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Journal of Alzheimer’s Disease 33 (2013) 393–406
DOI 10.3233/JAD-2012-121381
IOS Press
393
The Effect of an Aloe Polymannose
Multinutrient Complex on Cognitive and
Immune Functioning in Alzheimer’s Disease
John E. Lewisa,∗, H. Reginald McDanielb, Marc E. Agroninc, David A. Loewensteina, Jorge Riverosc,
Rafael Mestrec, Mairelys Martinezc, Niurka Colinac, Dahlia Abreua, Janet Konefala,
Judi M. Woolgerdand Karriem H. Alie
aDepartment of Psychiatry & Behavioral Sciences, Miami, FL, USA
bFisher Institute for Medical Research, Grand Prairie, TX, USA
cMiami Jewish Health Systems, Miami, FL, USA
dDepartment of Medicine at University of Miami Miller School of Medicine, Miami, FL, USA
ePharmacognosia, Rainier, WA, USA
Accepted 1 August 2012
Abstract. Alzheimer’s disease (AD) is a leading killer of Americans, imparts a significant toll on the quality of life of the
patient and primary caregiver, and results in inordinate costs in an already overburdened medical system. Prior studies on
cholinesterase inhibitors among AD patients have shown minimal amelioration of disease symptoms and/or restoration of lost
cognitive functioning. The effect of improved nutrition, particularly with dietary supplements, on cognitive functioning may offer
an alternative strategy compared to standard treatment. The present pilot study investigated the effect of an aloe polymannose
multinutrient complex (APMC) formula on cognitive and immune functioning over 12 months among adults diagnosed with AD.
Subjects participated in an open-label trial and consumed 4 teaspoons per day of the APMC. The ADAS-cog, MMSE, ADCS-
ADL, and SIB were administered at baseline and 3, 6, 9, and 12 months follow-up. Cytokines and lymphocyte and monocyte
subsets were assessed at baseline and 12 months. The mean ADAS-cog cognition score significantly improved at 9 and 12 months
from baseline, and 46% of our sample showed clinically-significant improvement (≥4-point change) from baseline to 12 months.
Participants showed significant decreases in tumor necrosis factor-␣, vascular endothelial growth factor, and interleukins-2
and -4. CD90+, CD95+CD3+, CD95+CD34+, CD95+CD90+, CD14+CD34+, CD14+CD90+, and CD14+CD95+ decreased
significantly, whereas CD14+significantly increased. Participants tolerated the APMC supplement with few, temporary adverse
reactions. Our results showed improvements in both clinical and physiological outcomes for a disease that otherwise has no
standard ameliorative remedy.
Keywords: Aloe, Alzheimer’s disease, B-lymphocyte subsets, cognition, cytokines, dietary supplementation, growth factors,
oligosaccharides, T-cell subsets
INTRODUCTION
In the U.S. today, roughly 5.5 million people suf-
fer from Alzheimer’s disease (AD), which accounts
∗Correspondence to: John E. Lewis, PhD, University of Miami
Miller School of Medicine, Department of Psychiatry & Behav-
ioral Sciences, 1120 NW 14th Street, Suite #1474 (D21), Miami,
FL 33136, USA. Tel.: +1 305 243 6227; Fax: +1 305 243 1619;
E-mail: jelewis@miami.edu.
for about 70% of the total cases of dementia [1]. The
incidence of dementia doubles every five years after
age 60 from 1% of those ages 60 to 64 to up to
50% of those over age 85, and dementia is the lead-
ing cause of institutionalization among the elderly [2].
AD is the sixth-leading cause of death in the U.S. and
is the only one among the top 10 killers of Ameri-
cans that has no cure or preventive measure, nor can
be delayed [1]. The current combined paid-for-care
ISSN 1387-2877/13/$27.50 © 2013 – IOS Press and the authors. All rights reserved
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394 J.E. Lewis et al. / Aloe Polymannose Complex in AD
(formal) and unpaid care (informal caregiving) costs
associated with dementia and AD in the U.S. are esti-
mated to be more than $410 billion per year [1]. Based
on the current costs and future estimates, any interven-
tion that can ameliorate the effects of AD would not
only improve the quality of life of the individual suf-
fering from the disease (and the patient’s caregivers),
but could also potentially save the American health
care system an inordinate sum of money. Random-
ized clinical trials for pharmacological agents (i.e., the
cholinesterase inhibitors and memantine) for efficacy,
safety, and treatment of AD have had no to moder-
ate success [3], and the effect of using compounds to
act against abnormal amyloid-(A) proteins within
the brain is unknown at this time [4]. Unfortunately,
current strategies have not been shown to prevent the
onset of dementia or cognitive decline and do not halt
the progression of disease [1, 5].
In light of the inability of pharmaceutical agents
to prevent AD or sufficiently restore the functioning
of AD-related symptoms, researchers and consumers
have turned to nutrient and herbal formulae to deter-
mine their possible efficacy on cognitive functioning.
Several studies have investigated the effects of antiox-
idants, particularly vitamins E and C. One study
received particular attention showing that vitamin E
(␣-tocopherol) delayed the time to several outcomes
(e.g., death, institutionalization, and loss of function-
ing) for moderate-severity AD patients [6]. However,
the results of the majority of trials suggest limited to no
beneficial effect of both antioxidants, due in part to the
types of agents studied (e.g., synthetic, unnatural) on
the primary prevention of cognitive decline or amelio-
rating the symptoms of AD patients [7, 8]. In fact, the
level of vitamin E studied (>400 IU) in many dementia
or AD trials has now been shown to be related to an
increased risk of all-cause death [7].
Fatty acids (particularly omega 3) have recently been
studied for their effects on cognitive functioning as
well. Using different types of omega 3 fatty acids, two
recent studies showed improvement in cognitive func-
tioning in people with mild cognitive impairment, but
not AD [9, 10]. Another study showed no effect of
docosahexaenoic acid (DHA) in persons with mild to
moderate AD, but a subgroup of subjects who were
normal according to the Mini-Mental State Exam-
ination (MMSE) had improved delayed recall, and
attention and cognitive function appeared to stabilize
[11]. Ginkgo biloba is another nutrient that has been
studied by several investigators for its possible effects
on cognitive functioning [12–16]. A meta-analysis of
studies of AD patients in 3 to 6 month treatment periods
with 120 to 240 mg of ginkgo revealed a small though
significant effect size of 0.40 (p< 0.01) on objective
measures of cognitive function [17].
