Three randomized controlled trials involving 1,011 patients found: 1) Souvenaid supplementation did not significantly improve cognition or functional ability compared to placebo based on meta-analyses. 2) One study found Souvenaid improved verbal recall in patients with very mild Alzheimer's disease. 3) No serious adverse events were reported with Souvenaid supplementation.

1. The efficacy of supplementation with the
novel medical food, Souvenaid, in patients
with Alzheimer’s disease: A systematic review
and meta-analysis of randomized clinical
trials
Igho J. Onakpoya, Carl J. Heneghan
Centre for Evidence-Based Medicine, Nuffield Department of Primary Care Health Sciences, University of
Oxford, UK
Background and rationale: Certain nutritional supplements are being marketed for the management of
Alzheimer’s disease (AD), but the evidence for their effectiveness is not established. The objective of this
review was to evaluate the evidence from randomized clinical trial (RCTs) examining the effect of
Souvenaid in patients with AD.
Methods: We conducted electronic searches in Medline, Embase, PsychINFO, CINAHL, and The Cochrane
Library. The reporting quality of the included studies was determined using the Cochrane collaboration tool
for assessing the risk of bias. Two reviewers independently determined eligibility, assessed the reporting
quality of included studies and extracted data.
Results: Three studies with a total of 1011 participants were included. All were of good reporting quality.
Meta-analyses revealed non-significant differences in cognition (ADAS-cog scores MD: 0.08, 95% CI:
−0.71 to 0.88) and function (ADCS-ADL scores MD: 0.36, 95% CI: −0.54 to 1.25) between Souvenaid
and placebo. One study showed significant increase in neuropsychological test battery composite z-score
with Souvenaid compared with placebo, and another reported significant improvement in delayed verbal
recall for a subgroup of patients with very mild AD. There was no significant effect on global clinical
function. No serious adverse events were observed.
Conclusions: The evidence from published clinical trials does not show that supplementation with Souvenaid
has beneficial effects on functional ability, behaviour, or global clinical change. Souvenaid may cause
improvements in verbal recall in patients at early stages of AD. Few RCTs examining the effect of
Souvenaid have been conducted, and they are all funded by same manufacturer. Future research should
include using unified tools to measure cognition, function, and behaviour in AD.
Keywords: Alzheimers, Nutrition, Souvenaid, Clinical Trial, Systematic Review
Introduction
Alzheimer’s disease (AD) is the most common form of
dementia, accounting for 50–60% of all cases.1
It is
characterized by an irreversible decline in global cog-
nitive function, resulting in marked impairment in
intellectual function.2
There is currently no cure for
the disease, with infection being the commonest
cause of death from its comorbidities.3
The global
prevalence of AD among ≥60 year olds varies from
5 to 7%, with a higher prevalence in South America
and lower prevalence in sub-Saharan Africa.4
The precise aetiology of AD is unclear, but a
complex interplay of genetic and environmental
factors is believed to play a role in its pathogenesis.5,6
Though data from observational studies have
suggested that some dietary components can play a
protective role against development of AD, results of
randomized clinical trials (RCTs) have been inconsist-
ent.7
Evidence for the role of nutritional intervention
in reducing the rate of cognitive decline is also incon-
clusive.8,9
One supplement purported to have ben-
eficial effects in AD is the novel medical food,
Souvenaid.
