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Acute Modulatory Effects of Apple Cider Vinegar, Garlic, Ginger, Lemon and Honey Mixture, with and Without Exercise on Postprandial Glycemia in Non-Diabetic Females

Jurnal Sains Kesihatan Malaysia Isu Khas 2018: 105-111
Acute Modulatory Effects of Apple Cider Vinegar, Garlic, Ginger, Lemon and
Honey Mixture, with and Without Exercise on Postprandial Glycemia in
Non-Diabetic Females
(Kesan Modulasi Akut Campuran Cuka Epal, Bawang Putih, Halia, Lemon dan Madu ke atas Glisemia
Posprandial dengan atau tanpa Senaman dalam Wanita Tanpa Diabetes)
Postprandial hyperglycemia is independently related to cardiovascular disease. Garlic, ginger, lemon, honey and apple
cider vinegar are known to have anti-glycemic properties. However, the effectiveness of combination of these natural
products on reducing postprandial glycemia is uncertain. The aim of the present study was to investigate the glucose-
lowering effect of a novel mixture consisting of apple cider vinegar, garlic, ginger, lemon, and honey; alone and in
combination with exercise in response to a high-carbohydrate meal in non-diabetic individuals. Ten, female subjects (mean
age: 25 ± 2.67 years, mean BMI: 22.6 ± 3.5 kg/m2) participated in this randomised, cross-over intervention consisting of
four trials: control (CON), mixture only (MIX), exercise only (EX), and exercise + mixture (EX-MIX). All trials involved
consumption of a high-carbohydrate breakfast, then followed by rest in CON, consumption of natural product mixture
in MIX, brisk-walking exercise in EX, and combination of mixture and exercise in EX-MIX. Blood glucose was measured
at fasting, and at 30, 60, 90, 120 minutes post meal. Postprandial glucose response was calculated as area under the
glucose curve. Two-way repeated measures ANOVA showed a signicant group and time interaction (p < 0.001). Compared
to CON, postprandial glucose responses were 8%, 13% and 15% lower in MIX (p = 0.049), EX (p = 0.001) and EX-MIX
(p = 0.005) respectively. Postprandial glucose was 8% lower in EX-MIX compared to MIX (p = 0.002). In conclusion,
consuming natural product mixture containing garlic, ginger, lemon, honey and apple cider vinegar reduced postprandial
glycemia to a certain extent, however, combining mixture with exercise produced a greater attenuation effect compared
to consuming mixture alone. This nding is indicative of a potential benet of the novel mixture as a complementary
management of hyperglycemia in high-risk individuals.
Keywords: Natural products; glucose; hyperglycemia; exercise
Hiperglisemia posprandial adalah berkait dengan penyakit kardiovaskular. Bawang putih, halia, lemon, madu dan cuka
epal terbukti mempunyai sifat anti-glisemik. Namun, keberkesanan campuran produk asli tersebut dalam mengurangkan
glisemia posprandial belum diketahui. Tujuan kajian ini adalah untuk menentukan kesan campuran bawang putih, halia,
lemon, madu dan cuka epal terhadap penurunan respons glukosa posprandial, dan dengan gabungan senaman selepas
diberi makanan tinggi karbohidrat dalam individu tanpa diabetes. Sepuluh subjek wanita (purata umur: 25 ± 2.67 tahun,
purata IJT: 22.6 ± 3.5 kg/m2) telah mengambil bahagian dalam intervensi berbentuk rawak silang yang terdiri daripada
empat jenis intervensi: kawalan (CON), campuran produk asli (MIX), senaman sahaja (EX) dan senaman + campuran
produk asli (EX-MIX). Kesemua intervensi melibatkan sarapan tinggi karbohidrat, diikuti dengan rehat bagi intervensi
CON, minuman campuran produk asli selepas sarapan bagi intervensi MIX, senaman selepas sarapan bagi intervensi
EX, dan gabungan minuman produk asli dan senaman bagi intervensi EX-MIX. Aras glukosa darah ditentukan sebelum
sarapan (0 minit) dan pada 30, 60, 90 dan 120 minit selepas sarapan. Respons glukosa posprandial diukur menggunakan
keluasan di bawah lengkuk glukosa. Analisis ANOVA dua-hala menunjukkan interaksi kumpulan dan masa yang signikan
(p < 0.001). Respons glukosa posprandial adalah lebih rendah sebanyak 8%, 13% dan 15% dalam MIX (p = 0.049), EX
(p = 0.001) and EX-MIX (p = 0.005) masing-masing berbanding kawalan. Respons glukosa posprandial juga adalah
8% lebih rendah dalam EX-MIX berbanding MIX (p = 0.002). Secara kesimpulan, gabungan campuran produk asli
mengandungi bawang putih, halia, lemon, madu dan cuka epal dapat menurunkan respons glukosa posprandial, namun
gabungan campuran produk asli dengan senaman menghasilkan penurunan glukosa posprandial yang lebih berkesan.
Dapatan kajian ini menunjukkan potensi campuran produk asli ini sebagai salah satu kaedah komplementari dalam
pengurusan hiperglisemia dalam individu yang berisiko.
Kata kunci: Produk asli; glukosa; hiperglisemia; senaman
Chap 15.indd 105 31/05/2018 15:30:24
support the ability of these combined agents to effectively
lower blood glucose levels. Nevertheless, the usage of
these herbal food supplements should not be discounted
by healthcare professionals now that they are becoming
increasingly popular, especially for those whose blood
glucose levels are on the borderline and pharmacological
therapies have not been initiated (Deng 2012).
