叶酸补充对认知衰老的积极影响取决于 ω-3 脂肪酸状况：FACIT 试验的事后分析。

Positive effects of folic acid supplementation on cognitive aging are dependent on ω-3 fatty acid status: a post hoc analysis of the FACIT trial.

机构信息

Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, The Netherlands.

出版信息

Am J Clin Nutr. 2021 Apr 6;113(4):801-809. doi: 10.1093/ajcn/nqaa373.

DOI:10.1093/ajcn/nqaa373

PMID:33564824

Abstract

BACKGROUND

Although epidemiological studies suggest a protective role of B vitamins and omega-3 (ω-3) fatty acids in cognitive decline, findings from intervention studies are conflicting. Mechanistic studies suggest that the ω-3 (n-3) fatty acid status can modulate the effects of B vitamins on cognitive decline.

OBJECTIVES

We investigated the interaction between baseline ω-3 fatty acid statuses and folic acid treatment on cognitive decline in a placebo-controlled trial [FACIT (Folic Acid and Carotid Intima-media Thickness)].

METHODS

This post hoc analysis included 791 older adults aged 50-70 y with plasma total homocysteine ≥13 µmol/L and ≤26 µmol/L and serum vitamin B12 ≥200 pmol/L. Participants received 800 µg folic acid or placebo daily for 3 y. Global cognitive functioning and domain-specific functioning (episodic memory, information processing speed, executive functioning) were assessed at baseline and after 3 y. The effect of the folic acid supplementation was analyzed according to tertiles of baseline ω-3 fatty acid concentrations using linear multiple regression.

RESULTS

The mean ± SD age of the study population was 60.2 ± 5.6 y, and the mean ± SD Mini-Mental State Examination score was 28.6 ± 1.5. The treatment effect of folic acid was significantly larger in participants in the low compared to high ω-3 fatty acid tertile for global cognition (difference in z-score: mean ± SE = 0.16 ± 0.059; P < 0.01). Regarding domain-specific functioning, similar results were observed for information processing speed (mean ± SE = 0.167 ± 0.068; P = 0.01). There were no overall interactions between folic acid treatment and ω-3 fatty acid tertiles for episodic memory (P = 0.14) and executive functioning (P = 0.21).

CONCLUSIONS

This post hoc analysis revealed that the efficacy of folic acid treatment on cognitive functioning is dependent on the ω-3 fatty acid status. Individuals with a lower ω-3 fatty acid status at baseline benefited from folic acid treatment, while individuals with a higher ω-3 fatty acid status did not. The results potentially explain the inconsistency in outcomes of B-vitamin supplementation trials and emphasize the importance of a personalized approach. This trial was registered at clinicaltrials.gov as NCT00110604.

摘要

背景

尽管流行病学研究表明 B 族维生素和 ω-3（ω-3）脂肪酸对认知能力下降具有保护作用，但干预研究的结果却存在矛盾。机制研究表明，ω-3（n-3）脂肪酸状况可以调节 B 族维生素对认知能力下降的影响。

目的

我们在一项安慰剂对照试验 [FACIT（叶酸和颈动脉内膜中层厚度）] 中，研究了基线 ω-3 脂肪酸状况与叶酸治疗对认知能力下降的相互作用。

方法

这项事后分析包括 791 名年龄在 50-70 岁之间、血浆总同型半胱氨酸≥13 μmol/L 和≤26 μmol/L 且血清维生素 B12≥200 pmol/L 的老年人。参与者每日接受 800μg 叶酸或安慰剂治疗 3 年。在基线和 3 年后评估整体认知功能和特定领域的功能（情景记忆、信息处理速度、执行功能）。使用线性多元回归，根据基线 ω-3 脂肪酸浓度的三分位数分析叶酸补充的效果。

结果

研究人群的平均年龄±标准差为 60.2±5.6 岁，平均 Mini-Mental State Examination 评分为 28.6±1.5。与高 ω-3 脂肪酸三分位组相比，低 ω-3 脂肪酸三分位组的叶酸治疗对整体认知的效果明显更大（z 分数差值：均值±SE=0.16±0.059；P<0.01）。在特定领域的功能方面，信息处理速度也观察到了类似的结果（均值±SE=0.167±0.068；P=0.01）。在情景记忆（P=0.14）和执行功能（P=0.21）方面，叶酸治疗与 ω-3 脂肪酸三分位组之间没有总体相互作用。

结论

这项事后分析表明，叶酸治疗对认知功能的疗效取决于 ω-3 脂肪酸状况。基线 ω-3 脂肪酸水平较低的个体从叶酸治疗中受益，而 ω-3 脂肪酸水平较高的个体则没有。结果可能解释了 B 族维生素补充试验结果不一致的原因，并强调了个性化方法的重要性。该试验在 clinicaltrials.gov 上注册为 NCT00110604。