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. 2015 Apr 24;37(3):38. doi: 10.1007/s11357-015-9782-0

Acute mood but not cognitive improvements following administration of a single multivitamin and mineral supplement in healthy women aged 50 and above: a randomised controlled trial

H Macpherson 1,2,✉, R Rowsell 1, K H M Cox 1, A Scholey 1, A Pipingas 1
PMCID: PMC4408300  PMID: 25903286

Abstract

A number of randomised controlled trials have indicated that multivitamin/mineral supplementation for a period of 4 weeks or greater can enhance mood and cognition. To date, no studies have investigated whether a single multivitamin dose can benefit mental function in older adults. This study investigated the acute effects of a single multivitamin and mineral and herbal (MVMH) supplement versus placebo on self ratings of mood and the performance of an effortful computerised cognitive battery in a sample of 76 healthy women aged 50–75 years. Mood was assessed using the depression anxiety stress scale (DASS), state trait anxiety inventory–state anxiety scale and visual analogue scales (VAS). Mood was rated at 1 h post supplementation and again after the competition of the cognitive assessments at 2 h post supplementation. It was demonstrated that the MVMH supplement improved overall DASS mood ratings; however, the most prominent effects appeared to be a reduction in ratings of perceived mental stress. These findings were confirmed using visual analogue scales, with these measures also demonstrating MVMH-related increased ratings of calmness. There were no benefits of the MVMH to mood ratings of depression and performance was not enhanced on the cognitive battery. Supplementation with a single multivitamin, mineral and herbal supplement reduces stress several hours after intake in healthy older people.

Keywords: Multivitamin, Multivitamin/mineral, Mood, Cognition, Stress, Elderly

Introduction

A growing literature has indicated that chronic multivitamin supplementation can benefit cognition (Grima et al. 2012) and mood (Long and Benton 2013). Randomised controlled trials have demonstrated that supplementation with multivitamins containing minerals and herbs, over a period of 2 to 4 months, can enhance various domains of memory in those over the age of 50 (Harris et al. 2012; Macpherson et al. 2012; Summers et al. 2010). In men aged 50–69 years, 8-weeks multivitamin/mineral and herbal (MVMH) supplementation has been shown to reduce symptoms of mood disorder, problems with day-to-day functioning and increase positive mood experience (Harris et al. 2011). Findings of elevated positive mood associated with chronic multivitamin use has been confirmed in a recent meta-analysis (Long and Benton 2013) which revealed that across eight studies of non-clinical samples, multivitamin supplements improved mild psychiatric symptoms and facets of mood including stress and subclinical anxiety.

Whilst behavioural effects of multivitamins have been generally observed in studies greater than a 4-week duration (Grima et al. 2012), very few investigations have focussed on the possibility that multivitamin supplements may influence cognition after a single dose. The first of these studies identified improvements to memory and attention, but not mood, in children aged 8 to 14 years, 3 h after the administration of a single multivitamin (Haskell et al. 2008). A more recent study, conducted in healthy adults aged 21–39 years, utilised brain imaging techniques to investigate the acute effects of multivitamins on neurocognitive function (White et al. 2014). Results from this trial revealed that a single multivitamin, 90 min post dose, increased activation in task-relevant, prefrontal brain regions during the completion of a continuous performance attention task. These findings provide evidence that multivitamins can exert effects on the central nervous system within several hours of ingestion.

Previously, mood benefits of an acute multivitamin dose have only been identified for supplements containing the plant extract guarana, and not for standard multivitamin preparations (Haskell et al. 2008; Kennedy et al. 2008; Scholey et al. 2013). Due to the small number of studies in this area, it is not certain whether these mood effects can be solely attributed to the caffeine content of the guarana extract. Furthermore, as these studies are limited to young adults and children, it is not known whether a single multivitamin dose would benefit cognition or mood in older people. We have previously suggested that chronic multivitamin use may be expected to exert greater effects in older people who are at great risk of nutritional deficiency and cognitive decline (Macpherson et al. 2012; Pipingas et al. 2014), but whether the same benefits would be observed following the administration of a single supplement has not been explored in older adults.

