Vitamins and minerals have many functions in the nervous system which are important
for brain health. It has been suggested that various different vitamin and mineral
supplements might be useful in maintaining cognitive function and delaying the onset
of dementia. In this review, we sought to examine the evidence for this in people
who already had mild cognitive impairment (MCI). To evaluate the effects of vitamin
and mineral supplementation on cognitive function and the incidence of dementia in
people with mild cognitive impairment. We searched ALOIS, the Cochrane Dementia and
Cognitive Improvement Group’s (CDCIG) specialised register, as well as MEDLINE, Embase,
PsycINFO, CENTRAL, CINAHL, LILACs, Web of Science Core Collection, ClinicalTrials.gov,
and the WHO Portal/ICTRP, from inception to 25 January 2018. We included randomised
or quasi‐randomised, placebo‐controlled trials which evaluated orally administered
vitamin or mineral supplements in participants with a diagnosis of mild cognitive
impairment and which assessed the incidence of dementia or cognitive outcomes, or
both. We were interested in studies applicable to the general population of older
people and therefore excluded studies in which participants had severe vitamin or
mineral deficiencies. We sought data on our primary outcomes of dementia incidence
and overall cognitive function and on secondary outcomes of episodic memory, executive
function, speed of processing, quality of life, functional performance, clinical global
impression, adverse events, and mortality. We conducted data collection and analysis
according to standard Cochrane systematic review methods. We assessed the risk of
bias of included studies using the Cochrane 'Risk of bias' assessment tool. We grouped
vitamins and minerals according to their putative mechanism of action and, where we
considered it to be clinically appropriate, we pooled data using random‐effects methods.
We used GRADE methods to assess the overall quality of evidence for each comparison
and outcome. We included five trials with 879 participants which investigated B vitamin
supplements. In four trials, the intervention was a combination of vitamins B6, B12,
and folic acid; in one, it was folic acid only. Doses varied. We considered there
to be some risks of performance and attrition bias and of selective outcome reporting
among these trials. Our primary efficacy outcomes were the incidence of dementia and
scores on measures of overall cognitive function. None of the trials reported the
incidence of dementia and the evidence on overall cognitive function was of very low‐quality.
There was probably little or no effect of B vitamins taken for six to 24 months on
episodic memory, executive function, speed of processing, or quality of life. The
evidence on our other secondary clinical outcomes, including harms, was very sparse
or very low‐quality. There was evidence from one study that there may be a slower
rate of brain atrophy over two years in participants taking B vitamins. The same study
reported subgroup analyses based on the level of serum homocysteine (tHcy) at baseline
and found evidence that B vitamins may improve episodic memory in those with tHcy
above the median at baseline. We included one trial (n = 516) of vitamin E supplementation.
Vitamin E was given as 1000 IU of alpha‐tocopherol twice daily. We considered this
trial to be at risk of attrition and selective reporting bias. There was probably
no effect of vitamin E on the probability of progression from MCI to Alzheimer's dementia
over three years (HR 1.02; 95% CI 0.74 to 1.41; n = 516; 1 study, moderate‐quality
evidence). There was also no evidence of an effect at intermediate time points. The
available data did not allow us to conduct analyses, but the authors reported no significant
effect of three years of supplementation with vitamin E on overall cognitive function,
episodic memory, speed of processing, clinical global impression, functional performance,
adverse events, or mortality (five deaths in each group). We considered this to be
low‐quality evidence. We included one trial (n = 256) of combined vitamin E and vitamin
C supplementation and one trial (n = 26) of supplementation with chromium picolinate.
In both cases, there was a single eligible cognitive outcome, but we considered the
evidence to be very low‐quality and so could not be sure of any effects. The evidence
on vitamin and mineral supplements as treatments for MCI is very limited. Three years
of treatment with high‐dose vitamin E probably does not reduce the risk of progression
to dementia, but we have no data on this outcome for other supplements. Only B vitamins
have been assessed in more than one RCT. There is no evidence for beneficial effects
on cognition of supplementation with B vitamins for six to 24 months. Evidence from
a single study of a reduced rate of brain atrophy in participants taking vitamin B
and a beneficial effect of vitamin B on episodic memory in those with higher tHcy
at baseline warrants attempted replication. Review question This review investigated
whether people with mild cognitive impairment can reduce their risk of developing
dementia, or can prevent their memory or other thinking skills from deteriorating
further, by taking vitamin or mineral supplements. Background Slight changes in memory
and thinking skills are common as people get older. When these changes are worse than
can be expected in normal ageing, but are not bad enough to make a person's usual
activities difficult to manage, then the person is said to have mild cognitive impairment
(MCI). People with MCI are at increased risk of developing dementia in the future.
Vitamins and minerals are naturally occurring substances which are needed in the diet
to maintain health. They have lots of different functions in the body and many are
essential to keep the brain working properly. It has been suggested that supplementing
a person's normal diet with extra doses of these vitamins or minerals might help to
maintain thinking skills or prevent dementia. Study characteristics We found eight
randomised controlled trials (RCTs), which investigated four different types of vitamin
or mineral pills by comparing them to a placebo (a dummy pill). The vitamins tested
were B vitamins (vitamin B6, vitamin B12 and folic acid), vitamin E, and vitamin E
and C given together. The only mineral tested was chromium. Key results and quality
of the evidence Vitamin B combination versus placebo Five trials with a total of 879
participants compared B vitamins with placebo. Four used combinations of vitamin B6,
vitamin B12, and folic acid; one small study tested folic acid on its own. None of
these studies reported whether or not participants developed dementia. These studies
did not find that memory or thinking skills differed between the group of people who
took vitamin B supplements and those who took placebo after treatment lasting six
months to two years. Our confidence in the results on different tests used in the
studies varied from moderate to very low. Two years of vitamin B supplements did seem
to help memory in a small subgroup of participants in one study who could be identified
by a particular blood test at the start of the trial. One study found that there was
probably no effect on participants' quality of life. One study scanned the brains
of some participants and reported that B vitamins may slow the rate of brain shrinkage.
Harmful effects and deaths were reported in very few participants and we cannot conclude
whether or not there are harms from taking these or similar combinations of B vitamins.
Vitamin E versus placebo. One study with 516 participants compared a relatively high
dose of vitamin E (2000 IU a day) to placebo in people who were also taking a multivitamin
containing 15 IU of vitamin E (the daily requirement for vitamin E is approximately
30 IU). The risk of developing dementia due to Alzheimer’s disease (the commonest
form of dementia) is probably not affected by three years of treatment with high‐dose
vitamin E. The quality of the evidence for other outcomes was lower, but there may
also be no effect of this dose of vitamin E on specific memory or thinking skills
or on how well people could manage their daily activities. Vitamin E and C versus
placebo One study with 256 participants compared a combination of vitamins C and E
with placebo. It found no effect on overall memory and thinking skills, but we had
little confidence in this result because of the quality of the evidence. Chromium
picolinate versus placebo Only one very small study with 26 participants investigated
the effect of chromium supplements. This study was too small for us to be able to
draw any conclusions. Conclusions The amount and quality of research evidence about
vitamin and mineral supplements for treating MCI in people without nutritional deficiency
is limited. At the moment, it is not possible to identify any supplements which can
reduce the risk of people with MCI developing dementia or which can effectively treat
their symptoms. More research is needed before we can answer our review question.