Effects of Aloe vera Supplementation in Subjects
with Prediabetes/Metabolic Syndrome
Sridevi Devaraj, Ph.D., DABCC,1Mesfin Yimam, D.V.M., M.S.,2Lidia A. Brownell, M.S.,2
Ishwarlal Jialal, M.D., Ph.D.,3Sital Singh, B.S.,3and Qi Jia, Ph.D.2
Background: Metabolic syndrome affects 1 in 3U.S. adults. The primary target of treatment of patients with
metabolic syndrome is therapeutic lifestyle change. Numerous animal trials have reported positive effects of Aloe
vera in in vivo models of diabetes, but there is a paucity of controlled clinical trials in patients with prediabetes.
Thus, the objective of this pilot study was to examine the effect of aloe compared to placebo on fasting blood
glucose, lipid profile, and oxidative stress in subjects with prediabetes/metabolic syndrome.
Methods: This was a double-blind, placebo-controlled Institutional Review Board (IRB)–approved pilot study of
two aloe products (UP780 and AC952) in patients with prediabetes over an 8-week period. A total of 45 subjects
with impaired fasting glucose or impaired glucose tolerance and having two other features of metabolic syn-
drome were recruited (n=15/group). Parameters of glycemia [fasting glucose, insulin, homeostasis model as-
sessment (HOMA), glycosylated hemoglobin (HbA1c), fructosamine, and oral glucose tolerance test (OGTT)]
and oxidative stress (urinary F2-isoprostanes) were measured along with lipid profile and high-sensitivity C-
reactive protein (hsCRP) levels before and after supplementation.
Results: There were no significant baseline differences between groups. Compared to placebo, only the AC952
Aloe vera inner leaf gel powder resulted in significant reduction in total and low-density lipoprotein cholesterol
(LDL-C) levels, glucose, and fructosamine. In the UP780 Aloe vera inner leaf gel powder standardized with 2%
aloesin group, there were significant reductions in HbA1c, fructosamine, fasting glucose, insulin, and HOMA.
Only the UP780 aloe group had a significant reduction in the F2-isoprostanes compared to placebo.
Conclusions: Standardized aloe preparations offer an attractive adjunctive strategy to revert the impaired fasting
glucose and impaired glucose tolerance observed in conditions of prediabetes/metabolic syndrome.
including obesity, insulin resistance, glucose intolerance,
hypertension, and dyslipidemia [hypertriglyceridemia and
low high-density lipoprotein cholesterol (HDL-C) levels],
which are established criteria for diagnosing metabolic syn-
drome in 2001.1–3Five criteria were selected by The Adult
Treatment Panel III (ATP III) of the National Cholesterol
Education Program (NCEP) to identify individuals with
metabolic syndrome—abdominal obesity, impaired fasting
glucose, high triglyceride (TG) and low HDL-C concentra-
tions, and increased blood pressure.1–3Metabolic syndrome
is diagnosed when any three of the components are present
etabolic syndrome, also referred to as prediabetes,
is a cluster of interrelated common clinical disorders,
in an individual. The metabolic syndrome is highly prevalent
worldwide and is associated with a greater risk of athero-
sclerotic cardiovascular disease than any of its individual
components and leads to a five-fold increase in diabetes and
a two-fold increase in cardiovascular disease. One in 3 in-
dividuals in the United States has metabolic syndrome. The
primary target of treatment of patients with metabolic syn-
drome is therapeutic lifestyle changes, which are difficult to
Numerous animal trials have reported positive effects of Aloe
vera in in vivo models of diabetes, including lower fasting blood
glucose levels in alloxan-induced diabetic mice4; enhanced
glucose tolerance in glucose-loaded rats compared to normals5;
decreased glucose levels in streptozotocin-induced diabetic
1Department of Pathology and Immunology, Baylor College of Medicine, and Texas Children’s Hospital, Houston, Texas.
2Unigen Inc., Seattle, Washington.
3Laboratory for Atherosclerosis and Metabolic Research, UC Davis Medical Center, Sacramento, California.
METABOLIC SYNDROME AND RELATED DISORDERS
Volume X, Number X, 2012
? Mary Ann Liebert, Inc.
