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Efficacy and Safety of Tremella fuciformis in Individuals with Subjective Cognitive Impairment: A Randomized Controlled Trial

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The efficacy and safety of Tremella fuciformis (TF) as a nutritional supplement were assessed in individuals with subjective cognitive impairment (SCI). Seventy-five individuals with SCI were enrolled in an 8-week, randomized, double-blind, placebo-controlled trial of TF (600 mg/day, n = 30 or 1200 mg/day, n = 30) or placebo (n = 15). The primary outcome measure was changes in total scores of the subjective memory complaint questionnaire. The secondary outcome measures were changes in performance on short-term memory and executive functions, which were assessed using standardized cognitive tests. In addition, voxel-based morphometry was performed to examine the effects of TF on changes in gray matter volume. The individuals in the TF group showed greater improvements in the total scores on the subjective memory complaint questionnaire compared with those in the placebo group. There were also significantly greater improvements in short-term memory and executive functions in the TF group relative to the placebo group. Exploratory analysis demonstrated that there were significant group-by-visit interactions on the left precuneus, right supramarginal gyrus, right middle frontal gyrus, and right postcentral gyrus at corrected P < .05. Overall frequency of adverse events did not differ among high-dose TF (40.4%), low-dose TF (35.1%), and placebo groups (41.4%). The current findings suggest that TF could be safely administered to relieve subjective memory complaints and enhance cognition in individuals with SCI.
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FULL COMMUNICATION
Efficacy and Safety of Tremella fuciformis in Individuals with Subjective
Cognitive Impairment: A Randomized Controlled Trial
Soonhyun Ban,
1
Suji L. Lee,
1
Hyeonseok S. Jeong,
2
Soo Mee Lim,
3
Shinwon Park,
1
Young Sun Hong,
3
and Jieun E. Kim
1
1
Department of Brain and Cognitive Sciences, Division of Convergence, Scranton College,
Ewha Womans University, Seoul, Korea.
2
Department of Radiology, Incheon St. Mary’s Hospital, College of Medicine,
The Catholic University of Korea, Seoul, Korea.
3
Department of Radiology, School of Medicine, Ewha Womans University, Seoul, Korea.
ABSTRACT The efficacy and safety of Tremella fuciformis (TF) as a nutritional supplement were assessed in individuals
with subjective cognitive impairment (SCI). Seventy-five individuals with SCI were enrolled in an 8-week, randomized,
double-blind, placebo-controlled trial of TF (600 mg/day, n=30 or 1200 mg/day, n=30) or placebo (n=15). The primary
outcome measure was changes in total scores of the subjective memory complaint questionnaire. The secondary outcome
measures were changes in performance on short-term memory and executive functions, which were assessed using stan-
dardized cognitive tests. In addition, voxel-based morphometry was performed to examine the effects of TF on changes in
gray matter volume. The individuals in the TF group showed greater improvements in the total scores on the subjective
memory complaint questionnaire compared with those in the placebo group. There were also significantly greater im-
provements in short-term memory and executive functions in the TF group relative to the placebo group. Exploratory analysis
demonstrated that there were significant group-by-visit interactions on the left precuneus, right supramarginal gyrus, right
middle frontal gyrus, and right postcentral gyrus at corrected P<.05. Overall frequency of adverse events did not differ among
high-dose TF (40.4%), low-dose TF (35.1%), and placebo groups (41.4%). The current findings suggest that TF could be
safely administered to relieve subjective memory complaints and enhance cognition in individuals with SCI.
KEYWORDS: cognitive impairment executive function short-term memory subjective subjective memory
complaint Tremella fuciformis
INTRODUCTION
Tremella fuciformis (TF) is one of the promising me-
dicinal mushrooms that has been reported to enhance
cognition, promote healthy brain aging, and prevent neu-
rodegenerative disorders as can be inferred from preclinical
studies.
1–3
TF extracts are rich in bioactive polysac-
charides,
4
which have antioxidant, anti-inflammatory, and
immunomodulation properties as well as lipid lowering and
hypoglycemic effects.
5–8
Tremella specieshavealong
history of usage in traditional Chinese medicine, and the
polysaccharides extract has been vigorously examined for
various therapeutic uses.
Recently, there has been increasing evidence that poly-
saccharides derived from medicinal mushrooms have
neuroplastic effects.
1,2,9
TF significantly enhances neurite
outgrowth, which was induced by nerve growth factor, and
reduced the neurotoxic effect of b-amyloid peptide in
PC12h cells.
3
TF also promoted peripheral nerve regen-
eration by increasing neurotrophic gene expression in the
animal nerve injury model.
9
Although the evidence of neuroprotective and neuro-
trophic effects of TF is accumulating, the efficacy and safety
of TF, as a nutritional supplement for cognitive improve-
ment, have not yet been studied.
Self-reported memory complaints are common problems,
which negatively impact the quality of life
10
in middle-aged
and elderly persons.