Souvenaid is a complex of omega-3 fatty acids (eico-
sapentaenoic and docosahexaenoic acids), the nucleo-
tide uridine monophosphate, phospholipids, B
Correspondence to: Igho J. Onakpoya, Centre for Evidence-Based
Medicine, Nuffield Department of Primary Care Health Sciences,
University of Oxford, New Radcliffe House, Radcliffe Observatory
Quarter, OX2 6GG Oxford, UK. Email: igho.onakpoya@phc.ox.ac.uk
© 2015 Taylor & Francis
DOI 10.1080/1028415X.2015.1110899 Nutritional Neuroscience 2015 VOL. 0 NO. 0 1

2. complex vitamins (pyridoxine, cyanocobalamin, and
folate), choline, vitamin E, and the micronutrient, sel-
enium.10
Omega-3 fatty acids, nucleotides, and choline
have been shown to increase the concentrations of
phosphatides and pre- and post-synaptic proteins,
and consequently promote the formation of synapses
between dendritic neurones.11–13
Oral supplemen-
tation with docosahexaenoic acids and uridine mono-
phosphate has been demonstrated to increase dendritic
spine density in the hippocampus of adult humans.13
The vitamin constituents of Souvenaid are thought
to act as co-factors for regeneration of methyl
groups, thereby promoting the synthesis of choline
precursors14
; and results of animal studies have
shown that the choline and phospholipid constituents
could enhance the release of neurotransmitters.15,16
The micronutrient, selenium, is thought to protect
the brain against oxidative damage,17
and low-sel-
enium status has been hypothesized to be a risk
factor for age-related cognitive decline.18
Clinical trials examining the effects of Souvenaid in
AD have been conducted, but its effectiveness in redu-
cing cognitive decline is not established as yet.
However, the investigators of a recently published
RCT involving 179 drug-naive AD subjects with
mild cognitive impairment hypothesized that
Souvenaid preserves synaptic integrity and function.19
Therefore, the objective of this review was to critically
appraise and evaluate the evidence from published
RCTs examining the effects of Souvenaid on cogni-
tion, functional abilities, and disease progression in
AD patients.
Methods
Electronic searches were conducted in the following
databases: Medline, Embase, PsychINFO, CINAHL,
and the Cochrane Library. Each database was
searched from inception up till May, 2015. Search
terms used included dementia, Alzheimers dementia,
AD, Souvenaid, fortasyn, cognitive function, cognitive
impairment, and derivatives of these (see Appendix 1,
Supplementary material for an Embase search strat-
egy). No age, language, or time restrictions were
imposed. We also searched Google Scholar for rel-
evant Internet proceedings, and hand searched the bib-
liography of retrieved articles. Where necessary, we
contacted authors of published clinical trials for
additional data.
Only double-blinded, placebo-controlled RCTs
were considered for inclusion. To be included in the
review, RCTs had to test the efficacy of orally adminis-
tered Souvenaid on cognitive function in patients with
mild, moderate, or severe AD. Included RCTs also
had to report cognitive function as an outcome.
Studies were included irrespective of duration of inter-
vention and/or lifestyle adjustments. RCTs where
Souvenaid was combined with other types of nutri-
tional therapy or those examining the effects of
Souvenaid in non-AD dementia patients were
excluded from the review. Our primary outcome was
cognition. Secondary outcomes were functional
ability and behaviour, clinical global change, and
adverse events.
The reporting quality of the included studies was
assessed using the Cochrane collaboration the risk of
bias criteria,20
which examines the following
domains: sequence generation; allocation conceal-
ment; blinding of care-providers and participants
(including care-givers); blinding of outcome assessors;
incomplete outcome data; selective reporting; and
other biases. Two reviewers (I.J.O. and C.J.H.) inde-
pendently determined the eligibility of studies for
inclusion, assessed the risk of bias in included
studies, and extracted data according to study design
and location, patients’ characteristics, outcome
measures, intervention, and results. Disagreements
were resolved via consensus.
Mean differences (MDs) with 95% confidence inter-
vals (95% CI) were used to express intervention effect
for continuous outcomes, while dichotomous outcomes
were expressed asoddsratios (ORs) with 95%CI.Where
the SD for changes from baseline was not reported for
continuous outcomes, we used the correlation co-effi-
cient for studies with adequate data to compute the
SD.21
We used the random-effect model of the standard
meta-analysis software (Revman 5.3, 2014)22
for meta-
analysis. I2
statistic was used to test for heterogeneity;
values of 25, 50, and 75% represented small, moderate,
and substantial heterogeneity, respectively. One
reviewer (I.J.O.) entered the data onto RevMan, and
these were independently verified by a second reviewer
(C.J.H.). Where it was not possible to statistically
combine the data from included studies, the results
were presented in a narrative format describing
between-group differences in intervention effect.