The emerging field of glycobiology, which is the
study of different forms of saccharides and their
biosynthetic activity [18], may offer a novel nutritional
approach for AD and its symptoms. Glycosylation is
the most common form of protein and lipid modifi-
cation, where saccharides are attached to proteins and
lipids through a complex, but ordered, process in the
ribosome, endoplasmic reticulum, and Golgi of the
cell to enable intracellular functioning and cell-to-cell
communication [19]. Glycolipids, glycoproteins, and
proteoglycans are critical components of the cell sur-
face recognition process throughout all organ systems
[20].
Following the intake of aloe polymannose (an
oligosaccharide), large CD14+ monocytes were noted
in peripheral blood [21]. It was recognized in 2002
that CD14+ monocytes had pleuripotent adult stem cell
capacities [22]. CD14+ cells purified in culture, when
cytokines and growth factors are added to the medium,
can be predictably transformed into neurons, among
other cell types [22]. In addition, a patent has been
issued for the increased production of adult stem cells
by the use of complex carbohydrates originating from
the cell wall of blue green algae and by complex fucans
(monosaccharides) of seaweed origin [23]. Thus, the
principle for the induction of adult stem cells by ingest-
ing complex carbohydrates of plant origin has been
well-established [24].
Supplementing with concentrated amounts of
dietary oligosaccharides has demonstrated benefit
for the following: cancer [25], HIV/AIDS [26, 27],
immune system functioning [28], hyperlipidemia [29,
30], atherogenesis [31], chronic fatigue syndrome [32],
and attention deficit hyperactivity disorder [33]. Addi-
tionally, a novel oligosaccharide-based, multinutrient
formula improved quality of life in an open-label, pilot
study of 48 AD patients [34]. Subjects were assessed
with a symptom severity measure adapted from the
Alzheimer’s Association [35]. At the end of 6 months,
25 subjects (52.1%) improved their AD severity score
by an average of 28.9%. The 23 non-responders
deteriorated in their severity score by an average of
34%. None of the subjects reported untoward side
effects.
Given the rising prevalence and cost of AD, treat-
ment options are limited, standard drugs and certain
nutrients have not been effective in restoring func-
tionality and quality of life, dietary supplement use
is highly prevalent among the elderly population [36,
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J.E. Lewis et al. / Aloe Polymannose Complex in AD 395
Table 1
Sociodemographic characteristics of the sample
Variable Category Baseline assessment
(n= 34)
Age – M = 79.9 (SD = 8.4; R= 60, 98)
Gender Male 6 (17.6%)
Female 28 (82.4%)
Race/ethnicity White, non-hispanic 10 (29.4%)
Black, non-hispanic 3 (8.8%)
Hispanic 21 (61.7%)
Education Up to high school 23 (67.6%)
Some post high school training 3 (8.8%)
College graduate 4 (11.8%)
Master’s degree or higher 4 (11.8%)
Marital status Never married 2 (5.9%)
Married 15 (44.1%)
Widowed 13 (38.2%)
Divorced 4 (11.7%)
Years diagnosed with
Alzheimer’s disease
– M = 3.2 (SD = 2.0; R= 1, 11)
M, mean; SD, standard deviation; R, range.
37], and the initial success of the aforementioned pilot
study, additional examination of the oligosaccharide-
based formula is justified. Thus, we investigated the
effect of a 12 month course of an oligosaccharide-
based multinutrient formula on cognitive and immune
functioning in a sample of persons with AD. Because
of the known links between chronic brain and sys-
temic inflammation and the neuropathology of AD
(i.e., cognitive impairment due to cytokine-mediated
interactions between neurons and glial cells) [38–43],
we evaluated a panel of cytokines and lymphocyte and
monocyte subsets in response to our intervention.
MATERIALS AND METHODS
Study participants
Participants (n= 34) were recruited from referrals
to the Miami Jewish Health Systems outpatient facil-
ity from 2008 to 2011. The study was conducted with
the approval of the Stein Gerontological Institute Insti-
tutional Review Board for human subjects research,
which operates within the standards set forth by the
Helsinki Declaration of 1975, and each subject (and/or
the primary caregiver) signed informed consent before
participating in the study. The sample comprised of
82% females (n= 28) and 18% males (n= 6) with
a mean age of 79.9 years (SD = 8.4; range = 60–98
years). The racial/ethnic distribution of the subjects
was as follows: 62% Hispanic (n= 21), 29% white,
non-Hispanic (n= 10), and 9% black, non-Hispanic
(n= 3). See Table 1 for all sociodemographic charac-
teristics of the sample. Subjects were not required to
stop or change their medication regimen for entry into
the study and continued taking their drugs as ordered
by the treating physician. Additionally, subjects had
to be diagnosed with moderate-to-severe AD for at
least 1 year prior to entering the study. Our partici-
pants were typically not eligible for other trials due to
the severity of their condition and/or other co-morbid
conditions. Each participant was evaluated by the study
psychiatrist prior to enrollment in the study to verify
the diagnosis of AD.
Intervention
The oligosaccharide-based multinutrient formula
used in this study is a nutritional supplement that has
been sold by several commercial entities for over 15
years. The formula used in the study is an aloe poly-
mannose multi-nutrient complex (APMC) composed
of the following constituents in a fixed combination by
weight, including: aloe powder containing more than
15% acetylated polymannose (BiAloe®), stabilized
rice bran, larch tree fiber, larch tree soluble extract,
cysteine, soy lecithin, UltraTerra®calcium alumino
silicate, cherry tart powder, inositol hexaphosphate,
dioscorea (yam) powder, omega 3 spherules, citric
acid, and glucosamine. The final product is a pow-
der, packaged in 300 gram containers, which dissolves
readily in any liquid. All participants consumed 1 tea-
spoon orally of the APMC four times per day (with
3 meals and before bedtime). The primary caregiver
was shown how to administer the APMC at the base-
line assessment, and the first dose was given to the
participant at our facility to ensure compliance with
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the method and to monitor for any complications or
adverse effects.
Outcomes and assessments
Each participant and caregiver completed a basic
demographics and medical history questionnaire at
baseline. In addition to a neuropsychological battery
to measure changes in cognitive functioning, activities
of daily living, and quality of life, a standard assess-
ment at each follow-up (3, 6, 9, and 12 months) was
conducted to monitor: (a) adverse reactions and com-
pliance to the intervention, (b) basic medical and health
status, and (c) current medications. A blood sample
was drawn at baseline and 12 months to assess changes
in cytokines and lymphocyte and monocyte subsets.