11
Subjective cognitive impairment (SCI)
could be defined when an individual has a self-perceived
cognitive problem without any diagnosable cause.
12
Al-
though the scores of cognitive tests are within a normal range,
the presence of subjective cognitive complaints is acknowl-
edged as an at-risk target population for early intervention to
prevent future development of neurodegenerative disorders,
including Alzheimer’s dementia.
13
Nutraceutical approaches,
administration of functional foods that exhibit neuroprotec-
tive effects, are increasingly studied to find an effective and
safe intervention in the individuals with SCI.
14,15
Address correspondence to: Jieun E. Kim, MD, PhD, Department of Brain and Cognitive
Sciences, Division of Convergence, Scranton College, Ewha Womans University, Inter-
national Educational Building #609, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760,
South Korea, E-mail: kjieun@ewha.ac.kr
JOURNAL OF MEDICINAL FOOD
J Med Food 00 (0) 2018, 1–8
#Mary Ann Liebert, Inc., and Korean Society of Food Science and Nutrition
DOI: 10.1089/jmf.2017.4063
1
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Although the relationship between SCI and objective
cognitive performance is inconsistently reported in the
previous studies,
16
impaired short-term memory and exec-
utive functions are suggested to be critical to daily life and
may be related to SCI. In addition, these cognitive domains
may decline as aging progresses and be affected earlier
during the neurodegenerative changes.
17
In this study, we conducted an 8-week, double-blind,
randomized, placebo-controlled trial to examine the efficacy
and safety of oral administration of TF in individuals with
SCI. The primary outcome measure was change in the de-
gree of subjective memory complaint. Changes in short-
term memory and executive performance were measured as
the secondary outcomes. The effects of TF administration
on structural brain changes were also assessed using voxel-
based morphometry to characterize the brain mechanisms
underlying its therapeutic actions. We hypothesized that oral
supplementation of TF would reduce memory complaints
and enhance cognitive performance accompanied by re-
gional gray matter volume alteration.
MATERIALS AND METHODS
Participants
The community-dwelling subjects, aged from 40 to 65
years, were recruited through local advertisements. The in-
clusion criteria were as follows: 12 years or more of edu-
cation and subjective cognitive complaints with no clinical
impairments, which were obtained by medical history taking
and evaluated by physical and neurological examinations,
including laboratory blood tests.
The exclusion criteria were as follows: suspected or di-
agnosed as mild cognitive impairment (MCI) of Alzhei-
mer’s dementia (Mini-Mental Status Examination score £24
or Clinical Dementia Rating Scale 0.5); present axis I
mental disorders; lifetime substance use disorders; severe
major illness that requires proper treatment; history of loss
of consciousness or seizure caused by head trauma; use of
central nervous system medications within the last 3
months; intelligence quotient below or same as 80; or con-
traindications to magnetic resonance imaging.
Before any study procedure was conducted, written in-
formed consent was obtained from the study participants.
The study protocol and consent forms were approved by the
Bioethics Committee of Ewha Womans University.
Study design and interventions
Seventy-five participants were enrolled in the 8-week
double-blind, placebo-controlled trial (clinicaltrials.gov
identifier: NCT002377024). Participants were randomly
assigned to low-dose TF (600 mg/day, n=30), high-dose TF
(1200 mg/day, n=30), or placebo (n=15) groups in a 2:2:1
ratio. Each group received a total six capsules per day and
ingested two capsules at three difference times. The ap-
pearance of each capsule did not differ, and placebo cap-
sules were indistinguishable from TF capsules. After the
baseline visit, participants visited at 4 and 8 weeks. The
detailed preparation method of TF supplementation is de-
scribed elsewhere.
2
The study participants were advised to discontinue any
nutritional supplements. When the participants needed to be
newly treated during the study period with the medication
potentially affecting the central nervous system, their par-
ticipation in this study was discontinued.
At each visit, the remaining capsules and diaries were
returned. Compliance was monitored by the returned cap-
sule counts, and the times of missed administration of the
capsules were recorded.
Outcome measures
Assessments of the primary and secondary outcome
measures were performed at baseline and 8 weeks after
baseline.
Primary outcome measure. The primary outcome vari-
able was changes in the Subjective Memory Complaints
Questionnaire (SMCQ) scores that assess self-reported
cognitive impairment and were validated questionnaires for
SCI.
10,18
SMCQ contains 14 items and consists of two do-
mains: global memory function and everyday memory
function. Global memory function is assessed by asking the
self-judgment of the subjects’ memory: whether they have
memory problems or recognize the cognitive decline.
10
Everyday memory function is assessed by asking common
situations of memory difficulty such as remembering
shopping items, recent events, and the location of objects.
10
The response is yes (1 point) or no (0 point) and the score
ranges from 0 to 14 points. The optimal cutoff score sug-
gested for screening dementia is 5 or 6 points.
10
The changes
in the SMCQ scores have been used as outcome variables in
the previous study of SCI.