The objective of the current study was to explore the mood and cognitive profile of any acute multivitamin effects in women aged 50 to 75 years of age free from clinical mood disturbances. Secondary results from a 4-week randomised controlled trial are reported from the acute testing session 1–2 h following the administration of a single MVMH supplement or placebo. Mood measures were selected which have previously demonstrated sensitivity to multivitamin supplementation over longer time durations (Harris et al. 2011; Long and Benton 2013; Pipingas et al. 2013). Mood ratings were assessed at 1 h post dose and again at 2 h post dose after participants had completed an effortful cognitive battery.

Methods

Study design and treatment

This study adopted a double-blind, placebo-controlled, randomised design. Baseline mood was assessed prior to and after completing a cognitive battery. This procedure was repeated at 1 h post dose. The MVMH treatment was the Swisse Women’s 50+ Ultivite supplement or a placebo matched for appearance and taste. The supplement was administered orally in tablet form. The full ingredients of the Swisse Women’s 50+ Ultivite supplement are published elsewhere (Macpherson et al. 2012). In brief, the MVMH contains 14 vitamins, 11 minerals, 3 strains of probiotics and 18 herbal extracts. The Swisse Women’s 50+ Ultivite supplement contains folic acid; vitamins A, B1, B2, B5, B6, B12, C, E; and zinc at levels above the recommended daily intake (RDI). Levels of B3, D3, calcium and magnesium are below the RDI. This study was approved by the Swinburne University Human Research Ethics Committee (SUHREC) and was carried out in accordance with the Declaration of Helsinki. The trial is registered on the Australian New Zealand Clinical Trials Registry (ACTRN12613001087741).

Participants

Participants were 76 women aged 50–75 years (M = 63.6 years, SD = 6.4 years) who were not engaged in full-time employment. All participants were non-smokers, with no history of diabetes, cardiovascular disease, dementia, stroke, other neurological conditions, head trauma, alcohol abuse, clinically diagnosed anxiety, depression, and psychiatric disorders and were not currently using anti-depressant medication, anti-anxiety medication, high-dose anti-coagulants, anti-cholinergic drugs or acetylcholinesterase inhibitors. Participants were required to abstain from supplementation with vitamin E, multivitamins, B vitamin complex, ginkgo biloba, fish oil, and St John’s Wort for 4 weeks preceding the study visit.

Procedure

On the testing day, participants were requested to consume their ‘usual’ breakfast and to refrain from caffeine consumption. Participants attended the laboratory between 0900 and 1100 h. All participants signed an informed consent form and completed a medical health questionnaire prior to enrolment in the study. The mini mental state examination (MMSE) (Folstein et al. 1975) and the National Adult Reading Test-Revised (NART-R) (Nelson and Willison 1991) were administered to provide an estimate of global cognitive performance and IQ, respectively. After completing baseline mood and cognitive measures, participants were randomised to receive the MVMH or placebo. Participants were provided with one supplement to take with a glass of water and a slice of wholemeal toast with a choice of two spreads. Following a delay of 1 h, mood measures were repeated followed by the cognitive battery. Mood measures were repeated a second time after the cognitive measures, corresponding 2 h post multivitamin dose. The testing procedure is illustrated in Fig. 1. The DASS and STAI-S measures were completed using pen and paper versions. The Bond-Lader and visual analogue scale (VAS) measures were completed using mobile phone devices to enable laboratory and in-home assessments (results for longer term supplementation effects and in-home assessments presented elsewhere).

Fig. 1.

Fig. 1

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Timing of tasks and treatment

Outcomes

All acute outcomes were secondary outcomes from the Behavioural Effects of Multivitamin Supplements (BEMS) study. The primary outcome was mood changes over a longer 4-week period (details of the 4-week methodology and findings presented elsewhere).

Mood ratings

Depression anxiety stress scale (Lovibond and Lovibond 1995)

The depression anxiety stress scale (DASS) is a brief questionnaire comprising 21 items which form depression, anxiety and stress subscales (Lovibond SH 1995). Responses to each item are made on a 4-point scale from 0 to 3, producing a maximal score of 63. Higher scores indicate more symptoms of dysphoric mood, whilst a score of 0 indicates the absence of disturbed mood symptoms. To facilitate the identification of acute mood changes, individuals were required to rate how they were feeling “right now”.

State trait anxiety inventory–state anxiety scale (Speilberger et al. 1969)

The state anxiety scale from the state trait anxiety inventory (STAI) consists of 20 items which assesses an individual’s current state of anxiety, asking how respondents feel “right now”. The state anxiety scale assesses intensity of current feelings of stress on a 4-point scale from 1 (not at all) to 4 (very much so). Scores range from 20 to 80 with higher scores indicating greater anxiety.