MET-2012-0066-ver9-Devaraj_3P.3d 09/29/1212:47pm Page 1
1 1 1
diabetic rats7; decreased oxidative damage in the brains of
streptozotocin-induced diabetic mice8; decreased lipid perox-
induced diabetic rats, decreased fasting glucose, normalized
lipids and fatty acid compositions in liver and kidney with
reduced liver transaminases, and improved plasma insulin
In contrast to animal studies, very few human clinical
trials have been reported in the literature. The two studies
most frequently cited to support the use of aloe in human
diabetes12,13have methodological flaws, which unfortu-
nately brings the significance of the results into question
(nonrandomized and nonblinded, apparently the same
population enrolled in both trials, the same decreases in both
blood glucose and serum triglycerides in the active groups
reported for both trials). A third study, evaluating the effects
of bread prepared with aloe gel consumed twice daily for
3 months in subjects with heart disease reported an inci-
dental finding of decreased fasting and postprandial blood
glucose levels in the subjects who also had a diagnosis
of diabetes.14Additionally, anecdotal reports of beneficial
effects of aloe in clinical diabetes also exist.
Recently, Huseini et al. examined the effect of Aloe vera gel
in hyperlipidemic type 2 diabetic patients who were already
on antiglycemic medications and reported that aloe gel
(300mg twice a day for 2 months compared to placebo)
significantly lowered fasting blood glucose, glycosylated
hemoglobin (HbA1c), total and low-density lipoprotein
cholesterol (LDL-C) levels with no other side effects.15
However, there are no reports of Aloe vera supplementation
in patients with prediabetes/metabolic syndrome. Thus, the
overall objective of this pilot study is to examine the effect of
two aloe products compared to placebo on fasting blood
glucose, lipid profile, and biomarkers of oxidative stress in
an 8-week study.
Subjects and Methods
This was a double-blind, placebo-controlled study. The
test products used were supplied by Unigen Inc., and in-
vestigators and volunteers were blinded to treatment as-
signment. The study received Institutional Review Board
(IRB) approval, and all subjects provided informed consent.
The products used were: Aloe product 1, UP780, an Aloe vera
inner leaf gel powder standardized with 2% aloesin, 500-mg
capsules, 1 capsule twice a day (b.i.d.); aloe product 2,
QMatrix or AC952, an Aloe vera inner leaf gel powder,
500-mg capsules, 1 capsule b.i.d; placebo capsules, 1 capsule
b.i.d. All products were dispensed to the subjects by the
Investigational Drug Services.
All study subjects had three features of the metabolic
syndrome, of which at least one feature was abnormal fast-
ing glucose (100–126mg/dL) or abnormal glucose tolerance
[2-h oral glucose tolerance test (OGTT) >140–199mg/dL]
but no history or current clinical evidence of diabetes (type I
or II). The selection criteria were as follows. Inclusion criteria
were: Females and males >18 years of age to 70 years of age;
prediabetes, defined as fasting plasma glucose (FPG) 90–
125mg/dL, or 2-h OGTT 149–199mg/dL plus any two of the
following criteria—waist >35 inches for women and >40
inches for men, triglycerides (TG) >150mg/dL, HDL-C
<40mg/dL in men and <50mg/dL in women, and systolic
(SBP) or diastolic blood pressure (DBP) >130/85mmHg.
Exclusion criteria were: Prior diagnosis of diabetes, preg-
nancy/lactation, history of gestational diabetes, currently on
any diabetes medication for any indication, history of any
other chronic disease, and known allergy to Aloe vera or any
products containing Aloe vera.
Only subjects who were willing to maintain a normal diet
and exercise at least 100min per week were included in the
study. The subjects also abstained from any other dietary
supplements or weight loss programs during the study. All
subjects were at least 95% compliant throughout the study as
monitored by pill counts. Fasting blood was obtained at
baseline and following 8 weeks of supplementation. All
subjects underwent a 75-g OGTT and fasting glucose levels
at 0, 1, and 2h was obtained and area under the curve (AUC)
Routine laboratory tests were performed in the Clinical
Pathology laboratory, which is Clinical Laboratory Im-
provement Amendments (CLIA)–certified and included
complete blood counts, lipid profile, glucose, HbA1c, liver
function tests, creatinine, and insulin. Fructosamine levels
were measured by an enzymatic assay from Diazyme.
Briefly, the Diazyme Glycated Serum Protein (GSP) uses
proteinase K to digest GSP into low-molecular-weight gly-
cated protein fragments (GPF), and uses Diazyme’s specific
fructosaminase?, a microorganism-originated amadoriase
to catalyze the oxidative degradation of Amadori product
GPF to yield PF or amino acids, glucosone, and hydrogen
peroxide (H2O2). The H2O2released is measured by a col-
orimetric Trinder end-point reaction. The absorbance at
600nm is proportional to the concentration of fructosamine
in the sample.