18
Secondary outcome measures. The secondary outcome
measures were changes in performance on short-term
memory and executive functions as well as changes in gray
matter volumes.
Short-term memory performance was evaluated at base-
line and 8 weeks using the immediate recall domain from
the pattern recognition memory task and the spatial span
task, both of which are taken from the Cambridge Neu-
ropsychological Test Automated Battery (CANTAB).
19
Executive function was assessed using the Wisconsin Card
Sorting Test (WCST).
20
Each test score was standardized to
Z scores, using the group means and standard deviation (SD)
of the placebo group after adjusting for age, sex, intelligent
quotient, and baseline performance. Total errors of the
spatial span and preservative errors of the WCST were re-
versed to indicate that positive Z score means better per-
formance. The composite score for each cognitive domain
(short-term memory and executive functions) was calcu-
lated by averaging the standardized Z score of each test.
Using voxel-based morphometry of high-resolution
three-dimensional T1-weighted magnetic resonance (MR)
images, changes in gray matter volumes were assessed as
2BAN ET AL.
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the secondary outcome measure. Detailed information on
image data acquisition and image data processing are de-
scribed in the sections of Image data acquisition and Voxel-
based morphometry analysis.
Safety measures. The Udvalg for Kliniske Undersogelser
(UKU) Side Effect Rating Scale
21
was used to assess safety
and tolerability of study medications, and spontaneous, self-
reported, adverse events were also recorded. Vital signs,
height, and weight were measured, and physical and neuro-
logical examinations were performed at each visit. Routine
laboratory examinations, including the complete blood cell
count, blood chemistry, differential white cell count, urine
analysis, and urine pregnancy test were performed at base-
line, 4 weeks, and 8 weeks (Green Cross Laboratories,
Yongin, South Korea). Electrocardiograms were obtained at
baseline and 8 weeks after baseline.
Image data acquisition
A 3.0 Tesla Philips Achieva MR scanner (Philips Medical
System, Netherlands) equipped with a 32-channel head coil
was used for acquisition of high-resolution multimodal
neuroimaging data, including T1-weighted and resting-state
functional images. Structural images were acquired using
a three-dimensional T1-weighted magnetization-prepared
rapid gradient echo imaging sequence with the follow-
ing acquisition parameters: repetition time =7.4 ms, echo
time =3.4 ms, flip angle =8, field of view =220 ·220 mm
2
,
slice thickness =1 mm, number of excitation =1, and 180
contiguous sagittal slices.
Voxel-based morphometry analysis
Optimized voxel-based morphometry was performed
using the software of FMRIB’s Software Library.
22
After
performing skull stripping to remove nonbrain tissues on
T1-weighted images, tissue-type segmentation was carried
out using FMRIB’s Automated Segmentation Tool. Gray
matter partial volume images were aligned to the Montreal
Neurological Institute standard space using FMRIB’s Linear
Image Registration Tool and averaged to create an initial
template. The final study-specific gray matter template was
created by averaging gray matter images, which were nor-
malized to an initial template using FMRIB’s Non-Linear
Image Registration Tool (FNIRT). Individual gray matter
images in the native space were nonlinearly registered to the
study-specific template using FNIRT. The registered images
were modulated by multiplying them with the determinant
of the Jacobian of the warp field to estimate gray matter
volume at each voxel
22
and were then smoothed with an
isotropic Gaussian Kernel with a sigma of 3 mm.
Statistical analyses
Demographic and clinical characteristics were compared
between the treatment groups by an analysis of variance
(ANOVA) for continuous variables and a chi-square test for
categorical variables. The intent-to-treatment population
was used in the analysis.
The mixed-effects model for repeated measures data was
performed for analyzing the primary outcome measure.
SMCQ scores were adjusted for age, sex, intelligent quo-
tient, and baseline value, and these adjusted SMCQ scores
were used as the dependent variables. The secondary out-
come measures for changes in short-term memory and
executive functions were also analyzed using the mixed-
effects model for repeated measures data. Treatment
groups (high-dose TF vs. low-dose TF vs. placebo), visits,
and treatment group-by-visit interaction were included as
fixed effects. The within-subject factor was considered as a
random effect.
Cook’s distance, which is often used to assess the in-
fluence of individual observations on the regression anal-
ysis and identify statistical outliers, was estimated in each
observation.
23
Four, three, and four observations with Cook’s
distance >0.058, were finally removed from the analysis of
changes in SMCQ, short-term memory, and executive func-
tions, respectively.
The secondary outcome measure for changes in gray
matter volumes was assessed using voxel-based morphome-
try. Treatment group-by-time interaction on gray matter
volumes was also analyzed on a voxel-by-voxel basis. The
results were corrected for multiple comparisons using Monte
Carlo simulation with 10,000 iterations implemented in the
ClusterSim utility (http://afni.nimh.nih.gov/pub/dist/doc/
program_help/3dClustSim.html). A threshold derived from
a combination of a voxel-wise t>2.0 and a cluster size of at
least 5128 mm
3
was used to correct for multiple comparisons
at P<.05.
