Honey and Cardiovascular Risk Factors, in Normal Individuals
and in Patients with Diabetes Mellitus or Dyslipidemia
Mohammad Javed Ansari,
and Thia Al-Waili
Waili Foundation for Science, Queens, New York, USA.
Unit of Bee Research, Department of Plant Protection,
College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia.
ABSTRACT Diabetes mellitus, hypercholesteremia, hypertension (HTN), and obesity are well-known risk factors
for cardiovascular diseases (CVD). Various medications are currently in use for management of these comorbidities.
Undesirablesideeffectsareunavoidableandtheultimateandideal goal is hardly achieved. Honey and other bee products
are widely used in traditional medicine for management of many diseases. Others and the authors have found potent
biological activities of these products. Honey is now reintroduced in modern medicine as part of wound and burn man-
agement. Honey has antioxidant, anti-inﬂammatory, and antimicrobial activities. More studies are exploring other aspects
of honey activity such as its effect on blood sugar, body weight, lipid proﬁle, C-reactive protein, nitric oxide, proin-
ﬂammatory prostaglandins, and homocysteine. Growing evidence and scientiﬁc data support the use of honey in patients
with diabetes, HTN, dyslipidemia, obesity, and CVD. This review discusses clinical and preclinical studies on potential
inﬂuence of honey on diabetes mellitus and cardiovascular risk factors, and emphasizes the importance of conducting more
clinical and controlled studies.
KEY WORDS: cholesterol C-reactive protein glucose honey insulin obesity triacylglycerol
Cardiovascular diseases (CVD) are associated with
hypercholesterolemia, hypertension (HTN) and diabe-
tes mellitus (DM). Atherosclerosis, which is due to endothelial
dysfunction, is the main cause of CVD. Cardiovascular dis-
orders remain the leading cause of death worldwide.
and diabetic patients have a high risk of dying from com-
plications associated with CVD.
In addition to normal BMI and blood pressure, main-
taining normal levels of serum homocysteine, C-reactive
protein (CRP), lipids, and insulin are essential to maintain a
healthy cardiovascular system. Normal biological activities
of the vasoactive factors, nitric oxide (NO) and prosta-
glandins are important to maintain a healthy heart and blood
Humans have used bee products in folk medicine since
ancient times. Ancient religious texts mentioned honey as a
popular remedy. In this regard, the Talmud, the Old and
New Testaments of the Bible, and the Holy Quran (1400
years ago) mentioned honey as a cure for diseases. A large
chapter (SORA) appears in the Holy Quran named BEE
(Al Nahl) and part of it says: ‘‘And thy LORD taught the bee
to build its cells in hills, on trees and in men’s habitations,
then to eat of all the produce of the earth and ﬁnd with skill
the spacious paths of its LORD, there issues from within
their bodies a drink of varying colors, wherein is healing for
men, verily in this is a sign for those who give thought.’’
The health beneﬁts attributed to bee products are based on
anecdotes or public observations with limited scientiﬁc data.
However, during the last few decades, these products have
been subjected for analysis and testing. Others and the au-
thors have published numerous scientiﬁc data showing the
medicinal and nutritional values of bee products.
literature shows that honey has antibacterial, antifungal,
antiviral, anti-inﬂammatory, antihypertensive, antioxidant,
antitumor, cardioprotective, hepatoprotective, and hypo-
A recent review showed that the
polyphenol content of various types of honey might prevent
CVD by improving coronary vasodilatation, decreasing the
ability of platelets in the blood to clot, and preventing low-
density lipoproteins (LDL) from oxidizing.
honey has received renewed interest as an important natural
substance that can be used in new therapies almost free from
side effects that are encountered with the use of synthetic
and chemical medicines.
Manuscript received November 14, 2012. Revision accepted August 22, 2013.
Address correspondence to: Noori Al-Waili, MD, PhD, DGO, CHT, Waili Foundation for
Science, Queens, NY 11418, USA, E-mail: email@example.com
JOURNAL OF MEDICINAL FOOD
J Med Food 16 (12) 2013, 1063–1078
#Mary Ann Liebert, Inc., and Korean Society of Food Science and Nutrition
Honey is a carbohydrate-rich syrup produced by bees, from
ﬂoral nectars. Color, ﬂavor, and aroma depend on its ﬂoral
origin. Aberrantly, honey composition is tightly associated to
its botanical origin, which is closely related to the geograph-
ical area in which it is originated. In this regard, soil and
climate characteristics determine melliferous ﬂora, in addition
to the presence of different minerals in soil.
characteristics of honey are strongly dependent on its botan-
ical origin and to some extent on its geographical origin.
Composition of different honeys from many regions of the
world has been studied, including the United Arab Emirates
(U.A.E.), the United States, Algeria, India, Slovenia, Ban-
gladesh, and Malaysia.
Honey contains 181 bioactive
More than 500 different volatile compounds
were identiﬁed in various types of honey.
glucose are the major components while disaccharides, tri-
saccharides, and oligosaccharides are present in small quan-
tities. In addition, honey contains protein, enzymes, amins
acids, vitamins, and minerals (Table 1).
The physical chemistry characteristics of honey are directly
related to ﬂoral origin.
Approximately 30 nonaromatic
organic acids have been identiﬁed.
Gluconic acid is the major
organic acid produced by enzymatic glucose oxidase reaction.
The glucose oxidase reaction in honey produces glutamic acid
and hydrogen peroxide from glucose. Invertase converts su-
crose to fructose and glucose.
Amylase splits starch chains
yielding dextrins and maltose.
