RANDOMISED DOUBLE-BLIND PLACEBO-CONTROLLED STUDY OF FOLIC ACID ADJUNCT FOR 8 WEEKS IN HYPERHOMOCYSTEINAEMIC HYPERTENSIVE PATIENTS IN ZARIA, NIGERIA
Abstract
Objectives: This study was aimed at determining the effect of folic acid adjunct therapy on homocysteine (HCY) and blood pressure (BP) levels in hypertensive subjects.
Method: The study was a double blind placebo-controlled trial on 100 hypertensive patients randomised into 50 folate and 50 placebo groups, where the folate group had 5 mg folic acid daily for 8 weeks. Fasting plasma homocysteine, folate and blood pressure levels were determined at baseline, at 4 and at 8 weeks. The Mixed Model Repeated Measures analysis of variance was applied for data analysis.
Results: Hyperhomocysteinaemia was found at baseline in the folate (21.3 ± 5.7 µmol/L) and placebo (21.6 ± 4.9 µmol/L) groups which did not differ statistically (p > 0.05). Folic acid adjunct therapy, reduced homocysteine levels at 4 weeks by 2.0 µmol/L (9.2 %, p < 0.05) and at 8 weeks by 1.2 µmol/L (5.6 %, p < 0.05), with no significant (p > 0.05) systolic and diastolic blood pressure lowering effect. High base-line folate levels were found in both folate (113.8 ± 51.2 ng/ml) and placebo groups (109.5 ± 51.4 ng/ml) with no statistically significant difference (p > 0.05).
Conclusion: Short-term daily folic acid supplementation over 8 weeks had a significant homocysteine reduction effect with no significant reduction in systolic and diastolic blood pressures of hypertensive subjects in Zaria, Nigeria. Hyperhomocysteinaemia could not be accounted for by suboptimal folate levels.
Keywords: Hypertension, Homocysteine, Blood pressure, Folate, Placebo, Nigeria.
Keywords:
Hypertension, Homocysteine, Blood pressure, PlaceboDOI
https://doi.org/10.22270/jddt.v8i5.1879References
Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J, Global burden of hypertension: analysis of worldwide data. Lancet, 2005; 365:217-223
Van de Vijver S, Akinyi H, Oti S, Olajide A, Agyemang CM, Aboderin I et al, Status report on hypertension in Africa-consultative review for the 6th session of the African Union Conference of Ministers of Health on non-communicable diseases. Pan African Medical Journal, 2013; 16: 38. doi:10.11604/pamj.2013.16.38.3100 PMCID: PMC3932118
Adeloye D, Basquill C, Aderemi AV, Thompson JY, Obi FA, An estimate of the prevalence of hypertension in Nigeria: systematic review and meta-analysis. Journal of Hypertension, 2015; 33:230-244.
Eikelboom JW, Lonn E, Genest JJ, Hankey G, Yusuf S, Homocysteine and cardiovascular disease: a critical review of the epidemiologic evidence. Annals of Internal Medicine, 1999; 131:363-375
Ueland PM, Refsum H, Stabler SP, Malinow MR, Anderson A, Allen R, Total homocysteine in plasma and serum: methods and clinical applications. Clinical Chemistry, 1993; 39:1764-1779
Ganeshan S, Karthikumar B A, Renjith AA, Alin B. Effect of folic acid on serum homocysteine levels in patients with cardiovascular diseases (CVD). Journal of Chemical and Pharmaceutical Research, 2014; 6(3):1141-1148
Ajuluchukwu J, Oluwatowoju IO, Adebayo K, Onakoya A, Plasma homocysteine in diverse cardiovascular diseases in urban Africans. World Life Science Medical Research, 2011; 1(6):126
Ubbink JB, Delport R. Reference ranges for homocysteine concentrations. In: Robinson K (editor). Homocysteine and Vascular Disease: Cleveland USA: Springer, Dordrecht; 2000. P. 41-57.
