern relates to plasma folate and homocysteine concentrations in the Framingham Heart Study. J Nutr 126:3025–3031

    Article  CAS  PubMed  Google Scholar 

  18. Konstantinova SV, Vollset SE, Berstad P et al (2007) Dietary predictors of plasma total homocysteine in the Hordaland Homocysteine Study. Br J Nutr 98:201–210. https://doi.org/10.1017/S0007114507691788

    Article  CAS  PubMed  Google Scholar 

  19. Gao X, Yao M, McCrory MA et al (2003) Dietary pattern is associated with homocysteine and B vitamin status in an urban Chinese population. J Nutr 133:3636–3642

    Article  CAS  PubMed  Google Scholar 

  20. Bigio RS, Verly E, de Castro MA et al (2013) Are plasma homocysteine concentrations in Brazilian adolescents influenced by the intake of the main food sources of natural folate? Ann Nutr Metab 62:331–338. https://doi.org/10.1159/000348883

    Article  CAS  PubMed  Google Scholar 

  21. Gorgulho BM, Fisberg RM, Marchioni DML (2014) Away-from-home meals: prevalence and characteristics in a metropolis. Rev Nutr 27:703–713. https://doi.org/10.1590/1415-52732014000600005

    Article  Google Scholar 

  22. ISA (2011) Inquéritos de Saúde no Município de São Paulo. ISA, São Paulo. http://www.fsp.usp.br/isa-sp/. Accessed 20 Nov 2017

  23. Selem SSADC, de Carvalho AM, Verly-Junior E et al (2014) Validity and reproducibility of a food frequency questionnaire for adults of São Paulo, Brazil. Rev Bras Epidemiol 17:852–859. https://doi.org/10.1590/1809-4503201400040005

    Article  PubMed  Google Scholar 

  24. StataCorp (2011) Stata statistical software: release 12

  25. Bagley PJ, Selhub J (2000) Analysis of folate form distribution by affinity followed by reversed-phase chromatography with electrical detection. Clin Chem 46:404–411

    Article  CAS  PubMed  Google Scholar 

  26. Kalmbach R, Paul L, Selhub J (2011) Determination of unmetabolized folic acid in human plasma using affinity HPLC. Am J Clin Nutr 94:343S–347S. https://doi.org/10.3945/ajcn.111.013433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Beckman Coulter, Inc. (2009) Vitamin B12—Access Immunoassay Systems®. California (Technical Lab Manual)

  28. Huang Z, Wang B, Crenshaw A (2006) A simple method for the analysis of trans fatty acid with GC–MS and ATTM-Silar-90 capillary column. Food Chem 98:593–598. https://doi.org/10.1016/j.foodchem.2005.05.013

    Article  CAS  Google Scholar 

  29. Oki E, Norde MM, Carioca AAF et al (2016) Interaction of SNP in the CRP gene and plasma fatty acid profile in inflammatory pattern: a cross-sectional population-based study. Nutrition 32:88–94. https://doi.org/10.1016/j.nut.2015.07.015

    Article  CAS  PubMed  Google Scholar 

  30. Abbott Diagnostics Division (2011) Homocysteine (technical lab manual)

  31. WHO (2014) Obesity and overweight. Fact sheet no. 311. WHO, Geneva

    Google Scholar 

  32. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Myakishev MV, Khripin Y, Hu S, Hamer DH (2001) High-throughput SNP genotyping by allele-specific PCR with universal energy-transfer-labeled primers. Genome Res 11:163–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kline R (2011) Principles and practice of structural equation modeling, 4th edn. The Guilford Press, New York

    Google Scholar 

  35. Huang T, Hu X, Khan N et al (2013) Effect of polyunsaturated fatty acids on homocysteine metabolism through regulating the gene expressions involved in methionine metabolism. Sci World J. https://doi.org/10.1155/2013/931626

    Article  Google Scholar 

  36. Browne MW, Cudeck R (1993) Alternative ways of assessing model fit. In: Testing structural equation models. Sage, Newbury Park

    Google Scholar 

  37. Chen F, Curran PJ, Bollen KA et al (2008) An empirical evaluation of the use of fixed cutoff points in RMSEA test statistic in structural equation models. Sociol Methods Res 36:462–494. https://doi.org/10.1177/0049124108314720