Polyphenols are an important
group of compounds present in honey.
An analytical survey of U.S. honey was reported.
includes analyses of 490 samples of U.S. ﬂoral honey and 14
samples of honeydew honey gathered from 47 of the 50 states
and representing 82 single ﬂoral types and 93 blends of known
composition. Floral honey is higher in fructose and dextrose,
lower in disaccharides and higher sugars, and contains much
less acid. The water content of honey varies greatly, ranging
between 13% and 25%. We have analyzed honey collected
from the U.A.E.; the acidity was 13%, and the composition
includes (out of 100 g): fructose 38 g, glucose 30 g, moisture
29 g, vitamin C 2.3 mg, copper 0.098 mg, zinc 0.6 mg, vitamin
E 0.74 mg, vitamin A 0.49 mg, selenium 0.44 mg, chromium
0.007 mg, iron 0.2 mg, cobalt 0.016 mg, calcium 17 mg, glu-
tathione reductase 0.52 mg, and the remainder consist of other
carbohydrates, proteins, and unidentiﬁed substances.
Electric conductivity, acidity, amino acids, mineral con-
tent, carbohydrate content, and pollen proteins are used to
assess provenience of honey.
Seventeen minerals in
Spanish honey have been determined, reporting a relation-
ship between mineral contents and geographical origin.
The authenticity of Galician-labeled honey has been con-
ﬁrmed by analyzing elemental composition of honey com-
bined with chemometrics modeling techniques.
was found that NO
is a potential reliable marker of a
honey’s origin and quality.
The acids have been used as
factors for the characterization of both botanical and
geographical origins of honeys.
Table 1. The Main Solid Contents of Honey
Groups Members References
Carbohydrates Dextrose and fructose account for about 85% of the solids in honey. Ten
disaccharides present in honey: sucrose, maltose, isomaltose, mal-
tulose, nigerose, turanose, kojibiose, laminaribiose, a, B-trehalose, and
gentiobiose. Ten trisaccharides are present: melezitose, 3-a-isomalto-
sylglucose, maltotriose, l-kestose, panose, isomaltotriose, erlose,
theanderose, centose, and isopanose. Two more complex sugars,
isomaltotetraose and isomaltopentaose, have been determined
Nonaromatic organic acids Butyric, malic, maleic, citric, succinic, fumaric, oxalic, pyroglutamic
acids, and gluconic acid
Trace elements and minerals Aluminum, lead, arsenic, lithium, barium, molybdenum, boron, nickel,
bromine, rubidium, cadmium, silicon, chlorine, strontium, sulfur,
ﬂorid, vanadium, iodide, zirconium, cobalt, sodium, calcium, potas-
sium, magnesium, phosphorus, zinc, copper, iron, manganese, chro-
mium, and selenium
Vitamins Thiamin, riboﬂavin, pyridoxin, vitamin A, niacin, panthothenic acid,
phyllochinon, vitamin E, and ascorbic acid
Amino acids Eighteen essential and nonessential amino acids; proline, glutamic acid,
alanine, phenylalanine, tyrosine, leucine, and isoleucine are the most
Enzymes Glucose oxidase, invertase, amylase, catalase, and acid phosphatase 30,33
Polyphenols Phenolic acids, ﬂavonoids, and phenolic acid derivatives; quercetin,
chrysin, galangin, luteolin, kaempferol, and apigenin are the main
ﬂavonoids in honey
NO NO end products 37,38,42
NO, nitric oxide.
1064 AL-WAILI ET AL.
Honey and glycemic response
Many studies showed that honey from various origins has
almost similar activity on blood sugar (Table 2).
Glycemic index of Malaysian honey and Australian honey
was studied in eight healthy volunteers. The patients re-
ceived 50 g carbohydrate; two varieties of honey or the
reference food. The results showed that the mean area under
curve and glycemic index of the Malaysian and Australian
honeys did not differ from each other but were signiﬁcantly
less than that after glucose.
In Germany, eight various
German honeys differing in their ﬂoral source and carbo-
hydrate composition were tested. Ten healthy fasting indi-
viduals received isoglucidic test meals (25 g carbohydrate)
and a 25 g glucose reference. Five of the eight tested sam-
ples of honey showed a low glycemic index below 55. In
addition, the glycemic index and insulinemic index signiﬁ-
cantly correlated with the fructose content of honey varie-
Another study compared the effects of basswood
honey, an identical sugar solution (containing 75 g of glu-
cose), and oral glucose tolerance test solution on serum
glucose, insulin, and C-peptide values in 12 healthy sub-
Serum insulin, C-peptide, and glucose values at
60 min were signiﬁcantly lower for honey. The area under
the concentration-time proﬁle for glucose response was
lower for honey than the honey-comparable glucose-fruc-
tose solution. Honey had less effect on serum glucose, C-
peptide, and insulin values than the honey-comparable
In the United States, the glycemic index of a 250 mL
solution serving of clover, buckwheat, cotton, and tupelo
honey providing 50 g carbohydrate were assessed in 12
healthy adults, relative to triplicate feedings of 50 g carbo-
hydrate as a glucose solution.
No signiﬁcant differences in
glycemic index between these varieties of honey were
found, and there was no relationship between glycemic in-
dex and the fructose-to-glucose ratio. Therefore, small dif-
ferences in fructose-to-glucose ratios do not substantially
affect honey glycemic index.
