Effects of Vitamin D Supplementation on Cognitive and
Emotional Functioning in Young Adults – A Randomised
Angela J. Dean1*, Mark A. Bellgrove1, Teresa Hall1, Wei Ming Jonathan Phan1, Darryl W. Eyles1,2, David
Kvaskoff1, John J. McGrath1,2,3
1Queensland Brain Institute, The University of Queensland, St Lucia, Australia, 2Queensland Centre for Mental Health Research, The Park Centre for Mental Health,
Richlands, Australia, 3Department of Psychiatry, School of Medicine, The University of Queensland, St Lucia, Australia
Background: Epidemiological research links vitamin D status to various brain-related outcomes. However, few trials
examine whether supplementation can improve such outcomes and none have examined effects on cognition. This study
examined whether Vitamin D supplementation led to improvements in diverse measures of cognitive and emotional
functioning, and hypothesised that supplementation would lead to improvements in these outcomes compared to placebo.
Methods/Principal Findings: Healthy young adults were recruited to a parallel-arm, double-blind trial conducted at The
University of Queensland. Participants were randomly allocated to receive Vitamin D (one capsule daily, containing 5000 IU
cholecalciferol) or identical placebo capsule for six weeks. All participants and outcome assessors were blinded to group
assignment. Primary outcome measures assessed at baseline and 6 weeks were working memory, response inhibition and
cognitive flexibility. Secondary outcomes were: hallucination-proneness, psychotic-like experiences, and ratings of
depression, anxiety and anger. 128 participants were recruited, randomised and included in primary analyses (vitamin D
n=63; placebo n=65). Despite significant increases in vitamin D status in the active group, no significant changes were
observed in working memory (F=1.09; p=0.30), response inhibition (F=0.82; p=0.37), cognitive flexibility (F=1.37;
p=0.24) or secondary outcomes. No serious adverse effects were reported.
Conclusions: Our findings indicate that vitamin D supplementation does not influence cognitive or emotional functioning
in healthy young adults. Future controlled trials in targeted populations of interest are required to determine whether
supplementation can improve functioning in these domains. Australian and New Zealand Clinical Trials Registry;
Citation: Dean AJ, Bellgrove MA, Hall T, Phan WMJ, Eyles DW, et al. (2011) Effects of Vitamin D Supplementation on Cognitive and Emotional Functioning in
Young Adults – A Randomised Controlled Trial. PLoS ONE 6(11): e25966. doi:10.1371/journal.pone.0025966
Editor: Kenji Hashimoto, Chiba University Center for Forensic Mental Health, Japan
Received August 9, 2011; Accepted September 14, 2011; Published November 4, 2011
Copyright: ? 2011 Dean et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: Funding was provided by Queensland Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation
of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: firstname.lastname@example.org
Vitamin D is a nuclear steroid hormone with diverse
physiological roles. In addition to its well-established role in
calcium homeostasis, vitamin D is being reconsidered as a
neuroactive steroid [1,2,3]: the distribution of the vitamin D
receptor in the human brain has been characterised ; the
enzyme responsible for synthesis of the active form of vitamin D is
present in the brain ; and animal research indicates that vitamin
D is important for brain development .
Epidemiological studies link vitamin D status to a range of
brain-related outcomes. Low concentrations of vitamin D have
been associated with impairments in cognitive functions such as
memory and orientation [6,7,8], executive function impairments
[9,10], and diagnosis of dementia and Alzheimer’s disease .