    Article  PubMed  PubMed Central  Google Scholar 

  38. R Core Team (2016) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna

    Google Scholar 

  39. Rosseel Y (2012) lavaan: an R package for structural equation modeling. J Stat Softw 48:1–36

    Article  Google Scholar 

  40. Zhong F, Zhuang L, Wang Y, Ma Y (2017) Homocysteine levels and risk of essential hypertension: a meta-analysis of published epidemiological studies. Clin Exp Hypertens 39:160–167. https://doi.org/10.1080/10641963.2016.1226888

    Article  CAS  PubMed  Google Scholar 

  41. Hu Q, Teng W, Li J et al (2016) Homocysteine and Alzheimer’s disease: evidence for a causal link from mendelian randomization. J Alzheimer’s Dis 52:747–756. https://doi.org/10.3233/JAD-150977

    Article  CAS  Google Scholar 

  42. Numata S, Kinoshita M, Tajima A et al (2015) Evaluation of an association between plasma total homocysteine and schizophrenia by a Mendelian randomization analysis. BMC Med Genet 16:54. https://doi.org/10.1186/s12881-015-0197-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Bhatia P, Singh N (2015) Homocysteine excess: delineating the possible mechanism of neurotoxicity and depression. Fundam Clin Pharmacol 29:522–528. https://doi.org/10.1111/fcp.12145

    Article  CAS  PubMed  Google Scholar 

  44. Welch GN, Loscalzo J (1998) Homocysteine and atherothrombosis. N Engl J Med 338:1042–1050. https://doi.org/10.1056/NEJM199804093381507

    Article  CAS  PubMed  Google Scholar 

  45. Steluti J, Carvalho A, Carioca A et al (2017) Genetic variants involved in one-carbon metabolism: polymorphism frequencies and differences in homocysteine concentrations in the folic acid fortification era. Nutrients 9:539. https://doi.org/10.3390/nu9060539

    Article  CAS  PubMed Central  Google Scholar 

  46. Födinger M, Buchmayer H, Heinz G et al (2001) Association of two MTHFR polymorphisms with total homocysteine plasma levels in dialysis patients. Am J Kidney Dis 38:77–84

    Article  PubMed  Google Scholar 

  47. Iglesia I, Huybrechts I, González-Gross M et al (2017) Folate and vitamin B12 concentrations are associated with plasma DHA and EPA fatty acids in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study. Br J Nutr 117:124–133. https://doi.org/10.1017/S0007114516004414

    Article  CAS  PubMed  Google Scholar 

  48. Baierle M, Vencato PH, Oldenburg L et al (2014) Fatty acid status and its relationship to cognitive decline and homocysteine levels in the elderly. Nutrients 6:3624–3640. https://doi.org/10.3390/nu6093624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. van Wijk N, Watkins CJ, Hageman RJJ et al (2012) Combined dietary folate, vitamin B-12, and vitamin B-6 intake influences plasma docosahexaenoic acid concentration in rats. Nutr Metab (Lond) 9:49. https://doi.org/10.1186/1743-7075-9-49

    Article  CAS  Google Scholar 

  50. Kulkarni A, Dangat K, Kale A et al (2011) Effects of altered maternal folic acid, vitamin B12 and docosahexaenoic acid on placental global DNA methylation patterns in Wistar rats. PLoS One 6:e17706. https://doi.org/10.1371/journal.pone.0017706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Khaire A, Rathod R, Randhir K et al (2016) A combined supplementation of vitamin B12 and omega-3 fatty acids across two generations improves cardiometabolic variables in rats. Food Funct 7:3910–3919. https://doi.org/10.1039/c6fo00148c

    Article  CAS  PubMed  Google Scholar 

  52. Kemse NG, Kale AA, Joshi SR (2014) A combined supplementation of omega-3 fatty acids and micronutrients (folic acid, vitamin B12) reduces oxidative stress markers in a rat model of pregnancy induced hypertension. PLoS One 9:e111902. https://doi.org/10.1371/journal.pone.0111902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Li J, Li B, Qi J, Shen B (2015) Meta-analysis of clinical trials of folic acid, vitamin B12 and B6 supplementation on plasma homocysteine level and risk of cardiovascular disease. Zhonghua Xin Xue Guan Bing Za Zhi 43:554–561

    CAS  PubMed  Google Scholar 

  54. Jacobs DR, Gross MD, Tapsell LC (2009) Food synergy: an operational concept for understanding nutrition. Am J Clin Nutr 89:1543S–1548S. https://doi.org/10.3945/ajcn.2009.26736B