Proportional differences in all adverse events were as-
sessed between the TF and placebo groups using a chi-
square test. We further explored potential differences in the
frequency of adverse events between the low and high dose
within the TF group.
An a-level of 0.05 (two-tailed) was considered significant
for all analyses. Data were analyzed using Stata v13.1
(StataCorp., College Station, TX, USA).
RESULTS
Participant characteristics
Among the 88 subjects who were assessed for the study
eligibility, 75 were randomly allocated to receive supple-
mentation, and 69 completed the study (Fig. 1). The com-
pletion rates did not differ among the high-dose TF, low-dose
TF, and placebo groups (93.3% vs. 90.0% vs. 93.3%, re-
spectively). The demographic and baseline assessments were
similar among the three groups (Table 1).
Adherence to treatment
Study compliance was >90% in all three groups. The
mean percentages of returned pill counts were similar
among the three groups (one-way ANOVA, P=.79): high-
dose TF group 8.0% (SD 6.5%), low-dose TF group 9.2%
(SD 7.6%), and placebo group 8.1% (SD 6.6%). Adherence
rate assessed by the intake diary also showed no significant
EFFECTS OF TREMELLA FUCIFORMIS ON COGNITIVE FUNCTION 3
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differences among the groups (one-way ANOVA, P=.09):
high-dose TF group 93.8 (SD 4.5%), low-dose TF group
91.9% (SD 6.5%), and placebo group 95.6% (SD 2.7%).
Primary outcome measure
The primary outcome of interest was the rate of improve-
ment in subjective complaints of cognitive impairment. The
rate of improvement in SMCQ scores was greater in indi-
viduals with the both high-dose (z=-3.16, P=.002) and low-
dose (z=-2.68, P=.007) TF groups compared with those of
the placebo group (Fig. 2). These results remained unchanged
when Hamilton Depression Rating Scale (HDRS) scores
were included as an additional covariate (high-dose group,
z=-3.25, P=.001; low-dose group, z=-2.70, P=.007).
There was no difference in changes of SMCQ sores between
the high-dose and lose-dose TF groups (z=-0.61, P=.54).
Over the treatment period, individuals of the high- and
low-dose TF groups showed 9.18% and 3.97% decrease in
SMCQ scores, while changes in SMCQ scores were mini-
mal (1.02% increase) in those of the placebo group.
Secondary outcome measures: short-term
memory and executive functions
Secondary outcome measures were changes in perfor-
mance on short-term memory and executive functions over
an 8-week period. We found significant treatment group-by-
visit interactions on both short-term memory and executive
functions. Improvement in short-term memory performance
was greater in the high-dose (z=3.35, P=.001) and low-
dose (z=3.31, P=.001) TF groups than in the placebo group
(Fig. 3A). Significant improvement with high-dose TF
(z=2.33, P=.02), but not with low-dose TF (z=1.75,
P=.08), relative to placebo administration was also ob-
served in executive function performance (Fig. 3A).
However, there was no differences in the rate of cognitive
improvement between the high-dose and low-dose TF
groups (short-term memory function, z=0.07, P=.94; ex-
ecutive function, z=0.77, P=.44).
Secondary outcome measures: gray matter volumes
Changes in gray matter volumes were also examined using
voxel-based morphometry as the secondary outcome mea-
sure. Significant treatment group-by-visit interactions were
found in the left precuneus, right supramarginal gyrus, right
middle frontal gyrus, and right postcentral gyrus (P<.05,
with correction for multiple comparisons, Fig. 3B; Supple-
mentary Table S1; Supplementary Data are available online
at www.liebertpub.com/jmf). Increases in gray matter vol-
umes of these clusters were greater in the high-dose and low-
dose groups than in the placebo group.
We explored the relationships between changes in gray
matter volumes and changes in cognitive performance in
FIG. 1. Screening, randomization, and disposition of participants with SCI randomly assigned to the high-dose TF (1200 mg daily), low-dose TF (600 mg
daily), or placebo groups. SCI, subjective cognitive impairment; TF, Tremella fuciformis. Color images available online at www.liebertpub.com/jmf
4BAN ET AL.
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individuals treated with TF. Gray matter volume increases
in the dorsolateral prefrontal cluster were correlated with
improvement in executive performance in the TF group
(r=0.33, P=.02).
Safety and tolerability
No serious adverse events were reported. All reported
adverse events are listed in Supplementary Table S2. There
were no differences in the overall frequency of adverse
events among the high-dose TF (n=23, 40.4%), low-dose
TF (n=20, 35.1%), and placebo groups (n=12, 41.4%)
(v
2
=0.46, P=.793). The most common adverse event re-
ported in the TF group was weight gain. However, there
was no difference in changes of body mass index between
groups (z=-0.64, P=.523). There were no participants
who discontinued the trial because of adverse events in either
treatment group. There were no differences in laboratory
findings between the treatment groups (Supplementary
Table S3).