Therefore, the aim of this study was to evaluate
the effect of a natural products mixture consumption
containing apple cider vinegar, garlic, ginger, lemon and
honey on postprandial blood glucose in response to a high-
carbohydrate meal. To further evaluate the effectiveness of
the mixture, we compared the effect of the mixture against
acute exercise, as exercise has been shown to effectively
attenuate postprandial hyperglycemia (Farah & Gill 2013).
Therefore, this study examined the effects of consumption
of natural products mixture, with or without exercise, on
postprandial hyperglycemia, in untrained, non-diabetic
young women. We postulated that the consumption of
the natural product mixture yielded glucose-lowering
effect comparable to that of exercise, and combination
of the mixture with exercise produced an additive effect
in lowering postprandial hyperglycemia compared to
consumption of natural product mixture alone.
Ten, untrained, apparently healthy females (mean age: 25
± 2.6 years; mean BMI: 22.6 ± 3.5 kg/m2) were recruited as
subjects for this study. The research protocol was conducted
in accordance with the ethical standards involving human
research and approved by the UKM Medical Center Ethical
Review Board (NN-2017-109). All participants gave
written informed consent to serve as study subjects. The
exclusion criteria include: 1) use of any tobacco product
or nutritional supplements that may affect blood glucose,
2) have a clinical diagnosis of cardiovascular or metabolic
diseases, and 3) regular exercise at least two d/week for
the past six months, and 4) allergy or intolerance to natural
products used in the study. Subjects were instructed not
to engage in any physical training, alter their habitual
dietary patterns or take any other supplements during the
study period.
The study employed a randomised, cross-over intervention,
consisted of four postprandial intervention trials: 1) control
(CON); 2) natural product mixture only (MIX); 3) exercise
only (EX); and 4) combination of exercise and natural
product mixture (EX-MIX). Subjects were required to
complete all trials. The wash-out period between each
trial was seven days. The order of trials was randomized
for each subject to minimise bias.
Postprandial hyperglycemia is characterized by abnormally
increased circulating levels of glucose in the blood
following a meal. Accumulating evidence supports the
critical role of acute postprandial hyperglycemia to
incrementally contribute to cardiovascular risk; it better
predicts CVD-related deaths compared with fasting glucose
concentrations, regardless of the presence of diabetes
(Gerich 2003). Hyperglycemia can cause serious damage
to the nerves and blood vessels, leading to macro- and
microvascular complications often seen in diabetes.
Mechanistic evidence suggests that the adverse effects
of hyperglycemia on vascular and nervous functions are
mediated through oxidative stress (Ceriello & Genovese
2016), increased formation of advanced glycation end
products (AGEs) (Nishikawa & Araki 2016) and more
importantly, promotion of inflammatory state (Hansen et
al. 2017). Due to the fact that postprandial hyperglycemia
is implicated in the altered metabolic flux contributing
to accelerated CVD progression, therefore reducing
postprandial hyperglycemia is now becoming a main target
in the prevention and treatment of metabolic diseases.
The management of hyperglycemia includes
pharmacological interventions, physical exercise, and
change of lifestyle and diet. The use of natural products as
an alternative therapy for management of hyperglycemia
has grown exponentially over the past decade. Studies
on the potential role of natural products preparation,
either as pure compounds or as extracts, as having
hypoglycemic effects is rapidly gaining focus. With a
good safety profile and convenience, natural product-based
supplements have increasingly become attractive additions
to the regular pharmacological therapies in the context of
prevention or treatment of cardiovascular and metabolic
diseases (Waltenberger et al. 2016). Indeed, many natural
products are currently being sold in the mass market as
food supplements for promoting general health or as
herbal remedies. Vinegar, garlic (Allium sativum), ginger
(Zingiber ofcinale) lemon (Citrus limon) and honey have
been widely used as dietary spices and natural remedies of
various ailments in folk medicine for centuries (Beidokhti
et al. 2017; Budak et al. 2014; Samarghandian et al. 2017).
Individually, they have been shown to exert hypoglycemic
effects by a number of mechanisms: facilitation of insulin-
dependent glucose uptake by increasing translocation of
glucose transporter GLUT4 to the cell membrane surface
(Li et al. 2012), delaying gastric emptying (Hlebowicz
et al. 2007), and enhanced hepatic glucose uptake and
glycogen synthesis (Erejuwa et al. 2012). Here in Malaysia,
the combination of these natural products is among the
widely-marketed food supplements for treating diabetes-
related symptoms as well as maintenance of general health.
While these natural products may have been shown to have
anti-hyperglycemic properties individually (Bayan et al.
2014; Erejuwa et al. 2012; Farideh et al. 2017; Sharma et
al. 2015; Shidfar et al. 2015), there is little to no evidence to
Chap 15.indd 106 31/05/2018 15:30:24
Figure 1 showed the general overview of the experimental
protocol. All test days started in the morning with a
standardised test meal, followed by a 2-hour observation
in the postprandial period. The four trials were described
Control (CON). Subjects consumed a standardised test meal
after reporting to the lab, followed by rest thereafter.
Natural product mixture (MIX). Subjects consumed a
standardised test meal along with 20 ml of the natural
product mixture, followed by rest thereafter.
Exercise (EX). Following a standardised test meal, subjects
performed a brisk walking exercise on a treadmill for 20
minutes, followed by rest thereafter.
Exercise and mixture (EX-MIX). Following a standardised
test meal along with 20 ml of the natural products mixture,
subjects performed a brisk walking exercise on a treadmill
for 20 minutes, and followed by rest thereafter.
0 30 60 90 120 min
FIGURE 1. Overview of experimental trials for CON: control; MIX: mixture only; EX: exercise only; EX-MIX: exercise + mixture.
Consumption of 400-kcal test meal ( ) and natural product mixture (M) are indicated. Blood samples () were collected at
times indicated.
