Intervention Review

Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people

  1. Reem Malouf1,*,
  2. John Grimley Evans2

Editorial Group: Cochrane Dementia and Cognitive Improvement Group

Published Online: 8 OCT 2008

Assessed as up-to-date: 21 JUL 2008

DOI: 10.1002/14651858.CD004514.pub2


How to Cite

Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD004514. DOI: 10.1002/14651858.CD004514.pub2.

Author Information

  1. 1

    Cochrane Dementia and Cognitive Improvement Group, Oxford, UK

  2. 2

    University of Oxford, Division of Clinical Geratology, Nuffield Department of Clinical Medicine, Oxford, UK

*Reem Malouf, Cochrane Dementia and Cognitive Improvement Group, John Radcliffe Hospital (4th Floor, Room 4401C), Headington, Oxford, OX3 9DU, UK. reemmalouf@yahoo.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 8 OCT 2008

SEARCH

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Folate deficiency can result in congenital neural tube defects and megaloblastic anaemia. Low folate levels may be due to insufficient dietary intake or inefficient absorption, but impaired metabolic utilization also occurs.

Because B12 deficiency can produce a similar anaemia to folate deficiency, there is a risk that folate supplementation can delay the diagnosis of B12 deficiency, which can cause irreversible neurological damage.  Folic acid supplements may sometimes therefore include vitamin B12 supplements with simultaneous administration of vitamin B12.

Lesser degrees of folate inadequacy are associated with high blood levels of the amino acid homocysteine which has been linked with the risk of arterial disease, dementia and Alzheimer's disease. There is therefore interest in whether dietary supplementation can improve cognitive function in the elderly.

However, any apparent benefit from folic acid which was given in combination with B12 needs to be "corrected" for any effect of vitamin B12 alone. A separate Cochrane review of vitamin B12 and cognitive function has therefore been published.

Objectives

To examine the effects of folic acid supplementation, with or without vitamin B12, on elderly healthy or demented people, in preventing cognitive impairment or retarding its progress.

Search methods

Trials were identified from a search of the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 10 October 2007 using the terms: folic acid, folate, vitamin B9, leucovorin, methyltetrahydrofolate, vitamin B12, cobalamin and cyanocobalamin. This Register contains references from all major health care databases and many ongoing trials databases. In addition MEDLINE, EMBASE, CINAHL, PsychINFO and LILACS were searched (years 2003-2007) for additional trials of folate with or without vitamin B12 on healthy elderly people.

Selection criteria

All double-blind, placebo-controlled, randomized trials, in which supplements of folic acid with or without vitamin B12 were compared with placebo for elderly healthy people or people with any type of dementia or cognitive impairment.

Data collection and analysis

The reviewers independently applied the selection criteria and assessed study quality. One reviewer extracted and analysed the data. In comparing intervention with placebo, weighted mean differences and standardized mean difference or odds ratios were estimated.

Main results

Eight randomized controlled trials fulfilled the inclusion criteria for this review. Four trials enrolled healthy older people, and four recruited participants with mild to moderate cognitive impairment or dementia with or without diagnosed folate deficiency. Pooling the data was not possible owing to heterogeneity in sample selections, outcomes, trial duration, and dosage. Two studies involved a combination of folic acid and vitamin B12.

There is no adequate evidence of benefit from folic acid supplemententation with or without vitamin B12 on cognitive function and mood of unselected healthy elderly people. However, in one trial enrolling a selected group of healthy elderly people with high homocysteine levels, 800 mcg/day folic acid supplementation over three years was associated with significant benefit in terms of global functioning (WMD 0.05, 95% CI 0.004 to 0.096, P = 0.033); memory storage (WMD 0.14, 95% CI 0.04 to 0.24, P = 0.006) and information-processing speed (WMD 0.09, 95% CI 0.02 to 0.16, P = 0.016).

Four trials involved people with cognitive impairment. In one pilot trial enrolling people with Alzheimer's disease, the overall response to cholinesterase inhibitors significantly improved with folic acid at a dose of 1mg/day (odds ratio: 4.06, 95% CI 1.22 to 13.53; P = 0.02) and there was a significant improvement in scores on the Instrumental Activities of Daily Living and the Social Behaviour subscale of the Nurse's Observation Scale for Geriatric Patients (WMD 4.01, 95% CI 0.50 to 7.52, P = 0.02). Other trials involving people with cognitive impairment did not show any benefit in measures of cognitive function from folic acid, with or without vitamin B12.

