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Hyperhomocysteinemia is associated with vitamin B-12 deficiency: A cross-sectional study in a rural, elderly population of Shanxi China

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The journal of nutrition, health & aging

Abstract

Objectives

To report the association of lifestyle factors and plasma vitamin B-12 with hyperhomocysteinemia in a large sample of men and women living in a region of China where there is an increased risk of NTDs.

Design

Community-based, cross-sectional study of Lvliang City, Shanxi Province, China.

Setting

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease (CVD) and a sensitive marker of vitamin B-12 and folate deficiency.

Participants

A total of 2355 (1044 men and 1311 women) participants born before 1 January 1958 (≥55 years of age) and living in Lvliang City for at least 2 months a year were included.

Measurements

The participants were assessed regarding demographic characteristics, height, weight, as well as having a physical examination and blood sampling for serum cholesterol, total homocysteine (tHcy), folate, and vitamin B12 levels.

Results

The median (25th–75th percentile) tHcy concentration was 21.5 (15.8–33.6) µmol/L in men and 18.0 (13.4–24.8) µmol/L in women. The overall prevalence of hyperhomocysteinemia (tHcy ≥15 µmol/L) was 72.6% (84.3% in men and 63.2% in women), inversely correlated with folate (r=–0.230, P=0.006) and vitamin B-12 (r=–0.540, P<0.001), and positively correlated with uric acid (r=0.054, P<0.001). Vitamin B-12 and folate deficiency, older age, and male gender were associated with elevated tHcy; with vitamin B-12 deficiency being the strongest.

Conclusions

Plasma tHcy concentration and hyperhomocysteinemia were significantly higher in this population than in previously studied populations. Vitamin B-12 and folate supplementation, concomitant lifestyle changes such as smoking cessation, and lipid-lowering treatments may help to decrease plasma tHcy concentrations and reduce the CVD risk in this population.

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References

  1. Selhub J, Miller JW. The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr 1992;55 (1):131–138

    CAS  PubMed  Google Scholar 

  2. Verhoef P, Stampfer MJ, Buring JF, Gaziano JM, Allen RH, Stabler SP, Reynolds RD, Kok FJ, Hennekens CH, Willett WC. Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. Am J Epidemiol 1996;143 (9):845–859

    Article  CAS  PubMed  Google Scholar 

  3. Lonn E, Yusuf S, Arnold M, Sheridan P, Pogue J, Micks M, McQueen M, Probstfield J, Fodor G, Held C. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354 (15):1567–1577

    Article  CAS  PubMed  Google Scholar 

  4. Veeranna V, Zalawadiya SK, Niraj A, Pradhan J, Ference B, Burack RC, Jacob S, Afonso L. Homocysteine and reclassification of cardiovascular disease risk. J Am Coll Cardiol 2011;58 (10):1025–1033

    Article  CAS  PubMed  Google Scholar 

  5. Wang X, Qin X, Demirtas H, Li J, Mao G, Huo Y, Sun N, Liu L, Xu X. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 2007;369 (9576):1876–1882

    Article  CAS  PubMed  Google Scholar 

  6. Berry RJ, Li Z, Erickson JD, Li S, Moore CA, Wang H, Mulinare J, Zhao P, Wong L-YC, Gindler J. Prevention of neural-tube defects with folic acid in China. N Engl J Med 1999;341 (20):1485–1490

    Article  CAS  PubMed  Google Scholar 

  7. Ebly EM, Schaefer JP, Campbell NR, Hogan DB. Folate status, vascular disease and cognition in elderly Canadians. Age Ageing 1998;27 (4):485–491

    Article  CAS  PubMed  Google Scholar 

  8. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002;346 (7):476–483

    Article  CAS  PubMed  Google Scholar 

  9. Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol 2006;5 (11):949–960

    Article  CAS  PubMed  Google Scholar 

  10. Selhub J, Jacques PF, Bostom AG, D’Agostino RB, Wilson PW, Belanger AJ, O’Leary DH, Wolf PA, Schaefer EJ, Rosenberg IH. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N Engl J Med 1995;332 (5):286–291

    Article  CAS  PubMed  Google Scholar 

  11. Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998;55 (11):1449

    Article  CAS  PubMed  Google Scholar 

  12. Mooijaart SP, Gussekloo J, Frölich M, Jolles J, Stott DJ, Westendorp RGJ, de Craen AJM. Homocysteine, vitamin B-12, and folic acid and the risk of cognitive decline in old age: the Leiden 85-Plus study. Am J Clin Nutr 2005;82 (4):866–871