A mixture consisting of apple cider vinegar, garlic, ginger,
lemon juice and pure ‘kelulut’ honey was prepared based on
a ratio of 1: 1: 1: 1: 1. A feasibility test was conducted to test
the palatability of the mixture for subjects’ consumption.
The formulation mixture contained equal quantities of 40
ml of ginger juice (225 g/milled and refined), garlic juice
(100 g/milled and refined), pure lemon juice, apple cider
vinegar and honey (modified from Naseem et al. 2016). All
liquid except honey were reduced to one-fourth of original
volume on medium heat for 30 minutes. The concentrated
mixture was then cooled at room temperature before adding
honey. The final product mixture was kept chilled in a
refrigerator and used within 48 hours.
In all trials, subjects consumed a standardised, high-
carbohydrate meal (400 kcal, 83 g carbohydrate) in the
morning after an 8-hr overnight fast. The meal consisted
of two slices of white bread with 20 g of mixed fruit jam,
two pieces of chocolate cookies and 250 ml of sweetened
beverage. Timing of meal was kept consistent for all
subjects in all trials.
Subjects performed a brisk-walking exercise on a
motorized treadmill at the intensity of 50-60% of heart
rate reserve (HRR), equivalent to a moderate intensity. This
was calculated for each individual using the following
Karvonen equation: [(220 – age) × % intensity)] + resting
heart rate (Swain et al. 1994). Subjects were required to
exercise within the individual target heart rates throughout
the exercise duration. The speed and inclination were
tailored to each subject’s preference. Heart rates were
recorded every five minutes during the exercise using heart
rate monitors (POLAR®, Finland).
Chap 15.indd 107 31/05/2018 15:30:26
Blood samples were collected at fasting (0 min) and at 30,
60, 90 and 120 minutes post test meal in all trials for the
determination of plasma glucose using a glucose analyzer
(ACCU-CHEK Active, Roche). The total area under
glucose versus time curve (AUC 0-120 min), calculated
using the trapezium rule, was used as a summary measure
of the postprandial glucose response in each trial.
Sample size calculation was primarily based on the number
of participants needed to detect a difference in area under
the curve (AUC) of postprandial glucose of approximately
20% (Mettler et al. 2009). A priori power calculation
indicated that 10 participants would enable detection
of a change in postprandial glucose response with 80%
power. Data were analyzed using the SPSS (version 22,
SPSS Inc.) One-way repeated measures ANOVA was used
to compare fasting glucose and area under curve values
for postprandial glucose responses across the four trials.
Two-way repeated-measures ANOVA (trial × time) were
used to compare postprandial glucose changes over time
and across the trials, followed by Bonferonni correction for
pair-wise comparisons to determine the mean differences
between and within trials. Percentages are used to quantify
the differences in total AUC (0-120 min) between trials.
Data are presented as mean values and their standard
errors, unless otherwise stated. Statistical significance was
accepted at p < 0.05.
The treadmill speed and gradient for both exercise sessions
(EX and EX-MIX) were identical within each subject.
Subjects walked for 20 min at an average speed of 5.5 ±
0.1 km/h on a gradient of 2.2 ± 0.8%. All exercise sessions
were completed without difficulty and subjects rated the
exercise as ‘fairly light’ on the Borg scale of 6-20 in both
the EX and EX-MIX trials. Mean exercise heart rates for
the EX and EX-MIX trials were 133 ± 4 bpm and 134 ± 5
bpm respectively. These values did not differ significantly
between both trials.
Table 1 and Figure 2 showed the fasting and postprandial
glucose responses in all trials. No significant differences
were observed in fasting glucose values across the four
trials. Two-way repeated measures ANOVA revealed a
significant group x time interaction: F(12, 108) = 6.63, p
< 0.001. Plasma glucose peaked at 30 min following the
standardized test meal and was lower in the MIX (-10%,
p > 0.05), EX (-26%, p = 0.002) and EX-MIX (-31%, p =
0.001) trials compared to CON. Plasma glucose remained
significantly lower in the following 60 min in MIX (p =
0.004), EX (p = 0.012) and EX-MIX (p = 0.006) trials
compared to CON. There were no differences in plasma
glucose across all trials following 120 min.
Analysis showed a significant effect of trials on
postprandial glucose AUC0-120 across all conditions [F(4,
12) = 9.89, p < 0.001]. Among all trials, the postprandial
glucose AUC was highest in the CON trial. Compared to
CON, the postprandial glucose AUC values were 13% and
15% lower in the EX (p = 0.005) and EX-MIX (p = 0.001)
respectively. The postprandial glucose AUC in MIX trial
showed an 8% attenuation compared to CON, however this
was borderline significant (p = 0.049). The postprandial
glucose AUC was significantly lower in EX-MIX (-8%, p
= 0.002) compared to MIX trial. No significant differences
were observed in postprandial glucose AUC between EX
and MIX and between EX and EX-MIX trials.