Folic acid plus vitamin B12 was effective in reducing serum homocysteine concentrations (WMD -5.90, 95% CI -8.43 to -3.37, P < 0.00001). Folic acid was well tolerated and no adverse effects were reported.

Authors' conclusions

The small number of studies which have been done provide no consistent evidence either way that folic acid, with or without vitamin B12, has a beneficial effect on cognitive function of unselected healthy or cognitively impaired older people. In a preliminary study, folic acid was associated with improvement in the response of people with Alzheimer's disease to cholinesterase inhibitors. In another, long-term use appeared to improve the cognitive function of healthy older people with high homocysteine levels.  More studies are needed on this important issue.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

No evidence that folic acid with or without vitamin B12 improves cognitive function of unselected elderly people with or without dementia. Long-term supplementation may benefit cognitive function of healthy older people with high homocysteine levels

In the economically developed world, folate deficiency is one of the commonest vitamin deficiencies. Several reports suggest a higher prevalence of various psychiatric disorders in elderly people with folate deficiency. There is interest in whether dietary supplements of folic acid (an artificial chemical analogue of naturally occurring folates) can improve cognitive function of people at risk of cognitive decline associated with ageing or dementia, whether by affecting homocysteine metabolism or through other mechanisms. Eight trials met the criteria for inclusion. It was not possible to pool the data because the trials studied different populations, tested folic acid in different doses, and used different outcome measures. There were two trials of folic acid in conjunction with B12. The analysis showed significant benefit of folic acid over placebo in some measures of cognition in a long-term trial recruiting elderly people with high homocysteine levels from a general population. In one pilot trial, 1 mg/day of folic acid was associated with significant improvement in behavioural response to cholinesterase inhibitors in people with Alzheimer's disease.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

使用含有或不含有維生素B12的葉酸來預防和治療健康老年人和失智症病患

缺乏葉酸可能導致先天性神經管缺陷和巨球形貧血。葉酸過低可能是因為飲食攝取不足或吸收差所致,當新陳代謝效用減弱也有可能會發生葉酸過低的現象。因為B12缺乏也會產生類似葉酸缺乏的貧血,所以補充葉酸可能延誤B12缺乏的診斷,而B12缺乏會造成不可逆的神經學損害。補充葉酸也許有時也包含到補充維生素B12。葉酸含量過低可能和血液中含有高含量半胱胺酸(一種胺基酸)有關,可能會有引發動脈疾病,失智症和阿茲海默氏症的風險。有趣的是在老年人身上飲食補充葉酸可以改善認知功能。然而,任何由葉酸對身體造成的益處需要去除因合併維生素B12產生的影響。目前已有一篇公開的Cochrane文獻是比較維生素B12和認知功能之間的關係。

目標

本研究的主要目的在於探討補充含有或不含有維生素B12的葉酸,對健康的老年人或失智患者在預防認知功能障礙或延遲其進展的影響。

搜尋策略

2007年10月10號搜尋Cochrane Dementia and Cognitive Improvement Group's Specialized Register 資料庫,針對:folic acid, folate, vitamin B9, leucovorin, methyltetrahydrofolate, vitamin B12, cobalamin 和 cyanocobalamin關鍵字進行檢索,這個資料庫包含從所有主要健康照顧資料庫而來的文獻和很多進行中的試驗。另外使用MEDLINE, EMBASE, CINAHL, PsychINFO 和LILACS資料庫(年份20032007)檢索其他健康老年人補充葉酸合併或不合併維生素B12的相關試驗。