    CAS  PubMed  Google Scholar 

  13. Kim J-M, Stewart R, Kim S-W, Shin I, Yang S, Shin H, Yoon J-S. Changes in folate, vitamin B12 and homocysteine associated with incident dementia. J Neurol Neurosurg Psychiatry 2008;79 (8):864–868

    Article  PubMed  Google Scholar 

  14. Guyonnet S, Secher M, Ghisolfi A, Ritz P, Vellas B. Nutrition, frailty and prevention of disabilities with aging. J Frailty Aging 2015;1 (4):13–25

    Google Scholar 

  15. Zhang L, Ren A, Li Z, Hao L, Tian Y, Li Z. Folate concentrations and folic acid supplementation among women in their first trimester of pregnancy in a rural area with a high prevalence of neural tube defects in Shanxi, China. Birth Defects Res A Clin Mol Teratol 2006;76 (6):461–466

    Article  CAS  PubMed  Google Scholar 

  16. Zhang T, Xin R, Gu X, Wang F, Pei L, Lin L, Chen G, Wu J, Zheng X. Maternal serum vitamin B12, folate and homocysteine and the risk of neural tube defects in the offspring in a high-risk area of China. Public Health Nutr 2009;12 (05):680–686

    Article  PubMed  Google Scholar 

  17. Wang Z-P, Shang X-X, Zhao Z-T. Low maternal vitamin B12 is a risk factor for neural tube defects: a meta-analysis. J Matern Fetal Neonatal Med 2012;25 (4):389–394

    Article  CAS  PubMed  Google Scholar 

  18. Ganji V, Kafai MR. Demographic, health, lifestyle, and blood vitamin determinants of serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr 2003;77 (4):826–833

    CAS  PubMed  Google Scholar 

  19. Husemoen L, Thomsen T, Fenger M, Jørgensen T. Changes in lifestyle and total homocysteine in relation to MTHFR (C677T) genotype: the Inter99 study. Eur J Clin Nutr 2005;60 (5):614–622

    Article  Google Scholar 

  20. Nurk E, Tell GS, Vollset SE, Nygård O, Refsum H, Nilsen RM, Ueland PM. Changes in lifestyle and plasma total homocysteine: the Hordaland Homocysteine Study. Am J Clin Nutr 2004;79 (5):812–819

    CAS  PubMed  Google Scholar 

  21. Selhub J. The many facets of hyperhomocysteinemia: studies from the Framingham cohorts. J Nutr 2006;136 (6):1726S–1730S

    CAS  PubMed  Google Scholar 

  22. Refsum H, Nurk E, Smith AD, Ueland PM, Gjesdal CG, Bjelland I, Tverdal A, Tell GS, Nygård O, Vollset SE. The Hordaland Homocysteine Study: a communitybased study of homocysteine, its determinants, and associations with disease. J Nutr 2006;136 (6):1731S–1740S

    CAS  PubMed  Google Scholar 

  23. Hao L, Ma J, Zhu J, Stampfer MJ, Tian Y, Willett WC, Li Z. High prevalence of hyperhomocysteinemia in Chinese adults is associated with low folate, vitamin B-12, and vitamin B-6 status. J Nutr 2007;137 (2):407–413

    CAS  PubMed  Google Scholar 

  24. Elmrghni S, Kaddora M. Effect of Smoking on Plasma Homocysteine Level in Some Libyans as a Risk Factor for Cardiovascular Disease. Ind J Foren Med Toxicol 2012;6 (2):167

    Google Scholar 

  25. Stein JH, Bushara M, Bushara K, McBride PE, Jorenby DE, Fiore MC. Smoking cessation, but not smoking reduction, reduces plasma homocysteine levels. Clin Cardiol 2002;25 (1):23–26

    Article  PubMed  Google Scholar 

  26. Chrysohoou C, Panagiotakos DB, Pitsavos C, Skoumas J, Toutouza M, Papaioannou I, Toutouzas PK, Stefanadis C. Effects of chronic alcohol consumption on lipid levels, inflammatory and haemostatic factors in the general population: the ‘ATTICA’ Study. Eur J Cardiovasc Prev Rehabil 2003;10 (5):355–361