The aims of this study were to determine the effect of
natural product mixture consumption on postprandial
glycemia in response to a high-carbohydrate meal, as
well as to determine whether the consumption of natural
product mixture in combination with exercise produced
an additive effect compared to consumption of mixture or
exercise alone. To the best of our knowledge, this is the first
study employing a novel mixture of apple cider vinegar,
garlic, ginger, lemon and honey, and in combination with
TABLE 1. Postprandial glucose responses (mmol/l) and total area under curve (AUC0-120 min) across all trials
Trials 0 min 30 min 60 min 90 min 120 min AUC0-120
CON 4.42 ± 0.35 8.10 ± 2.36 7.21 ± 1.00 6.21 ± 0.93 5.38 ± 0.76 792 ± 115
MIX 4.48 ± 0.32 7.30 ± 0.75b 6.13 ± 1.37a 6.42 ± 0.80 5.25 ± 0.47 730 ± 86b
EX 4.58 ± 0.38 5.94 ± 1.34a 5.75 ± 0.84a 6.14 ± 0.78 5.50 ± 0.61 684 ± 88a
EX-MIX 4.54 ± 0.20 5.56 ± 0.97a 6.01 ± 0.95a 5.86 ± 0.50a 5.27 ± 0.77 670 ± 75a
Values are expressed as mean ± SEM, n = 10
CON: control; MIX: mixture only; EX: exercise only; EX-MIX: exercise + mixture
a significantly different compared to CON
b significantly different compared to EX-MIX
Chap 15.indd 108 31/05/2018 15:30:26
a single bout of exercise in examining its acute effects on
postprandial glycemia in humans.
The present data demonstrated that the consumption
of the natural product mixture resulted in a trend of
reduction in postprandial glycemia by an average of
13% compared to control. Apple cider vinegar, garlic,
ginger, lemon and honey are among the functional foods
commonly used all around the world, particularly in the
Asian countries. So far, the anti-glycemic effects of these
products have been investigated in isolation particularly in
animal studies. However, the effect of these products when
combined is relatively unknown, especially in humans.
Previously, Naseem et al. (2016) had demonstrated that
administration of a similar mixture (i.e. combination of
apple cider vinegar, garlic, ginger, honey and lemon) in
rabbits fed with atherogenic diet for 15 days attenuated
fasting blood glucose levels by 34% compared to the
control group. In our study, consumption of the mixture
caused a pronounced reduction in postprandial glucose
concentration at 60 min post meal, compared to control, in
addition to an overall reduction on postprandial glycemia
though the difference was not apparent. Nevertheless, the
finding can be considered novel and seems to be indicative
of the anti-glycemic potential of the products combined
together. It is possible that the attenuation would appear
significant in hyperglycemic individuals in contrast to
normoglycemic or non-diabetic individuals, due to higher
glucose peaks and exaggerated postprandial responses in
the former population.
While there is no clear mechanism on how the
combination of these natural products can lower glycemic
response, it is plausible that the anti-glycemic effect was
mediated by the synergistic effect of individual products
in the mixture, which is consistent with the known benefits
of individual products. The hypoglycemic potency of
garlic has been attributed to allicin-derived organosulphur
compounds, which protect insulin from –SH inactivation
by reacting with endogenous thiol-containing molecules
such as cysteine, glutathione and serum albumin (Eidi et
al. 2006). Compelling data show that ginger extract has
hypoglycemic, insulinotropic, and sensitiser effects on
diabetic humans (Shidfar et al. 2015) and on experimental
animals (Ojewole et al. 2006). Meanwhile, the anti-
glycemic effect of acetic acid, the active ingredient in
vinegar, has been attributed to delay gastric emptying
(Liljeberg & Bjorck 1998) as well as to modulate glycolysis/
gluconeogenic cycle in skeletal muscles (Fushimi et al.
2001). Fructose, one the major form of monosaccharide
sugar found in honey, was suggested to contribute to the
anti-glycemic effects of the honey by delaying gastric
emptying and increases hepatic uptake of glucose resulting
in decreasing blood glucose concentrations (Erejuwa et
al. 2012). The anti-glycemic effect of the mixture in the
present study was consistent with the aforementioned
reports, which may explain the combined beneficial effects
of apple cider vinegar, garlic, ginger, lemon and honey on
postprandial glucose response.
The hypoglycemic effects of exercise have been
widely documented. Most studies have shown that
moderate intensity exercise between 30 to 60 min was
effective at lowering postprandial glucose responses
post-meal in healthy subjects (Hashimoto et al. 2013;
FIGURE 2. Postprandial glucose responses across time 0 to 120 min following standardised test meal ( ) for all trials. Values are
means, with SEM represented by vertical bars. CON: control; MIX: mixture only; EX: exercise only; EX-MIX: exercise + mixture.
Exercise in EX and EX-MIX trials is indicated on the timeline. * significantly different compared to CON, # significantly different
compared to EX-MIX.
0.0 0
30 60
Time (min)
Mean plasma glucose
90 120
Chap 15.indd 109 31/05/2018 15:30:27
Roberts et al. 2013; Farah & Gill 2013) as well as in
diabetic individuals (Kearney et al. 2016). Consistent
with published literature, our findings showed that brisk-
walking exercise lowered postprandial glycemia by 15%
following a high-carbohydrate meal compared to no-
exercise control. Exercise is effective in lowering plasma
glucose concentration by increasing uptake of glucose
into cells by up to 50-fold through the simultaneous
stimulation of three key steps: delivery, transport across the
muscle membrane and intracellular flux through metabolic
processes of glycolysis and glucose oxidation (Sylow
et al. 2017). It is noteworthy that the lowering effect of
exercise on postprandial glycemia was evident despite
the shorter exercise duration (20 min) employed in this
study, compared to prolonged duration in previous studies.
This finding is somewhat encouraging in the sense that
brisk-walking is feasible for most people, which could be
generalised into everyday life of hyperglycemic individuals
with little motivation for exercise.
When comparing the reduction in postprandial
glycemia following consumption of mixture alone, the
reduction in glycemic response induced by brisk-walking
exercise alone was slightly greater, i.e. 15% vs. 8% in
the former, though this finding was not significant. Quite
interestingly, this may be indicative of the potential of
the natural product mixture to exert an anti-glycemic
effect that is comparable to the effect induced by exercise
alone. One might speculate that with larger doses than 20
ml used in the study, or with repeated consumption, the
lowering effects would be more pronounced. We used a 20
ml dose of mixture, which was approximately equivalent
to two tablespoons, a volume that many would typically
consume under real-life circumstances with regards to
commercially-available natural product supplements.