Increased dietary intake of vitamin D has been associated with
lower rates of self-reported psychotic-like experiences , and
vitamin D status at birth or in early life is associated with reduced
risk of schizophrenia in later life [13,14]. Many studies report an
association between low vitamin D status and depressive
In response to such findings, The Institute of Medicine  has
called for well-conducted, randomised controlled trials to examine
whether vitamin D supplementation can improve brain-related
outcomes. A number of trials have assessed the effects of vitamin D
on depression, but results have been conflicting [19,20]. No trials
were identified that examined the effect of vitamin D supplemen-
tation on cognition or psychotic-like experiences. To address this
gap, we conducted a randomised controlled trial to assess whether
vitamin D supplementation would lead to improvement in (i) key
cognitive functions of working memory, response inhibition and
cognitive flexibility; (ii) psychotic-like experiences and hallucina-
tion proneness; and (iii) key emotional states of depression, anxiety
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Participants were healthy volunteers recruited through adver-
tising at the University of Queensland. Inclusion criteria were at
least 18 years of age, with sufficient English language skills
required to complete the study protocol. Individuals were excluded
if they met any of the following criteria: current use of vitamin D
or calcium supplements; history of adverse reactions to vitamin
supplements; current or past diagnosis of a mood or psychotic
disorders; history of neurologic illnesses including cerebrovascular
accident, CNS tumours, head trauma, multiple sclerosis, epilepsy,
movement disorders or migraine treatment; current or recent (1
year) history of dependence on alcohol or illicit substances;
intellectual disability; pregnancy or current breast feeding, or
potential to become pregnant during the trial; history of severe
renal impairment. After telephone screening, potentially eligible
participants were invited to attend the research clinic for
assessment. After they had been provided with verbal and written
information about the study (including the patient information
sheet), eligible participants provided written informed consent. No
changes to eligibility criteria or other methods were made after
trial commencement. The trial was approved by the University of
Queensland Medical Research Ethics Committee, and pre-
registered with the Australian and New Zealand Clinical Trials
Registry (ACTRN12610000318088). The study was funded by
Queensland Health. The protocol for this trial and supporting
CONSORT checklist are available as supporting information; see
Checklist S1 and Protocol S1.
This study was a randomised controlled, parallel-arms trial,
comparing vitamin D supplementation to placebo (1:1 allocation
Participants were randomly assigned to receive either Vitamin
D (5000IU cholecalciferol) or placebo. These were provided as
identical microcellulose capsules, prepared by an external clinical
trials service. Placebo capsules contained lactose. Participants were
provided with 6 weeks of study medication, and instructed to take
one capsule daily. To optimise adherence, participants were sent
weekly reminders via email or text message.
Implementation of randomisation and blinding
Randomisation sequence was generated by the external clinical
trials site. To ensure that each treatment group was uniformly
represented over the time course of the study, a varying-block
randomisation protocol was used (randomly determined block
sizes of 4 or 6). After provision of written consent, each participant
was assigned to the next consecutive participant number by two
researchers not involved in the generating the randomisation
sequence. All investigators, outcome assessors and participants
were blinded to treatment allocation procedures and treatment
group throughout the study. After completion of the final
assessment, participants were asked to guess whether they had
received vitamin D or placebo based on their overall subjective
impression of change during the study.
The following assessments were conducted at baseline and after
6 weeks of vitamin D supplementation. The cognitive measures
were selected based on their limited capacity to generate ceiling
effects in healthy populations.
Working memory – N-back.
used computer-based test of visuospatial working memory .
Participants were presented with a screen containing a scattered
arrangement of ten squares: every 500 ms, a different square
would become shaded. Participants were required to identify
whether the position of the shaded square was the same as that
presented three screens previously (3-back). After a demon-
stration and practice block to ensure participants understood the
task, four blocks were administered, each containing 50 trials.
The dependent measure used was the proportion of correct
Response inhibition- Stop
inhibition is a specific executive function which involves
suppression of behavioural impulses and is measured using tasks
such as the Stop Signal Task . The stop-signal task requires the
cancellation of a prepotent ‘go’ response upon presentation of an
infrequent ‘stop’ signal. Stop-signal inhibition can be viewed as a
race between two competing ‘go’ and ‘stop’ processes. By
introducing a delay between the presentation of the go and any
subsequent stop signal, one can bias the outcome of the race. The
stop-signal reaction time (SSRT) was derived as the mean reaction
time to go-stimuli minus the stop signal delay for the 50%
inhibition threshold . A lower (i.e. faster) SSRT is indicative of
better inhibitory control. In this study, there was a 64-trial practice
block, followed by four 128-trial blocks with a break scheduled in
between each block.
Cognitive flexibility- Set
computer-based measure that requires alternating between
responses to different categories of stimuli . Participants
were presented with coloured shapes and required to identify
either the colour or shape depending on an alternating response
cue. This task comprised four blocks of 48 trials. The dependent
measure was the switch-cost reaction time, calculated as difference
in reaction time between shift trials (where the response cue was
the opposite of the previous trial) and non-shift trials (where the
response cue was the same as the previous trial). A lower switch-
cost represents better cognitive flexibility.