Balakumar P, Singh P, Subrahmanya, SG, Singh M, Hyperhomocysteinemia and cardiovascular disorders: is there a correlation? Trends Medical Research, 2007; 2:160-166
Ranjith V, Serum Homocysteine Levels in Cerebrovascular Accidents. Dissertation submitted to the Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore in partial fulfilment of the requirement for a degree of Doctor of Medicine in General Medicine. 2011. P. 76.
Osunkalu VO, Akanmu AS, Adediran A, Abudu O, Homocysteine levels in Nigerian women with pre-eclampsia/ecclampsia. Sierra Leone Journal of Biomedical Research, 2009; 1(1):55-60
Welch GN, Loscalzo J, Homocysteine and atherothrombosis. New England Journal of Medicine, 1998; 338: 1042-1050
Akande AA, Salisu OT, Kolo PM, Plasma total homocysteine (tHcy) Levels in Healthy Nigerian Volunteers. Nigerian Hospital Practice, 2009; 1:3-6.
Glew RH, Okolie H, Crossey M, Suberu O, Trujillo M, Pereyra M, Vanderjagt DJ, Serum lipid profiles and homocysteine levels in adults with stroke or myocardial infarction in the town of Gombe in Northern Nigeria. Journal of Health Population Nutrition, 2004; 22(4):341-347
Alkali NH, Watt H, Bwala SA, Gadzama A, Association of plasma homocysteine and ischaemic stroke in a Nigerian population. Pakistan Journal of Medical Science, 2006; 22:405-408
Ubbink JB, Christianson A, Bester MJ, Van Allen MI, Venter PA, Delpert R, Blom HJ, Folate status, homocysteine metabolism and methylene tetrahydrofolate reductase genotype in rural South African blacks with a history of pregnancy complicated by neural tube defects. Metabolism, 1999; 48:209-274
Vanderjagt DJ, Spelman K, Ambe J, Datta P, Blackwell W, Glew RH, Folate and vitamin B12 status of adolescent girls in Northern Nigeria. Journal of National Medical Association, 2000; 92(7):334-340
McLean E, de Benoist B, Lindsay HA, Review of the magnitude of folate and vitamin B12 deficiencies worldwide. Food Nutrition Bulletin, 2008; 29(2): 38-51
Ubbink JB, Veermaak WJ, vader Merwe A, Becker PJ, Delport R, Portgieter CH, Vitamin requirements for the treatment of hyperhomocysteinaemia in humans. Journal of Nutrition, 1994; 124(10):1927-1933
Clarke R, Frost C, Sherliker P, Lewington S, Collins R, Dose-dependent effect of folic acid on blood concentrations of homocysteine: a meta-analysis of randomised trials, homocysteine lowering trialists collaboration. American Journal of Clinical Nutrition, 2005; 82(4):806-812
McMahon JA, Skeaff CM, Williams SM, Green TJ, Lowering B vitamins has no effect on blood pressure in older adults. Journal of Nutrition, 2007; 137(5):1183-1187
Spence DJ, Bang H, Chambless EL, Stampfer JM, Vitamin intervention for stroke prevention trial: An efficacy analysis. Stroke, 2005; 36:2404-2409
Sharifi F, Fakhrzadeh H, Mirarefin, M, Pourebrahim R, Nouri M, Forouzanfar MH et al, The effects of high-dose folic acid on blood pressure of hypertensive adults with hyperhomocysteinemia: a randomised double-blind placebo controlled clinical trial (Tehran Homocysteine Survey). Iranian Journal of Diabetes and Lipid Disorders, 2010; 9:13-20
Cockroft DW and Gault MH, Prediction of creatinine clearance from serum creatinine. Nephron, 1976; 16:31-41
Frantzen F, Alfheim I, Faaren AI, Nordhei AK, Enzyme conversion immunoassay for determining total homocysteine in plasma or serum. Clinical Chemistry, 1998; 44(2):311-316 •
Manufacturers manual for folate assay: https://www.civicbio.com/product/fa-vb9-folic-acid-vitamin-b9-elisa-kit-e-el-0009/
Scazzone C, Bono A, Tornese F, Arsena R, Schillaci R, Butera D, Cottone S, Correlation between low folate levels and hyperhomocysteinemia but not vitamin B12 in hypertensive patients. Annals of Clinical Laboratory Science, 2014; 44(3):286-290
Sicińska E, Brzozowska A, Roszkowski W, Finglas PM, Supplementation with [6S ]-5-methyltetrahydrofolate or folic acid equally reduces serum homocysteine concentration in older adults. Internet Journal of Food Science and Nutrition, 2017; 0(0):1-10
Mozzaffarian D, Benjamin EJ, Gofor AS, American heart association statistics committee and stroke statistics sub-committee. Heart disease and stroke statistics-2015 update: a report from the american heart association. Circulation, 2015; 131:29-32
Marek-Trzonkowska N, Kwieczyńska A, Reiwer-Gostomska M, Koliński T, Molisz A, Siebert J, Arterial hypertension is characterized by imbalance of pro-angiogenic versus anti-angiogenic factors. PLoS One, 2015; 10 (5):e0126190. doi: 10.1371/journal.pone.0126190.