Further investigation may bring more insight regarding
the effective dose mixture in lowering postprandial
hyperglycemia that is comparable to exercise. Lastly, the
study also showed that consumption of the mixture in
combination with a short bout of brisk-walking exercise
produced greater attenuation in postprandial glycemia
compared to mixture alone. This finding was somewhat
expected. On the other hand, combining consumption of
mixture with exercise did not produce an additive effect
in lowering postprandial glycemia compared to exercise
alone. The absence of an additive effect could presumably
be due to the acute consumption of the natural product
mixture. Karimi et al. (2015) in their study in obese women,
demonstrated that the combination of water-based exercise
and ginger supplement for six weeks had better effect on
insulin resistance in comparison to water-based exercise or
ginger supplement alone. It is therefore possible, that with
prolonged consumption, the additive effect of the natural
product mixture and exercise would be more evident.
The findings of the present study might be interpreted
in the light of the fact that this was the first study of its
kind in human subjects, which could limit our ability to
determine the appropriate dose and ratio of the natural
product mixture. We believe the dose and ratio of the
natural products are vital in determining the anti-glycemic
properties of the mixture. Certainly, the conclusion about
the modulatory effect of the natural product mixture is
only limited to glycemic responses in healthy individuals.
Therefore, similar studies examining the effects of different
doses and treatment protocol of the mixture on a wider
range of variables (e.g. insulin, insulin resistance, blood
lipids) would shed more light on the potential benefits of
this mixture. No unfavorable effects were observed with the
consumption of the natural product mixture in the study.
The combination of apple cider vinegar, garlic, ginger,
lemon and honey appears to have an anti-hyperglycemic
effect on postprandial glycemia in non-diabetic females.
In addition, combination of brisk-walking exercise and
the mixture produced a greater lowering effect, rather than
consuming the mixture alone. The findings of this study
may represent a practical, non-pharmacological option
in the prevention and management of hyperglycemia in
individuals at risk. Future studies with clinically-defined
participants, standardised preparation and dose, and across
a wide range of metabolic parameters are warranted.
This study was supported by the Fundamental Research
Grant Scheme, Ministry of Higher Education Malaysia
[FRGS/2/2014/SS02/UKM/02/2]. The authors would like to
thank all the participants who took part in the study.
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Ismarulyusda Ishak
Penny George
Farah Wahida Ibrahim
School of Diagnostics and Applied Health Sciences
Faculty of Health Sciences
Universiti Kebangsaan Malaysia
53000 Kuala Lumpur
Hanis Mastura Yahya
School of Healthcare Sciences
Faculty of Health Sciences
Universiti Kebangsaan Malaysia
53000 Kuala Lumpur
Nor Farah Mohamad Fauzi
School of Rehabilitation Sciences
Faculty of Health Sciences
Universiti Kebangsaan Malaysia
53000 Kuala Lumpur
Corresponding author: Nor Farah Mohamad Fauzi
Tel: 03-26878049
Fax: 03-26810200
Received: August 2017
Accepted for publication: January 2018
Chap 15.indd 111 31/05/2018 15:30:28
... Saat ini, campuran poliherbal yang mengandung bahan-bahan seperti lemon, jahe, bawang putih, cuka sari apel dan madu telah banyak digunakan sebagai salah satu minuman nutrisi yang mengurangi kadar kolesterol. Beberapa penelitian sebelumnya menunjukkan potensi efek dari campuran dalam meningkatkan profil lipid dan meningkatkan kesehatan pembuluh darah pada model hewan yang diinduksi hiperlipidemia ketika diberi makan secara oral atau dimasukkan dalam makanan [3,[11][12][13][14][15]. Ini juga menunjukkan hasil yang baik dalam menunda dan menurunkan glukosa postprandial bila diberikan sendiri atau disertai dengan olahraga pada wanita manusia nondiabetes setelah makan karbohidrat tinggi dibandingkan dengan kelompok kontrol [13]. ...
... Saat ini, campuran poliherbal yang mengandung bahan-bahan seperti lemon, jahe, bawang putih, cuka sari apel dan madu telah banyak digunakan sebagai salah satu minuman nutrisi yang mengurangi kadar kolesterol. Beberapa penelitian sebelumnya menunjukkan potensi efek dari campuran dalam meningkatkan profil lipid dan meningkatkan kesehatan pembuluh darah pada model hewan yang diinduksi hiperlipidemia ketika diberi makan secara oral atau dimasukkan dalam makanan [3,[11][12][13][14][15]. Ini juga menunjukkan hasil yang baik dalam menunda dan menurunkan glukosa postprandial bila diberikan sendiri atau disertai dengan olahraga pada wanita manusia nondiabetes setelah makan karbohidrat tinggi dibandingkan dengan kelompok kontrol [13]. Sebuah penelitian mencatat perubahan glukosa sebanyak 8% pada kelompok campuran, 13% pada kelompok latihan dan 15% pada campuran yang disertai dengan kelompok latihan [13]. ...