Criteria used to select the assessment included: (a)
appropriateness and sensitivity, (b) ease of administra-
tion and scoring, (c) adequate psychometric properties,
(d) sufficient content coverage, while not becom-
ing too much of a response burden for this sample,
(e) experience administering these measures, and (f)
employment of measures involving a multi-method
(i.e., self-report and observational tests and biologi-
cal measures) approach to enhance the validity of the
overall assessment.
The neuropsychological battery consisted of four
measures to assess changes in disease severity, over-
all cognitive functioning, and activities of daily living.
The Alzheimer’s Disease Assessment Scale-cognitive
score (ADAS-cog) [44] is a sensitive and reliable
psychometric scale and is considered the benchmark
measure to assess cognitive functioning in dementia
studies [45]. It has 11 subscales that evaluate mem-
ory, orientation, attention, language, reasoning, and
constructional and ideational praxis that are summed
to create a total cognition score [46]. The total score
can range from zero (no impairment) to 70 (severe
impairment). Different, counterbalanced word lists
were used at the follow-up visits to ensure that prac-
tice and carry-over effects would not confound our
results. The ADAS-cog assessment included an addi-
tional concentration score with values ranging from
zero (no impairment) to 5 (severe impairment). The
MMSE [47] is one of the most widely utilized and
popular brief cognitive assessments, providing a rapid
screen of orientation, registration, attention and cal-
culation, recall, and language domains. The score can
range from zero to 30 (25+ is normal) and can indi-
cate severe (≤9 points), moderate (10–20 points), or
mild (21–24 points) cognitive impairment [48]. The
modified 19-item Alzheimer’s Disease Cooperative
Study-Activities of Daily Living (ADCS-ADL) [49]
is a structured measure originally designed to assess
functional capacity over a wide range of dementia
severity. Each statement includes a series of hierarchi-
cal questions designed to determine the patient’s ability
to perform one of the activities of daily living, rang-
ing from total independence to total inability. A total
score of 54 signifies optimal performance, and lower
scores indicate worse performance. Caregivers were
asked to assess a patient’s activities during the preced-
ing four-week interval. The Severe Impairment Battery
(SIB) [50, 51] is a 40-item questionnaire designed to
assess the severity of cognitive dysfunction in AD and
is divided into nine domains: memory, language, ori-
entation, attention, praxis, visuospatial, construction,
orientation to name, and social interaction. The total
score on the SIB ranges from zero (greatest impair-
ment) to 100 (no impairment).
Sample collection and processing
Venous blood was obtained at two different time
points (baseline and 12 months) from all participants.
Blood samples were collected in EDTA tubes and
delivered to the laboratory within 2 hours of collection.
All specimens were subjected to complete blood cell
counts and auto 5-part differential count determina-
tions by a fully-automated Coulter AcT5 hematology
analyzer (Beckman Coulter, Fullerton, CA). Flow
cytometric enumeration of T, B, and NK cell subsets
were performed on a 4-color flow cytometer, FACS
Calibur (BD Biosciences, San Jose, CA), and the dif-
ferent cell populations were analyzed using Cell Quest
Pro software (version 5.2, BD Biosciences, San Jose,
CA).
Peripheral blood mononuclear cells (PBMC) were
isolated by Ficoll-Hypaque gradient centrifugation.
PBMC were recovered from the gradient interface
and washed in phosphate buffered saline. Blood was
diluted with 1 : 1 RPMI 1640 (Gibco, Grand Island,
NY), layered over Ficoll-Hypaque solution (Pharma-
cia, Piscataway, NJ), and centrifuged for 30 minutes
at 1,500 rpm at ambient temperature. The PBMC were
collected, washed with RPMI 1640, and counted and
assessed for viability in trypan blue dye. Plasma for
cytokine detection was separated and stored at −80◦C
until used.
Multiplex cytokine and growth factor testing
Due to their central role as signaling compounds in
the immune system, cytokines and growth factors are
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J.E. Lewis et al. / Aloe Polymannose Complex in AD 397
involved in a variety of immunological, inflammatory,
and infectious diseases. New microarray-based biochip
cytokine technologies combine the latest technological
advances with innovative system design to present a
fully-automated system for rapid multiplex testing. It
enables up to 12 cytokines and growth factors to be
detected simultaneously in a single sample, providing
valuable information related to each molecule being
tested and possible associations between them in each
sample. This system saves time, costs, and resources
and also provides high-quality, reliable results.
Cytokine and growth factor levels in plasma spec-
imens were measured using a biochip array system,
Evidence InvestigatorTM (Randox Laboratories Ltd.,
Crumlin, UK) as reported previously [52]. The testing
platform consists of biochips secured in the base of a
well placed in a carrier holding nine biochips in a 3×3
format. Each biochip is coated with the capture anti-
bodies specific for each of the 12 cytokines and growth
factors (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10,
IL-1␣, IL-1, interferon [IFN]-␥, tumor necrosis fac-
tor [TNF]-␣, monocyte chemotactic protein [MCP]-1,
vascular endothelial growth factor [VEGF], and epi-
dermal growth factor [EGF]) on a particular test region.
A sandwich chemiluminescent assay was performed
with 100 l plasma using reagents (including the cal-
ibrators and controls) and protocols supplied by the
same manufacturer. The light signal generated from
each of the test regions on the biochip was detected
using a charge-coupled detector camera and imaging
system and compared with a calibration curve gener-
ated with known standards during the same run. All
specimens were run in duplicate, and the concentra-
tion of each cytokine present in each plasma specimen
was calculated from the standard curve and reported in
pg/ml.
Statistical analysis
Data were analyzed using SPSS 19 (IBM Inc.,
Chicago, IL) for Windows. Frequency and descrip-
tive statistics were calculated on all variables. We
utilized linear mixed modeling (LMM) to assess the
fixed effect of time on changes in our outcome vari-
ables from baseline to follow-up. If the type III test
of the fixed effect of time was significant, then we
evaluated the parameter estimate between baseline
and 12 month follow-up. If that parameter estimate
was significant, then we used pairwise comparisons to
determine the unique differences between baseline and
follow-up at 3, 6, 9, and 12 months for the cognitive
assessment and between baseline and 12 months for
the physiological variables. LMM with heterogeneous
compound symmetry covariance allowed us to account
for subject attrition, inter-correlated responses between
time points, and non-constant variability. Given that
the ADAS-cog is widely recognized as the primary
neuropsychological measure to determine cognitive
functioning in AD trials, we categorized subjects at
each follow-up assessment as improved (≤−4), worse
(≥4), and no change (−3 to 3) according to other meth-
ods [45], as an additional measure of assessing the
efficacy of the intervention [53–56]. We examined the
relationships between the cognitive assessments and
the physiological outcomes at baseline and 12 months
follow-up with Pearson product-moment correlations.