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Jacobs DR, Steffen LM (2003) Nutrients, foods, and dietary patterns as exposures in research: a framework for food synergy. Am J Clin Nutr 78:508–513. https://doi.org/10.1016/J.NUMECD.2005.08.006

    Article  Google Scholar 

  56. Maddock J, Ambrosini GL, Griffin JL et al (2018) A dietary pattern derived using B-vitamins and its relationship with vascular markers over the life course. Clin Nutr. https://doi.org/10.1016/j.clnu.2018.06.969

    Article  PubMed  Google Scholar 

  57. Öhrvik V, Lemming EW, Nälsén C et al (2018) Dietary intake and biomarker status of folate in Swedish adults. Eur J Nutr 57:451–462. https://doi.org/10.1007/s00394-016-1328-4

    Article  CAS  PubMed  Google Scholar 

  58. McCourt HJ, Draffin CR, Woodside JV et al (2014) Dietary patterns and cardiovascular risk factors in adolescents and young adults: the Northern Ireland Young Hearts Project. Br J Nutr 112:1685–1698. https://doi.org/10.1017/S0007114514002682

    Article  CAS  PubMed  Google Scholar 

  59. Castro MA, Baltar VT, Marchioni DM, Fisberg RM (2016) Examining associations between dietary patterns and metabolic CVD risk factors: a novel use of structural equation modelling. Br J Nutr 115:1586–1597. https://doi.org/10.1017/S0007114516000556

    Article  CAS  PubMed  Google Scholar 

  60. de Castro Selem SS, de Castro MA, César CL et al (2014) Associations between dietary patterns and self-reported hypertension among Brazilian adults: a cross-sectional population-based study. J Acad Nutr Diet 114:1216–1222. https://doi.org/10.1016/j.jand.2014.01.007

    Article  Google Scholar 

  61. Olinto MTA, Willett WC, Gigante DP, Victora CG (2011) Sociodemographic and lifestyle characteristics in relation to dietary patterns among young Brazilian adults. Public Health Nutr 14:150–159. https://doi.org/10.1017/S136898001000162X

    Article  PubMed  Google Scholar 

  62. de Andrade LOM, Pellegrini Filho A, Solar O et al (2015) Social determinants of health, universal health coverage, and sustainable development: case studies from Latin American countries. Lancet 385:1343–1351. https://doi.org/10.1016/S0140-6736(14)61494-X

    Article  PubMed  Google Scholar 

  63. Hill RJ, Davies PS (2001) The validity of self-reported energy intake as determined using the doubly labelled water technique. Br J Nutr 85:415–430

    Article  CAS  PubMed  Google Scholar 

  64. Claro RM, Carmo HCE do, Machado FMS, Monteiro CA (2007) Income, food prices, and participation of fruit and vegetables in the diet. Rev Saúde Públ 41:557–564

    Article  Google Scholar 

  65. Levy RB, Claro RM, Mondini L et al (2012) Regional and socioeconomic distribution of household food availability in Brazil, in 2008–2009. Rev Saúde Públ 46:6–15

    Article  Google Scholar 

  66. CSDH (2008) Closing the gap in a generation: health equity through action on the social determinants of health. Final Report of the Commission on Social Determinants of Health, Geneva

    Google Scholar 

  67. Hosmer D, Sturdivant SL R (2013) Applied logistic regression. Wiley, Hoboken

    Book  Google Scholar 

  68. von Elm E, Altman DG, Egger M et al (2007) Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ 335:806–808. https://doi.org/10.1136/bmj.39335.541782.AD

    Article  Google Scholar 

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Acknowledgements

We would like to acknowledge the participants and all the members of the ISA-Capital study. In addition, we acknowledge the Sao Paulo Research Foundation (FAPESP) for the doctoral scholarship granted to Juliana Araujo Teixeira (2014/12647-1).

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Correspondence to Dirce Maria Marchioni.

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This study was approved by the Ethical Committee of School of Public Health, University of São Paulo (nº 2001, 275/09 and nº 1.501.677/16) and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Participants provided written consent in each stage of the study to be involved.

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The authors declare that they have no conflict of interest.

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Teixeira, J.A., Steluti, J., Gorgulho, B.M. et al. Prudent dietary pattern influences homocysteine level more than folate, vitamin B12, and docosahexaenoic acid: a structural equation model approach. Eur J Nutr 59, 81–91 (2020). https://doi.org/10.1007/s00394-018-1886-8

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