Results
Our electronic searches identified 83 non-duplicate
citations, out of which eight studies were considered
eligible (Fig. 1). Four studies19,23–25
were excluded
because they were all secondary analyses reports of
primary studies which were already identified and
included in the review, and one26
because it included
subjects with frontotemporal dementia. Thus, three
RCTs27–29
with a total of 1011 participants were
included in the review.
All of the RCTs were of parallel design, and multi-
centred; two were multi-country, while one was con-
ducted in the USA alone (Table 1). Two RCTs27,28
included participants with mild AD, while one29
included participants with mild-to-moderate AD. In
all three studies, the included participants were at
Onakpoya and Heneghan Efficacy of supplementation with the novel medical food, Souvenaid, in AD
Nutritional Neuroscience 2015 VOL. 0 NO. 02

3. least 50 years old, with mean ages ranging from 73 to 77
years. In all the RCTs, probable diagnosis of AD was
based on National Institute of Neurological and
Communicative Disorders and Stroke and the
Alzheimer’s disease and Related Disorders
Association (NINCDS-ADRDA) criteria. At baseline,
there were no significant differences in cognitive rating
(mini-mental status examination (MMSE) score) of
participants between the Souvenaid and placebo
group in the three studies. Cognitive function was
measured using the Delayed verbal recall test of the
Wechsler Memory Scale–revised (WMS-r),27
WMS-r
immediate verbal (logical) memory task,27
Alzheimer’s disease Assessment Scale–cognitive sub-
scale (ADAS-cog),27,29
neuropsychological test
battery (NTB),28
and cognitive test battery (CTB).29
Function and behaviour was assessed using
Alzheimer’s disease Co-operative Study–Activities of
Daily Living (ADCS-ADL),27,29
quality of life
(QOL),28
12-item neuropsychological inventory,27
NTB,28
and disability assessment in dementia
(DAD).28
Clinical global change was measured using
Clinician Interview Based Impression of Change plus
Caregiver Input (CIBIC-plus)27
and Clinical
Dementia Rating scale–Sum of Boxes.29
The duration of intervention in the included RCTs
was between 12 and 24 weeks. In all RCTs, the active
intervention was Souvenaid at a dose of 125 ml daily,
and the placebowas an isocaloric milk drink. The inves-
tigators of two RCTs27,28
excluded participants who
used cholinesterase inhibitors from their trials, while
participants in the third study29
were allowed to use
cholinesterase inhibitors and/or memantine as conco-
mitant medication. All RCTs were funded by same
Souvenaid manufacturer (Danone Research, The
Netherlands).
Overall, the reporting quality of the included RCTs
was good (Fig. 2A and B). All the studies adequately
reported the procedures used for random sequence
generation, allocation concealment, or blinding of par-
ticipants and study personnel. One study28
had a low
risk of bias for blinding of outcome assessments,
while the risk of bias in the other two studies27,29
was unclear. There was a low risk of attrition, selective
reporting, or other biases across the three studies.
Effect of Souvenaid on cognitive function
Two RCTs27,29
reported cognitive function using the
ADAS-cog scores. Meta-analysis of these RCTs (n =
727; Fig. 3) revealed a non-significant difference in
ADAS-cog scores between groups, MD: 0.08 (95%
CI: −0.71 to 0.88, I2
= 0%).
Because of discrepancies in the types of tests used to
measure of cognitive function across the RCTs, meta-
Figure 1 Flow chart for the inclusion of RCTs evaluating the effect of Souvenaid in AD.
