Prof. Aron M. Troen, Director, Nutrition and Brain Health Laboratory, Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel, Phone ++972-54-8820420, E-mail:
J Prev Alzheimers Dis. 2017;4(3):174-182. doi: 10.14283/jpad.2017.15.
Objectives: Elevated plasma total homocysteine (tHcy) is associated with increased risk of cardiovascular disease, stroke and dementia. Results of clinical trials using B-vitamins to reduce the cognitive risks attributed to tHcy have been inconsistent. The high prevalence of both hyperhomocysteinemia and cognitive impairment among kidney transplant recipients makes them an important population in which to evaluate the effect of lowering homocysteine on cognitive function. We therefore evaluated whether B-vitamin therapy to lower tHcy would prevent cognitive-decline in a cohort of stable kidney transplant recipients.
The study was a longitudinal ancillary of the FAVORIT trial, a randomized, placebo-controlled multi-site trial of high-dose B vitamins to reduce cardiovascular and cerebrovascular events in clinically stable kidney transplant recipients with elevated tHcy.
584 participants from 18 sites across North America.
The intervention consisted of a daily multivitamin containing high-doses of folate (5.0 mg), vitamin B12 (1.0 mg) and vitamin B6 (50 mg). The placebo consisted of a daily multi-vitamin containing no folate and recommended daily allowances of vitamins B12 and B6 (0 mg folate; 2.0 µg vitamin B12; 1.4 mg vitamin B6).
Annual neuropsychological assessment for up to 5 years (mean 3.3 years) using a standardized test battery. Efficacy was analyzed on an intention-to-treat basis using end-of-trial data. Subgroup analyses included stratification for baseline plasma B-vitamin and tHcy concentrations.
At baseline, cognitive impairment was common with 61% of participants falling more than one standard deviation below published norms for at least one cognitive test. Fewer than 1% of participants had insufficient plasma folate < 5 ng/ml or vitamin B12 < 148 pmol/L. However, 44.6% had plasma B6 concentrations < 30 nmol/L. At follow-up, processing speed and memory scores were modestly but significantly better in the B-vitamin supplement group than in controls (p≤0.05). There was no interaction between baseline tHcy, B-vitamin status and treatment on the cognitive outcomes.
High-dose B-vitamin supplementation provided modest cognitive benefit for kidney transplant recipients with elevated baseline tHcy. Since nearly all participants were folate and vitamin B12 sufficient at baseline, the potential cognitive benefits of folate and B12 supplementation in individuals with poor B-vitamin status remains to be determined.
目的：血浆总同型半胱氨酸（tHcy）升高与心血管疾病、中风和痴呆的风险增加有关。使用 B 族维生素降低归因于 tHcy 的认知风险的临床试验结果并不一致。高同型半胱氨酸血症和认知障碍在肾移植受者中的高发率使他们成为评估降低同型半胱氨酸对认知功能影响的重要人群。因此，我们评估了 B 族维生素治疗是否会降低 tHcy，从而预防稳定肾移植受者的认知衰退。
该研究是 FAVORIT 试验的一项纵向辅助研究，该试验是一项随机、安慰剂对照的多地点试验，旨在评估高剂量 B 族维生素治疗是否能降低 tHcy 升高的临床稳定肾移植受者的心血管和脑血管事件。
来自北美 18 个地点的 584 名参与者。
干预措施包括每日服用含有高剂量叶酸（5.0mg）、维生素 B12（1.0mg）和维生素 B6（50mg）的复合维生素。安慰剂组服用每日复合维生素，其中不含叶酸，维生素 B12 和维生素 B6 的推荐日摄入量为（0mg 叶酸；2.0μg 维生素 B12；1.4mg 维生素 B6）。
使用标准化测试组合进行长达 5 年（平均 3.3 年）的年度神经心理学评估。根据试验结束时的数据，采用意向治疗方法进行疗效分析。亚组分析包括根据基线血浆 B 族维生素和 tHcy 浓度进行分层。
基线时，认知障碍很常见，超过 61%的参与者在至少一项认知测试中低于发表的正常值一个标准差以上。只有不到 1%的参与者血浆叶酸<5ng/ml 或维生素 B12<148pmol/L。然而，44.6%的人血浆 B6 浓度<30nmol/L。随访时，B 族维生素补充组的处理速度和记忆评分略有但显著优于对照组（p≤0.05）。在认知结果方面，基线 tHcy、B 族维生素状态和治疗之间没有交互作用。
高剂量 B 族维生素补充对基线 tHcy 升高的肾移植受者有适度的认知益处。由于几乎所有参与者在基线时都有足够的叶酸和维生素 B12，因此在 B 族维生素状态不佳的个体中，叶酸和 B12 补充的潜在认知益处仍有待确定。