DISCUSSION
This randomized clinical trial demonstrated that oral ad-
ministration of TF improved subjective memory complaints
and cognitive performance in individuals with SCI. Spe-
cifically, subjects in the groups with TF oral supplemen-
tation showed greater improvement in short-term memory
and executive performance than those in the placebo
group. Along with these findings, TF supplementation was
associated with increases in gray matter volumes of several
brain regions, including the dorsolateral prefrontal cortex.
The changes in the SMCQ scores have been used as out-
come variables in a previous study of the SCI.
18
The results
of the study extends the previously reported preclinical
evidence of TF as a potential nootropics in middle-aged
individuals with SCI. TF oral administration may be a safe
prevention strategy for individuals with SCI.
TF extract is rich in polysaccharides, which consist of D-
mannan backbone with various side chains, including glu-
curonic acid, xylose, and fucose.
4,24
The improvement in
subjective memory complaints is consistent with a previous
study, which reported that dietary saccharide intake is as-
sociated with greater ratings of self-reported everyday
memory in middle-aged adults.
25
These results remained
significant after adjusting for the effects of smoking, drinking,
and exercise status.
25
The daily amount of polysaccharide
intake could be inadequate if an individual consumes a
minimal amount of fruit and vegetable, which are rich in
saccharides.
26
Although there is little evidence about the effect of TF
extract on cognition in humans, one randomized clinical
trial has examined the effects of 12-week saccharide sup-
plementation and reported benefits on short-term memory
and well-being.
25
Another clinical trial explored the acute
FIG. 2. Changes in SMCQ scores in individuals with SCI randomly assigned to high-dose TF, low-dose TF, and placebo administration. Changes
in SMCQ scores were analyzed using the mixed-effects model for repeated measures data. Main effects for treatment groups (high-dose TF vs. low-
dose TF vs. placebo) and visits as well as their interaction terms were included into the model. Pvalues for the treatment group-by-visit interaction on
SMCQ scores were calculated. Absolute scores at baseline and at endpoint are presented in Supplementary Table 4. Error bars represent standard
errors of the mean. SMCQ, subjective memory complaints questionnaire. Color images available online at www.liebertpub.com/jmf
Table 1. Baseline Demographic and Clinical Characteristics
Characteristics
Treatment groups
P
High-dose
TF group
a
(n=30)
Low-dose
TF group
a
(n=30)
Placebo
(n=15)
Age, mean
(SD), years
54.5 (4.9) 52.3 (5.6) 54.7 (5.9) .22
Women, n(%) 26 (86.7) 26 (86.7) 13 (86.7) 1.0
Education, mean
(SD), years
14.3 (2.9) 15.2 (2.0) 14.1 (2.6) .23
Socioeconomic status, n(%)
Upper 9 (30) 7 (23.3) 4 (26.7) .85
Middle 16 (53.3) 21 (70) 10 (66.7) .40
Lower 5 (16.7) 2 (6.7) 1 (6.7) .40
Marriage, n(%)
Married 26 (86.7) 24 (80) 13 (86.7) .75
Never married 2 (6.7) 3 (10) 2 (13.3) .77
Divorced, widowed,
or separated
2 (6.7) 3 (10) 0 (0) .46
Living alone, n(%) 3 (10) 2 (6.7) 1 (6.7) .88
IQ, mean (SD), score 116.8 (11.3) 117.4 (8.3) 112.6 (6.9) .25
MMSE, mean
(SD), score
27.5 (1.5) 27.7 (1.3) 27.8 (0.7) .72
SMCQ, mean
(SD), score
4.0 (2.9) 3.6 (2.4) 4.2 (3.3) .78
a
TF was administered in two different dosing schedules; a low-dose
schedule with 600 mg and a high-dose schedule with 1200 mg of TF.
IQ, Intelligence Quotient; MMSE, Mini-Mental Status Examination; SD,
standard deviation; SMCQ, subjective memory complaints questionnaire; TF,
Tremella fuciformis.
EFFECTS OF TREMELLA FUCIFORMIS ON COGNITIVE FUNCTION 5
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effect of nonstarch polysaccharide and reported higher
levels of performance in short-term memory and executive
performance.
27
Supplementing polysaccharide extracted
from TF could be a safe and efficient approach to ensure
sufficient uptake of saccharides and promote memory.
26
While the exact mechanism of subjective and objective
cognition improvement is not clear, preclinical studies
suggest that F extract scavenges reactive oxygen species,
28
modulates the immune system,
29
and reverses risk factors
of metabolic syndrome.
5,7
Along with these indirect effects,
TF extract also has direct neurological effects, including
stimulation of neurite outgrowth,
3
promotion of hippocampal
long-term potentiation,
30
increased acetylcholine release and
choline acetyltransferase activity, and reduced scopolamine-
induced impairment of learning and memory in rats.
