The current study demonstrates that 33 days supplementation with a B complex, vitamin C and minerals product (Berocca®) benefited healthy males in terms of significantly improved ratings of general mental health (GHQ-12), reduced subjective stress (PSS) and increased ratings of ‘vigour’ (POMS), with a strong trend towards an overall improvement in mood as assessed by the POMS. Task performance, in terms of the number of correct Serial 3s subtractions throughout the six repetitions of the CDB tasks, and Serial 7s during the first repetition, was also improved. This was accompanied by reduced ratings of ‘mental tiredness’ during CDB task performance and a trend towards reduced ‘mental fatigue’. The analysis omitting ‘fruit and vegetable’ consumption as a covariate showed a similar pattern, albeit with slightly weaker results on the GHQ-12 and POMS measures (see Tables , and ). Prior to treatment, there were no significant differences between the placebo and multi-vitamin/minerals groups in performance or ratings for any of the study outcomes.
The results presented here with regards the general mental health and mood questionnaires directly confirm previous findings in cohorts of healthy adults administered the same or similar supplement. Specifically, Schlebusch et al. (2000
) found that 28 days supplementation led to decreased anxiety, improved well-being and decreased stress in both men and women and Carroll et al. (2000
) found that the same period of administration led, amongst other effects, to lower GHQ scores and decreased ratings of stress as assessed by the PSS in a sample of males. The results are also broadly in line with those seen following supplementation with multiple vitamins for a longer time period (12 months) by Benton et al. (1995a
), with the exception that significant benefits to mood were seen only in the females within their sample of 129 healthy adults. However, it may be relevant that in this previous study only vitamins were administered, but at very high doses, and the sample employed was somewhat smaller than the current study.
The benefits to task performance were largely restricted here to an increase in correct subtractions across repetitions on the Serial 3s task following vitamins/minerals, with a similar effect seen only on the very first repetition of the Serial 7s task. This differential treatment related enhancement of the two tasks has been seen previously (e.g., Reay et al. 2005
; Scholey et al. 2009) and has been interpreted as reflecting the differing cognitive demands of the two tasks. In the case of the easier, and therefore faster, Serial 3s task, successful completion requires resources in terms of psychomotor function, attention, working memory and modest amounts of executive function. However, the Serial 7s task is subjectively more difficult, has little reliance on psychomotor speed (as response rates are approximately halved), requires a similar amount of working memory but entails the recruitment of much greater attentional and executive resources. It is interesting to note that the improvements in mental arithmetic tasks that require attentional and executive resources are broadly in line with improved performance seen in adult females on two executive tasks (mental arithmetic and Stroop) within a multi-tasking battery following 9 weeks supplementation with multi-vitamins/minerals (Haskell et al. under review).
Overall, the underlying rationale for the choice of cognitive tasks employed in the study was that both the high cognitive demands of performing the difficult CDB battery tasks for 60 min and the general declines in executive task performance and increased mental fatigue that can be observed following extended cognitive task performance in the laboratory (Kato et al. 2009
; Lorist et al. 2009
) would provide a more sensitive paradigm for detecting treatment related effects. Whilst the improved performance on the Serial 3s task suggested that this may have been the case for the CDB portion of the assessment, there were no treatment related improvements seen during either the Stroop task or in performance of the two executive function tasks at the end of the assessment.
Recent Food Standards Agency surveys of the UK population show that small percentages of this and all other age/gender groups suffer biochemical deficiencies with regards each of the vitamins administered in the current study (Ruston et al. 2004
), with a bias towards poorer micronutrient status in lower socio-economic status groups (Nelson et al. 2007
). The sample employed here were healthy males in full-time employment. Evidence also suggests that those who participate in research tend to be better educated and more affluent than those who do not participate in research (Stopponi et al. 2009
). Whilst no reference was made to any nutritional parameter as an inclusion factor and no direct analyte data was collected, the assumption was made here that the sample enjoyed typical nutritional status. However, the very fact of being able to improve mood, ratings of mental health and vigour and aspects of task performance by simple supplementation with B vitamins, Vitamin C and minerals indicates that the cohort must have been suffering from less than optimal micronutrient status at the outset. However, it is important to note that the pre-treatment scores and ratings on all of the measures employed in the study were equivalent between groups, suggesting that the results are not predicated on any pre-treatment differences in nutritional status between groups. Given that physiological levels of vitamin analytes were not established for practical reasons, the adequacy of the nutritional status of the cohort and whether the results seen here represent alleviation of deficiencies as currently defined or whether the current definitions of deficiency leave further room for functional improvement is something of a moot point. Overall, these results suggest that improving nutritional status, by supplementation if necessary, may be beneficial to males within the general population as a whole.
Interestingly, a recent study undertaken in a similar, unselected (on a nutritional basis) cohort of females who were administered a wider range of vitamins and minerals for 9 weeks demonstrated improved multi-tasking and reduced tiredness (Haskell et al. under review). In that study a sub-section of participants also volunteered to give blood samples and significant reductions in the blood levels of homocysteine were seen following supplementation in comparison to the placebo group. Whilst the relevance and causal effect of increased homocysteine levels with regards decrements in brain function have yet to be fully delineated (Elias et al. 2006
), the changes seen in this potentially important physiological parameter also suggest less than optimal micronutrient status in a similar cohort of females.