Onakpoya and Heneghan Efficacy of supplementation with the novel medical food, Souvenaid, in AD
Nutritional Neuroscience 2015 VOL. 0 NO. 0 3

4. analysis of the other cognitive outcome measures was
not possible. We did not receive positive responses to
requests for additional information from study investi-
gators. Any reported increases in various cognitive
measures, where reported, indicated an improvement
in the patient’s condition. One RCT27
reported a sig-
nificant increase in the proportion of participants
with improved WMS-r delayed verbal recall test with
Souvenaid compared with placebo (40 vs. 24%, P =
0.02; Table 2), but there was no significant difference
when testing with the WMS-r immediate verbal
recall test (50 vs. 40%, P = 0.13). In the same trial,
there was no significant difference for MMSE scores
(24.1 ± 3.5 vs. 24.0 ± 3.4, P = 0.53); however, in a
subgroup with very mild AD (MMSE 24–26; n =
120), a significant improvement in the WMS-r
immediate verbal recall test was reported with
Souvenaid compared with placebo (P = 0.03).27
Another RCT28
reported no significant difference in
NTB memory domain z-score between Souvenaid
and placebo groups (0.20 ± 0.40 vs. 0.11 ± 0.46, P
= 0.09); however, there was a significant increase in
NTB total composite z-score with Souvenaid com-
pared with placebo (0.120 ± 0.278 vs. 0.035 ± 0.286,
P = 0·035). The third RCT29
reported no significant
difference in CTB performance between Souvenaid
and placebo groups (0.10 ± 0.47 vs. 0.05 ± 0.40,
P = 0.30; Table 2).
Effect of Souvenaid on functional ability and
behaviour
Two RCTs27,29
measured functional ability and behav-
iour using ADCS-ADL scores. Meta-analysis of these
RCTs (n = 739; Fig. 4) showed no significant
difference in ADCS-ADL scores with Souvenaid com-
pared with placebo (MD: 0.36, 95% CI: −0.54 to 1.25,
I2
= 0%).
Because of discrepancies in the other tests of func-
tional ability and behaviour across the RCTs, meta-
analysis of these outcome measures was considered
inappropriate. In one RCT,27
there was no significant
difference in the proportion of participants with
improved NPI-12 scores (31.7 vs. 28%, P = 0.73). In
another RCT,28
there was no significant difference in
Table 1 Main characteristics of RCTs evaluating the effectiveness of supplementation with Souvenaid in AD.
Study ID Study design Setting
Type of
participants*
Primary
outcomes
Secondary
outcomes Intervention Placebo
Study
duration
Scheltens
et al.27
Double-blinded,
placebo-
controlled
Outpatients in
Netherlands (11),
Belgium (5),
Germany (11),
UK (1), and
USA (1)
Age ≥50
years
MMSE
20-26
WMS-r
ADAS-
cog (13-
item)
MMSE score;
WMS-r
immediate
verbal
(logical)
memory task;
CIBIC-plus;
NPI-12;
ADCS-ADL;
QOL
Souvenaid
(125 ml)
once-daily
Isocaloric
milk
drink
12 weeks†
Scheltens
et al.28
Double-blinded,
placebo-
controlled
Outpatients in
Spain (3),
Italy (3),
Netherlands (9),
Germany (5),
Belgium (4),
France (3)
Age ≥50
years
MMSE
≥20
NTB** NTB***
executive
function
domain score
(z-score);
DAD scores;
NTB total
composite z-
score
Souvenaid
(125 ml)
once-daily
Isocaloric
milk
drink
24 weeks
Shah
et al.29
Double-blinded,
placebo-
controlled
Forty-eight sites in
the USA
Age ≥50
years
MMSE 14-
24
ADAS-cog
(11-
item)
Cognitive test
battery;
ADCS-ADL
scores; CDR-
SB****
Souvenaid
(125 ml)
once-daily
Isocaloric
milk
drink
24 weeks
WMS-r, delayed verbal recall test of the Wechsler Memory Scale–revised; ADAS-cog, Alzheimer’s Disease Assessment
Scale–cognitive subscale; MMSE, Mini-mental state examination; CIBIC-plus, Clinician Interview Based Impression of Change plus
Caregiver Input; NPI-12: 12-item Neuropsychiatric Inventory; ADCS-ADL, Alzheimer’s disease Co-operative Study–Activities of Daily
Living; QOL, Quality of life; NTB, neuropsychological test battery; DAD, disability assessment for dementia scale; CDR-SB, Clinical
Dementia Rating scale—Sum of Boxes.