1
This study is the first to use structural neuroimaging
measures to investigate the efficacy of TF supplementation.
There was only one experimental study that utilized func-
tional brain measures with cognitive tests.
31
Acute changes in
electroencephalography were found after administering a
mixed carbohydrate formula,
31
but it is hard to determine the
underlying brain changes related to cognitive improvement.
In this study, several brain regions showed gray matter vol-
ume increase after TF administration, and it is worthwhile to
note that the extent of gray matter change in the dorsolateral
prefrontal cortex was associated with improvement in ex-
ecutive function. These findings may support the in vivo
evidence of neurotrophic effect of TF. For instance, TF
may increase the gray matter volume due to neurite out-
growth or synaptic plasticity, which was repeatedly reported
in preclinical studies.
3,30
Individuals with SCI may suffer from subtle declines
in short-term memory and executive functions in daily life,
even though standardized neuropsychological tests fail to
detect changes in cognitive performance.
10,17
Middle-aged
adults who do not show a clear cognitive decline, but have
early signs of brain aging, are an important target population
that may benefit from nutritional interventions.
32
Short-term
memory and executive functions are closely related to handling
information needed in everyday activities. Thus, TF-induced
improvement may promote better quality of life and the self-
perception of memory in middle-aged adults with SCI.
High- and low-dose TF were well tolerated with similar
overall rates of adverse events. There was no difference in
laboratory findings and body mass index among the groups.
In East Asia, Tremella is a common food widely used. To
the best of our knowledge, there are no reports of major health
risks associated with Tremella. One thousand two hundred
milligrams per day of TF administration would be a safe and
easily accessible intervention for individuals with SCI.
In this study, we did not find a dose-dependent response.
Although executive performance was significantly improved
only in the high-dose TF group, the dose group-by-time in-
teraction effect was not significant. The negative findings
could be interpreted as a ceiling effect or inadequate sample
size to detect differences between the two different doses.
The optimal dosage of TF should be studied in further large-
scale studies.
Medicinal mushrooms are a good source of bioactive
polysaccharides, which are increasingly receiving attention
for various biological effects. The supplementation could
exhibit different effects on cognition according to the types,
FIG. 3. Changes in adjusted Z scores of short-term memory and executive functions in individuals with SCI randomly assigned to high-dose TF,
low-dose TF, and placebo administration (A) and clusters of treatment-by-visit interactions on gray matter volumes (B). Absolute scores of short-
term memory test and executive function test at baseline and at endpoint are presented in Supplementary Table 4. Color images available online at
www.liebertpub.com/jmf
6BAN ET AL.
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preparation method, and the main source of polysaccha-
rides. Further studies are needed to replicate our findings in
a larger population and examine the effects in other cogni-
tive domains and neuroimaging measures.
In conclusion, the results of this study demonstrate that
oral administration of TF as a potential method to reduce
subjective memory complaints in individuals with SCI is
effective for improving short-term memory and executive
performance. The safety and tolerability profile are fa-
vorable. Thus, we could consider TF as a promising option
that could be used to prevent further cognitive decline in
adults with subjective cognitive complaints.
ACKNOWLEDGMENTS
Fire Fighting Safety and 119 Rescue Technology Re-
search and Development Program funded by the Ministry
of Public Safety and Security (MPSS-Fire Fighting Safety-
2016-86), and the Brain Research Program through the
National Research Foundation of Korea (NRF) funded
by the Ministry of Science, ICT and Future Planning
(2015M3C7A1028376), grant from Pulmuone holdings.
AUTHOR DISCLOSURE STATEMENT
No competing financial interests exist.
REFERENCES
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... The effect of low (600 mg/d, n = 30) and high-doses (1200 mg/d, n = 30) of Tremella fuciformis (TF) consumption on cognition was evaluated in 60 young adults after 4 and 8 weeks of intervention, and subjects in the intervention group showed fewer self-reported cognitive complaints, better short-memory and executive functions compared to placebo in a non-dependent dose manner. Along with this, TF supplementation was related to increases in gray matter volumes of specific brain regions [84]. Another study conducted in 30 older subjects (60-80 y) evaluated the administration of a daily dose of 750 mg of spermidine-rich plant extract containing 1.2 mg of the natural polyamine plus 510 mg cellulose compared to the placebo containing 750 mg potato starch and 510 mg cellulose and revealed a moderate enhancement of memory performance and mnemonic discrimination ability after 3 months of intervention [85]. ...