The criterion for statistical significance was ␣= 0.05.
RESULTS
Safety and tolerability
During the 12 month study period, one subject’s
caregiver reported an initial 3-day period of loose
stool that was remedied by halving the amount of
supplement given per day and then increased to the
4 teaspoon/day amount in one week. A second sub-
ject’s caregiver reported elevations in blood pressure
and pulse, which were remedied by reducing the daily
amount to 1 teaspoon/day and increased by 1 tea-
spoon/day/week until achieving the desired dose of 4
teaspoons/day. No other adverse events were reported
in this study. Three participants died during the course
of the intervention, which were deemed unrelated to the
study: one male due to myocardial infarction and two
females due to stroke. Five other participants dropped
out of the study due to non-compliance with the proto-
col according to the caregivers (e.g., the participant was
unwilling to take the APMC 4 times per day), leaving
26 subjects who completed the 12 month intervention.
Table 2 shows the descriptive values of the ADAS-
cog cognition and concentration scores, MMSE,
ADCS-ADL, and SIB at baseline and 3, 6, 9 and
12 months follow-up. For the ADAS-cog cognition
score, a significant fixed effect was found for time
(F[4, 71.5] = 3.2, p< 0.05), and the parameter esti-
mate between baseline and 12 month follow-up was
also significant (t[74.4] = 2.0, p< 0.05). Pairwise com-
parisons revealed that ADAS-cog cognition score
significantly improved at 9 months (mean differ-
ence = 3.7; SE = 1.9; 95% CI: −0.02, 7.4; p= 0.05)
and at 12 months (mean difference = 3.8; SE = 1.8;
95% CI: 0.1, 7.5; p< 0.05) compared to baseline. For
the ADAS-cog concentration score, a non-significant
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398 J.E. Lewis et al. / Aloe Polymannose Complex in AD
Table 2
Descriptives for the ADAS-cog, MMSE, ADCS-ADL, and SIB
Variable Baseline 3 Months 6 Months 9 Months 12 Months
ADAS-cog cognition score* 42.0 ±14.0 43.8 ±15.5 41.7 ±15.2 37.8 ±14.5 37.8 ±12.9
(13, 69) (11, 69) (13, 69) (9, 68) (8, 70)
ADAS-cog concentration score 1.56 ±1.65 1.38 ±1.70 1.39 ±1.78 1.30 ±1.82 1.23 ±1.63
(0, 5) (0, 5) (0, 5) (0, 5) (0, 5)
MMSE 10.7 ±6.5 10.1 ±8.2 9.0 ±7.8 9.5 ±8.7 9.2 ±8.0
(0, 23) (0, 28) (0, 25) (0, 28) (0, 26)
ADCS-ADL* 17.7 ±12.6 18.4 ±13.4 15.0 ±11.0 14.1 ±9.9 13.2 ±10.9
(0, 47) (0, 53) (0, 50) (0, 43) (0, 49)
SIB* 58.1 ±31.4 57.5 ±32.2 53.6 ±32.5 49.5 ±34.1 48.9 ±35.3
(0, 96) (0, 95) (0, 93) (0, 95) (0, 97)
*Values are significantly different (p< 0.05) from Baseline to 12 Months, mean±standard deviation (minimum, maximum), and higher scores
indicate better performance on the MMSE, ADCS-ADL, and SIB, otherwise lower scores indicate improvement on the ADAS-cog cognition
and concentration scores.
Table 3
Cytokines and growth factors at baseline and 12 months follow-up
Variable Baseline 12 Months
IL-2 (pg/mL)* 6.4 ±4.6 (0, 19.1) 4.3 ±6.7 (0, 29.8)
IL-4 (pg/mL)* 0.94 ±1.42 (0, 4.3) 0.25 ±0.89 (0, 3.8)
IL-6 (pg/mL) 5.2 ±7.6 (0, 37.7) 5.1 ±11.6 (0, 56.5)
IL-8 (pg/mL) 7.4 ±11.3 (0, 62.9) 11.5 ±34.3 (0, 174.0)
IL-10 (pg/mL) 0.34 ±0.62 (0, 2.4) 0.97 ±3.65 (0, 18.4)
IL-1␣(pg/mL) 0.21 ±0.31 (0, 0.75) 0.13 ±0.60 (0, 3.0)
IL-1(pg/mL) 1.8 ±2.3 (0, 8.6) 4.0 ±10.8 (0, 44.0)
IFN-␥(pg/mL) 0.91 ±1.79 (0, 7.4) 0.47 ±1.21 (0, 5.0)
TNF-␣(pg/mL)* 2.8 ±1.6 (0, 5.0) 1.7±1.4 (0, 4.0)
MCP-1 (pg/mL) 127.3 ±62.8 (45.6, 302.5) 122.1 ±44.7 (47.6, 212.6)
VEGF (pg/mL)* 50.4 ±31.6 (12.8, 150.1) 31.2 ±22.6 (0, 79.9)
EGF (pg/mL) 10.1 ±14.0 (0, 53.7) 10.1 ±15.0 (0, 68.6)
*Values are significantly different (p< 0.05) from Baseline to 12 Months; mean ±standard deviation (minimum,
maximum).
fixed effect was found for time (F[4, 63.5] = 0.6,
p= 0.70). For the MMSE, a non-significant fixed
effect was found for time (F[4, 65.3] = 2.2, p< 0.10).
For the ADCS-ADL, a significant fixed effect was
found for time (F[4, 69.7] = 5.1, p< 0.01), and the
parameter estimate between baseline and 12 month
follow-up was also significant (t[75.7] = 3.2, p< 0.01).
Pairwise comparisons revealed that the ADCS-ADL
worsened from baseline to 9 months (mean differ-
ence = 3.1; SE= 1.3; 95% CI: 0.5, 5.7; p<0.05) and 12
months (mean difference = 4.3; SE=1.3; 95% CI: 1.6,
6.9; p< 0.01). The score at 3 months improved non-
significantly (mean difference = 1.9; SE = 1.5; 95%
CI: −1.1, 4.9; p= 0.20) above the baseline value.
For the SIB, a significant fixed effect was found for
time (F[4, 75.6] = 5.6, p< 0.01), and the parameter
estimate between baseline and 12 month follow-up
was also significant (t[81.8] = 3.7, p< 0.01). Pairwise
comparisons revealed that the SIB score worsened at
6 months (mean difference = 3.8; SE = 1.9; 95% CI:
0.01, 7.5; p= 0.05), 9 months (mean difference = 8.1;
SE = 2.1; 95% CI: 3.9, 12.4; p< 0.01), and 12 months
(mean difference = 8.0; SE = 2.2; 95% CI: 3.6, 12.4;
p< 0.01) compared to baseline. The score at 3 months
was unchanged from baseline (mean difference = 1.6;
SE = 2.0; 95% CI: −2.2, 5.5; p= 0.40).