In another U.S. study, oral glucose tolerance testing
comparing sucrose, fructose, and honey was conducted in 33
individuals. Fructose showed minimal changes in plasma
glucose level (PGL) while sucrose gave higher PGL
readings than honey, producing signiﬁcantly greater glucose
In Pakistan, oral glucose tolerance test was conducted in
26 healthy individuals with use of natural honey, simulated
honey, or D-glucose (1 g/kg body weight). Glucose response
Table 2. Effects of Honey on Blood Sugar in Normal Individuals
Study Origin of honey
of individuals Results
Robert et al. (2009)
Malaysia and Australia 8 Mean AUC/glycemic index of both honeys were
signiﬁcantly less than that after glucose
Deibert et al. (2010)
Germany; eight samples
10 5/8 samples of honey show a low glycemic index
¨nstedt et al. (2008)
Germany; basswood honey 12 Serum insulin, C-peptide, and glucose values at
60 min were signiﬁcantly lower for honey. AUC
for glucose response was lower for the honey than
the honey-comparable glucose-fructose solution
Ischayek and Kern. (2006)
United States; clover, buck-
wheat, cotton, and tupelo
12 No signiﬁcant differences in glycemic index between
the honey samples
Shambaugh et al. (1990)
United States 33 Sucrose gave higher PGL readings than honey,
producing signiﬁcantly greater glucose intolerance
Ahmad et al. (2008)
Pakistan 26 Glycemic responses were signiﬁcantly lower in
subjects who consumed natural honey than those
who consumed glucose or artiﬁcial honey
Yaghoobi et al. (2008)
Iran 38 Honey reduces fasting PGL (4.2%) compared with
United Arab Emirates 10 Honey reduced fasting blood sugar by 5%
United Arab Emirates 24 Honey inhalation lowers PGL and elevates plasma
insulin and C-peptide
United Arab Emirates 16 In glucose toleance test, dextrose raised PGL at 1 h
(53%) and 2 h (3%), and lowered PGL after 3 h by
20%. Honey elevated PGL after 1 h by 14% and
decreased it after 3 h by 10%. Elevation of insulin
and C-peptide was signiﬁcantly higher after dextrose
than after honey. Daily consumption of 75 g of
honey for 15 days reduced fasting PGL by 6%
AUC, area under curve; PGL, plasma glucose level.
HONEY AND CARDIOVASCULAR RISK FACTORS 1065
was signiﬁcantly lower in the natural honey group compared
with the artiﬁcial honey and D-glucose groups.
At 60 min,
individuals in D-glucose and simulated honey group ex-
hibited 20% increments in PGL compared with natural honey
group. However, at 180 min, 20% decrease in PGL was ob-
served in the D-glucose group compared with 9.75% reduc-
tion in the honey group. Therefore, glycemic responses were
signiﬁcantly lower in subjects who consumed natural honey
than those who consumed glucose or artiﬁcial honey.
Another study from Iran has shown that a regimen of a 30-day
natural honey intake (70 g) in 38 overweight individuals slightly
reduced fasting PGL (4.2%) compared with 70 g of sucrose.
In the U.A.E., 10 normal individuals received a normal
diet supplemented with daily consumption of 1.2 g/kg body
weight honey dissolved in 250 mL of water during a 2-
week test period. Honey reduced fasting blood sugar by 5%
after 2 weeks.
In 24 normal individuals, 10% dextrose
inhalation caused mild reduction of plasma insulin and C-
peptide and unremarkable changes in PGL. Honey inha-
lation caused lowering of PGL and elevation of plasma
insulin and C-peptide.
In eight healthy subjects, effects of
dextrose solution (250 mL of water containing 75 g of
dextrose) or honey solution (250 mL of water containing
75 g of natural honey) on PGL was studied in the U.A.E.
Further, in eight other normal individuals, effects of honey
solution, administered for 15 days, on PGL was studied. It
was found that dextrose raised PGL at 1 h (53%) and 2 h
(3%), and lowered PGL after 3 h by 20%. Honey elevated
PGL after 1 h by 14% and decreased it after 3 h by 10%.
Elevation of insulin and C-peptide was signiﬁcantly higher
after dextrose than after honey. In addition, daily con-
sumption of 75 g of honey for 15 days reduced fasting PGL
In the U.A.E., food restriction with 50% honey feeding in
rats caused greater reduction in fasting blood sugar com-
pared with total food restriction with 50% dextrose feeding.
Similar results were obtained after acute blood loss in rats on
total food restriction with 50% honey feeding compared
with the other groups.
In addition, the authors assessed the
effects of four diets on blood variables in rats: a commercial
regular diet as control, total food restriction with honey, a
commercial regular diet with dextrose, or total food re-
striction with dextrose after administrating carbon tetra-
chloride. Honey feeding ameliorated reduction in PGL
observed after carbon tetrachloride toxicity.
Intravenous infusion of 40 g of honey collected in the
U.A.E. in healthy sheep caused elevation of PGL for 90min
postinfusion, whereas it decreased PGL at 2 and 3h post-
infusion compared with fasting blood sugar. Dextrose caused
signiﬁcant elevation of PGL at all time intervals. Similar
results were obtained with the use of 10% dextrose compared
to 80 g of honey. Inhalation of honey caused signiﬁcant
lowering of PGL during and after inhalation compared with
In the United Kingdom, hyperglycemic effects of glucose,
sucrose, and honey equivalent to 20 g in 12 normal volun-
teers were studied. Honey attenuated the postprandial gly-
cemic response in normal volunteers.