21 (PDI-21) is a 21-item self-report measure of delusional-like
experiences . Items were statements of experiences that
illustrate misattribution of emotions in everyday situations. One
such item was ‘Do you ever feel as if things in magazines or on TV
were written especially for you?’ Participants received a total score
out of 21, with higher scores indicating greater proneness to
presenting participants with one of three types of auditory stimuli
via headphones: (a) white noise only; (b) white noise and audible
speech of neutral content; and (c) white noise and barely audible
speech of neutral content. Twenty-five fragments of each group
were presented in random order. Participants were asked to
indicate whether they had heard a voice or not. The primary
outcome for analysis was the number of times participants
indicated hearing a voice in the white noise only condition. This
measure of speech illusion is thought to indicate proneness to
psychosis, and higher scores have been associated with schizotypy
compared to controls .
The Beck Depression Inventory
(BDI) is a 21-item self-report questionnaire with item scores
ranging from 0 to 3 and a total score ranging from 0 to 63. It has
been verified as a reliable and valid screening instrument to detect
intensity of depression in a variety of populations and has also
been employed to measure treatment response when used in a pre-
and post-test design .
The N-Back task is a widely
This is a
The Peters Delusion Inventory-
The white noise task involves
Can Vitamin D Improve Cognitive Function?
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40-item self-report questionnaire used to measure both current
anxiety (state) (20 items) and anxiety as a more enduring stable
personality characteristic (trait) (20 items). In this study we utilised
the State Anxiety subscale .
The State-Trait Anger Expression Inventory
(STAXI-2) is a 57-item self report questionnaire which measures
the experience, expression and control of anger. In this study, the
key outcome was the State Anger subscale .
The Treatment Emergent Symptom Scale
isa 31-item self-report questionnaire
psychopharmacology trials . A total score was utilised to
assess a range of potential adverse effects. Participants were also
invited to spontaneously report any other potential symptoms
occurring during the study.
The State-Trait Anxiety Inventory (STAI) is a
Quantification of vitamin D status
Blood samples were collected as finger prick capillary whole
blood spots. These were collected at baseline and at the 6-week
follow-up using a single-use, automated lancet device. Vitamin D
status is internationally quantified as 25-hydroxyvitamin D3
(25OHD3). 25OHD was extracted from the dried blood spots,
and assayed using a highly sensitive tandem mass spectroscopy
assay optimised for these samples . Results are reported as sera
concentrations after correction for peripheral haematocrit .
Sample size calculation
For the primary two-group comparisons, a sample size of
approximately 128 will have a power of 80% to detect a small-
medium effect size (equivalent to d=0.4). This is based on two
occasions of response, a moderate within-subject correlation of
0.5, and a two-sided significance level of 5%.
Treatment outcomes were analysed using mixed-effects model-
ling. A mixed effects model was created for each outcome variable.
Primary analysis examined the effect of treatment allocation group
(vitamin D versus placebo) on treatment outcome, with time and
treatment group entered as fixed effects. The adequacy of each
model was assessed by examining residuals for heterogeneity and
normality. Primary analysis included all randomised participants
(i)The effect of change in vitamin D concentrations on treatment
outcome. Two groups were determined based on the mean
change in concentrations of 25OHD3; change in vitamin D
group and time were entered as fixed factors in mixed models.
(ii) The effect of change in vitamin D concentrations on
treatment outcome, in the subset of individuals who had
lower serum concentrations of 25OHD3 at baseline. Vitamin
D deficiency is often defined by serum concentrations of
25OHD3 less than 50 nmol/L. However, results indicated
that too few participants met this criterion. As such, for this
analysis, participants were classified post hoc as having low
baseline serum 25OHD3 concentrations if they scored below
the median value. Within this subgroup, secondary analysis
(i) was repeated.
Recruitment and participant flow
Trial recruitment began in February 2010 and was follow-up
was completed in September 2010 after successful recruitment of
the target sample size. One hundred and thirty nine individuals
contacted the recruitment team and were screened for eligibility.