... Beberapa penelitian sebelumnya menunjukkan potensi efek dari campuran dalam meningkatkan profil lipid dan meningkatkan kesehatan pembuluh darah pada model hewan yang diinduksi hiperlipidemia ketika diberi makan secara oral atau dimasukkan dalam makanan [3,[11][12][13][14][15]. Ini juga menunjukkan hasil yang baik dalam menunda dan menurunkan glukosa postprandial bila diberikan sendiri atau disertai dengan olahraga pada wanita manusia nondiabetes setelah makan karbohidrat tinggi dibandingkan dengan kelompok kontrol [13]. Sebuah penelitian mencatat perubahan glukosa sebanyak 8% pada kelompok campuran, 13% pada kelompok latihan dan 15% pada campuran yang disertai dengan kelompok latihan [13]. Selain itu, penelitian lainnya menjelaskan bahwa perubahan metabolit pada campuran poliherbal dengan dosis tinggi (500 mg/kg) lebih baik dibandingkan dengan dosis sedang (250 mg/kg) karena berhasil mereduksi biomarker primer pada tikus hiperlipidemia, TMAO. ...
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Hiperlipidemia menjadi suatu kondisi yang perlu diterapi untuk menghindari terbentuknya aterosklerosis dan menjadi penyakit kardiovaskular akut. Salah satu terapinya yaitu obat komplementer berupa poliherbal yang mengandung bawang putih, jahe merah, lemon, cuka apel, dan madu. Kontrol kualitas sediaan herbal menjadi sangat penting dan diperlukan untuk dilakukan agar khasiat bisa dicapai. Studi literatur ini dibuat untuk memberikan informasi mengenai sediaan herbal yang mengandung poliherbal tersebut sebagai antihiperlipidemia serta berbagai pengujian dalam standarisasi sediaannya. Pencarian literatur dilakukan pada jurnal nasional dan internasional dengan mesin telusur Google, Google scholar, Pubmed, NCBI, Sciencedirect dan lainnya menggunakan kata kunci yang terkait. Literatur yang terkumpul dilakukan skrining dengan kriteria inklusi yaitu waktu terbit pada 2007-2021 dan penelusuran lanjutan dengan melihat secara manual pada referensi yang relevan. Berdasarkan kajian literatur yang diperoleh, sediaan campuran poliherbal ini memiliki efek antihiperlipidemia secara in vivo yang setara dengan simvastatin dengan mekanisme yang mirip. Masing-masing bahan memiliki kumpulan senyawa aktif yang berperan dalam efek antihiperlipidemia yang dapat dijadikan senyawa penanda. Informasi karakterisasi senyawa penanda tersebut bisa menjadi acuan dalam mempelajari stabilitasnya baik secara fisika maupun kimia. Maka dari itu, perlu dikaji lebih lanjut mengenai stabilitas campuran poliherbal ini agar dapat stabil lebih lama dan memberikan manfaat yang lebih luas di masyarakat.
... Vinegar is perceived as a healthy beverage as it lowers blood sugar in the presence of probiotics, the good bacteria (Ishak et al., 2018;Sahar & Shehata, 2012;Thinathayalan et al., 2019). Production of vinegar requires raw materials containing sugar or starch which undergo double fermentation processes, i.e., alcoholic and acetous fermentations . ...
Soursop (Annona muricata L.) is a highly perishable fruit and is often rejected by the market due to external injury or rapid aging process that leads to unacceptable senescence for further processing. A previous study has optimised the alcoholic fermentation of soursop to produce soursop wine using an alternative fermentative starter culture. Therefore, this study was aimed to produce soursop vinegar using an acetous fermentation and investigate the physicochemical, toxicity and organoleptic properties. Soursop vinegar showed significantly (p ≤ 0.05) higher acetic acid (3.5 ± 0.3%), total phenolic content (220 ± 20 ppm gallic acid equivalence) and FRAP (ferric reducing antioxidant power) activity (222 ± 2 μM ascorbic acid equivalence), with lower pH, sugar, ethanol and DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging activity while retaining ascorbic acid, compared to those of soursop wine. A toxicity assay carried out using the fish embryos toxicity (FET) showed that the median lethality concentration (LC50) for fish embryos was 11.8 mg/mL, which was considered as non-toxic. Meanwhile, toxicity with human liver tissue (HepG2) using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay suggested that the cells’ survivability increased when the concentration of soursop vinegar was ≤6.25%. Sensory evaluation was carried out using quantitative descriptive analysis and the soursop vinegar was less sour and sweeter than commercial vinegar. This study offers an alternative way of reducing wastage of soursop fruit by the conversion of soursop into vinegar using a combination of alternative alcoholic and acetous fermentations.
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Vinegar intake is considered a food item that improves blood glucose in humans. This review aimed to discuss studies that investigated the impact of vinegar intake on the glycemic profile in humans and the putative mechanistic cellular pathways in both human and animal models. A search of literature was performed on the Cochrane, MEDLINE and Web of Science databases for articles published between 1995 and 2018. There is considerable support for vinegar having a positive acute effect on blood glucose levels when combined with carbohydrate-rich meals. Conversely, there are few chronic interventions analyzing the impact of vinegar intake on blood glucose. Based on available evidence, we hypothesize three pathways by which vinegar may improve blood glucose: The inhibition of α-amylase action; increased glucose uptake; and mediation by transcription factors. When evaluating the current body of literature, daily vinegar intake in amounts of ∼10-30 mL (∼2-6 tablespoons) appear to improve the glycemic response to carbohydrate-rich meals; however, there is a paucity of studies investigating chronic effects of vinegar intake.