Bond-Lader visual analogue scale (Bond and Lader 1974)

The Bond-Lader mood scales require participants to mark the appropriate position on a horizontal line. The scales comprise 16 lines anchored at either end by adjective pairs, e.g. happy-sad. Participants are required to mark their current subjective state between the antonyms on the line, and each line is scored as the percentage of the total distance from the negative anchor (i.e. a higher score indicates a more positive mood state). Three subscales are calculated on the basis of scores from the 16 adjective pairs, representing the factors “alert”, “content” and “calm”.

Stress, anxiety, concentration, physical fatigue and mental fatigue visual analogue scales

Each visual analogue scale consists of a single unmarked 100-mm line with end points labelled ‘Not at all’ and ‘Very much so’. Individuals are instructed to indicate on the line how they feel at that moment in time. Each scale gives a single subjective score between 0 and 100, with lower scores indicative of more desirable mood states on the mood scales and higher energy levels on the fatigue scales. Separate scales were used to assess stress, anxiety, concentration, physical fatigue and mental fatigue.

Cognition

Swinburne University computerised cognitive assessment battery

The Swinburne University computerised cognitive assessment battery (SUCCAB) stimuli were presented via PC using the E-Prime 2.0 software (Psychology Software Tools, Pittsburgh, PA), and a hand-held button box was used to deliver all responses. Tasks from the SUCCAB have been demonstrated to be sensitive to the effects of chronic MVMH supplementation in older people (Harris et al. 2012; Macpherson et al. 2012). A practice trial was performed immediately prior to each task. An alternate task version was used for the acute 1-h post treatment time point. The following tasks were undertaken:

Simple reaction time

Speeded response to a white square.

Stroop congruent

Response to the words RED, YELLOW, GREEN and BLUE presented in the same colour as the written word.

Stroop incongruent

Response to the words RED, YELLOW, GREEN and BLUE presented in a different colour to the written word. Stroop interference score was calculated from Stroop congruent reaction time subtracted from Stroop incongruent reaction time.

Immediate and delayed recognition memory

Immediate recognition of a series of abstract patterns and delayed recognition at the end of the test battery (30-min delay).

Contextual recognition memory

Recognition of the location of pictures of everyday items presented at one of four locations on the computer screen.

Working memory

The location of six white squares in a 4 × 4 grid was memorised. Participants indicated if squares presented individually were shown in the original array.

Analysis

Baseline group differences on all measures were examined using independent group t tests. Mixed design, analysis of variance (ANOVA) models were used to examine the effects of the MVMH on mood and cognition. To determine whether mood effects were most prominent before or after completing the effortful cognitive assessments, mixed design ANOVAS were conducted for the DASS, STAI, and all VAS measures using 2 (treatment: multivitamin, placebo) × 2 (time: pre dose, post dose) × 2 (task: pre cognitive task performance, post cognitive task performance). On the identification of a significant treatment × time interaction, post hoc Bonferroni tests were used to examine the difference between baseline and post treatment measures for each group individually. A series of 2 (treatment: multivitamin, placebo) × 2 (time: baseline, post treatment) mixed design, repeated measures ANOVAs were used to examine the effects of the MVMH on the cognitive measures. Statistical significance was set at p < 0.05.

Results

Demographics and baseline performance

A total of 39 participants were allocated the multivitamin and 37 allocated placebo. Independent group t tests indicated the groups did not differ significantly in terms of age (multivitamin M = 64.4, placebo M = 62.8, p = 0.28) or MMSE score (multivitamin M = 29.3, placebo M = 29.4, p = 0.75). The multivitamin group had completed significantly greater years of education (multivitamin M = 17.0, placebo M = 15.4, p = 0.03) and had a higher NART-IQ score (multivitamin M = 119, placebo M = 116, p = 0.02). The most commonly reported medications were cardiac medications (multivitamin n = 13, placebo n = 10) and arthritis medications (multivitamin n = 3, placebo n = 4). Independent group t tests indicated there were no significant baseline differences between the multivitamin and placebo groups on any of the mood or SUCCAB outcome measures. Mean correct was over 95 % for the simple reaction time and Stroop measures indicating these tasks were performed at ceiling; therefore, only response time was examined as an outcome for these tasks. A log transformation was applied to the DASS total score, and anxiety and depression subscale scores to correct for a positive skew. Means and standard deviations for each measure are shown in Tables 1 and 2.