Eight individuals declined to participate (not available for the
follow-up session), and three were excluded (one had an acquired
brain injury and two were taking psychotropic medication). This
left 128 eligible participants who consented to participate. Sixty-
three were randomly allocated to vitamin D capsules, and 65 were
allocated to placebo capsules. Only one participant was lost to
follow-up. All participants were included in analysis of primary
outcomes. Participant screening and flow is described in Fig. 1.
Participant characteristics at baseline
The mean age of participants was 21.8 years (s.d.=2.9; Range
18–30), and more than half were female (57%; 73/128). Table 1
describes participant characteristics at baseline for all key
demographic and outcome variables. Participants allocated to
placebo exhibited higher scores on the PDI compared to those
allocated to vitamin D (t=2.02; p,0.05). No other differences
were observed between participant groups.
Vitamin D status
In all participants, mean concentrations of 25OHD3 at baseline
were 76.6 nmol/L (SD 19.9; Range 41.1–149.3 nmol/L; median
75.0 nmol/L). Only ten participants had baseline concentrations
lower than 50 nmol/L, the cut-off typically used for insufficiency
There was a significant difference between treatment groups
with regard to changes in vitamin D status over time (F=21.44;
p,0.001; d=0.83). Participants allocated to vitamin D exhibited
an increase over time (from a mean of 76.2 nmol/L at baseline to
98.0 nmol/L) whereas those allocated to placebo did not (baseline
77.20 nmol/L; follow-up 75.37 nmol/L) (Table 2).
The following cut-offs were used for secondary analysis: (i) the
mean change in 25OHD3 concentrations was 10.04 nmol/L and
outcomes were compared between those scoring above this and
those scoring below; (ii) the median baseline concentration of
25OHD3 was 75.0 nmol/L and the effects of supplementation
was examined in the sub-group of participants scoring below this
Primary analysis demonstrated that vitamin D supplementation
was associated with no change on any of the outcome measures.
For example, working memory (as measured by number of correct
hits on the N-back task) exhibited an improvement over time in all
participants (F=16.31; p,0.001) but no significant difference
between groups over time (F=1.09; p=0.30). Similar results were
observed with all other measures, with no significant differences
over time between participants receiving vitamin D and those
receiving placebo for response inhibition (F=0.82; p=0.37),
cognitive flexibility (F=1.37; p=0.24), hallucination proneness
(F=0.02; p=0.88), delusions (F=1.01; p=0.32), depressive
symptoms (F=0.44; p=0.51), state anxiety (F=1.44; p=0.23),
and state anger (F=1.30; p=0.26). Results for all treatment 6
time analyses are provided in Table 2.
Secondary analysis examining the effect of change in vitamin D
concentrations on treatment outcome in (a) all participants, and (b)
participants with low serum concentrations of 25OHD3 at
baseline (,75.00 nmol/L) reported similar findings. No differenc-
es between participants exhibiting higher than average change in
25OHD3 concentrations over time and remaining participants
were observed on any outcome measure (data not shown).
Vitamin D was well tolerated. There was one report of transient
rectal bleeding from one participant receiving placebo. No other
Can Vitamin D Improve Cognitive Function?
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Figure 1. Flow chart of trial participation.
Table 1. Comparison of baseline characteristics between participants allocated to Vitamin D and placebo (continuous variables
are expressed as mean (standard deviation); categorical variables are expressed as a proportion).
Vitamin D Placebo
Age (years)21.45 (2.96) 22.06 (2.74)t=1.21
Gender (% female) 61.9% (39/63)52.3% (34/65)
Ethnicity European 41.9% (26/62)European 33.8% (22/65)
Asian 45.2% (28/62) Asian 55.4% (36/65)
Other 12.9% (8/62) Other 10.8% (7/65)
Outdoor time (hours/week)16.95 (4.19)16.46 (5.44) t=20.57
25OHD3 (nmol/L)76.25 (19.63)77.23 (20.95)t=0.26
Working memory (Correct hits)0.57 (0.18)0.55 (0.20)t=20.61
Response inhibition (SSRT)210.42 (40.77)207.15 (39.22)t=20.45
Cognitive flexibility (ms)246.34 (166.29)256.93 (185.25)t=0.34
PDI total score6.11 (3.05)7.45 (4.33)t=2.02*
White noise task (count)0.29 (0.73)0.31 (0.81) t=0.20
BDI 7.24 (7.82)5.72 (5.56) t=21.27
State anxiety36.29 (10.10) 34.15 (8.31)t=21.31
State anger 16.41 (3.95)16.26 (3.76)t=2.22
Can Vitamin D Improve Cognitive Function?