Urine was collected at baseline and following 8 weeks
supplementation (24-h urine) for assessment of urinary
microalbumin:creatinine ratio in the Clinical Pathology
laboratory and for assessment of urinary F2-isoprostanes.
using the Cayman enzyme immunoassay as described
Table 1.Baseline Subject Characteristics
Total cholesterol (mg/dL)
50.5–10.7 50.6–10.6 57.2–9.5
Data are provided as mean–standard deviation (SD).
BMI, body mass index; M/F, male/female; HDL-C, high-density
lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol;
HbA1c, glycosylated hemoglobin; AUC, area under the curve; Glu-
OGTT, glucose tolerance.
2DEVARAJ ET AL.
MET-2012-0066-ver9-Devaraj_3P.3d09/29/12 12:47pmPage 2
All data were analyzed using SAS. Kruskal–Wallis anal-
ysis of variance (ANOVA) was computed followed by Wil-
coxon tests to assess statistical significance.
A total of 45 subjects with impaired fasting glucose or
impaired glucose tolerance and having two other features of
the metabolic syndrome were recruited. A total of 14 subjects
in placebo, 14 subjects in UP780, and 15 subjects in AC952
groups completed the study, and results are reported. No
side effects were reported. Table 1 gives the subject charac-
teristics of all subjects in the study. There were no significant
baseline differences between groups. There were no significant
changes in complete blood count, aspartate aminotransferase
(AST), alanine aminotransferase (ALT), creatinine, before and
after supplementation (data not shown). Compliance was very
Table 2 provides the effect of Aloe vera supplementation
versus placebo on the lipid profile and high-sensitivity
C-reactive protein (hsCRP) levels. As seen, compared to
placebo, only the AC952 regular Aloe vera inner leaf gel
powder preparation resulted in significant reduction on total
cholesterol and LDL-C levels. None of the other parameters
With regard to parameters of insulin resistance and dys-
glycemia, which are reported in Table 3, in the UP780 Aloe
vera inner leaf gel powder standardized with 2% aloesin
group, there were significant reductions in HbA1c as well as
in fructosamine levels, indicators of glycemic control. While
fasting blood glucose was significantly reduced, there were
no changes in the AUC of glucose values obtained from the
2-h OGTT. Also, insulin levels were significantly decreased.
Thus, in the UP780 group, there was significant reduction in
homeostasis model assessment (HOMA), a marker of insulin
sensitivity (Fig. 1). In the AC952 aloe group, in addition to a
decrease in fructosamine, there were significant reductions in
glucose values after supplementation. There were no chan-
ges in the urinary microalbumin:creatinine ratios in any of
Because aloe has been shown to improve oxidative stress
in diabetic rats and because oxidative stress can contribute to
diabetic complications, we tested the effect of two Aloe vera
supplementations on a prototypic biomarker of lipid oxida-
tion, urinary F2-isoprostanes. As seen in Fig. 2, only the
UP780 aloe group showed a significant reduction in the F2-
isoprostanes; the reduction in the AC952 group was not
significantly different compared to placebo.
The metabolic syndrome is highly prevalent worldwide
and is associated with a greater risk of atherosclerotic
cardiovascular disease than any of its individual compo-
nents and leads to a five-fold increase in diabetes and a
two-fold increase in cardiovascular disease.1–3The primary
target of treatment of patients with metabolic syndrome is
therapeutic lifestyle changes, which are difficult to achieve
and, thus, any adjunctive measures to reduce the burden
of diabetes and cardiovascular disease in this population
Numerous animal trials have reported positive effects
of Aloe vera in rat models of diabetes; however, there are
very few clinical trials in humans.4–11There are several
Table 2. Effect of Aloe vera Supplementation on the Lipid Profile and hsCRP
Total cholesterol (mg/dL)
Data are provided as mean–standard deviation (SD) except hsCRP, for which the median is provided.
**P<0.05 compared to placebo and baseline.
hsCRP, high-sensitivity C-reactive protein; HDL-C, high-density lipoprotein; LDL-C, low-density lipoprotein.
Table 3.Effect of Aloe vera Supplementation on Parameters of Glycemia and Insulin Resistance
Data are provided as mean–standard deviation (SD).
*p<0.02 and **p<0.05 compared to placebo and baseline.
HbA1c, glycosylated hemoglobin; AUC, area under the curve; Glu-OGTT, glucose tolerance.