Honey and diabetes
Animal experimentation. In Malaysia, honey (0.2, 1.2,
and 2.4 g/kg/day) given by oral gavage for 4 weeks signiﬁcantly
increased body weight, total antioxidant status, activities of
catalase, glutathione peroxidase, glutathione reductase, gluta-
thione-S-transferase, and superoxide dismutase activity in dia-
betic rats. In addition, honey ameliorated side effects of DM on
kidney rats and signiﬁcantly reduced fasting blood sugar.
Tualang honey signiﬁcantly reduced elevated malondialdehyde
levels in streptozotocin-induced diabetic rats and restored su-
peroxide dismutase and catalase activities. These results suggest
that hypoglycemic effect of tualang honey might be attributed to
its antioxidative effect on the pancreas.
duced diabetic rats, it was found that the combination of glib-
enclamide or metformin with honey improved glycemic
control. Glibenclamide or metformin combined with honey
signiﬁcantly reduced the elevated levels of creatinine, bilirubin,
triacylglycerol, and VLDL.
In Pakistan, oral administration of Apis ﬂorea (small-bee)
and Apis dorsata (large-bee) honey in a dose of 5 mL/kg did
not produce a signiﬁcant increase in PGL in normal and
alloxan-diabetic rabbits, whereas the adulterated honey
signiﬁcantly raised the PGL in normal and hyperglycemic
In higher doses of 10 mL/kg and 15 mL/kg body
weight, all the three honeys produced a signiﬁcant rise in
PGL of normal and alloxan-diabetic rabbits.
In this study,
the animals received very high doses of the interventions
and that may be why PGL increased in all groups.
In New Zealand, a study conducted on rats showed that
HbA1c levels were signiﬁcantly reduced in 10% honey-fed
compared with rats fed 7.9% sucrose or a sugar-free diet.
Human experimentation. In the United Kingdom, hy-
perglycemic effects of glucose, sucrose, and honey equivalent
to 20 g in eight patients with type 1 DM, and six patients with
type 2 DM were studied. Honey attenuated postprandial gly-
cemic response in the patients with DM.
In Italy, honey,
compared to an isoglucidic amount of bread, had no additional
hyperglycemic effect in 21 type 2 diabetic individuals when
consumed for breakfast.
In Greece, the metabolic effects of
honey (alone or combined with other foods) were investigated
in 31 type 2 diabetics. Honey caused a hyperglycemia similar
to that produced by consuming bread in individuals with type 2
In India, 30 individuals with a proven parental history of
type 2 DM were subjected to an oral glucose tolerance test
with the use of either honey or glucose. The subjects with
impaired glucose tolerance showed signiﬁcantly lower PGL
after consumption of honey in comparison with the glucose
tolerance test. In diabetic patients, high degree of tolerance
to honey was recorded too.
In Egypt, a case–control cross-sectional study was con-
ducted on 20 children and adolescents with type 1 DM and 10
healthy children and adolescents. Oral glucose tolerance tests
using glucose, sucrose, or honey were conducted measuring
fasting and postprandial serum C-peptide levels. Honey,
compared with sucrose, had a lower glycemic index and in-
cremental index in both diabetic patients and control.
1066 AL-WAILI ET AL.
In the U.A.E., the effects of 70 g of dextrose or 90 g of
honey on PGL in seven patients with type 2 DM and the
effects of 30 g of sucrose or 30 g of honey on PGL, plasma
insulin, and plasma C-peptide in ﬁve diabetic patients were
Honey compared with dextrose caused a signiﬁ-
cantly lower rise of PGL. Elevation of PGL was greater after
honey than after sucrose at 30 min, and was lower after
honey than it was after sucrose at 60, 120, and 180 min.
Honey caused a greater elevation of insulin than sucrose did
after 30, 120, and 180 min in diabetics.
Sixteen patients with type 2 DM were treated with in-
trapulmonary inhalation of honey. Fasting PGL was esti-
mated in each patient and was re-estimated during 3 h after
honey inhalation, at 30 min intervals. Glucose tolerance
tests were performed in another eight patients with type 2
DM and after 1 week, the procedure was repeated with
inhalation of honey after ingestion of glucose. Honey in-
halation caused lowering of PGL and elevation of plasma
insulin and C-peptide, and signiﬁcantly reduced random
PGL after 30 min. Fasting PGL was reduced after honey
inhalation at hour three postinhalation, which was sig-
niﬁcant at hour three. Honey inhalation was effective in
reducing PGL, suggesting it could improve glucose toler-
ance and elevate plasma insulin and C-peptide in diabetic
The blood glucose and plasma insulin responses to some
simple carbohydrates (glucose, fructose, and lactose) and
honey were studied in 32 type 2 DM patients. Ingestion of
25 g glucose, fructose, or lactose, or 30 g honey was tested.
Sixty minutes after ingestion of each meal, the increases in
PGL and in plasma insulin were signiﬁcantly higher after
glucose, fructose, and lactose than after honey.
The above studies showed that honey collected from
different regions had almost similar glycemic effect. Honey
compared with dextrose reduced PGL and insulin in normal
subjects. This is important since hyperinsulinemia is a single
independent determinant for coronary artery diseases and it
increases homocysteine in healthy normal weight, over-
weight, and obese premenopausal women.
increases circulatory cytokine concentrations by an oxida-
tive mechanism, particularly in subjects with impaired
Table 3 summarizes studies conducted
on patients with type 1 and type 2 diabetes.
Mechanism of action. Honey contains fructose, oligo-
saccharides, minerals, and antioxidants.