According to the change in ADAS-cog cognition
score from baseline to 3 months, 16.7% of the sub-
jects improved, 46.7% did not change, and 36.7%
worsened. From baseline to 6 months, 29.0% of the
subjects improved, 38.7% did not change, and 32.3%
worsened. From baseline to 9 months, 47.8% of the
subjects improved, 26.1% did not change, and 26.1%
worsened. From baseline to 12 months, 46.2% of the
subjects improved, 23.1% did not change, and 30.8%
worsened.
Table 3 shows the descriptive values for all 12
cytokines and growth factors at baseline and 12 months
follow-up. For IL-2, a significant fixed effect was found
for time (F[1, 24.1] = 7.9, p= 0.01), and the parame-
ter estimate between baseline and 12 month follow-up
was also significant (t[24.1] = 2.8, p= 0.01). Pairwise
comparisons revealed that IL-2 declined from baseline
to 12 months (mean difference = 2.5; SE = 0.9; 95%
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J.E. Lewis et al. / Aloe Polymannose Complex in AD 399
Table 4
T cell subsets at baseline and 12 months follow-up
Variable Baseline 12 Months
WBC (Cells/L) 6,891.2 ±2,168.1 (2,700, 11,600) 6,652.0 ±2089.9 (3,300, 10,800)
Lymphs (%) 28.3 ±7.6 (14.3, 41.4) 29.9 ±8.0 (18.7, 48.1)
CD45+ (Cells/L) 1,897.2 ±709.3 (840, 3,828) 1,936.2 ±625.6 (780, 3,402)
CD3+ (%) 71.3 ±9.5 (46, 86) 71.8±8.6 (54, 88)
CD3+ (Cells/L) 1,342 ±503.7 (551, 2,666) 1,381.4 ±470.3 (507, 2,888)
CD3+ CD4+ (%) 46.6 ±9.8 (26.3, 68) 46.6 ±9.7 (31, 71)
CD3+ CD4+ (Cells/L) 861.7 ±293.3 (337, 1,514) 881.1 ±291.9 (398, 1,592)
CD3+ CD8+ (%) 24.4 ±9.8 (7, 43) 24.7 ±9.9 (2, 44)
CD3+ CD8+ (Cells/L) 476.2 ±292.6 (97, 1,418) 489.4 ±279 (32, 1,238)
B Cells CD19+ (%) 9.4 ±5.7 (0.9, 30) 9.2 ±6.4 (1, 28)
B Cells CD19+ (Cells/L) 193.4 ±191.4 (14, 1,093) 197.7 ±170.5 (16, 772)
NK Cells CD16 +56 (%) 18.5 ±9.1 (5.5, 46) 17.8 ±7.3 (4, 31)
NK Cells CD16 +56 (Cells/L) 346.2 ±203.8 (92, 838) 338.4 ±167.2 (71, 676)
CD3 + CD4 +/CD3 + CD8 + Ratio* 2.5±2.0 (0.6, 9.7) 3.4 ±6.8 (0.7, 35.5)
*Values are significantly different (p< 0.05) from Baseline to 12 Months; Values are mean ±standard deviation (minimum,
maximum).
Table 5
CD14, CD34, CD90, and CD95 subsets at baseline and 12 month follow-up
Variable Baseline 12 Months
CD34+ (%) 24.5 ±20.5 (0.3, 66.3) 13.1 ±18.2 (0.5, 56.9)
CD34+ (Cells/L) 441.6 ±378.8 (5, 1,251) 231.1 ±322.3 (6, 990)
CD90+ (%)* 9.3 ±15.1 (0.9, 48.1) 1.2 ±1.7 (0.1, 6.1)
CD90+ (Cells/L)* 154.4 ±251.0 (17, 775) 23.5 ±38.0 (2, 133)
CD95+ CD3+ (%)* 52.5 ±19.9 (7.1, 85.8) 15.6±16.6 (1.1, 65.5)
CD95+ CD3+ (Cells/L)* 937.7 ±396.9 (134, 1,586) 305.7 ±361.8 (15.0, 1,427)
CD95+ CD34+ (%)* 24.9 ±12.6 (5.7, 47.7) 4.3±10.3 (0.1, 39.5)
CD95+ CD34+ (Cells/L)* 427.3 ±198.8 (127, 796) 87.3±222.7 (2, 861)
CD95+ CD90+ (%)* 7.5 ±12.0 (0.8, 40.9) 1.7 ±2.7 (0, 9.4)
CD95+ CD90+ (Cells/L) 125.3 ±196.0 (13, 659) 31.1 ±44.2 (0, 129)
CD14+ (%)* 10.3 ±5.0 (5.5, 17.6) 39.8 ±22.6 (5.2, 80.0)
CD14+ CD34+ (%) 7.5 ±14.3 (0, 38.4) 3.4 ±4.9 (0.3, 18.5)
CD14+ CD90+ (%)* 18.0 ±16.4 (1.9, 61.3) 2.4 ±3.6 (0.1, 14.3)
CD14+ CD95+ (%)* 77.5 ±19.0 (23.7, 97.3) 26.2 ±19.2 (4.9, 82.7)
*Values are significantly different (p< 0.05) from Baseline to 12 Months; Values are mean ±standard deviation (minimum,
maximum).
CI: 0.7, 4.4; p= 0.01). For IL-4, a significant fixed
effect was found for time (F[1, 32.6] = 5.2, p< 0.05),
and the parameter estimate between baseline and 12
month follow-up was also significant (t[32.6] = 2.3,
p< 0.05). Pairwise comparisons revealed that IL-4
declined from baseline to 12 months (mean differ-
ence = 0.69; SE = 0.30; 95% CI: 0.07, 1.30; p< 0.05).
For TNF-␣, a significant fixed effect was found for
time (F[1, 34.3] = 7.3, p< 0.05), and the parameter esti-
mate between baseline and 12 month follow-up was
also significant (t[34.3] = 2.7, p< 0.05). Pairwise com-
parisons revealed that TNF-␣declined from baseline
to 12 months (mean difference = 1.13; SE=0.42; 95%
CI: 0.28, 1.98; p< 0.05). For VEGF, a significant fixed
effect was found for time (F[1, 29.2] = 13.5, p< 0.01),
and the parameter estimate between baseline and 12
month follow-up was also significant (t[29.2] = 3.7,
p< 0.01). Pairwise comparisons revealed that VEGF
declined from baseline to 12 months (mean differ-
ence = 19.5; SE = 5.3; 95% CI: 8.6, 30.3; p< 0.01).