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adverse effects were reported during the trial. There were no
differences between vitamin D and placebo groups on total score
on the Treatment Emergent Symptom Scale (t=21.13; p=0.26).
There was no difference in participant perceptions of their
treatment allocation, with the majority believing they received
placebo: 73.8% (45/61) of participants receiving vitamin D and
76.6% (49/64) of those receiving placebo believed they received
placebo (x2=0.13; p=0.84).
This trial was the first study, to our knowledge, specifically
designed to assess the effects of vitamin D supplementation on key
measures of cognitive and emotional functioning. Our findings
indicate that vitamin D supplementation or increasing serum
concentrations of 25OHD3 had no beneficial effects on (i) core
executive functions of working memory, response inhibition or
cognitive flexibility, (ii) psychotic-like experiences and hallucina-
tion proneness, or (iii) ratings of depression, anxiety or anger. This
trial utilised an adequate dose of vitamin D, was placebo-
controlled, was adequately powered for primary analyses and
displayed high retention rates. As such, our findings appear to
represent a true non-effect of vitamin D supplementation on
cognitive and emotional functioning in healthy young adults.
These findings should be viewed in the context of an increasing
number of studies associating low vitamin D status with
impairments in mood and cognitive function and subsequent
recommendations of widespread supplementation [32,33]. The
Institute of Medicine issued a recent report on vitamin D .
This report drew attention to the fact that biological claims
linking vitamin D status to brain-related outcomes have some
biological plausibility, but observational studies related to these
outcomes have been difficult to interpret due to residual
confounding and/or reverse causality. In particular, individuals
with depression and impaired cognition are prone to reduced
outdoor activity, which in turn could lead to reduced vitamin D
status. Even if low serum vitamin D was found to be causally
contributing to cognitive and emotional impairments, it cannot
be assumed that supplementation will ameliorate the impairment.
The Institute of Medicine called for well-conducted, randomised
controlled trials to examine whether changing vitamin D status
can improve outcomes.
Our cognition findings support other studies which have
examined the relationship between vitamin D status and cognitive
functioning in young adults. For example, the NHANES study
 reported no association between vitamin D status and
neurocognitive functioning in adolescents and adults. Fewer
clinical studies have examined the relationship between vitamin
D status and psychotic-like experiences. Our findings indicate that
vitamin D supplementation is unlikely to influence psychotic-like
experiences or delusion ratings in healthy volunteers. The
relationship between vitamin D supplementation and mood is
more complex. A number of controlled trials report no effect of
vitamin D on mood [20,34]. Two double-blind controlled trials do
report some positive effects of vitamin D supplementation on
mood [19,35]. However, these studies have a number of
limitations, such as using analyses that do not incorporate the
effects of both treatment group and time , or reporting only
minor reductions on depression measures that are unlikely to be
clinically significant . As such, no well-conducted trials to date
suggest that vitamin D supplementation is associated with
clinically significant changes in mood. No previous studies have
examined the relationship between vitamin D and other emotional
states such as anger and anxiety.
Table 2. Pre and post data for vitamin D status and all outcome measures for primary analysis comparing outcomes between
participants allocated to Vitamin D and those allocated to placebo (All randomised participants were included in all analyses:
Vitamin D n=63; placebo n=65).