Naturally, given the multiple components of the supplement administered here it is not possible to identify the specific component(s) or physiological mechanism(s) underlying the beneficial effects. Whilst, a reduction in homocysteine is plausible, the B vitamins also contribute to the integrity and synthesis of monoamine and catecholamine neurotransmitters, DNA, proteins, and phospholipids via their roles in decarboxylation and methylation processes (Mattson and Shea 2003
). Vitamin C is the brain’s most prevalent antioxidant and is found at its greatest concentrations in neuron rich areas. Its one-electron donor properties also make it an essential co-factor in a plethora of neural maturation, neuroprotection and neurotransmission processes relevant to brain function including as a modulator of cholinergic, GABAergic, dopaminergic and glutamatergic activity (Harrison and May 2009
). Vitamin C was also included here at a dose (500 mg) that approximates to the intake necessary to fully saturate plasma and circulating cells in healthy adults (Levine et al. 2001
) but which is far in excess of the recommended daily allowance of 60 mg (which is based on the levels necessary to prevent deficiency diseases).
Similarly the minerals zinc, magnesium and calcium have been highlighted as those most relevant to cognitive performance (Huskisson et al. 2007
). Numerous nerve processes depend on calcium (Gareri et al. 1995
) and it is a universal messenger of extracellular signals in a number of cells (Rasmussen 1986a
). Magnesium plays an important role in a variety of metabolic reactions, particularly energy-requiring processes (Ryan 1991
), and has been implicated in ensuring capacity for increased energy expenditure (Lukaski 2000
). Zinc is essential to the structure and function of proteins and is highly concentrated in synaptic vesicles of a sub-set of glutamatergic neurons, which are particularly prevalent in the fore-brain (Frederickson et al. 2000
). Neuropsychological impairment has also been highlighted as one of the major health consequences of zinc deficiency (Sandstead 2000
The lack of data confirming pre-treatment dietary habits and circulating levels of the relevant vitamins/minerals is a limitation of the study and reduces the range of interpretations of the results. However, it is important to note that the two treatment groups did not differ in terms of cognitive task performance or their ratings on the various psychometric instruments employed in the study before treatment commenced, and given the randomised methodology and sample size, it seems reasonable to attribute the benefits seen across a number of measures in the multi-vitamin/mineral group to the treatment administered. Interestingly the groups did differ significantly on their self-reported consumption of fruit and vegetables (as per current definitions of ‘portions’). However, this reflected greater consumption in the vitamins/minerals group. If this factor had any significant impact on the results, it might be conceived as reducing the liability of finding a positive result. The fact that including fruit/vegetable consumption as a second covariate marginally strengthens the results on two of the psychometric questionnaire measures, but does not modify the general tenor of the results, suggests that this factor may have a slight influence on the results seen here. However, it should be noted that there was no interpretable statistical relationship between this factor and scores on any measures pre-treatment across groups.
A further potential limitation of this study is that the consumption of vitamin B2 at the levels administered here can lead to discolouration of urine due to excretion of any excess. This could potentially have led to loss of blind in the current study. However, all participants (both those in the placebo group and the multi-vitamin/mineral group) were informed that ingestion of the investigational substance could lead to a slight yellowish discolouration of urine and that this was harmless. No information was given that might indicate that this phenomena would be linked solely to the active treatment. Participants were also instructed to record and report any health observations/changes throughout the study period, and from a total of 210 participants, only 19 reported discolouration of urine, with four of these in the placebo group (Chi-square, non-significant). This is in keeping with previous findings (Carroll et al. 2000
) and suggests that the participants remained blind to treatment condition throughout the trial.
In general, few studies have assessed the cognitive performance effects of vitamins/minerals in healthy, non-elderly cohorts. Whilst the merits of investigating focussed interventions in populations at risk of disease or age-related decrements in nutritional status and physiological parameters are obvious, a good case can also be made for conducting research with multiple micronutrients delivered in the combinations that healthy end consumers are likely to purchase in their everyday lives. Taken together with previous results showing beneficial effects of vitamin/mineral supplementation in healthy children (for reviews see Benton 2001
; Eilander et al. 2010
) and adults (Benton et al. 1995b
; Carroll et al. 2000
; Schlebusch et al. 2000
), these findings further suggest that augmenting vitamin/mineral levels in healthy, normal populations may provide beneficial effects in terms of brain function. It is unclear whether these effects represent a an offset of impairment due to marginal deficiencies or an improvement due to sub-optimal levels that would not, under current guidelines, be classed as deficiency. However, given that a large section of the population are unable or unwilling to eat the adequately balanced diet that would satisfy their micronutrient requirements (Scientifc Advisory Committee on Nutrition 2008
), it seems that supplementation with multi-vitamins/minerals may be a useful and possibly necessary option for this portion of the population.