Table 1.

Mean and standard deviations (SD) for the mood assessments, with p values shown for the main effects of task (pre and post battery), time (pre and post dose) and time × treatment interaction

Mood measure Treatment group Number Baseline mean (SD) Post dose mean (SD) Time p Task p Interaction p
DASS
 Total (pre battery) Multivitamin 38 10.4 (12.2) 6.7 (9.9) <0.001*** 0.13 0.02*
Placebo 36 7.6 (9.9) 6.4 (8.5)
 Total (post battery) Multivitamin 38 10.1 (10.6) 6.7 (8.8)
Placebo 36 8.3 (9.9) 7.4 (10.7)
 Depression (pre battery) Multivitamin 38 2.4 (4.3) 1.6 (3.2) 0.002** 0.50 0.32
Placebo 36 1.6 (3.5) 1.2 (3.1)
 Depression (post battery) Multivitamin 38 2.0 (3.8) 1.1 (2.7)
Placebo 36 1.7 (3.5) 1.6 (4.4)
 Anxiety (pre battery) Multivitamin 38 2.1 (3.5) 1.3 (2.3) 0.02* 0.97 0.23
Placebo 36 1.5 (2.7) 1.3 (1.9)
 Anxiety (post battery) Multivitamin 38 1.8 (2.4) 1.4 (2.6)
Placebo 36 1.9 (2.9) 1.2 (2.2)
 Stress (pre battery) Multivitamin 38 5.8 (5.8) 3.8 (5.3) <0.001*** 0.06 0.01*
Placebo 36 4.4 (5.0) 3.9 (5.3)
 Stress (post battery) Multivitamin 38 6.3 (5.9) 4.2 (5.1)
Placebo 36 4.7 (5.0) 4.6 (5.5)
VAS
 Alert (pre battery) Multivitamin 37 68.1 (18.0) 68.2 (19.0) 0.14 <0.001*** 0.31
Placebo 36 72.5 (15.3) 71.5 (17.4)
 Alert (post battery) Multivitamin 37 57.7 (18.0) 56.5 (18.1)
Placebo 36 61.0 (15.6) 56.6 (15.9)
 Content (pre battery) Multivitamin 37 77.1 (17.3) 78.8 (15.1) 0.98 <0.001*** 0.11
Placebo 36 83.0 (14.5) 83.5 (16.3)
 Content (post battery) Multivitamin 37 64.9 (17.3) 66.0 (16.1)
Placebo 36 72.5 (16.4) 69.2 (15.8)
 Calm (pre battery) Multivitamin 37 66.5 (21.7) 74.3 (17.4) 0.04* <0.001*** 0.02*
Placebo 36 75.9 (17.5) 75.6 (23.3)
 Calm (post battery) Multivitamin 37 55.6 (19.1) 59.7 (19.1)
Placebo 36 63.5 (20.9) 63.2 (18.2)
 Stress (pre battery) Multivitamin 37 23.9 (24.4) 15.4 (17.9) 0.06 <0.001*** 0.008**
Placebo 36 14.3 (17.7) 15.1 (20.3)
 Stress (post battery) Multivitamin 37 43.7 (23.7) 35.9 (17.9)
Placebo 36 34.2 (23.8) 36.2 (23.6)
 Anxiety (pre battery) Multivitamin 37 18.2 (22.1) 14.1 (14.5) 0.95 <0.001*** 0.04*
Placebo 36 13.9 (19.1) 15.9 (22.3)
 Anxiety (post battery) Multivitamin 37 31.5 (22.1) 29.4 (16.0)
Placebo 36 29.4 (20.9) 33.2 (23.3)
 Concentration (pre battery) Multivitamin 37 65.7 (29.0) 59.8 (26.1) 0.19 <0.001*** 0.83
Placebo 36 63.8 (26.7) 60.8 (27.1)
 Concentration (post battery) Multivitamin 37 54.7 (25.6) 53.6 (21.2)
Placebo 36 56.9 (20.9) 54.9 (19.9)
 Mental fatigue (pre battery) Multivitamin 38 23.1 (24.0) 30.3 (24.3) 0.003** <0.001*** 0.97
Placebo 36 22.4 (22.0) 27.1 (23.6)
 Mental fatigue (post battery) Multivitamin 38 43.4 (23.7) 48.3 (20.4)
Placebo 36 41.9 (21.0) 49.1 (20.5)
 Physical fatigue (pre battery) Multivitamin 37 21.3 (23.3) 27.0 (23.4) 0.01* <0.001*** 0.35
Placebo 36 16.7 (18.9) 22.6 (20.2)
 Physical fatigue (post battery) Multivitamin 37 36.4 (22.7) 35.5 (20.7)
Placebo 36 27.7 (16.8) 32.0 (19.3)
STAI-S
 STAI (pre battery) Multivitamin 39 33.2 (10.8) 30.3 (8.0) 0.001** <0.001*** 0.24
Placebo 36 30.5 (9.0) 28.7 (9.5)
 STAI (post battery) Multivitamin 39 35.5 (11.4) 32.6 (9.4)
Placebo 36 32.6 (12.0) 31.4 (9.9)
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DASS depression anxiety stress scale, VAS visual analogue scale, STAI-S state trait anxiety inventory–state