In normal in-
dividuals, a daily consumption of 1.2 g/kg body weight
honey during a 2-week test increased blood vitamin C con-
centration by 47%, b-carotene by 3%, uric acid by 12%, and
glutathione reductase by 7%. Honey increased serum copper
Many studies have shown that ﬂavonoids exert diverse
normoglycemic effects and lead to a lower incidence of
complications associated with DM.
as myricetin, ﬁsetin, quercetin, and their glycoside precursor
(isoquercitrin) showed a strong inhibition of the fructose and
glucose transport mediated by GLUT2.
are all present in beehive products.
Zinc lowers PGL by improvement of insulin sensitivity
and copper sulfate signiﬁcantly decreases PGL.
and copper are important for insulin and glucose metabo-
lism; both minerals were increased with consumption of
We have found that honey reduces prostaglandin levels
and elevates NO.
It has been shown that prostaglandin
E2 is one of the main physiological inhibitors of insulin.
Higher levels of NO and various NO donors stimulate in-
Glycemic carbohydrates present in natural
honey decrease saccharide absorption.
It has been found
that hydrogen peroxide can effectively mimic the function
Oligosaccharides may play a role in the anti-
diabetic effect of honey.
gastric emptying, slowed rate of digestion, and delayed in-
Infusion of small amounts of fructose induced ampliﬁ-
cation of the counter regulatory response to mild hypo-
glycemia in normal individuals.
It has been proposed that
due to presence of fructose in addition to glucose, the
augmentation of hormonal response to hypoglycemia by
using honey might have a place in the prevention of hy-
poglycemia frequently encountered with use of insulin in
patients with diabetes.
Fructose could increase hepatic
glucose uptake and glycogen storage, and reduce periph-
eral glycemia and insulin levels; this could be beneﬁcial in
This suggests that honey might be a
suitable food for diabetics and nondiabetics. However,
fructose consumption causes undesirable effects such as
hyperinsulinemia, induction of insulin resistance, hyper-
triglyceridemia, increased weight gain, hepatic de novo
lipogenesis, and HTN in animal models.
Honey contains more than 181 bioactive constituents in-
cluding free radical scavenging and antioxidant com-
In addition, honey contains arginine and NO
metabolites and it increases NO production in animals and
L-Arginine is able to prevent fructose-induced
HTN and hyperinsulinemia.
Therefore, we have proposed
that NO might inhibit fructose-induced hyperinsulinemia
after ingestion of honey.
Honey compared with dextrose
or sucrose decreased insulin levels in normal subjects. The
mild effect of honey on PGL and plasma insulin and
C-peptide in normal subjects might be due to fructose
content, as fructose does not stimulate insulin secretion from
Fructose reduces hyperglycemia in rodent models of di-
abetes, healthy subjects, and diabetic patients.
prolongs gastric emptying and it lowers food intake.
low or moderate fructose diet resulted in weight loss in
Obese subjects on the moderate fructose
diet lost more weight than those on the low fructose diet.
However, some studies have found that fructose feeding
or consumption at high doses is associated with increased
Fructose increases hepatic glucose phos-
phorylation via activation of glucokinase, and inhibits
glycogenolysis via suppression of phosphorylase.
Fructose increased hepatic glycogen synthesis in diabetic
and nondiabetic rats.
HONEY AND CARDIOVASCULAR RISK FACTORS 1067
Honey tastes sweeter than sucrose, so it was suggested
that a pure natural honey in low doses might be recom-
mended as sources of carbohydrates and even as sweetening
agents in place of sucrose to diabetic patients.
of honey or its constituents on gastric emptying, insulin
secretion, rate of intestinal absorption, prostaglandin inhi-
bition, NO production, fructose transporter, antioxidants
level, hepatic glucose uptake, zinc and copper levels, and
food intake, and perhaps the synergistic effect of glucose
on fructose may contribute to the lowering of glucose
Honey and lipids
In Iran, 48 patients with type 2 DM received oral natural
honey intake for eight weeks; honey decreased total cho-
lesterol, low-density lipoprotein–cholesterol (LDL-C), and
triacylglycerol, and increased high-density lipoprotein–
Another study showed that 70 g of
natural honey collected in Iran decreased total cholesterol
(3%), LDL-C (5.8%), and triacylglycerol (11%), and in-
creased HDL-C (3.3%) in subjects with normal values and
in patients who were overweight or obese.
In New Zealand, rats fed 10% honey increased the HDL-C
signiﬁcantly compared with rats fed 7.9% sucrose or a sugar-
In Germany, among patients who had high cho-
lesterol, LDL-C values did not signiﬁcantly reduce in males
after ingesting a 75-g honey solution for 14 days. However, in
women, these values increased in the sugar solution group,
but not in that fed honey.
It was suggested that although
ingesting honey did not reduce LDL-C values, women might
beneﬁt from substituting honey for sugar in their diet.
In the United States, a study conducted in rats showed
that honey lowered serum concentrations of triacylglycerol
compared with diets of equal energy densities. However,
there were no signiﬁcant differences in serum total choles-
terol or HDL-C.
In Nigeria, a recent study showed that
consumption of unreﬁned Nigerian honey signiﬁcantly im-
proved lipid proﬁles and the computed CVD predictive in-
dex in male albino rats.