*Probable diagnosis of AD based on National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s
Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
**NTB is comprised of the following components: Rey Auditory Verbal Learning Test immediate recall; Delayed recall and recognition
performance; Wechsler Memory Scale-revised (WMS-r) verbal paired associates immediate and delayed recall; Orientation task of
the ADAS-cog; and Letter Digit Substitution Test.
***Based on the WMS-r Digit Span; †Trail Making Tests parts A and B (Delis Kaplan Executive Function System™ condition 2 and
condition 4, respectively); Category Fluency; Controlled Oral Word Association Test.
****Comprised of Digit Span from the Wechsler Memory Scale; Letter Digit Substitution Test; Category Fluency.
†Study followed by a 12-week similarly designed exploratory and optional extension study.
Onakpoya and Heneghan Efficacy of supplementation with the novel medical food, Souvenaid, in AD
Nutritional Neuroscience 2015 VOL. 0 NO. 04

5. NTB executive function domain z-score (0.048 ±
0.333 vs. 0.006 ± 0.323, P = 0.39), and in DAD
scores (P = 0.36).
Effect of Souvenaid on global clinical function
Two RCTs reported data on this outcome. One of
these27
reported no significant difference in CIBIC-
plus scores between Souvenaid and placebo groups
(P = 0.91), and the other29
reported no significant
difference in the CDR-SB score (0.77 ± 1.96 vs.
0.69 ± 1.90, P = 0.50; Table 2).
Adverse events, compliance, and attrition
All RCTs reported data on adverse events. These
events included gastrointestinal symptoms, headache,
dizziness, musculoskeletal pain. Souvenaid was well
Figure 2 (A) Risk of bias summary of RCTs examining the effect of Souvenaid in AD. (B) Risk of bias graph of RCTs examining the
effect of Souvenaid in AD.
Figure 3 Effect of Souvenaid supplementation of cognition (ADAS-cog).
Onakpoya and Heneghan Efficacy of supplementation with the novel medical food, Souvenaid, in AD
Nutritional Neuroscience 2015 VOL. 0 NO. 0 5

6. tolerated across the RCTs. Meta-analysis (n = 1007)
did not reveal any significant difference in risk of
any adverse event (OR: 0.78, 95% CI: 0.61–1.26,
I2
= 50%), or of serious adverse events (OR: 0.83,
95% CI: 0.54–1.28, I2
= 0%). Compliance rates were
≥94% across all RCTs. In total, 111 drop-outs were
reported: 14,27
21,28
and 76.29
There were no signifi-
cant differences in drop-out rates between the
Souvenaid and placebo groups in all RCTs.
Discussion
Main findings
The results of our meta-analyses suggest that sup-
plementation with Souvenaid has no significant
effects on ADAS-cognition scores and ADCS-ADL
scores. The results of one study showed inconsistent
effects of Souvenaid on memory, with improvement
in the delayed verbal recall subscale of the WMS-r
for those participants taking Souvenaid, but no signifi-
cant difference between the Souvenaid and placebo
groups on the memory subscale of the NTB. The
results of included RCTs also show that Souvenaid
has no significant beneficial effects on function, behav-
iour, or clinical global change. To our knowledge, this
is the first review which systematically evaluates the
effectiveness of Souvenaid in the treatment of AD.
In AD, synaptic loss in the brain hippocampus cor-
relates with the cognitive deficits,30–32
and Souvenaid
Table 2 Main results of RCTs evaluating the effectiveness of Souvenaid supplementation in AD.
Study ID
Randomized/
analysed Cognition
Functional ability
and behaviour
Clinical global
change Adverse events
Scheltens
et al.*27
225/212 Sig ↑ in number of subjects
with WMS-r delayed verbal
recall test with Souvenaid
compared with placebo,
P = 0.02
No significant
difference in
ADCS-ADL
scores, P = 0.31
No significant
difference in
CIBIC-plus
scores
P = 0.91
Gastrointestinal symptoms.
