Effect of Folic Acid therapy on Homocysteine Level in patients with Atherosclerosis or Buerger’s Disease and in Healthy individuals

A clinical trial

Authors

  • Hassan Ravari M.D., Vascular Surgeon, Associate Professor, Department of Vascular Surgery, Vascular and Endovascular Surgery Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Keywords:

Buerger’s disease; Atherosclerosis; Homocysteine; Folic acid

Abstract

Background: Hyperhomocysteinemia is considered a risk factor for atherosclerosis and some other vascular diseases such as Buerger’s disease. 

Objective: The aim of this study was to measure the Homocysteine levels in 3 different groups of participants (Buerger’s disease, atherosclerosis patients, and healthy cases) and determine the therapeutic effect of folic acid therapy on homocysteine levels for these three groups.

Methods: This nonrandomized clinical trial study was conducted in the vascular and endovascular surgery research center of Mashhad University of Medical Sciences in Mashhad, Iran. This interventional study consisted of 44 participants of which 22 patients had Buerger’s disease and a control group of 22 healthy individuals, all of which were enrolled in this study. All of the study’s participants had their serum homocysteine levels measured both before and after 12 weeks of folic acid (5mg/day) therapy. The data analysis used fo data analysis was a Chi square and t-test or their non-parametrical equivalents for data analysis by means of Statistical Package for the Social Sciences (SPSS) version 16.

Results: The homocysteine levels were found to be significantly higher in patients with Buerger’s disease as compared to other groups before treatment with folic acid (Buerger = 21.8 ± 8.5 Mm/L, atherosclerosis = 17.3 ± 6.9, healthy = 13.8 ± 3.1; p < 0.001). After treatment with folic acid at 5 mg/daily for 12 weeks, the new plasma homocysteine levels did not show any significant difference (p = 0.38) between the Buerger’s disease group (14.6 ± 4.5 Mm/L) and atherosclerosis group (13.9 ± 4.7), but it was found to besignificantly higher in both groups when compared to the healthy group (10.7 ± 3.9, p<0.05). The plasma homocysteine level was reduced significantly when compared to its initial level in all 3 groups. The comparison of differences among three groups was found not to be significant (p=0.41).

Conclusions: It seems that supplementary therapy with folic acid at a dose of 5 mg daily may reduce the serum homocysteine levels significantly and may have a role in the development of vascular diseases such as Buerger’s disease. We suggest that folic acid should be considered as a routine agent in the Buerger’s disease therapeutic regime.

Clinical trial registration: The trial was registered at the Thai Clinical Trials Registry (http://www.clinicaltrials.in.th) with the ID: TCTR20160601003.

Funding: This study was not funded by any organization.

References

Ueland PM, Refsum H. Plasma homocysteine, a risk factor for vascular disease: plasma levels in health,

disease, and drug therapy. J Lab Clin Med. 1989; 114(5): 473-501. doi: 5/1/15088. PMID: 2681479.

Den Heijer M, Rosendaal FR, Blom HJ, Gerrits WB, Bos GM. Hyperhomocysteinemia and venous

thrombosis: a meta-analysis. Thromb Haemost. 1998; 80(6): 874-7. PMID: 9869152.

Božič-Mijovski M. Hyperhomocysteinemia and thrombophilia. Clin Chem Lab Med. 2010; 48(1): 89-95.

doi: 10.1515/CCLM.2010.365. doi: 10.1515/CCLM.2010.365. PMID: 21105837.

Di Micco P, Di Fiore R, Di Micco G, Cardillo G, Bellia C, Quaranta S, et al. Buerger’s Disease and

Hyperhomocysteinemia: Is there a Relationship? J Atheroscler Thromb. 2008; 1: 6-8. doi: 1876-5068/08.

Fiessinger JN. Juvenile arteritis revisited. Buerger's disease-Takayasu's disease. Pathophysiol Haemost

Thromb. 2002; 32(5-6): 295-8. doi:10.1159/000073584. PMID: 13679660.