The authors found that a single dose of glucose or artiﬁ-
cial honey (consisting of 40 g fructose +35 g glucose in
Table 3. Effects of Various Samples of Honey on Blood Sugar in Patients with Type 1and Type 2Diabetes Mellitus
Origin of honey/method
of administration Number of patients Results
Samanta et al. (1985)
United Kingdom; oral 8 type 1 DM Honey attenuated postprandial
glycemic response6 type 2 D
Bornet et al. (1985)
Italy; oral 21 type 2 DM Honey, compared to an isoglu-
cidic amount of bread, has no
additional hyperglycemic ef-
fect in 21 type 2 diabetic indi-
viduals when consumed for
Katsilambros et al. (1988)
Greece; oral 31 type 2 DM Hyperglycemia similar to that
produced by consuming bread
Agrawal et al. (2007)
India; oral 30 with impaired glucose
tolerance test or type 2 DM
Signiﬁcantly lower PGL after
consumption of honey in
comparison to the glucose
tolerance test. In diabetic pa-
tients, the high degree of tol-
erance to honey was recorded
Abdulrhman et al. (2011)
Egypt; oral 20 children and adolescents
with type 1 DM and 10
healthy children and
Honey, compared to sucrose, had
lower glycemic index and in-
cremental index in both dia-
betic patients and control
United Arab Emirates; oral 12 type 2 DM Honey compared with dextrose
caused a signiﬁcantly lower
rise of PGL after GTT. Honey
caused greater elevation of
insulin than sucrose did after
30, 120, and 180 min in dia-
United Arab Emirates; inhalation 24 type 2 DM Honey inhalation was effective
in reducing PGL; it could
improve glucose tolerance test
and elevate plasma insulin and
C-peptide in diabetic patients
DM, diabetes mellitus; GTT, glucose tolerance test.
1068 AL-WAILI ET AL.
250 mL water) increased cholesterol and triacylglycerol;
this effect was not observed with natural honey collected in
In this regard, daily consumption of 75 g honey
for 15 days decreased total cholesterol (8%), LDL-C (11%),
and CRP (75%) in normal and hyperlipidemic subjects.
Natural honey decreased total cholesterol and LDL-C in
healthy and hyperlipidemic subjects while artiﬁcial honey
increased lipids because of the presence of fructose. It was
proposed that the difference between the effects of artiﬁcial
and natural honeys on lipids might be due to the presence
of certain substances in natural honey that are able to re-
duce blood lipids in healthy and hyperlipidemic subjects.
Fructose potentiates postprandial lipidemia in both diabetic
and nondiabetic subjects and very high intake of sucrose or
fructose increased fasting triacylglycerol.
In patients with hypercholesterolemia, the formation
of the F2-isoprostane 8-epi-PGF2ais enhanced, which is
suppressed by vitamin E supplementation.
It has been
reported that high doses of B complex vitamin may be useful
in lowering blood cholesterol and triacylglycerole levels.
Vitamin E reduces atherosclerosis plaque, coronary ar-
tery diseases, and myocardial infarction.
showed that ascorbic acid deﬁciency involved in the de-
velopment of hypercholesterolemia and atherosclerosis.
Antioxidants can modulate the activity and/or the protein
levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase
(the rate-limiting enzyme of cholesterol biosynthetic path-
Polyphenols derived from tea were shown to have
antioxidative, antithrombogenic, anti-inﬂammatory, hypo-
tensive, and hypocholesterolemic properties.
polyphenols have vasodilating effects, and they can improve
the lipid proﬁle and lessen the oxidation of LDL.
effects of honey on lipid proﬁle might be related to NO, an-
tioxidants, vitamin E, prostaglandins, and antioxidant prop-
However, the exact mechanisms through which
honey exerts its effect on lipid values are not well identiﬁed.
Honey and blood pressure
It is well known that HTN is one of the major risk factors
for cardiovascular and renal diseases. Most of patients fail to
maintain goal blood pressure despite using various antihy-
Administration of Malaysian tualang honey for 3 weeks
in streptozitocine-induced diabetic spontaneously hyperten-
sive rats resulted in reduction in systolic blood pressure.
This effect was mediated via amelioration of oxidative stress
in the kidney.
The authors found that systolic and dia-
stolic blood pressure was reduced by honey inhalation in
hypertensive patients; signiﬁcant changes were obtained at
60 and 120 min after inhalation.
Oxidative stress and free radicals are involved in the
pathogenesis and/or maintenance of elevated blood pressure
In addition, there is strong evidence of a
close relationship between NO deﬁciency and development
Further, chronic NO inhibition with L-nitro-ar-
ginine methyl ester, an antagonist for L-arginine, causes
salt-sensitive HTN and the development of renal injury.
Therefore, honey might mitigate HTN by its antioxidant
constituents and its ability to increase NO. Further studies
are needed to explore the exact mechanism of action.
Honey and CRP
CRP is an acute phase protein that is produced by hepa-
tocytes in response to inﬂammatory cytokines in the body.
CRP serves as a biomarker of CVD risk and inﬂammation.
Increased levels of CRP are correlated with cardiac risk
factors such as type 2 diabetes mellitus, obesity, and
CRP functions as a pro-atherosclerotic
In the previous study, oral ingestion of honey
Further, daily ingestion of 70 g of natural
honey caused 3.2% reduction in CRP in subjects with nor-
mal values and in patients with elevated variables in obese
and overweight individuals.
However, in the United
States, a study conducted in rats showed that there were no
signiﬁcant differences in CRP in rats fed honey or diets of
equal energy densities.
It has been shown that antioxidants and vitamin E reduce
the concentration of CRP.
An increased intake of
foods rich in polyphenolic compounds is inversely associ-
ated with CRP concentrations.
many antioxidants. Therefore, honey might reduce CRP by
its antioxidant properties.