Vitamin D Placebo
Mean (SE) 95% CI (mean) Mean (SE) 95% CI (mean)F
25OHD3 (nmol/L)Baseline 76.2 (2.6)71.0–81.4 77.2 (2.6)72.0–82.4 21.44
Follow-up 98.0 (3.3) 91.4–104.675.4 (3.3)68.9–81.9
Working memoryBaseline 0.57 (0.02) 0.52–0.620.55 (0.02) 0.50–0.591.09 0.300.19
(N Back - Correct hits)Follow-up0.62 (0.02) 0.57–0.66 0.62 (0.02)0.58–0.67
Response inhibitionBaseline 211.13 (5.18) 200.87–221.38208.83 (5.08) 198.77–218.880.820.370.16
(Stop Signal SSRT, ms)Follow-up 195.71 (4.67) 186.45–204.96198.85 (4.59) 189.78–207.93
Cognitive flexibility Baseline246.34 (22.18)202.44–290.24 255.59 (21.96)212.12–299.051.37 0.24 0.21
(Switch cost RT, ms)Follow-up 143.91 (17.15)109.98–177.84 185.75 (16.98) 152.16–219.34
White noise task Baseline0.29 (0.10) 0.09–0.480.31 (0.10) 0.12–0.500.02 0.880.03
(Hallucination count) Follow-up 0.37 (0.16)0.05–0.68 0.35 (0.16)0.04–0.67
PDI (total)Baseline 6.11 (0.48)5.16–7.067.45 (0.47)6.51–8.38 1.01 0.320.18
Follow-up 5.58 (0.48)4.62–6.536.49 (0.48)5.56–7.43
BDI (total)Baseline7.24 (0.84) 5.58–8.905.72 (0.83)4.09–7.36 0.440.510.12
Follow-up 6.40 (0.85)4.73–8.07 5.38 (0.83)3.74–7.02
State anxietyBaseline36.29 (1.20)33.91–38.6634.15 (1.19)31.81–36.50 1.440.230.21
Follow-up36.68 (1.21) 34.28–39.0836.08 (1.19) 33.73–38.42
State angerBaseline16.41 (0.49) 15.45–17.3716.26 (0.48)15.32–17.211.300.260.20
Follow-up15.81 (0.33) 15.15–16.4716.43 (0.32) 15.79–17.07
Can Vitamin D Improve Cognitive Function?
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Our study has a number of limitations. Our sample consisted of
healthy young adults, who were free of major psychiatric illness
and cognitive impairment. As such, our findings may not
generalise to clinical populations exhibiting cognitive impairment
or emotional disorders. Further controlled trials need to be
conducted in key populations of interest, including those with
established deficiency. Existing studies have not identified a
putative ‘effective dose’ or ‘necessary threshold’ for vitamin D to
improve brain function. The dose used in this study was higher
than that used in many other studies, and thus, our negative
findings are unlikely to have resulted from inadequate doses. The
putative mechanism of action of vitamin D on the adult brain is
not established. It is unclear whether vitamin D is active only in
individuals who are deficient, or whether it also exerts specific
pharmacological effects in those with adequate concentrations of
vitamin D. Whilst our sample was adequately powered for primary
analyses and the first stage of secondary analyses, it is possible that
too few participants exhibited low baseline concentrations of
25OHD3 to conduct well-powered analysis in this potentially
important subgroup. Analyses were not adjusted for multiple
outcome analyses; however, this strengthens the likelihood that our
negative findings represent a true lack of effect in this group. It is
also feasible that low vitamin D status operates over many years,
and that brain-related outcomes are ‘long latency’ disorders .
Just as hip fracture and osteoporosis only emerge as adverse health
outcomes associated with decades of vitamin D insufficiency,
perhaps a similar latency is required for brain outcomes. There is
robust evidence from in vitro and animal studies indicating that
the active form of vitamin D has neuroprotective properties .
Thus, it is possible that chronic hypovitaminosis D could leave
individuals more vulnerable to subsequent neurobiological insults.
In conclusion, our findings indicate that vitamin D supplemen-
tation does not influence cognitive or emotional functioning in
healthy young adults. Despite promising clues from observational
studies, there are currently no clinical data that supports the use of
vitamin D supplementation as a treatment for cognitive or
emotional impairments. Although detection and treatment of
vitamin D insufficiency remains important for a range of health
outcomes (e.g. bone health), future controlled trials in targeted
populations of interest are required to elucidate the causal
contribution of vitamin D status to brain-related outcomes and
determine whether supplementation can improve functioning in
Conceived and designed the experiments: AJD MAB DWE DK JJM.
Performed the experiments: DK TH WMJP. Analyzed the data: AJD TH
WMJP JJM. Contributed reagents/materials/analysis tools: MAB DWE
DK JJM. Wrote the paper: AJD MAB DWE DK TH WMJP JJM.
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