... Other dietary supplements that have shown significant improvements on different cognitive domains are fungi and algae extracts (Hericiumerinaceus, Tremella fuciformis and Laminaria japonica), other plant extracts (Eleutherococcussenticosus leaf, Drynariafortuneirhizome, combined sage, rosemary and melissa, auraptene, astaxanthin and matured hop bitter acids), minerals such as magnesium, medium-chain triglycerides and the complex Twendee X (supplement containing a mix of eight antioxidants). The consumption of the above antioxidant and anti-inflammatory supplements not only significantly improved subjective memory complaints [84] and scores in different cognitive domains such as psychomotor and processing speed [73], working memory [76,77,79,81], short-term memory [74,76,77,84], spatial working memory [75,79,81,87], verbal episodic memory [78], verbal fluency [75,82,83], language [75,79,81,87], executive functions [79,82,84] and attention [79,83,87], but also cortical gray matter integrity in AD-related brain regions [84]. The spermidine-rich plant extract also had an impact on memory performance in subjects with SCD, although this was not significant, probably due to the small sample size (n = 30) and/or the short follow-up period (3 months) [85]. ...
... Other dietary supplements that have shown significant improvements on different cognitive domains are fungi and algae extracts (Hericiumerinaceus, Tremella fuciformis and Laminaria japonica), other plant extracts (Eleutherococcussenticosus leaf, Drynariafortuneirhizome, combined sage, rosemary and melissa, auraptene, astaxanthin and matured hop bitter acids), minerals such as magnesium, medium-chain triglycerides and the complex Twendee X (supplement containing a mix of eight antioxidants). The consumption of the above antioxidant and anti-inflammatory supplements not only significantly improved subjective memory complaints [84] and scores in different cognitive domains such as psychomotor and processing speed [73], working memory [76,77,79,81], short-term memory [74,76,77,84], spatial working memory [75,79,81,87], verbal episodic memory [78], verbal fluency [75,82,83], language [75,79,81,87], executive functions [79,82,84] and attention [79,83,87], but also cortical gray matter integrity in AD-related brain regions [84]. The spermidine-rich plant extract also had an impact on memory performance in subjects with SCD, although this was not significant, probably due to the small sample size (n = 30) and/or the short follow-up period (3 months) [85]. ...
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New dietary approaches for the prevention of cognitive impairment are being investigated. However, evidence from dietary interventions is mainly from food and nutrient supplement interventions, with inconsistent results and high heterogeneity between trials. We conducted a comprehensive systematic search of randomized controlled trials (RCTs) published in MEDLINE-PubMed, from January 2018 to July 2021, investigating the impact of dietary counseling, as well as food-based and dietary supplement interventions on cognitive function in adults with or without cognitive impairment. Based on the search strategy, 197 eligible publications were used for data abstraction. Finally, 61 articles were included in the analysis. There was reasonable evidence that dietary patterns, as well as food and dietary supplements improved cognitive domains or measures of brain integrity. The Mediterranean diet showed promising results, whereas the role of the DASH diet was not clear. Healthy food consumption improved cognitive function, although the quality of these studies was relatively low. The role of dietary supplements was mixed, with strong evidence of the benefits of polyphenols and combinations of nutrients, but with low evidence for PUFAs, vitamin D, specific protein, amino acids, and other types of supplements. Further well-designed RCTs are needed to guide the development of dietary approaches for the prevention of cognitive impairment.
... T. fuciformis is a popular food and herbal medicine ingredient due to having low energy and lipid content, but it serves as a rich source of polysaccharides and dietary fiber; it is widely used for nutritive and tonic actions in Asian countries [15]. T. fuciformis has been used for medicinal purposes due to its possible bioactivity, which includes antioxidant properties [16], antiinflammatory functions [17], antineoplastic [18] and immunomodulatory effects [19], and prevention of neurodegenerative disorders [20]. Fresh T. fuciformis supplies rapidly lose their general quality due to fruit body autolysis and high respiration rate. ...
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This study focuses on assessing the effects of various food processing silver ear (Tremella fuciformis) powders in sugar-reduced ice cream through melting kinetic simulation, sensory properties and functional ingredients. T. fuciformis, a natural anti-melting stabilizer in ice cream, has the advantage of functional ingredients. Using 100, 200, and 300 mesh of particle sizes, and then selecting a suitable particle size, those are added to the additive ratios of 0.4, 0.9, and 1.4% T. fuciformis powder to replace fresh T. fuciformis fruit body. Decreased particle size of T. fuciformis powder significantly increased ice cream stability. Comparisons of sensory evaluation and melting properties, in order to learn the differences of T. fuciformis ice cream under various stabilizer models, were evaluated and elucidated. Therefore, we obtained 300 mesh at 0.9% additive ratio of T. fuciformis powder, which is closest to the fresh fruit body/base ice cream. The enrichment of ice cream with T. fuciformis is to enhance the nutritional aspects and develop a functional food. Overall, the kinetic parameters of T. fuciformis ice cream melting can be provided as a reference for frozen dessert processing technology.
