Brief Report
No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study

https://doi.org/10.1016/S0165-0327(03)00169-1Get rights and content

Abstract

Background: Associations between vitamin B-12 deficiency and impaired cognitive function and depression have been reported. Methods: A randomized placebo controlled study including 140 individuals with an increased plasma methylmalonic acid (0.40–2.00 μmol/l) not previously treated with vitamin B-12. Cognitive function was assessed by the Cambridge Cognitive Examination (CAMCOG), Mini-Mental State Examination (MMSE), and a 12-words learning test. Symptoms of depression were evaluated by the Major Depression Inventory. The main outcome measure was change in cognitive function and depression score from baseline to follow-up 3 months later. Results: At baseline 78 (56%) individuals had cognitive impairment judged from the CAMCOG score and 40 (29%) according to the MMSE; 18 (13%) individuals had symptoms of depression. No improvement was found in cognitive function comparing the treatment and placebo group (total CAMCOG score: P=0.43), nor among individuals with only slightly impaired cognitive function (n=44, total CAMCOG score: P=0.42). The treatment group did not improve in depression score as compared to the placebo group (P=0.18). Limitations: The duration of impaired cognitive function was unknown. Conclusions: A high proportion of individuals with an increased plasma methylmalonic acid had impaired cognitive function, and a rather high prevalence of depression was observed. However, vitamin B-12 treatment did not improve cognitive function or symptoms of depression within the 3-months study period.

Introduction

In the early phase of vitamin B-12 deficiency the clinical manifestations are subtle (Beck, 1991; Carmel, 1997). As delayed diagnosis may result in irreversible damage to the central nervous system (Healton et al., 1991; Martin et al., 1992) strong incentives have existed to establish new sensitive diagnostic tests such as plasma methylmalonic acid (P-MMA) and plasma total homocysteine (P-tHcy) which accumulate if vitamin B-12 is lacking (Allen et al., 1990).

Dementia is suggested to affect around 14% of the elderly (Rogan and Sullivan, 1993; Lauritzen and Korner, 1996), and the prevalence of moderate to severe depression is around 5% in the general population (Ustun and Sartorius, 2002). As summarized by Selhub et al. (2000) several studies report an association between vitamin B-12 deficiency and dementia, but studies of the effect of vitamin B-12 treatment on cognitive function have been inconclusive (Martin et al., 1992; Eastley et al., 2000; Kwok et al., 1998; Teunisse et al., 1996; Nilsson et al., 2001; Cunha et al., 1995). Some report that depressed patients were found to have abnormal vitamin B-12 status (Bell et al., 1991) and others that vitamin B-12 deficiency was associated with a twofold risk of severe depression (Penninx et al., 2000).

The aims of the present randomized placebo-controlled trial were to assess the cognitive function and symptoms of depression in individuals with an elevated P-MMA and to evaluate the effect of vitamin B-12 treatment.

Section snippets

Protocol

As described in detail elsewhere we included 140 individuals with an increased P-MMA (0.40–2.00 μmol/l) in a randomized trial (Hvas et al., 2001). Each participant was randomized to receive injections of either 1 mg Cyanocobalamin (Betolvex®) or 1 ml isotonic sodium chloride weekly for 4 weeks. Both the investigator (AMH) and the participants were blinded to the intervention. The examinations were performed at the day of randomization and at the final visit 3 months later.

Examination of

Results

CAMCOG, MMSE, and the 12-words learning test as well as the MDI were performed at the baseline examination and by 134 individuals at the follow-up examination 3 months later, as 65 in the treatment group and 69 in the placebo group completed the trial.

The characteristics of the treatment and placebo groups are shown in Table 1. At the time of randomization the two groups were very similar regarding distribution of the biochemical parameters as well as the scores in cognitive function and

Discussion

In this randomized placebo controlled trial among 140 individuals with an increased P-MMA we examined the prevalence of cognitive impairment and depression as well as the effect of vitamin B-12 treatment.

For those below 80 years we found that the prevalence of cognitive impairment was about three times as high among individuals with biochemical signs of vitamin B-12 deficiency as compared to the Danish general population (Lauritzen and Korner, 1996). This might indicate that impaired cognitive

Acknowledgements

The study was in part supported by a grant from Danish Medical Research Council (9903063), The Health Found of ‘danmark’s’ Sygeforsiking, EU Biomed (BMH4-98-3549), The Institute of Experimental Clinical Research, Aarhus University, E. Danielsen and Wife’s Foundation, The Novo Nordisk Foundation, Hans and Nora Buchard Foundation, Mogens Svarre Mogensen Foundation, Velux Foundation, and The Family Hede Nielsen Foundation.

We also thank Dumex-Alpharma for the donation of the Betolvex® and placebo

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