All other cytokines and growth factors showed non-
significant changes from baseline to 12 months.
Table 4 shows the descriptive values of the T
cell subsets, including CD45+, CD3+, CD3+CD4+,
CD3+CD8+, CD19+, and CD16+56+, none of which
significantly changed from baseline to 12 months
follow-up. For the CD3+CD4+/CD3+CD8+ratio, a
significant fixed effect was found for time (F[1,
520.7] = 4.0, p< 0.05), and the parameter estimate
between baseline and 12 month follow-up was also
significant (t[520.7] = 2.0, p< 0.05). Pairwise compar-
isons revealed that the CD3+CD4+/CD3+CD8+ ratio
increased from baseline to 12 months (mean differ-
ence = 2.7; SE=1.4; 95% CI: 0.04, 5.4; p< 0.05).
AUTHOR COPY
400 J.E. Lewis et al. / Aloe Polymannose Complex in AD
Table 5 shows the descriptive values of the
CD14+, CD34+, CD90+, and CD95+ protein sub-
sets, which revealed significant changes other than in
the CD34+ cells. For CD90+ (%), a significant fixed
effect was found for time (F[1, 286.6] = 4.2, p< 0.05),
and the parameter estimate between baseline and 12
month follow-up was also significant (t[286.6] = 2.1,
p< 0.05). Pairwise comparisons revealed that the
CD90+ (%) decreased from baseline to 12 months
(mean difference = 8.9; SE = 4.3; 95% CI: 0.39, 17.4;
p< 0.05). For CD95+CD3+ (%), a significant fixed
effect was found for time (F[1, 29.0] = 26.4, p< 0.01),
and the parameter estimate between baseline and 12
month follow-up was also significant (t[29.0] = 5.1,
p< 0.01). Pairwise comparisons revealed that the
CD95+CD3+ (%) decreased from baseline to 12
months (mean difference = 36.8; SE = 7.2; 95% CI:
22.1, 51.4; p< 0.01). For CD95+CD34+ (%), a
significant fixed effect was found for time (F[1,
29.8] = 25.3, p< 0.01), and the parameter estimate
between baseline and 12 month follow-up was
also significant (t[29.8] = 5.0, p< 0.01). Pairwise
comparisons revealed that the CD95+CD34+ (%)
decreased from baseline to 12 months (mean differ-
ence = 22.1; SE = 4.4; 95% CI: 13.1, 31.0; p< 0.01).
For CD95+CD90+ (%), a significant fixed effect was
found for time (F[1, 41.6] = 10.2, p< 0.01), and the
parameter estimate between baseline and 12 month
follow-up was also significant (t[41.6] = 3.2, p< 0.01).
Pairwise comparisons revealed that the CD95+CD90+
(%) decreased from baseline to 12 months (mean dif-
ference = 9.0; SE = 2.8; 95% CI: 3.3, 14.6; p< 0.01).
For CD14+ (%), a significant fixed effect was found for
time (F[1, 50520.3] = 42.8, p< 0.01), and the parame-
ter estimate between baseline and 12 month follow-up
was also significant (t[50520.3] = 6.5, p< 0.01). Pair-
wise comparisons revealed that the CD14+ (%)
increased from baseline to 12 months (mean differ-
ence = 25.4; SE = 3.9; 95% CI: 17.8, 33.0; p< 0.01).
For CD14 + CD90+ (%), a significant fixed effect
was found for time (F[1, 119.3] = 10.9, p< 0.01),
and the parameter estimate between baseline and 12
month follow-up was also significant (t[119.3] = 3.3,
p< 0.01). Pairwise comparisons revealed that the
CD14 + CD90+ (%) decreased from baseline to 12
months (mean difference = 15.9; SE = 4.8; 95% CI:
6.3, 25.4; p< 0.01). For CD14 + CD95+ (%), a
significant fixed effect was found for time (F[1,
30.2] = 47.7, p< 0.01), and the parameter estimate
between baseline and 12 month follow-up was also
significant (t[30.2] = 6.9, p< 0.01). Pairwise compar-
isons revealed that the CD14 + CD95+ (%) decreased
from baseline to 12 months (mean difference = 50.7;
SE = 7.3; 95% CI: 35.7, 65.7; p< 0.01).
At baseline, the ADAS-cog cognition score was
inversely related to VEGF (r=−0.35, p< 0.05),
CD90+ (%; r=−0.57, p= 0.05 and cells/uL; r=−0.58,
p= 0.05), and CD95 + CD90+ (%; r=−0.60, p< 0.05
and cells/uL; r=−0.62, p< 0.05). The MMSE was
linearly related to CD90+ (%; r= 0.57, p= 0.05 and
cells/uL; r= 0.57, p= 0.05) and CD95 + CD90+ (%;
r= 0.61, p< 0.05 and cells/uL; r= 0.61, p< 0.05). The
ADAS-cog concentration score was inversely related
to CD14+ (%; r=−0.59, p= 0.05).
At 12 months follow-up, the ADCS-ADL was
linearly related to IL-4 (r= 0.44, p< 0.05). The ADAS-
cog concentration score was linearly related to IL-2
(r= 0.45, p< 0.05), IL-6 (r= 0.49, p< 0.05), IL-10
(r= 0.58, p< 0.01), IL-1␣(r= 0.57, p< 0.01), IL-1
(r= 0.44, p< 0.05), and IFN-␥(r= 0.54, p< 0.01).
The ADAS-cog cognition score was inversely related
to CD19+ (%; r=−0.49, p< 0.05 and cells/uL;
r=−0.46, p< 0.05) and linearly related to the
CD3+CD4+/CD3+CD8+ ratio (r= 0.51, p< 0.01). The
ADAS-cog concentration score was linearly related
to CD3+CD4+ (%; r=−0.47, p< 0.05) and the
CD3+CD4+/CD3+CD8+ ratio (r= 0.58, p< 0.01) and
was inversely related to CD3+ CD8+ (%; r=−0.45,
p< 0.05 and cells/uL; r=−0.46, p< 0.05).
DISCUSSION
The loss, agony, and frustration of the victims of
AD and their caregivers are collectively immeasur-
able and call science to continued and urgent action to
counteract this debilitating disease. Additionally, the
prevalence of AD and its associated financial costs are
a significant drain on an already overburdened U.S.
health system and are getting worse. This cause of
death shows signs of spiraling out of control with an
aging U.S. population and no options for prevention
or treatment of the disease. Thus, any intervention that
demonstrates promise for improving the condition of
the AD patient is urgently needed.