    Article  PubMed  Google Scholar 

  27. Wang Y, Li X, Qin X, Cai Y, He M, Sun L, Li J, Zhang Y, Tang G, Wang B. Prevalence of hyperhomocysteinaemia and its major determinants in rural Chinese hypertensive patients aged 45–75 years. Brit J Nutrit 2013;109 (07):1284–1293

    Article  CAS  PubMed  Google Scholar 

  28. Gao X, Yao M, McCrory MA, Ma G, Li Y, Roberts SB, Tucker KL. Dietary pattern is associated with homocysteine and B vitamin status in an urban Chinese population. J Nutr 2003;133 (11):3636–3642

    CAS  PubMed  Google Scholar 

  29. Chen MS K-J, PanPhD W-H, Yang F-L, Wei I-L, ShawPhD N-S, LinPhD B-F. Association of B vitamins status and homocysteine levels in elderly Taiwanese. Asia Pac J Clin Nutr 2005;14 (3):250–255

    CAS  PubMed  Google Scholar 

  30. Fakhrzadeh H, Ghotbi S, Pourebrahim R, Nouri M, Heshmat R, Bandarian F, Shafaee A, Larijani B. Total plasma homocysteine, folate, and vitamin b12 status in healthy Iranian adults: the Tehran homocysteine survey (2003–2004)/a cross–sectional population based study. BMC Public Health 2006;6 (1):29

    Article  PubMed  PubMed Central  Google Scholar 

  31. Huo YR, Suriyaarachchi P, Gomez F, Curcio CL, D B, Gunawardene P, Demontiero O, Duque G. Comprehensive nutritional status in sarco-osteoporotic older fallers. J Nutr Health Aging 2015;19 (4):474–480

    Article  CAS  PubMed  Google Scholar 

  32. González-Gross M, Benser J, Breidenassel C, Albers U, Huybrechts I, Valtueña J, Spinneker A, Segoviano M, Widhalm K, Molnar D. Gender and age influence blood folate, vitamin B12, vitamin B6, and homocysteine levels in European adolescents: the Helena Study. Nutr Res, 2012

    Google Scholar 

  33. Kim HJ, Kim MK, Kim JU, Ha HY, Choi BY. Major determinants of serum homocysteine concentrations in a Korean population. J Korean Med Sci 2010;25 (4):509–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hak AE, Polderman KH, Westendorp IC, Jakobs C, Hofman A, Witteman J, Stehouwer CD. Increased plasma homocysteine after menopause. Atherosclerosis 2000;149 (1):163–168

    Article  CAS  PubMed  Google Scholar 

  35. Huemer M, Vonblon K, Födinger M, Krumpholz R, Hubmann M, Ulmer H, Simma B. Total homocysteine, folate, and cobalamin, and their relation to genetic polymorphisms, lifestyle and body mass index in healthy children and adolescents. Pediatr Res 2006;60 (6):764–769

    Article  CAS  PubMed  Google Scholar 

  36. Sanlier N, Yabanci N. Relationship between body mass index, lipids and homocysteine levels in university students. J Pak Med Assoc 2007;57 (10):491

    PubMed  Google Scholar 

  37. Nakazato M, Maeda T, Takamura N, Wada M, Yamasaki H, Johnston KE, Tamura T. Relation of body mass index to blood folate and total homocysteine concentrations in Japanese adults. Eur J Nutr 2011;50 (7):581–585

    Article  CAS  PubMed  Google Scholar 

  38. Chrysohoou C, Panagiotakos DB, Pitsavos C, Zeimbekis A, Zampelas A, Papademetriou L, Masoura C, Stefanadis C. The associations between smoking, physical activity, dietary habits and plasma homocysteine levels in cardiovascular disease-free people: the ‘ATTICA’study. Vasc Med 2004;9 (2):117–123

    Article  PubMed  Google Scholar 

  39. Mouhamed DH, Ezzaher A, Neffati F, Douki W, Najjar MF. Effect of cigarette smoking on plasma homocysteine concentrations. Clin Chem Lab Med 2011;49 (3):479–483

    Article  CAS  Google Scholar 

  40. El Safoury OS, Ezzat M, Abdelhamid MF, Shoukry N, Badawy E. The evaluation of the impact of age, skin tags, metabolic syndrome, body mass index, and smoking on homocysteine, endothelin-1, high-sensitive C-reactive protein, and on the heart. Indian J Dermatol 2013;58 (4):326