Italic font indicates a significant time × treatment interaction; *p < 0.05 level, **p < 0.01 level, ***p < 0.001 level

Table 2.

Mean and standard deviations (SD) for the cognitive assessments, with p values shown for the main effect of time (pre and post dose) and the time × treatment interaction

SUCCAB task Treatment group Number Baseline mean (SD) Post dose mean (SD) Time p Interaction p
Simple reaction rt Multivitamin 37 320 (107) 332 (104) 0.94 0.38
Placebo 36 311 (82) 301 (35)
Stroop congruent rt Multivitamin 39 795 (114) 759 (124) <0.001*** 0.97
Placebo 37 766 (109) 731 (102)
Stroop incongruent rt Multivitamin 37 898 (131) 909 (146) 0.29 0.99
Placebo 35 877 (108) 889 (123)
Stroop interference rt Multivitamin 37 104 (69) 152 (82) <0.001*** 0.40
Placebo 34 118 (100) 149 (89)
Contextual recognition rt Multivitamin 35 1019 (97) 1022 (94) 0.39 0.58
Placebo 36 995 (106) 1013 (121)
Contextual recognition % Multivitamin 35 79.3 (14.1) 81.6 (12.1) 0.23 0.98
Placebo 35 77.1 (15.1) 79.4 (13.1)
Immediate recognition rt Multivitamin 39 1015 (111) 1014 (115) 0.04* 0.06
Placebo 35 1036 (136) 990 (112)
Immediate recognition % Multivitamin 39 71.0 (12.9) 76.7 (11.0) <0.001*** 0.71
Placebo 35 70.8 (12.1) 77.6 (12.1)
Delayed recognition rt Multivitamin 37 1017 (86) 1009 (114) 0.24 0.64
Placebo 36 1000 (88) 982 (106)
Delayed recognition % Multivitamin 37 69.4 (14.3) 73.6 (12.4) 0.01* 0.56
Placebo 36 70.5 (10.6) 73.0 (12.4)
Working memory rt Multivitamin 39 1056 (147) 1020 (154) 0.03* 0.70
Placebo 36 1029 (131) 994 (125)
Working memory % Multivitamin 39 69.8 (15.0) 72.8 (14.3) 0.01** 0.58
Placebo 37 67.3 (15.6) 72.0 (13.0)
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*p < 0.05 level, **p < 0.01 level, ***p < 0.001 level

Acute mood effects of the multivitamin

Depression anxiety stress scale

A significant time × treatment interaction for the DASS total score was identified (F (1.72) = 5.54, p = 0.02, η2 = 0.07). Post hoc Bonferroni tests indicated there was a significant reduction in DASS score for the multivitamin group only (p < 0.001). A significant time × treatment interaction for the DASS stress score was identified (F (1.72) = 6.97, p = 0.01, η2 = 0.09). Post hoc Bonferroni tests indicated there was a significant reduction in DASS score for the multivitamin group only (p < 0.001). Change from baseline DASS scores are shown in Fig. 2 to demonstrate the magnitude of these changes.

Fig. 2.