In the current study, we have demonstrated in an
open-label trial that cognitive functioning improved
in AD victims over a 12 month period according to
the ADAS-cog cognition score, the most widely uti-
lized tool of its type for dementia research [57]. While
cognitive functioning briefly worsened at the 3-month
assessment, we showed improvement in our partici-
pants from 6 to 12 months in response to taking the
APMC dietary supplement. Almost half (46%) of our
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J.E. Lewis et al. / Aloe Polymannose Complex in AD 401
sample showed clinically-significant improvement at
12 months according to the change (≤−4 points) on
the ADAS-cog cognition score [45].
Given that cognitive functioning worsens over time
in the typical AD patient regardless of treatment [1],
our finding that cognitive functioning improved on the
ADAS-cog cognition score is promising. The MMSE
showed essentially no difference in score over the
course of the intervention, while the average score at
baseline was consistent with an indication of severe
impairment in this sample. Although our subjects
appeared to decline according to the SIB and the
ADCS-ADL, we are encouraged by the findings in
the ADAS-cog cognition score. Given the dissimilar-
ities between the ADAS-cog cognition score and the
SIB and the ADCS-ADL scores, we can only specu-
late that discrepancies in our battery occurred because
these assessments have different items and scales (and
units of measure) and are evaluating different domains.
Additionally, we are uncertain about the clinical mean-
ingfulness of the change in SIB (9-point drop at 12
months) and ADCS-ADL (4-point drop at 12 months)
scores, unlike the ADAS-cog, which has been cited
consistently as the most important cognitive assess-
ment in research for AD participants [45, 53–56].
Our study may also be one of the first of its kind
to assess a panel of 12 cytokines (pro- and anti-
inflammatory) and growth factors before and after
dietary supplementation in AD. To our knowledge,
cytokines have been assessed (e.g., IL-1, TNF-␣,
and IL-6) in AD patients and compared to controls
or other disease groups, such as vascular dementia or
cerebrovascular disease, but typically these are cross-
sectional or observational studies, not clinical trials
[43, 58]. Thus, the scope of our assessment contributes
to a broader understanding of the links (or lack thereof)
between selected markers of immune functioning and
AD in response to improved nutritional status with
APMC. Additionally, we did not observe changes over
time in some of our markers (e.g., IL-1, IL-6, and
IL-10), even though they have previously been associ-
ated with AD in some mechanistic fashion [42, 43].
In the present study, we showed that IL-2 decreased
in response to APMC, which is consistent with the
normal decline in IL-2 production and expression over
time found among the elderly [59]. Other investigators
have noted that while weakened immune functioning
in AD is also a hallmark of aging generally, low IL-
2 production in this population may determine their
increased susceptibility to infections [60], although
no change in co-morbid infections was noted in our
study. We also showed a non-significant decrease in
IFN-␥that paralleled the reduction in IL-2 (values were
significantly correlated at baseline [r= 0.50, p< 0.01]
and 12 months [r= 0.68, p< 0.01]), which is consistent
with other findings that IL-2 induces interferons [61].
Thus, our results may suggest the presence of altered
Th-1 clones (secretors of IL-2 and IFN-␥) in our sam-
ple of moderate-to-severe AD participants in response
to APMC [62].
We also found a significant decrease in the
anti-inflammatory IL-4, which is posited as capa-
ble of reducing neuroinflammation by blunting the
pro-inflammatory activity of IL-1[39]. Given the
non-significant rise in IL-1, our results are consis-
tent with that hypothesis. Although IL-4 decreased in
our sample, the 12 month level was still higher than
that found in another study of AD participants [63].
Thus, as with most cytokines, a clinically-determined
level that is directly related to AD symptomatology and
functioning is essentially unknown at this time. TNF-␣
significantly declined in response to supplementation
with APMC, perhaps offering a promising means to
reduce the chronic inflammatory load consistent with
AD, neurodegeneration, and neuroinflammation. TNF-
␣has many recognized physiological functions, but
it has been historically linked to a variety of human
diseases and in particular is now related to neuroin-
flammation, neurodegeneration, and an etiology of
cognitive dysfunction and AD through several mech-
anisms [64–66]. In fact, TNF-␣and other cytokines
have been shown to be elevated in the cerebrospinal
fluid and plasma of persons with AD compared to con-
trols [43, 67, 68], but the findings are not unequivocal
as other studies show no differences [69, 70]. Nonethe-
less, anti-TNF-␣therapy has been posited as way to
prevent or decrease the effects of neuroinflammation
and perhaps cognitive disorders, but that position is
controversial [65, 66]. Our results suggest that APMC
has an anti-TNF-␣effect.
We also found a substantial drop in VEGF levels at
the 12 month follow-up assessment. Others have sug-
gested that VEGF might be linked to the progression of
AD through abnormal endothelial activation, resulting
in neuronal loss and Adeposits [42]. Another group
identified associations between well-known VEGF
genotypes and specific genotype combinations and the
risk for development of AD [71]. Our higher VEGF
concentration at baseline may also support the hypoth-
esis that VEGF lacks a neuroprotective effect among
neurodegenerative disorders [71, 72].
We studied an extensive panel of T and B cell (lym-
phocyte and monocyte) subsets, which may also be a
unique contribution to the AD literature in response
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402 J.E. Lewis et al. / Aloe Polymannose Complex in AD
to a dietary supplement intervention. Several similar
lymphocytes were studied in response to methylpred-
nisolone in multiple sclerosis patients [73], which
has an obvious similar neurodegeneration etiology
to AD. We found no relative or absolute changes
in T cell (CD3+, CD3+CD4+, and CD3+CD8+), B
cell (CD19+), or natural killer cell (CD16+56+) sub-
sets. The CD3+CD4+/CD3+CD8+ ratio increased at
follow-up, perhaps suggestive of a positive response
to supplementing with APMC, as this ratio classi-
cally has been shown to decline with age [74] and/or
in the presence of immunodeficiency, such as HIV
[75]. Thus, our study might be the first to demonstrate
an increase in this ratio in a sample of persons with
AD. Conversely, relative and absolute decreases were
noted in lymphocyte regions (CD90+, CD95+CD3+,
CD95+CD34+, and CD95+CD90+) and relative
decreases in monocyte regions (CD14+CD90+ and
CD14+CD95+). Only the relative CD14+ monocytes
increased at follow-up. We noted inverse correlations
at baseline between the ADAS-cog cognition score
with CD90+ and CD95+CD90+ and with CD19+at 12
months follow-up, thus providing some evidence for
clinical performance being observed in parallel with
decreases in T and B cell activity.