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The endothelial cell (EC) layer constitutes a barrier that controls movements of fluid, solutes and cells between blood and tissue. Further, the endothelial layer regulates vascular tone and directs local humoral and cellular inflammatory processes. The strategic position makes it an important player for maintenance of health and for development of a number of diseases. Endothelial dysfunction is known to be an important component of type 2 diabetes, but is also assumed to be involved in many other diseases, for example, rheumatoid arthritis, inflammatory bowel disease, asthma, and cardiovascular diseases. We here suggest that the EC plays a pivotal role in disease pathophysiology through initiation, potentiation, and maintenance of several inflammatory mechanisms. Our contention is based on the observation that hyperglycemia—intermittent or sustained, local or systemic—is a major culprit for several endothelial dysfunctions. There is also mounting epidemiological evidence that dietary intake of refined sugars is important for the development of a number of diseases beyond obesity and type 2 diabetes. Various diseases involving inflammatory and immunological components are accelerated by hyperglycemic events because the endothelium transduces “high glucose” signaling into significant pathophysiological phenomena leading to reduced endothelial barrier function, compromised vascular tone regulation and inflammation (e.g., cytokine secretion and RAGE activation). In addition, endothelial extracellular proteins form epitopes for potential specific antibody formation upon interactions with reducing sugars. This paper reviews the endothelial metabolism, biology, inflammatory processes, physical barrier functions, and summarizes evidence that although stochastic in nature, endothelial responses to hyperglycemia are major contributors to disease pathophysiology. We present molecular and mechanistic evidence that both biological and physical barriers, protein function, specific immunity, and inflammatory processes are compromised by hyperglycemic events and thus, hyperglycemic events alone should be considered risk factors for numerous human diseases. © 2017 IUBMB Life, 69(3):148–161, 2017
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Skeletal muscle extracts glucose from the blood to maintain demand for carbohydrates as an energy source during exercise. Such uptake involves complex molecular signalling processes that are distinct from those activated by insulin. Exercise-stimulated glucose uptake is preserved in insulin-resistant muscle, emphasizing exercise as a therapeutic cornerstone among patients with metabolic diseases such as diabetes mellitus. Exercise increases uptake of glucose by up to 50-fold through the simultaneous stimulation of three key steps: delivery, transport across the muscle membrane and intracellular flux through metabolic processes (glycolysis and glucose oxidation). The available data suggest that no single signal transduction pathway can fully account for the regulation of any of these key steps, owing to redundancy in the signalling pathways that mediate glucose uptake to ensure maintenance of muscle energy supply during physical activity. Here, we review the molecular mechanisms that regulate the movement of glucose from the capillary bed into the muscle cell and discuss what is known about their integrated regulation during exercise. Novel developments within the field of mass spectrometry-based proteomics indicate that the known regulators of glucose uptake are only the tip of the iceberg. Consequently, many exciting discoveries clearly lie ahead.
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Natural products have always been exploited to promote health and served as a valuable source for the discovery of new drugs. In this review, the great potential of natural compounds and medicinal plants for the treatment or prevention of cardiovascular and metabolic disorders, global health problems with rising prevalence, is addressed. Special emphasis is laid on natural products for which efficacy and safety have already been proven and which are in clinical trials, as well as on plants used in traditional medicine. Potential benefits from certain dietary habits and dietary constituents, as well as common molecular targets of natural products, are also briefly discussed. A glimpse at the history of statins and biguanides, two prominent representatives of natural products (or their derivatives) in the fight against metabolic disease, is also included. The present review aims to serve as an "opening" of this special issue of Molecules, presenting key historical developments, recent advances, and future perspectives outlining the potential of natural products for prevention or therapy of cardiovascular and metabolic disease.
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Type 2 diabetes is characterized by a gradual decline in insulin secretion in response to nutrient loads; hence, it is primarily a disorder of postprandial glucose regulation. However, physicians continue to rely on fasting plasma glucose and glycated hemoglobin to guide management. There is a linear relationship between the risk of cardiovascular death and the 2-h oral glucose tolerance test, while a study confirms postprandial hyperglycemia as independent risk factor for cardiovascular disease in type 2 diabetes. At the same time, several studies show that postprandial hypertriglyceridemia may also be a cardiovascular risk factor. Interestingly, the simultaneous presence of postprandial hyperglycemia and postprandial hypertriglyceridemia has an additive effect in worsening endothelial function and inflammation. Evidence supports the hypothesis glucose postprandial hyperglycemia and hypertriglyceridemia may favor the appearance of the cardiovascular disease through the generation of an oxidative stress. Furthermore, clinical data suggest that postprandial hyperglycemia is a common phenomenon even in patients who may be considered in “good metabolic control”. Therefore, physicians should consider monitoring and targeting postprandial plasma glucose, as well as glycated hemoglobin and fasting plasma glucose, in patients with type 2 diabetes.
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Background: Breast neoplasms has known as the most common cancer among the women worldwide, and relationship between obesity, metabolic syndrome, inflammation and cancer has been recognized since many years ago. Objectives: The aim of this study was to determine the individual and concomitant effect of 6-weeks water-based exercise and oral ginger supplement on markers that have related to metabolic syndrome and systemic inflammation in obese women with breast neoplasms. Patients and methods: Forty women whose have diagnosed with breast neoplasms have volunteered to participate in the study. Subjects have randomly assigned into four groups; placebo, exercise training, ginger supplement and exercise training+ ginger supplement groups. Subjects in the ginger supplement group and the exercise training+ ginger supplement group have orally received 4 capsules, 7 days a week and for 6 weeks. The water-based exercise training program have collected at a progressive intensity and time, have ranged from 50% to 75% of heart rate reserve, in a pool, 4 times a week for 6 weeks. Fasting blood sampling has collected at the pretest and post-test. Results: The ginger supplementation and the water-base exercise have resulted in a reduction of hs-CRP, IL-10, insulin, glucose, insulin resistance, LDL-C, TG; but an increase in HDL-C and HDL-C/LDL-C. The water-base exercise and ginger supplement group have significantly shown larger positive effect in all outcomes, in comparison with the water-base exercise or ginger supplement alone groups. Conclusions: Findings have suggested that obese breast neoplasms survivors have commonly shown metabolic syndrome and elevated inflammation, which placed them at an increased risk for cardiovascular diseases. Moreover, data has indicated a protective effect of the nondrug strategies, such as water-base exercise and ginger supplementation have played an important role in pathogenesis of inflammatory and metabolic responses, among diagnosed breast neoplasms.