選擇標準

收錄所有雙盲、安慰劑對照組、隨機試驗,而這些試驗主要是比較使用含有或不含有維生素B12的葉酸以及安慰劑對健康老年人或有任何型態的失智症或認知功能障礙患者的影響。

資料收集與分析

審查者獨立的選擇適合納入研究的試驗,並評估試驗品質,一個審查者擷取和分析數據。為了與安慰劑做比較,也估算了重量平均偏差和標準平均偏差或OR值。

主要結論

在這個研究中有8組隨機對照試驗滿足納入規範,4組試驗收錄健康老年人,和4組收錄輕度到中度認知障礙合併或不合併葉酸缺乏的失智症患者。因為在選擇的族群,治療成果,試驗持續期間,和劑量上具有異質性,因此無法將數據進行彙整。有2個試驗將葉酸和維生素B12合併使用進行研究。研究中並沒有適當的證據可以說明補充含有或不含有維生素B12的葉酸對於健康的老年人的認知功能和非選擇情緒是有幫助的。然而,有1個試驗納入一群健康老年人合併有較高的半胱胺酸濃度,每天使用800微克葉酸補充三年以上,在整體性功能(WMD 0.05, 95% 信心區間 0.004 to 0.096, P = 0.033);記憶強度(WMD 0.14, 95%信心區間0.04 to 0.24, P = 0.006)和資訊處理速度(WMD 0.09, 95%信心區間0.02 to 0.16, P = 0.016)方面有具有顯著的提升。有四組試驗收錄認知障礙的患者,在其中1組pilot試驗納入阿茲海默症患者,每天補充1 mg葉酸的患者明顯的增加對膽鹼?抑制劑的反應 (odds ratio: 4.06, 95% CI: 1.22 to 13.53; P = 0.02),也明顯改善 Instrumental Activities of Daily Living and the Social Behaviour subscale of the Nurse's Observation Scale for Geriatric Patients的評量分數(WMD 4.01, 95% 信心區間 0.50 to 7.52, P = 0.02)。其他試驗收錄認知功能障礙的患者,但補充含有或不含有維生素B12的葉酸,在認知功能測量上並沒有顯示任何益處。添加維生素B12的葉酸在降低血清半胱胺酸濃度是有效的(WMD −5.90, 95% 信心區間 −8.43 to −3.37, P < 0.00001)。葉酸有很好的耐受性也沒有被報告過在這個研究中有8組隨機對照試驗滿足納入規範,4組試驗收錄健康老年人,和4組收錄輕度到中度認知障礙合併或不合併葉酸缺乏的失智症患者。因為在選擇的族群,治療成果,試驗持續期間,和劑量上具有異質性,因此無法將數據進行彙整。有2個試驗將葉酸和維生素B12合併使用進行研究。研究中並沒有適當的證據可以說明補充含有或不含有維生素B12的葉酸對於健康的老年人的認知功能和非選擇情緒是有幫助的。然而,有1個試驗納入一群健康老年人合併有較高的半胱胺酸濃度,每天使用800微克葉酸補充三年以上,在整體性功能(WMD 0.05, 95% 信心區間 0.004 to 0.096, P = 0.033);記憶強度(WMD 0.14, 95%信心區間0.04 to 0.24, P = 0.006)和資訊處理速度(WMD 0.09, 95%信心區間0.02 to 0.16, P = 0.016)方面有具有顯著的提升。有四組試驗收錄認知障礙的患者,在其中1組pilot試驗納入阿茲海默症患者,每天補充1 mg葉酸的患者明顯的增加對膽鹼?抑制劑的反應 (odds ratio: 4.06, 95% CI: 1.22 to 13.53; P = 0.02),也明顯改善 Instrumental Activities of Daily Living and the Social Behaviour subscale of the Nurse's Observation Scale for Geriatric Patients的評量分數(WMD 4.01, 95% 信心區間 0.50 to 7.52, P = 0.02)。其他試驗收錄認知功能障礙的患者,但補充含有或不含有維生素B12的葉酸,在認知功能測量上並沒有顯示任何益處。添加維生素B12的葉酸在降低血清半胱胺酸濃度是有效的(WMD −5.90, 95% 信心區間 −8.43 to −3.37, P < 0.00001)。葉酸有很好的耐受性也沒有被報告過副作用。

作者結論

有關補充含有或不含有維生素B12的葉酸在健康老人或是具有認知障礙的老人的研究太少,所以並沒有一致性的結論。。在一個初步的試驗,葉酸對於使用膽鹼?抑制劑的阿茲海默症患者是有幫助的。另一個試驗顯示,長期使用葉酸對合併有高濃度半胱胺酸老年人的認知功能會出現改善。因此需要更多的研究來探討這個重要的議題。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

在已發展國家,葉酸缺乏是維生素缺乏常見的一種。有幾個研究指出老年人身上常見的幾種精神疾病都與葉酸缺乏有關。大家有興趣的是補充葉酸(從天然的人工化學類似物產生葉酸)是否可以改善與年齡有關的認知衰退或罹患失智症的風險,而這關係是否透過改變半胱胺酸的代謝或是其他機轉。研究中共有8組試驗符合納入規範,因為試驗中係採用不同族群的受試者、使用不同的葉酸劑量、和使用不同的治療成果評估項目,因此無法將數據匯集。這裡有2個試驗是使用含有維生素B12的葉酸。其中一個研究顯示對於高半胱胺酸濃度的老年人,補充葉酸比起安慰劑來說,對老年人的認知功能是有顯著的益處。在另一個1個pilot試驗中,每日服用1毫克的葉酸可以明顯改善阿茲海默症患者對於乙醯膽鹼?抑制劑的反應。