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

Zhang, Yuanyuan; Wu, Hongxu; Li, Youbao; Ban, Qianyun; Huang, Xiao; Chen, Lulu; Li, Jianping; Zhang, Yan; Chen, Yimin; He, Minqiang; Tang, Guping; Yin, Dou; Li, Junnong; Huo, Yong; Xu, Xiping

doi:10.1017/s0007114518002477

Cited by 9 publications

(6 citation statements)

References 37 publications

(53 reference statements)

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“…The extent by which such criteria have been adopted in published trials will be considered in our comments below. Critically, the interpretation of the results must take into account that the effect of B vitamins may be very different in different populations or subgroups of the population, as most convincingly demonstrated in the China Stroke Primary Prevention Trial (CSPPT, to be described below) [54].…”

Section: Homocysteine and Disease Prevention – Clinical Trials Of B Vitamin Supplementationmentioning

confidence: 99%

Homocysteine – from disease biomarker to disease prevention

2021

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We have reviewed the literature and have identified more than 100 diseases or conditions that are associated with raised concentrations of plasma total homocysteine. The commonest associations are with cardiovascular diseases and diseases of the central nervous system, but a large number of developmental and age‐related conditions are also associated. Few other disease biomarkers have so many associations. The clinical importance of these associations becomes especially relevant if lowering plasma total homocysteine by B vitamin treatment can prevent disease and so improve health. Five diseases can at least in part be prevented by lowering total homocysteine: neural tube defects, impaired childhood cognition, macular degeneration, primary stroke, and cognitive impairment in the elderly. We conclude from our review that total homocysteine values in adults of 10 μmol/L or below are probably safe, but that values of 11 μmol/L or above may justify intervention. Homocysteine is more than a disease biomarker: it is a guide for the prevention of disease.

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Section: Homocysteine and Disease Prevention – Clinical Trials Of B Vitamin Supplementationmentioning

confidence: 99%

Homocysteine – from disease biomarker to disease prevention

2021

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“…Participants with higher neutrophil counts had lower folate and elevated tHcy levels at baseline. Folic acid is effective in lowering tHcy levels (31,32) . Elevated tHcy has been reported to be an independent determinant of the development of albuminuria (33) .…”

Section: Laboratory Resultsmentioning

confidence: 99%

Interaction of neutrophil counts and folic acid treatment on new-onset proteinuria in hypertensive patients

et al. 2020

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We aimed to examine whether baseline neutrophil counts affected the risk of new-onset proteinuria in hypertensive patients, and, if so, whether folic acid treatment is particularly effective in proteinuria prevention in such a setting. A total of 8208 eligible participants without proteinuria at baseline were analysed from the renal substudy of the China Stroke Primary Prevention Trial. Participants were randomised to receive a double-blind daily treatment of 10 mg of enalapril and 0·8 mg of folic acid (n 4101) or 10 mg of enalapril only (n 4107). The primary outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit. The mean age of the participants was 59·5 (sd, 7·4) years, 3088 (37·6 %) of the participants were male. The median treatment duration was 4·4 years. In the enalapril-only group, a significantly higher risk of new-onset proteinuria was found among participants with higher neutrophil counts (quintile 5; ≥4·8 × 109/l, OR 1·44; 95 % CI 1·00, 2·06), compared with those in quintiles 1–4. For those with enalapril and folic acid treatment, compared with the enalapril-only group, the new-onset proteinuria risk was reduced from 5·2 to 2·8 % (OR 0·49; 95 % CI 0·29, 0·82) among participants with higher neutrophil counts (≥4·8 × 109/l), whereas there was no significant effect among those with neutrophil counts <4·8 × 109/l. In summary, among hypertensive patients, those with higher neutrophil counts had increased risk of new-onset proteinuria, and this risk was reduced by 51 % with folic acid treatment.

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“…Our research revealed that history, hypertension, stroke, CHD, and Hcy were statistically meaningful between the success group and the failure group. Wang et al [10] found that the efficacy of oral folic acid therapy may be influenced by sex, baseline Hcy level, and smoking. A study explored the influence factors of the old's Hcy level in Beijing, and they concluded that Hcy level may be associated with education, blood folate levels, age, sex, and drinking.…”

Section: Discussionmentioning

confidence: 99%

“…Oral folic acid therapy is the most common intervention in HHcy therapy to reduce the concentration of Hcy [10]. However, at home and abroad, the conclusions of the previous studies on the efficacy of folic acid therapy to HHcy were inconsistent [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Using the optimal method—explained variance weighted genetic risk score to predict the efficacy of folic acid therapy to hyperhomocysteinemia

et al. 2022

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BACKGROUND: Genetic risk score (GRS) is a useful way to explore genetic architectures and the relationships of complex diseases. Several studies had revealed many single nucleotide polymorphisms (SNPs) associated with the efficacy of folic acid treatment to hyperhomocysteinemia (HHcy). METHODS: We aimed to construct and screen out the optimal predictive model based on four GRSs and traditional risk factors. Four GRSs enrolled four SNPs (MTHFR rs1801131, MTHFR rs1801133, MTRR rs1801394, BHMT rs3733890) were presented as follows: (a) simple count genetic risk score (SC-GRS), (b) direct logistic regression genetic risk score (DL-GRS), (c) polygenic genetic risk score (PG-GRS), and (d) explained variance weighted genetic risk score (EV-GRS). We performed a prospective cohort study including 638 HHcy patients. Then we evaluated the associations of four GRSs with folic acid's efficacy and the performance of four GRSs. RESULTS: Four GRSs were independently associated with efficacy of treatment (p < 0.05). When combining GRSs with traditional risk factors, the AUC of the four models were all above 0.900 in the training set (Tradition + SC-GRS: 0.909, Tradition + DL-GRS: 0.909, Tradition + PG-GRS: 0.904, Tradition + EV-GRS: 0.910). And EV-GRS got the highest AUC. When evaluating the models in the testing set, we got the same conclusion that EV-GRS was optimal among four GRSs with the highest AUC (0.878) and the highest increase of AUC (0.008). CONCLUSION: A more precise predictive model combing the optimal GRS with traditional risk factors was constructed to predict the efficacy of folic acid therapy to HHcy.

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

Cited by 9 publications

References 37 publications

Homocysteine – from disease biomarker to disease prevention

Homocysteine – from disease biomarker to disease prevention

Interaction of neutrophil counts and folic acid treatment on new-onset proteinuria in hypertensive patients

Using the optimal method—explained variance weighted genetic risk score to predict the efficacy of folic acid therapy to hyperhomocysteinemia

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