Fig. 2

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Change from baseline scores for the Depression Anxiety Stress Scale (DASS) total score and DASS stress subscale for mood ratings prior to and after performance of the effortful cognitive battery

Visual analogue scales

A significant time × treatment interaction for the Bond-Lader VAS calmness score was identified (F (1.71) = 5.37, p = 0.02, η2 = 0.07). Post hoc Bonferroni tests indicated there was a significant increase in calmness for the multivitamin group only (p = 0.003). A significant time × treatment interaction for the VAS stress score was identified (F (1.71) = 7.44, p = 0.008, η2 = 0.10). Post hoc Bonferroni tests indicated there was a significant reduction in VAS stress rating for the multivitamin group only (p = 0.001). A significant time × treatment interaction for the VAS anxiety score was identified (F (1.71) = 4.38, p = 0.04, η2 = 0.06). Post hoc Bonferroni tests indicated the reduction in VAS anxiety did not reach statistical significance for either group.

Controlling for group differences in years of education and NART-IQ did not alter the statistical significance of any mood ratings, with the exception of the VAS rating of anxiety which was diminished to a trend following adjustment for baseline differences in IQ (1.69) = 3.24, p = 0.08, η2 = 0.05. Main effects of time are shown in Table 2. There were no significant main effects of treatment identified for any mood measures.

Effects of the cognitive battery on mood ratings

As shown in Table 2, a significant main effect of task was identified for a number of VAS ratings, indicating that regardless of treatment, participants reported a reduction in alertness, contentedness, calmness, higher levels of stress, anxiety, greater mental fatigue, physical fatigue and reduced concentration after completing the cognitive battery.

Acute cognitive effects of the multivitamin

There were no significant time × treatment interactions for the cognitive measures. As shown in Table 2, performance on a number of SUCCAB measures improved significantly from baseline to post treatment, regardless of which treatment was administered. There were no other significant main effects identified for the SUCCAB measures. Controlling for group differences in years of education and NART-IQ did not alter the statistical significance of any cognitive measures.

Discussion

The results of the present study indicated that MVMH supplementation can benefit mood 1–2 h post dose. Specifically, it was found that taking a single multivitamin improved overall mood ratings on the DASS, and this effect appeared to be driven by a significant reduction in stress ratings. The MVMH was associated with decreased ratings of stress and increased ratings of calmness on the visual analogue scales. There were no benefits to aspects of mood including depression or ratings of physical and mental fatigue. In contrast to chronic studies in older people, which have shown improvements to memory (Harris et al. 2012; Macpherson et al. 2012; Summers et al. 2010), a single MVMH dose did not exert any effects on cognitive performance.

The potential for a single multivitamin dose to modulate mood and cognition has not previously been investigated in an older sample. Similar to a 4-week study in men of a comparable age range (Harris et al. 2011), the current study identified improvements on the overall DASS score following MVMH administration. In the current study, the acute mood benefits were most apparent on ratings of perceived stress, with two measures of stress and a measure of calmness and anxiety all showing an improvement following the MVMH dose. However, it must be noted that the effect of the multivitamin on anxiety was attenuated when controlling for baseline group differences in IQ. Relative to assessments taken both before and after completing the effortful cognitive assessments, the MVMH reduced DASS stress score by over 30 %. By contrast, stress reductions attributed to the placebo were in the order of 11 % and less. Interestingly, stress is the mood facet which has also been reported to show the greatest improvements following chronic multivitamin supplementation (Long and Benton 2013). Benefits to stress ratings following ≤1 month of multivitamins containing high-dose vitamin B have been observed in non-clinical samples in a number of randomised controlled trials (Carroll et al. 2000; Kennedy et al. 2010; Schlebusch et al. 2000; Stough et al. 2011), whilst lower dose B vitamin supplements have been associated with both positive (Harris et al. 2011) and negative findings (Haskell et al. 2010).

Mood benefits of chronic multivitamin supplementation have largely been attributed to folate, B6 and B12, which have important roles in neurotransmitter synthesis (serotonin, noradrenaline and dopamine) (Huskisson et al. 2007) and in the remethylation of homocysteine to SAMe (Bottiglieri 2005). For instance, B12 and folate deficiencies have been associated with higher levels of depression (Alpert et al. 2000; Baldewicz et al. 2000; Tolmunen et al. 2003). The potential of folate in the reduction of clinical mood states is well documented (Bottiglieri 2005) and may also have an effect in non-clinical populations (Malouf et al. 2003). Additionally, poorer mood has been associated with lower levels of vitamin D, zinc and selenium (Benton 2002; Levenson 2006; Wilkins et al. 2006). Thiamine and the minerals calcium, magnesium and iron have also been postulated to influence mood through a number of biological pathways (Kaplan et al. 2007).