Honey and NO
NO is a gaseous signaling molecule, which plays an im-
portant role in a variety of human biological processes. It is
synthesized by NO synthase; neuronal, inducible and en-
dothelial. NO plays an important role in vasodilation via the
relaxation of vascular smooth muscle, in increasing circu-
lation in the body and in the protection against the onset and
progression of CVD. The cardioprotective roles of NO in-
clude regulation of blood pressure and vascular tone,
vasodilatation, prevention of smooth muscle cell prolifera-
tion, inhibition of platelet aggregation, and leukocyte acti-
Patients with atherosclerosis, DM, or HTN
show impaired NO pathways.
We have found that honey contains NO end products.
In addition, honey increases NO end products in various
biological ﬂuids such as urine, saliva, and plasma.
travenous honey increased NO end product in plasma and
Tualang honey inhibited UVB-induced inﬂammatory
cytokines and inducible NO synthase protein expression.
Intravenous honey reduced cytokine (tumor necrosis
factor-a, and interleukins 1band 10) and NO levels
and increased heme oxygenase-1 levels in rats with LPS-
In inﬂammatory processes, it was found that honey in-
hibits NO and prostaglandins.
In this situation, honey
might inhibit inducible harmful NO. Inhibition of inducible
nitric oxide synthase (iNOS) activity produces a marked
anti-inﬂammatory effect in acute and chronic inﬂamma-
Further, the anti-inﬂammatory effect of honey might
be due to the presence of polyphenolic compounds.
HONEY AND CARDIOVASCULAR RISK FACTORS 1069
Polyphenolic compounds have potent antioxidative activi-
ties that might scavenge iNO.
In this regard, it has been demonstrated that many plant
polyphenolic compounds could modulate NO levels and/or
Therefore, honey could prevent or ameliorate
CVD with upregulation of NO. More studies are required to
explore this important ﬁeld.
Honey and prostaglandins
It is well documented that prostaglandins are mediators of
inﬂammation and pain. Prostaglandins reduce immunity and
play a critical role in cancer development.
The main vasoactive factors released by endothelial
cells are NO and prostaglandins.
PGI2 and PGD2
are vasodilators, whereas PGH2, PGF2a, and thromboxane
A2 are vasoconstrictors and platelet aggregation indu-
PGE2 can induce vasodilation or vasocon-
Interaction between PGF2aand its receptor
triggers potent vasoconstriction.
Studies have shown that serum
levels of 8-iso-PGF2-aincreased in obesity, DM, arthritis,
Thromboxane A2 elicits platelet aggre-
gation and vascular smooth muscle contraction.
production of thromboxane A2 is increased in patients with
unstable angina, infarction, cerebral vasospasm, and
Gelam honey was also shown to depress production of
PGE2 and NO on exudates of rat’s paw induced with car-
rageenan and lipopolysaccharide.
It was found that tua-
lang honey inhibited UVB-induced COX-2 expression and
The authors have reported for the ﬁrst time that oral honey
could reduce plasma and urinary PGE2, PGF2-a, and
Its inhibitory effect was increased with
time. The site of actions could be either at COX-1 or
COX-2, or both. In addition, it was found that artiﬁcial
honey made of glucose and fructose, increased prostaglan-
Hydrogen peroxide induces PGE2 production by forming
ROS that oxidizes phospholipids in the membrane.
Gelam and Nenas monoﬂoral honeys showed signiﬁcant
anti-inﬂammatory effects on inﬂammation induced-HT29
cells by decreasing the level of PGE2 of cells as effective
Polyphenols can reduce serum 8-Iso
Therefore, natural honey might contain raw ma-
terials that are capable of inhibiting prostaglandin synthe-
Obviously, it appears that honey has anti-inﬂammatory
properties that make it a suitable nutrient to be used in acute
or chronic inﬂammatory conditions.
Honey and homocysteine
Homocysteine, an amino acid that is produced in the
human body, impairs the generation and decreases bio-
availability of NO. Individuals with lower homocysteine
have lower rate of CVD.
Homocysteine is an important
risk factor for cancer and CVD and increases in its con-
centrations are associated with an increased risk for ne-
phropathy and proliferative retinopathy.
decreases homocysteine level by 8% in normal subjects after
15 days of consumption. Vitamin C protects LDL-C from
In healthy and dia-
betic subjects homocysteine inhibited platelet NO produc-
We found that honey increased the NO
concentration and antioxidant levels in humans.
This might explain, in part, the hypohomocysteinemic ef-
fects of honey.
Honey and obesity
Obesity is a global epidemic.
It is associated with
CVD, type 2 DM, HTN, cancer, and sleep apnea. Obesity
is an independent risk factor for CVD.
thelial function as a results of decreased NO is found in
HTN is more common in obese than in lean in-
A strong correlation was demonstrated be-
tween obesity and IL-6 and CRP levels. In general, obesity
is a low-grade systemic inﬂammation. Diet modulation,
physical activity, pharmacotherapy, and surgery are re-
commended as part of the management of obesity.
loss improves or prevents many of the obesity-related risk
factors for CVD.
In the United States, a study conducted in rats showed that
honey lowered serum concentrations of leptin and reduced
weight gain and adiposity compared with diets of equal
In New Zealand, a study was conducted
in rats to determine whether 10% honey and 7.9% sucrose
would have differential effects on weight gain during 52
weeks feeding. Overall weight gain and body fat levels were
signiﬁcantly higher in sucrose-fed rats than those fed honey
or a sugar-free diet.
In New Zealand, despite a similar food
intake, the percentage weight gain was signiﬁcantly lower in
honey-fed rats than those fed sucrose or mixed sugars.