Fischbash F, Dunning MB. Manual of Laboratory and Diagnostic Tests. Philadelphia: Lippincott William & Wilkins; 2008
Galukande M, Zambwe J, Fualal J, Baingana R, Gakwaya A, Reference values for serum levels of folic acid and vitamin B12 in a young adult Ugandan population. African Health Science, 2011; 11(2):240-243
Osondu CK, Nwadike FC, Ijioma JC, Udah SC, Ugboaja CI, Marketing performance of salad vegetables: the case of cabbage marketing in abia state, nigeria. International Journal of Agricultural Science, Research and Technology in Extension and Education Systems, 2014; 4(3):151-162
Ezebuiro P. Hausa tribe, language, people, culture, history, religion, food, marriage {Web Log Comment} Answer Africa, 2018; Retrieved from https://answersafrica.com/this-is-everything-youll-love-to-know-about-the-hausa-tribe.html
Brustolin M, Giugliani R, Felix TM. Genetics of homocysteine metabolism and associated disorders. Brazilian Journal of Medical Biological Research, 2010; 43(1):1-7
Tripathi P. Homocysteine-the hidden factor and cardiovascular disease: cause or effect? Analytical Biochemistry, 2015; 4(2):4
Danjuma N, Zezi AU, Abdu-Aguye J, Prevelence and prognosis of cardiovascular accident in Zaria, Kaduna State, Nigeria. Journal of Pharmacology and Biological Research, 2005; 2(2):169-173
Owolabi MO, Akarolo-Anthony S, Akinyemi R, Arnett D, Gebregziabher M, Jenkins C et al, The burden of stroke in Africa: a glance at the present and a glimpse into the future. Cardiovascular Journal of Africa, 2017; 26(3):123-133
Flemming FA., Ogunfunmilade TA, Carmel R, Serum vitamin B12 levels and vitamin B12 binding proteins of serum and saliva of healthy nigerians and europeans. American Journal of Clinical Nutrition, 1978; 31(10):1732-1738
Refsum H, Fiskerstrand T, Guttormson AB, Ueland PM, Assessment of homocysteine status. J Inherited Metabolic Disorders, 1997; 20:296-294
Refsum H, Nurk E, Smith AD, Ueland PM, Gjesdal CG, Bjelland I, Vollset SE, The Hordaland homocysteine study: Community-based study of homocysteine, its determinants, and associations with disease. Journal of Nutrition, 2006; 136(6):1731-1740
Thambyrajah J, Landray M J., McGlynn FJ, Townend JN, Does folic acid decrease plasma homocysteine, improve endothelial function in patients with pre-dialysis renal failure. Circulation, 2000; 102(8):871-875
Jaques PF, Selhub J, Boston AG, Wilson PW, Rosenberg IH, The effect of folic acid fortification on plasma folate and total homocysteine concentrations. New England Journal of Medicine, 1999; 340:1449-1454
Homocysteine Lowering Trialists Collaboration, Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. British Medical Journal, 1998; 316 (7135):894-898
Lim U, Cassano PA, Homocysteine and blood pressure in the Third National Health and Nutrition Examination Survey, 1988-1994. American Journal of Epidemiology, 2002; 156(12):1105-1113.
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