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Objective We aimed to investigate the effects of Korean red ginseng (KRG) supplementation on gray matter volume of the human brain which could be related to cognitive enhancing effects of KRG. Methods In this randomized, double‐blind, placebo‐controlled study, 51 healthy individuals were assigned to receive either KRG (1000 mg/day, n = 26) or placebo (n = 25) for 8 weeks. Gray matter volume of the whole brain was measured using voxel‐based morphometry based on high‐resolution T1‐weighted magnetic resonance images acquired at baseline and week 8. The standardized composite cognitive scores of executive function, attention, and memory were also evaluated at baseline and week 8. Changes in gray matter volume as well as the composite cognitive scores were compared between the KRG and placebo groups. Results Following 8 weeks of KRG supplementation, the gray matter volume of the left parahippocampal gyrus increased significantly in the KRG group, relative to the placebo group (p for interaction < 0.001). The KRG group also showed greater magnitude of enhancement in the composite cognitive scores relative to the placebo group (p for interaction = 0.03). Conclusions Gray matter volume increase in the parahippocampus may be a key neural change as induced by KRG supplementation, which could be associated with cognitive enhancement.
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Objectives: The association between sleep disturbances and cognitive decline in the elderly has been putative and controversial. We evaluated the relation between subjective sleep quality and cognitive function in the Korean elderly. Method: Among 459 community-dwelling subjects, 352 subjects without depression or neurologic disorders (mean age 68.2 ± 6.1) were analyzed in this study. All the participants completed the Korean version of the consortium to establish a registry for Alzheimer's disease neuropsychological battery (CERAD-KN) as an objective cognitive measure and subjective memory complaints questionnaire (SMCQ). Based on the Pittsburgh sleep quality index, two types of sleepers were defined: 'good sleepers' and 'poor sleepers'. Results: There were 192 good sleepers (92 men) and 160 poor sleepers (51 men). Poor sleepers reported more depressive symptoms and more use of sleep medication, and showed higher SMCQ scores than good sleepers, but there was no difference in any assessments of CERAD-KN. In the regression analysis, depressive symptoms and subjective sleep quality were associated with subjective memory complaints (β = 0.312, p < 0.001; β = 0.163, p = 0.005). Conclusion: In the elderly without depression, poor sleep quality was associated with subjective memory complaints, but not with objective cognitive measures. As subjective memory complaints might develop into cognitive disorders, poor sleep quality in the elderly needs to be adequately controlled.
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Novel peripheral nerve conduits containing the negatively charged Tremella fuciformis polysaccharide (TF) were prepared, and their efficacy in bridging a critical nerve gap was evaluated. The conduits were made of poly(D,L-lactide) (PLA) with asymmetric microporous structure. TF was immobilized on the lumen surface of the nerve conduits after open air plasma activation. The TF-modified surface was characterized by the attenuated total reflection Fourier-transformed infrared spectroscopy and the scanning electron microscopy. TF modification was found to enhance the neurotrophic gene expression of C6 glioma cells in vitro. TF-modified PLA nerve conduits were tested for their ability to bridge a 15 mm gap of rat sciatic nerve. Nerve regeneration was monitored by the magnetic resonance imaging. Results showed that TF immobilization promoted the nerve connection in 6 weeks. The functional recovery in animals receiving TF-immobilized conduits was greater than in those receiving the bare conduits during an 8-month period. The degree of functional recovery reached ~90% after 8 months in the group of TF-immobilized conduits.
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We examined the neuroprotective and neurotrophic effects of Tremella fuciformis. The neurotrophic effects of the hot water extract of T. fuciformis was evaluated by microscopically monitoring its potency to induce neurite outgrowth in PC12h cells. The hot water extract of T. fuciformis promoted neurite outgrowth in PC12h cells in this study, superior to other natural substances which was reported previously. When cells were treated with the hot water extract of T. fuciformis prior to β-amyloid peptide treatment (active domain of A peptide 25~35 treated), toxicity was significantly diminished (p<0.01). These results suggest that T. fuciformis might potentially be used as a precautionary agent in neurodegenerative disease, such as Alzheimer's disease, etc.
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An NIH State of the Science Conference panel concluded in 2010 that insufficient evidence is available to recommend the use of any primary prevention therapy for Alzheimer’s disease or cognitive decline with age. Despite the insufficient evidence, candidate therapies with varying levels of evidence for safety and efficacy are taken by the public and discussed in the media. One example is the long-chain n-3 (omega-3) polyunsaturated fatty acids (n-3 LC-PUFA), DHA and EPA, found in some fish and dietary supplements. With this report, we seek to provide a practical overview and rating of the level and type of available evidence that n-3 LC-PUFA supplements are safe and protective against cognitive aging and Alzheimer’s disease, with additional discussion of the evidence for effects on quality of life, vascular aging, and the rate of aging. We discuss available sources, dose, bioavailability, and variables that may impact the response to n-3 LC-PUFA treatment such as baseline n-3 LC-PUFA status, APOE ɛ4 genotype, depression, and background diet. Lastly, we list ongoing clinical trials and propose next research steps to validate these fatty acids for primary prevention of cognitive aging and dementia. Of particular relevance, epidemiology indicates a higher risk of cognitive decline in people in the lower quartile of n-3 LC-PUFA intake or blood levels but these populations have not been specifically targeted by RCTs.