    Article  PubMed  PubMed Central  Google Scholar 

  41. Kim D-B, Oh Y-S, Yoo K-D, Lee J-M, Park CS, Ihm S-H, Jang SW, Shim BJ, Kim H-Y, Seung KB. Passive Smoking in Never-Smokers Is Associated With Increased Plasma Homocysteine Levels Analysis of NHANES III Data. Int Heart J 2010;51 (3):183–187

    Article  CAS  PubMed  Google Scholar 

  42. Ortega RM, Requejo AM, López-Sobaler AM, Navia B, Mena MC, Basabe B, Andrés P. Smoking and passive smoking as conditioners of folate status in young women. J Am Coll Nutr 2004;23 (4):365–371

    Article  CAS  PubMed  Google Scholar 

  43. Kapoor P, Ansari MN, Bhandari U. Modulatory effect of curcumin on methionineinduced hyperlipidemia and hyperhomocysteinemia in albino rats. Indian J Exp Biol 2008;46 (7):534

    CAS  PubMed  Google Scholar 

  44. Clarke R, Evans JG, Schneede J, Nexo E, Bates C, Fletcher A, Prentice A, Johnston C, Ueland P, Refsum H. Vitamin B12 and folate deficiency in later life. Age Ageing 2004;33 (1):34–41

    Article  PubMed  Google Scholar 

  45. Green R. Indicators for assessing folate and vitamin B12 status and for monitoring the efficacy of intervention strategies. Food Nutr Bull 2008;29 (Supplement 1):52–63

    Article  Google Scholar 

  46. Qin L, Yang Z, Gu H, Lu S, Shi Q, Xing Y, Li X, Li R, Ning G, Su Q. Association between serum uric acid levels and cardiovascular disease in middle-aged and elderly Chinese individuals. BMC Cardiovasc Disord 2014;14 (1):26

    Article  PubMed  PubMed Central  Google Scholar 

  47. Ohta Y, Tsuchihashi T, Kiyohara K, Oniki H. Increased Uric Acid Promotes Decline of the Renal Function in Hypertensive Patients: A 10-year Observational Study. Intern Med 2012;52 (13):1467–1472

    Article  Google Scholar 

  48. Naik S, Bhide V, Babhulkar A, Mahalle N, Parab S, Thakre R, Kulkarni M. Daily milk intake improves vitamin B-12 status in young vegetarian Indians: an intervention trial. Nutr J 2013;12 (1):136

    Article  PubMed  PubMed Central  Google Scholar 

  49. Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular diseases. JAMA 2006;296 (22):2720–2726

    Article  CAS  PubMed  Google Scholar 

  50. Crider KS, Zhu J-H, Hao L, Yang Q-H, Yang TP, Gindler J, Maneval DR, Quinlivan EP, Li Z, Bailey LB. MTHFR 677C→ T genotype is associated with folate and homocysteine concentrations in a large, population-based, double-blind trial of folic acid supplementation. Am J Clin Nutr 2011;93 (6):1365–1372

    Article  CAS  PubMed  Google Scholar 

  51. Husemoen L, Thomsen T, Fenger M, Jørgensen T. Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR (C677T) genotype. Inter99 (7). Eur J Clin Nutr 2004;58 (8):1142–1150

    Article  CAS  PubMed  Google Scholar 

  52. Semmler A, Moskau S, Stoffel-Wagner B, Weller M, Linnebank M. The effect of MTHFR c.677C>T on plasma homocysteine levels depends on health, age and smoking. Clin Invest Med 2009;32 (6):E310–E314

    CAS  PubMed  Google Scholar 

  53. Holmes MV, Newcombe P, Hubacek JA, Sofat R, Ricketts SL, Cooper J, Breteler M, Bautista LE, Sharma P, Whittaker JC. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet 2011;378 (9791):584–594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Xiao-Yuan Niu.

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Zhang, J., Liu, TT., Zhang, W. et al. Hyperhomocysteinemia is associated with vitamin B-12 deficiency: A cross-sectional study in a rural, elderly population of Shanxi China. J Nutr Health Aging 20, 594–601 (2016). https://doi.org/10.1007/s12603-015-0650-5

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