ALOE SUPPLEMENTATION AND METABOLIC SYNDROME3
MET-2012-0066-ver9-Devaraj_3P.3d09/29/12 12:47pmPage 3
anecdotal reports of antidiabetic activity of aloe in hu-
mans,12,13but there is a paucity of controlled clinical tri-
als. Thus, in this pilot study, we wished to test the effect
of two aloe products in a double-blind, randomized, pla-
cebo-controlled study. The results from our pilot study
show that among the two aloe supplements, UP780 was
more effective in affecting parameters of insulin sensitiv-
ity, such as the fasting glucose, fructosamine, HbA1c,
HOMA, and insulin. AC952 was effective in lowering
LDL-C, fasting blood glucose, and fructosamine. Also,
UP780 reduced a marker of whole body oxidation, urinary
supplementation on homeo-
(HOMA). Fasting glucose and
insulin levels were measured
and HOMA calculated in pa-
tients before and after placebo,
UP780, or AC952 supplemen-
tation. (*) P<0.05 compared to
placebo and baseline.
Effect of Aloe vera
supplementation on urinary
F2-isoprostanes. Urinary F2-
urinary creatinine in patients
UP780, or AC952 supplemen-
tation. (*) P<0.05 compared to
placebo and baseline.
Effect of Aloe vera
4 DEVARAJ ET AL.
MET-2012-0066-ver9-Devaraj_3P.3d 09/29/1212:47pmPage 4
UP780 (aloe product 1) consists of aloe gel fillet powder
(the inner gel fillet that remains after removal of the outer
rind of the leaf), standardized with 2% aloesin by weight,
using aloe chromones and other biologically active compo-
nents that may be important in maintenance of normal blood
glucose levels. Qmatrix or AC 952 (aloe product 2) is aloe gel
fillet powder (without aloesin) standardized to a minimum
of 10% polysaccharide by weight. It is currently on the
market and in use in the finished products of approximately
100 companies, including dietary supplements and other
ingestible products; however, its effects have not been pre-
viously tested with regard to its antiglycemic effects in a
With regard to hypoglycemic effects, several reports
agree with ours with regard to effects in diabetic mice and
rat models.4–11There is a single placebo-controlled study
in the literature in hyperlipidemic type 2 diabetic pa-
tients14that showed the benefit of aloe in reducing the
burden of diabetes; however, all of the subjects were al-
ready on one or two diabetic medications and aloe was
given in conjunction with these. Thus, this is the first study
showing that even in patients with impaired fasting glu-
cose or impaired glucose tolerance, an 8-week supple-
mentation with Aloe vera gel powder with 2% aloe
chromone (UP780) is effective in reducing fasting glucose,
fructosamine, HbA1c, and HOMA, a marker of insulin
resistance. It is not surprising that UP780 did not lower
cholesterol levels, because previous reports regarding hy-
polipidemic effects of aloe are contradictory. In fact, while
acemannan, an active ingredient in the Aloe vera gel, is
thought to be responsible for the hypoglycemic effect of
aloe, no active ingredient has previously been isolated to
explain its hypolipidemic effects.
Oxidative stress plays a critical role in metabolic syn-
drome and diabetes.15,16F2-isoprostanes are biomarkers of
whole-body lipid oxidation, which have been shown to be
increased in diabetes.17We show that UP780 aloe supple-
mentation significantly decreased F2-isoprostanes. In sup-
port of our observations, Rajasekaran et al. have previously
reported that oral administration of an alcoholic extract of
Aloe vera leaf gel at a concentration of 300mg/kg to diabetic
rats, in addition to improving glycemic control, significantly
decreased the levels of lipid peroxidation and hydroperox-
ides in tissues of diabetic rats and also resulted in a signifi-
cant increase in reduced glutathione, superoxide dismutase,
catalase, glutathione peroxidase, and glutathione S-transferase
in the liver and kidney of diabetic rats.18
Because UP780 is a standardized Aloe vera gel preparation,
these exciting effects of its hypoglycemic activity as well as
lowering of lipid oxidation are promising, especially due to
the excellent safety profile and compliance. Thus, such
standardized aloe preparations offer an attractive adjunctive
strategy to revert the impaired fasting glucose and impaired
glucose tolerance observed in conditions of prediabetes/
metabolic syndrome and need to be tested in multicenter
clinical trials. Future studies will also examine the active
ingredient in aloe that is responsible for these effects and
examine mechanisms to elucidate these findings.
Unigen Inc., AloeCorp., for financial support and aloe
products and placebo.
Author Disclosure Statement
S.D received a grant from Unigen and MY, LAB, QJ are
employed at Unigen.
1. Grundy SM. Pre-diabetes, metabolic syndrome, and car-
diovascular risk. J AmColl Cardiol 2012;59:635–643.
