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Br J Nutr. 2018 Nov;120(10):1122-1130. doi: 10.1017/S0007114518002477.

Effect of long-term low-dose folic acid supplementation on degree of total homocysteine-lowering: major effect modifiers.

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1Institute for Biomedicine,Anhui Medical University,Hefei 230032,People's Republic of China.
2National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Key Laboratory of Organ Failure Research (Ministry of Education), Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China.
3Department of Cardiology,Second Affiliated Hospital,Nanchang University,Nanchang 330006,People's Republic of China.
4Department of Cardiology,Peking University First Hospital,Beijing 100034,People's Republic of China.
5Department of Pharmacy,Peking University First Hospital,Beijing 100034,People's Republic of China.
6Department of Neurology,First People's Hospital,Lianyungang 222061,People's Republic of China.
7Department of Cardiology,First People's Hospital,Lianyungang 222061,People's Republic of China.
8Department of Cardiology,Weinan Center Hospital,Weinan 714000,People's Republic of China.


We sought to examine the potential modifiers in the association between long-term low-dose folic acid supplementation and the reduction of serum total homocysteine (tHcy) among hypertensive patients, using data from the China Stroke Primary Prevention Trial (CSPPT). This analysis included 16 867 participants who had complete data on tHcy measurements at both the baseline and exit visit. After a median treatment period of 4·5 years, folic acid treatment significantly reduced the tHcy levels by 1·6 μmol/l (95 % CI 1·4, 1·8). More importantly, after adjustment for baseline tHcy and other important covariates, a greater degree of tHcy reduction was observed in certain subgroups: males, the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, higher baseline tHcy levels (≥12·5 (median) v. <12·5 μmol/l), lower folate levels (<8·0 (median) v. ≥8·0 ng/ml), estimated glomerular filtration rate (eGFR) <60 ml/min per 1·73 m2 (v. 60-<90 and ≥90 ml/min per 1·73 m2), ever smokers and concomitant use of diuretics (P for all interactions <0·05). The degree of tHcy reduction associated with long-term folic acid supplementation can be significantly affected by sex, MTHFR C677T genotypes, baseline folate, tHcy, eGFR levels and smoking status.


CCB calcium channel blockers; CSPPT China Stroke Primary Prevention Trial; MTHFR methylenetetrahydrofolate reductase; SBP systolic blood pressure; eGFR estimated glomerular filtration rate; tHcy total homocysteine; Effect modifiers; Folic acid; Hypertension; Total homocysteine


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