No significant difference in
overall frequency, P = 0.29
No significant difference in
WMS-r immediate verbal
recall, P = 0.13
No significant
difference in QOL
scores, P = 0.31
No significant difference in
ADAS-cog scores,
P = 0.83
No significant
difference in NPI-
12 scores,
P = 0.73
No significant difference in
MMSE scores, P = 0.53
Scheltens
et al.28
259/259 No significant difference in
NTB memory domain
z-score, P = 0.09
No significant
difference in NTB
executive function
domain z-score,
P = 0.39
Not reported Constipation, diarrhoea,
nausea, headache, weight
gain, dizziness
Sig ↑ in NTB total composite
z-score compared with
placebo, P = 0·035
No significant
difference in DAD
scores, P = 0.36
Shah
et al.29
527/527 No significant difference in
ADAS-cog scores,
P = 0.55
No significant
difference in
ADCS-ADL
scores, P = 0.93
No significant
difference in
CDR-SB,
P = 0.68
Nausea, vomiting, diarrhoea,
headache, dizziness. No
significant difference in
overall frequency, P = 0.29
No significant difference in
cognitive test battery
performance, P = 0.30
WMS-r, delayed verbal recall test of the Wechsler Memory Scale–revised; ADAS-cog, Alzheimer’s Disease Assessment
Scale–cognitive subscale; MMSE, mini-mental state examination; CIBIC-plus, Clinician Interview Based Impression of Change plus
Caregiver Input; NPI-12: 12-item neuropsychological inventory; ADCS-ADL, Alzheimer’s disease Co-operative Study–Activities of
Daily Living; QOL, quality of life; NTB, neuropsychological test battery; DAD, Disability Assessment for Dementia scale; CDR-SB,
Clinical Dementia Rating scale—Sum of Boxes.
*All randomized participants were included in the safety analyses.
Figure 4 Effect of Souvenaid supplementation on function (ADCS-ADL).
Onakpoya and Heneghan Efficacy of supplementation with the novel medical food, Souvenaid, in AD
Nutritional Neuroscience 2015 VOL. 0 NO. 06

7. supplementation in patients with mild AD has been
shown to improve local brain network connectivity
and global network integration19
– events which are
thought to correlate with memory performance. The
results of the included studies showed that Souvenaid
caused significant improvements in the total compo-
site score for NTB, WMS-r delayed verbal recall test,
and WMS-r immediate verbal recall test for a sub-
group of patients with very mild AD. This finding
suggests that Souvenaid may have some beneficial
effects on some aspects of cognition in patients at
early stages of AD. However, beneficial effects were
not observed with memory scores and other measures
of cognitive function, nor did we observe any ben-
eficial effects on functional ability and behaviour.
These cast major doubts as to whether the purported
enhancement in brain connectivity reported with
Souvenaid translates to improvements in cognition
and function. Indeed the results of recent research
demonstrated that in AD, there is no relationship
between functional connectivity and structural
connectivity.33
The outcomes measures CDR-SB and CIBIC-plus
are validated tools used to assess global change in
AD by clinicians, and thus help with grading the sever-
ity of the disease and examining changes over
time.34,35
In both RCTs that reported this outcome,
Souvenaid had no significant effect, suggesting that
it does not affect the progression of AD; this finding
is corroborated by the results of ADAS-cog scores of
participants which decreased in both Souvenaid and
placebo groups.
Souvenaid appeared well tolerated, and no serious
adverse events were observed with its use. However,
longer-term surveillance is warranted to monitor for
any potential risks which may occur with its use –
this includes unwanted effects which may arise from
possible interactions with other medications.