2. Alberti KG, Eckel RH, Grundy SM, et al.; International Dia-
betes Federation Task Force on Epidemiology and Preven-
tion; Hational Heart, Lung, and Blood Institute; American
Heart Association; World Heart Federation; International
Atherosclerosis Society; International Association for the
Study of Obesity. Harmonizing the metabolic syndrome: A
joint interim statement of the International Diabetes Federa-
tion Task Force on Epidemiology and Prevention; National
Heart, Lung, and Blood Institute; American Heart Associa-
tion; World Heart Federation; International Atherosclerosis
Society; and International Association for the Study of Obe-
sity. Circulation 2009;120:1640–1645.
3. Grundy SM, Cleeman JI, Daniels SR, et al.; American Heart
Association; National Heart, Lung, and Blood Institute.
Diagnosis and management of the metabolic syndrome: An
American Heart Association/National Heart, Lung, and
Blood Institute Scientific Statement. Circulation 2005;112:
4. Ajabnoor MA. Effect of aloes on blood glucose levels in
normal and alloxan diabetic mice. J Ethnopharmacol 1990;28:
5. Ghannam N, Kingston M, Al-Meshaal IA, et al. The antidi-
abetic activity of aloes: Preliminary clinical and experimental
observations. Horm Res 1986;24:288–294.
6. Rajasekaran S, Sivagnanam K, Ravi K, et al. Hypoglycemic
effect of Aloe vera gel on streptozotocin-induced diabetes in
experimental rats. J Med Food 2004;7:61–66.
7. al-Awadi F, Fatania H, Shamte U. The effect of a plants
mixture extract on liver gluconeogenesis in streptozotocin
induced diabetic rats. Diabetes Res 1991;18:163–168.
8. Parihar MS, Chaudhary M, Shetty R, et al. Susceptibility of
hippocampus and cerebral cortex to oxidative damage in
streptozotocin treated mice: Prevention by extracts of With-
ania somnifera and Aloe vera. J Clin Neurosci 2004;11:
9. Bolkent S, Akev N, Ozsoy N, et al. Effect of Aloe vera (L.)
Burm. fil. leaf gel and pulp extracts on kidney in type-II
diabetic rat models. Indian J Exp Biol 2004;42:48–52.
10. Can A, Akev N, Ozsoy N, et al. Effect of Aloe vera leaf gel
and pulp extracts on the liver in type-II diabetic rat models.
Biol Pharm Bull 2004;27:694–698.
11. Rajasekaran S, Ravi K, Sivagnanam K, et al. Beneficial effects
of aloe vera leaf gel extract on lipid profile status in rats with
streptozotocin diabetes. Clin Exp Pharmacol Physiol 2006;33:
12. Yongchaiyudha S, Rungpitarangsi V, Bunyapraphatsara N,
et al. Antidiabetic activity of Aloe vera L juice. I. Clinical trial in
new cases of diabetes mellitus. Phytomedicine 1996;3:241–243.
13. Bunyapraphatsara N, Yongchaiyudha S, Rungpitarangsi V,
et al. Antidiabetic activity of Aloe vera L juice.I. Clinical trial in
diabetes mellitus patients in combination with glibenclamide.
14. Huseini HF, Kianbakht S, Hajiaghaee R, et al. Anti-hypergly-
cemic and anti-hypercholesterolemic effects of Aloe vera leaf
gel in hyperlipidemic type 2 diabetic patients: A randomized
double-blind placebo-controlled clinical trial. Planta Med
ALOE SUPPLEMENTATION AND METABOLIC SYNDROME5
MET-2012-0066-ver9-Devaraj_3P.3d 09/29/1212:47pmPage 5
15. Devaraj S, Hirany SV, Burk RF, et al. Divergence between Download full-text
LDL oxidative susceptibility and urinary F(2)-isoprostanes
as measures of oxidative stress in type 2 diabetes. Clin Chem.
16. Vega-Lo ´pez S, Devaraj S, Jialal I. Oxidative stress and anti-
oxidant supplementation in the management of diabetic
cardiovascular disease. J Investig Med 2004;2:24–32.
17. Tsai IJ, Croft KD, Mori TA, et al. 20-HETE and F2-
isoprostanes in the metabolic syndrome: the effect of weight
reduction. Free Radic Biol Med 2009;46:263–270.
18. Rajasekaran S, Sivagnanam K, Subramanian S. Antioxidant
effect of Aloe vera gel extract in streptozotocin-induced di-
abetes in rats. Pharmacol Rep 2005;57:90–96.
Address correspondence to:
Sridevi Devaraj, Ph.D., DABCC, FACB
Medical Director of Clinical Chemistry and POCT
Texas Children’s Hospital
Professor of Pathology and Immunology
Baylor College of Medicine
Director of Proteomic and Metabolomics Core
Texas Children’s Microbiome Center
6621 Fannin Street, Suite WB110.06
Houston, TX 77030
6 DEVARAJ ET AL.