In the University of Wyoming, Laramie, a double-blind,
randomly assigned study evaluated whether the meal-
induced responses of ghrelin and peptide YY (3–36) and/or
meal-induced thermogenesis differ following a honey-
versus a sucrose-containing meal. It was found that honey
delayed the postprandial ghrelin response, enhanced the
total peptide YY response, and blunted the glucose response
compared with consumption of the sucrose-containing
In Iran, daily ingestion of 70 g of natural honey
caused reduction in body weight (1.3%), body fat (1.1%) in
overweight and obese individuals.
Honey does not cause a signiﬁcant reduction in PGL 3 h
after consumption compared with sucrose or D-glucose.
This might reduce hunger and food intake.
In animal models and clinical studies, DM, hypercho-
lesterolemia, or HTN are associated with increased vascular
free radicals generation.
CVD is a disease of oxidative
damage and inﬂammation, which results in elevation of
proinﬂammatory mediators and low NO bioavailability.
Increased free radicals cause a functional inactivation NO
due to the reaction with superoxide anion. A cross-sectional
1070 AL-WAILI ET AL.
study performed on 71 patients clinically diagnosed with
CVD showed a signiﬁcant reduction in antioxidant status
(enzymatic and nonenzymatic) with a concomitant increase
in the concentrations of lipid peroxidation products.
Polyphenols and ﬂavonoids inhibit LDL oxidation and
platelet aggregation; reduce atherosclerotic lesion formation;
reduce blood pressure; improve endothelial function; and de-
crease vascular cell adhesion molecule expression, iNO gen-
eration, and inﬂammatory responses.
reduces risk of CVD.
Flavonoids have antithrombotic, anti-
ischemic, antioxidant, and vasorelaxant properties.
are scavengers of superoxide anions, singlet oxygen, and
lipid peroxy-radicals and they prevent LDL-C oxida-
The beneﬁcial effect of polyphenols on CVD is
attributed to modulation of NO bioavailability to the endo-
b-carotenoids have anti-inﬂammatory activity in the vascu-
lature and this might explain the protective effects of carotenoid-
rich diets against CVD risk.
b-carotene affect endothelial
response to TNF-aand reduce nitro-oxidative stress.
Improvement of endothelial function and the antihyperten-
sive effects of quercetin might be mediated by enhanced eNOS
activity and decreased NADPH oxidase-mediated superoxide
anion generation associated with reduced p47 expression.
Various types of honey contain many antioxidants and
antioxidant enzymes including vitamins E and C, ascorbic
acid, phenolic acids, ﬂavonoids, carotenoid derivatives,
organic acids, Maillard reaction products, glucose oxidase,
catalase, and glutathione perioxidase.
The polyphenols in honey are caffeic acid, caffeic acid
phenyl ester, chrysin, galangin, quercetin, acacetin, kaemp-
ferol, pinocembrin, pinobanksin, and apigenin.
honey protects normal rats from the incidence of epinephrine-
induced cardiac disorders and vasomotor dysfunction.
The beneﬁcial effect of honey on CVD might be attrib-
uted to its antioxidative and anti-inﬂammatory properties,
increment of NO production, and improvement of blood
sugar and blood pressure (Table 4).
Natural honey has many biological activities besides its
antimicrobial activity (Figure 1). Honey ingestion increases
blood vitamin C level, b-carotene, uric acid, glutathione
reductase, copper, zinc, NO end products, and decreases
PGL, CRP, homocysteine, and plasma prostaglandin E2,
F2-a, and thromboxane B2 concentrations. Moreover, honey
Table 4. Effects of Honey on Common Cardiovascular Risk Factors
Variables Effect of honey Possible mechanism of action
Blood sugar Reduces blood sugar in normal indi-
viduals and in patients with diabetes
Flavonoids and antioxidants
Increases copper and zinc
Inhibition of prostaglandin
Elevation of NO
HTN Lowers blood pressure Antioxidant constituents and increment of NO
Lipid proﬁle Decreases total cholesterol, LDL-cho-
lesterol, and triacylglycerol, and in-
creases HDL-cholesterol in healthy
and hyperlipidemic subjects
Antioxidants, polyphenols, and vitamin content, elevation
of NO, and suppression of prostaglandins
CRP Decreases CRP Antioxidants, polyphenols, and vitamin E content
Homocysteine Decreases homocysteine Vitamin C content
Body weight Decreases body weight in normal,
overweight and obese individuals
Honey delays the postprandial ghrelin response, enhances the
total PYY response, and blunts the glucose response
Honey reduces hunger and food intake
CRP, C-reactive protein; HDL, high-density lipoprotein; HTN, hypertension; LDL, low-density lipoprotein; PYY, peptide YY.
FIG. 1. Biological effects of honey on blood glucose, lipids and
HONEY AND CARDIOVASCULAR RISK FACTORS 1071
improves lipid proﬁles and modulates C-peptide and insulin
secretion. Honey has powerful antioxidative activity and its
ingestion increases antioxidative materials. Honey appears
to have many effects on various metabolic parameters. Its
contents and effects on metabolic parameters might result in
beneﬁcial effects seen in patients with DM, HTN, and CVD.
From studies reviews, honey appears to be a powerful nat-
ural biological syrup that may be recommended to be used in
healthy individuals, and in patients with DM, HTN, and CVD.
The authors are thankful to National Plan for Science and
Technology (NPST) program of King Saud University,
Project No. 11-AGR1748-02 for ﬁnancial support.
AUTHOR DISCLOSURE STATEMENT
The authors declared that there is no conﬂict of interest
regarding the publication of this article.
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