In support of other prior sub-clinical work men-
tioned below, our study showed an increase in CD14+
(%) in response to the intervention, and we also
found that the ADAS-cog concentration score was
inversely related to the CD14+level at the baseline
assessment. CD14+ is known as the monocyte receptor
for Gram-negative bacterial lipopolysaccharide (LPS)
[76]. Monocytes express many pro-inflammatory
cytokines, when stimulated with LPS through the
CD14+ receptor [77]. CD14+ expression is greater in
microglia in an AD-mouse model, and microglia from
CD14-insufficient mice showed reduced activation of
Apeptide, signifying that CD14+ is necessary for
A-induced microglia activation [78]. However, an
AD case-control human study found no relationship
between the CD14+ (−260) polymorphism, several
pro-inflammatory cytokine genes, and AD [77].
In summary, neuroinflammation is suspected of
being causative in the pathogenesis of neurodegenera-
tive diseases [79], and many studies have demonstrated
mechanistic links among multiple inflammatory path-
ways in AD [39]. Nonetheless, due to the inconsistency
in the prior findings of these mechanisms and immune
markers [43, 80], the field is incapable of making
absolute treatment or diagnostic recommendations for
those suffering from the disease. However, few studies
have showed changes in biomarkers of neuroinflam-
mation in neurodegenerative diseases, particularly in
AD after 12 months of intervention. In our study,
we have showed multi-directional immunomodulation
in response to APMC in the profile of this sample
of AD patients. We showed statistically significant
changes in the values of IL-2, IL-4, TNF-␣, and VEGF,
and multiple lymphocyte and monocyte regions, along
with several correlations in these markers with cogni-
tive functioning according to the ADAS-cog cognition
score.
Limitations
We note several limitations of the current investi-
gation. In this study, we did not assess dietary intake,
physical activity level, depression, anxiety, or caregiver
support, so we are unsure how these variables could
have affected the results of the study. Our neuropsy-
chologist was not blinded to the study participants, but
she assessed subjects for all studies occurring simul-
taneously at our center, so her influence on this study
should have been no different than on any other. It
was not possible to objectively determine compliance
with the protocol, as the APMC formula does not
readily lend itself to metabolite analysis. The findings
of our study are limited by a small sample size. A
larger sample size could result in even more signifi-
cant findings for cognitive functioning, cytokines, and
lymphocyte and monocyte subsets. A larger sample
could have also helped to resolve the discrepancy in our
findings between the ADAS-cog cognition score and
the SIB and ADCS-ADL. The results of our cytokine
and growth factor assays could have been unduly
influenced by the combination of our participants’
medications, although that position is not definitive
[80]. As the purpose of our study was to evaluate the
effect of improved nutritional status with APMC on
cognitive and immune functioning, we did not restrict
or change the use of medications by our participants,
given the ethical considerations associated with such
decision. For our blood sampling procedures, we uti-
lized all leukocyte cell populations (e.g., lymphocytes,
macrophages, and monocytes), which also could have
affected the results of our immune functioning mark-
ers [80]. Nonetheless, the Ficoll-Hypaque gradient is
easily replicated clinically, is simple, does not alter the
function of isolated cells, and thus is routinely used
in many settings. Using this methodology, 60–70% of
the cells are lymphocytes, while the remaining cells
are monocytes and macrophages. Although we found
significant changes in several key cytokines and T and
B cell subsets from baseline to 12 months follow-up,
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J.E. Lewis et al. / Aloe Polymannose Complex in AD 403
we are uncertain if these markers demonstrate lin-
ear or quadratic responses during that time. Because
of the complexity in the cytokine network involving
bi-directional feedback, pleiotropism makes it com-
plicated to surmise the exact mechanisms of individual
markers. Additionally, these cells have been noted to
drift between neuroprotection and neuroinflammation,
so even within the same marker lies complex answers
to questions about how the immune system works
(i.e., the role of IL-6 in AD etiology) [39]. Thus, hav-
ing more frequent assessments of these markers might
help to better elucidate their responses to the APMC
formula and its ability to modulate immune system
function over an extended period of time.
CONCLUSIONS
AD is an escalating burden for patients and their
families. In addition, with the global population of aged
individuals increasing exponentially, AD represents a
significant economic drain on society. The develop-
ment of an effective approach for the treatment of
AD is thus of major importance, as current strategies
are limited to agents that attempt to attenuate disease
symptomatology without addressing the causes of dis-
ease. A considerable need exists for the development
of an effective therapy to prevent, or at least delay, the
progression of AD.
The APMC formula used in the current study was
well-tolerated among all subjects. The product showed
a significant improvement in the ADAS-cog cogni-
tion score and demonstrated sound immunomodulator
activity with noteworthy responses in cytokines and
several lymphocyte and monocyte subsets. Several
correlations were found between the cognitive assess-
ments and the physiological outcomes at baseline
and 12 months follow-up. Our results are consistent
with prior work by other investigators using similar
oligosaccharide-based formulae, who also demon-
strated improvements in various indices of quality of
life and functioning in other disease states. At this
time, the mechanism by which APMC influences cog-
nitive functioning in AD is unclear. The amelioration
of cognitive functioning may be associated with some
modulation of host immune activity, but additional
immune functioning data are required to understand
with more certainty. However, what is clear is that our
results compel further study, especially in the inves-
tigation of an AD-type neurodegeneration model that
may eventually enable elucidation of the mechanism(s)
at work. Utilizing an AD-type neurodegeneration
model would allow us to gain deeper, if not novel,
insights into the pathophysiology of a disease that is
the source of much human suffering.
Thus, our study shows that a high-quality, con-
centrated dietary supplement may offer an alternative
option for persons with AD. This APMC formula may
not only facilitate cognitive improvement, but may also
improve the inflammatory and immune functioning
profile as well, thereby enhancing host recovery and
improving overall quality of life.
ACKNOWLEDGMENTS
We are thankful to all the volunteers and their care-
givers and key family members who participated in this
study. This study was supported by gifts from Ray and
Ann Brazzel, the Fisher Institute for Medical Research,
and NutraSpace. The University of Miami Labora-
tory for Clinical and Biological Studies performed all
immune functioning assays and assessments. Study
products were supplied by Mannatech, Inc. and Well-
ness Quest, Inc.
Authors’ disclosures available online (http://www.j-
alz.com/disclosures/view.php?id=1479).
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