To date, the mechanism regarding acute effects of multivitamin supplementation on mood is unexplored in the literature. It has been proposed that improved vascular endothelial function and improvements in mitochondrial function serve as a potential mechanism for acute cognitive improvements (Kennedy et al. 2008). For instance, improved vasodilation and blood flow to the brain results in the increased delivery of metabolites to active tissue, leading to improved task performance (Scholey et al. 2001). Without the measurement of blood metabolites in this study, potential mechanisms can only be speculated. Bioavailability data has demonstrated that when taken in tablet form, 1000 μg of folic acid leads to peak serum folate levels 2 h after ingestion, with levels approaching the peak even at 1 h post dose (Maki et al. 2012). A lower level of 500-μg folic acid was included in the MVMH treatment examined in the current study; however, the timeframe for mood benefits appears to be consistent with the peak folate concentration described by Maki et al. (2012).

In the current study, we examined whether any mood effects were strongest following the completion of an effortful cognitive battery, which was demonstrated to increase anxiety, stress, mental fatigue and physical fatigue, whilst reducing alertness, calmness and concentration. Acute psychological stressors, even for short durations, can induce cardiovascular, digestive and immune system changes and increase circulating levels of the hormone cortisol, due to activation of the hypothalamic-pituitary-adrenal (HPA) axis (Kemeny 2003). It has also been suggested that psychological stress impairs methylation reactions, resulting in alterations to the availability of nutrients for neurotransmitter synthesis and function (Kaplan et al. 2007). Given the MVMH contained a range of B vitamins (including vitamin B6, B12 and folate at levels equivalent to the recommended daily intake), it may have been anticipated that any stress induced by the cognitive assessments would be offset by the supplement. Instead, the results provided evidence of a general reduction to stress levels which were not indicative of protection against short-term increases to stress levels. A limitation of this study was that mood assessments were only taken 1 and 2 h post dose; therefore, it is not known how long any benefits were sustained.

It is not clear why mood, but not cognitive benefits, were observed in this study, as cognitive improvements and brain functional changes have been identified several hours after a single multivitamin dose in younger participant groups (Haskell et al. 2008; White et al. 2014). The same working memory (Macpherson et al. 2012) and episodic memory measures (Harris et al. 2012) used in the current study have previously demonstrated benefits following 2 to 4 months of MVMH supplementation, indicating the assessments used in this study were suitable to detect improvements due to multivitamin supplementation. It may be that in an older sample, who are more prone to nutritional insufficiencies (Brownie 2006), our previously reported cognitive benefits of multivitamins (Harris et al. 2012; Macpherson et al. 2012) are due to a cumulative effect of improving nutritional status over time. More studies are required across both males and females to confirm or negate this premise, particularly as the current study solely focussed on women, and cannot confirm whether males would demonstrate the same acute response following multivitamin intake. A final note of consideration is that some chronic studies which have identified mood benefits of multivitamins have not reported whether participants consumed the supplement on the day of post treatment testing (Carroll et al. 2000; Kennedy et al. 2010; Stough et al. 2011). This gives rise to the possibility that the stress reductions reported in these trials may be due to acute effects of multivitamins, if participants did not abstain from supplementation on the day of post treatment assessments. Findings from the current study suggest that mood may be elevated for several hours following multivitamin intake. Therefore, the timing of supplement intake may be an important methodological consideration when comparing results across different trials.

In summary, findings from this study indicate that there is acute mood, but not cognitive effects of multivitamin supplements. Specifically, in healthy older women, a single multivitamin, mineral and herbal dose may lead to general mood enhancements, predominantly by reducing stress levels.

Disclosures

This work was supported by funding from Swisse Wellness Pty Ltd. Swisse provided the multivitamin and placebo supplements used in this trial. Aside from input into the broad aims of the study, Swisse Wellness Pty Ltd was not involved in any other aspects of the conduct of the trial, analysis or interpretation of the trial findings. Andrew Pipingas is currently a member of the Scientific Advisory Panel for Swisse Wellness Pty Ltd. Helen Macpherson’s Postdoctoral fellowship was previously funded by Swisse Wellness Pty Ltd.

References

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