Ravari H, Zafarghandi MR, Alvandfar D, Saadat S. Serum homocysteine in deep venous thrombosis,

peripheral atherosclerosis and healthy Iranians: a case-control study. Pak J Biol Sci. 2009; 12(14): 1019-24.

doi: 10.3923/pjbs.2009.1019.1024. PMID: 19947180.

Sunder-Plassmann G, Födinger M, Buchmayer H, Papagiannopoulos M, Wojcik J, Kletzmayr J, et al.

Effect of High Dose Folic Acid Therapy on Hyperhomocysteinemia in Hemodialysis Patients Results of the

Vienna Multicenter Study. J Am Soc Nephrol. 2000; 11(6): 1106-16. doi: 1046-6673/1106-1106. PMID:

Koyama K, Usami T, Takeuchi O, Morozumi K, Kimura G. Efficacy of methylcobalamin on lowering total

homocysteine plasma concentrations in haemodialysis patients receiving high ‐ dose folic acid

supplementation. Nephrol Dial Transplant. 2002; 17(5): 916-22. doi: 10.1093/ndt/17.5.916. PMID:

de Jong SC, Stehouwer CD, van den Berg M, Kostense PJ, Alders D, Jakobs C, et al. Determinants of

fasting and post-methionine homocysteine levels in families predisposed to hyperhomocysteinemia and

premature vascular disease. Arterioscler Thromb Vasc Biol. 1999; 19(5): 1316-24. doi:

1161/01.ATV.19.5.1316. PMID: 10323785.

Nygård O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and

mortality in patients with coronary artery disease. N Engl J Med. 1997; 337(4): 230-6. doi:

1056/NEJM199707243370403. PMID: 9227928.

Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine

as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA. 1995;

(13): 1049-57. doi: 10.1001/jama.1995.03530130055028. PMID: 7563456.

Stammler F, Diehm C, Hsu E, Stockinger K, Amendt K. The prevalence of hyperhomocysteinemia in

thromboangiitis obliterans. Does homocysteine play a role pathogenetically? Dtsch Med Wochenschr.

; 121(46): 1417-23. doi: 10.1055/s-2008-1043162. PMID: 8974873.

Bergmark C, Mansoor MA, Swedenborg J, de Faire U, Svardal AM, Ueland PM. Hyperhomocysteinemia

in patients operated for lower extremity ischaemia below the age of 50-effect of smoking and extent of

disease. European Journal of Vascular Surgery. 1993; 7(4): 391-6. doi: 10.1016/S0950-821X(05)80255-5.

PMID: 8359294.

Van den Berg M, Boers GH, Franken DG, Blom HJ, Van Kamp GJ, Jakobs C, et al.

Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive

disease. Eur J Clin Invest. 1995; 25(3): 176-81. doi: 10.1111/j.1365-2362.1995.tb01545.x. PMID: 7781664.

van den Berg M, Franken DG, Boers GH, Blom HJ, Jakobs C, Stehouwer CD, et al. Combined vitamin B<

sub> 6 plus folic acid therapy in young patients with arteriosclerosis and hyperhomocysteinemia. J

Vasc Surg. 1994; 20(6): 933-40. doi: 10.1016/0741-5214(94)90230-5. PMID: 7990188.

Wilcken DE, Dudman NP, Tyrrell PA, Robertson MR. Folic acid lowers elevated plasma homocysteine in

chronic renal insufficiency: possible implications for prevention of vascular disease. Metabolism. 1988;

(7): 697-701. PMID: 3386535.

Bostom AG, Shemin D, Lapane KL, Hume AL, Yoburn D, Nadeau MR, et al. High dose B-vitamin

treatment of hyperhomocysteinemia in dialysis patients. Kidney Int. 1996; 49(1): 147-52. doi:

1016/0026-0495(88)90093-5. PMID: 8770960.

Collaboration HLT. Lowering blood homocysteine with folic acid based supplements: meta-analysis of

randomised trials. BMJ. 1998; 316(7135): 894-8. doi: 10.1136/bmj.316.7135.894. PMID: 9569395,

PMCID: PMC28491.

Published

2022-03-08