Comparison with existing literature
Our results are consistent with the findings of a pre-
vious review, which suggested beneficial effects of
vitamin B supplementation on memory, but not on
general cognitive function.36
Our results also support
the findings of another review which concluded that
vitamin E supplementation has no beneficial effects
in the management of AD.37
The positive findings
on cognition in a subset of patients with very mild
AD are consistent with the findings of a clinical trial
which found similar effects with omega-3 fatty acid
supplementation.38
In contrast to those reports,
Souvenaid is a combination of the individual sup-
plements assessed in each of the three reviews. Our
results also corroborate the findings of another sys-
tematic review, which showed that nutritional sup-
plements when combined with cholinesterase
inhibitors have no additional beneficial effects on cog-
nitive decline in AD.39
In contrast to that review, we
statistically synthesized data from included clinical
trials.
Compared with the cholinesterase inhibitors which
have shown benefits in delaying progression in patients
with mild to moderately severe AD,40
Souvenaid is less
effective at slowing cognitive decline. However, it is
important to note, that Souvenaid is not a pharmaco-
logical agent for disease management, but is only a
product with some effects based on its constituents.
Furthermore, Souvenaid appears to have a superior
safety profile compared with this group of agents.
Strengths and limitations
We used a robust strategy to search for studies, and we
accounted for the reporting quality of the included
studies. In addition, the low heterogeneity observed
in our meta-analyses indicates that there was consist-
ency in design and methodology across the three
included studies. However, we recognize several limit-
ations. We may not have identified all RCTs investi-
gating the effects of Souvenaid in patients with AD,
especially unpublished studies. The variation in the
outcome measures (and overlap in their domains)
also prevented us from conducting meta-analyses for
other outcomes. Furthermore, due to the small
number of studies identified, we could not test for pub-
lication bias, and we could not perform sensitivity or
subgroup analyses.
Implications for research
All published trials evaluating the effects of Souvenaid
in AD have been funded by same manufacturer, and
have largely been conducted by same group of investi-
gators. Industry-sponsored trials have been reported to
bias research outcomes.41
Therefore, publicly funded
clinical trials examining the effects of Souvenaid in
AD are warranted. Indeed, we have identified an
ongoing clinical study funded by the European
Union.42,43
Outcome measures in AD differ signifi-
cantly when same patients are compared using differ-
ent tests.44
Because of the variation in the methods
used to measure outcomes across the studies, a
unified test for assessing patients diagnosed with
mild or pre-clinical AD should be agreed among
experts. This will allow for a more objective and
reliable assessment of the effect of Souvenaid (and
other interventions) on various outcomes in AD.
Implications for practice
In patients with mild-to-moderate AD, supplemen-
tation with Souvenaid does not appear to cause
improvements in functional ability and behaviour.
The effect of Souvenaid on memory is inconclusive;
however, some evidence suggests that Souvenaid may
improve verbal recall in patients with very mild AD.
Onakpoya and Heneghan Efficacy of supplementation with the novel medical food, Souvenaid, in AD
Nutritional Neuroscience 2015 VOL. 0 NO. 0 7

8. Souvenaid has no significant effects on the severity of
AD and does not prevent cognitive decline in AD
patients. However, its ingestion appears safe and
tolerable.
Conclusions
The results of published clinical trials do not suggest
that supplementation with Souvenaid has any ben-
eficial effects on functional ability, behaviour, or
global clinical change. Souvenaid may cause improve-
ments in verbal recall in patients with mild AD. Few
clinical trials evaluating the effects of Souvenaid
have been conducted. They are of good methodologi-
cal quality, but vary in the methods used to measure
outcomes. All published studies have been funded by
one manufacturer. Future clinical trials should
measure AD variables with tools that will allow for
easier assessment of research outcomes.
Disclaimer statements
Contributors
All authors contributed equally.
Funding
None.
Conflict-of-interests
C.J.H. receives payment for running educational
courses at the University of Oxford and University
of Oxford ISIS consulting services for external teach-
ing and training. He also receives royalties for books
(Evidence Based Toolkit series by Blackwell BMJ
Books). I.J.O. has no interests to disclose.
Ethics Approval
None.
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