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The aim of diabetes treatment is to prevent diabetic complications. However, many patients still suffer from diabetic complications. Therefore, it is important to elucidate the mechanism that connects hyperglycemia to the development of diabetic complications. Several hyperglycemia-induced metabolic abnormalities, such as activation of the polyol pathway, formation of advanced glycation end products (AGEs), activation of protein kinase C (PKC) isoforms, and oxidative stress have been reported to involve in the development of diabetic complications1. In addition, we previously demonstrated that reactive oxygen species (ROS) from mitochondria was the major cause of diabetes-induced oxidative stress, and this mitochondrial ROS could cause the activation of three other metabolic abnormalities2. However, there remain many unanswered questions in the mechanism of diabetic complications.This article is protected by copyright. All rights reserved.
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Individuals with type 2 diabetes (T2D) have poor glycemic control which contributes to cardiovascular disease and other diabetic comorbidities. The often relied upon measures of fasting glucose and glycosylated hemoglobin (HbA1c) do not accurately represent glycemic control because they do not reflect what occurs after meals and throughout the day in the free-living condition. An accumulating body of evidence now suggests that postprandial glucose fluctuations are more tightly correlated with microvascular and macrovascular morbidities and cardiovascular mortality than HbA1c or fasting glucose, stagnant measure of glycemia. Thus, effective therapies are needed which will improve not only HbA1c and fasting glucose, but also regulation of postprandial glycemia. Further, testing for glycemic control should employ a challenge that simulates the free-living condition to best determine how glucose is regulated after meals and throughout the day. Unlike medications, which generally have a poor effect at improving postprandial glucose, exercise is effective in reducing postprandial glycemic excursions in as little as a few days. However, how this is accomplished and the optimal prescription for reducing postprandial glycemic excursions and maintaining improvements in postprandial glycemic control have yet to be elucidated. Still further, the utility of a mixed meal test in providing the optimal challenge for detecting exercise-induced changes in postprandial glycemic control has value that warrants further investigation. Thus, the purpose of this review is to summarize the literature regarding exercise in treating postprandial glycemia in T2D and to review strengths and weaknesses in the current methodology for assessing changes in glycemic control.
Honey is one of the most appreciated and valued natural products introduced to humankind since ancient times. Honey is used not only as a nutritional product but also in health described in traditional medicine and as an alternative treatment for clinical conditions ranging from wound healing to cancer treatment. The aim of this review is to emphasize the ability of honey and its multitude in medicinal aspects. Traditionally, honey is used in the treatment of eye diseases, bronchial asthma, throat infections, tuberculosis, thirst, hiccups, fatigue, dizziness, hepatitis, constipation, worm infestation, piles, eczema, healing of ulcers, and wounds and used as a nutritious supplement. The ingredients of honey have been reported to exert antioxidant, antimicrobial, anti-inflammatory, antiproliferative, anticancer, and antimetastatic effects. Many evidences suggest the use of honey in the control and treatment of wounds, diabetes mellitus, cancer, asthma, and also cardiovascular, neurological, and gastrointestinal diseases. Honey has a potential therapeutic role in the treatment of disease by phytochemical, anti-inflammatory, antimicrobial, and antioxidant properties. Flavonoids and polyphenols, which act as antioxidants, are two main bioactive molecules present in honey. According to modern scientific literature, honey may be useful and has protective effects for the treatment of various disease conditions such as diabetes mellitus, respiratory, gastrointestinal, cardiovascular, and nervous systems, even it is useful in cancer treatment because many types of antioxidant are present in honey. In conclusion, honey could be considered as a natural therapeutic agent for various medicinal purposes. Sufficient evidence exists recommending the use of honey in the management of disease conditions. Based on these facts, the use of honey in clinical wards is highly recommended. Summary: There are several evidence that suggesting the usage of honey in the management of disease. Therefore, honey in clinical wards is highly recommended. Abbreviations Used: WA: Water activity, RDI: Recommended daily intake, Si: Silicon, RB: Rubidium, V: Vanadium, Zr: Zirconium, Li: Lithium, Sr: Strontium, Pb: Lead, Cd: Cadmium, As: Arsenic, MIC: Minimum inhibitory concentration, PARP: Poly (ADP-ribose) polymerase, ROS: Reactive oxygen species, iNOS: Inducible nitric oxide synthase, NKcells: Natural killer cells, SCFA: Short-chain fatty acid, CRP: C-reactive protein.
Objective: Postprandial hyperglycemia plays a decisive role in the development of chronic metabolic disorders. The effect of vinegar intake with a meal on postprandial glucose has been studied in several trials with conflicting results. Research methods and procedures: The purpose of the current study was to systematically review control trials that report on the effect of vinegar intake on postprandial glucose response. Postprandial insulin response was considered as secondary outcome. Results: The pooled analysis of studies revealed a significant mean glucose and insulin area under the curve (AUC) reduction in participants who consumed vinegar compared with the control group (standard mean difference=-0.60, 95%CI -1.08 to -0.11, p=0.01 and -1.30, 95%CI -1.98 to -0.62, p<0.001, respectively). Conclusions: The findings suggest that vinegar can be effective in reducing postprandial glucose and insulin levels, indicating it could be considered as an adjunctive tool for improving glycemic control.
Ethnopharmacological relevance: Type 2 diabetes is the most common type of diabetes and its prevalence is rapidly increasing throughout the world. Modifications of lifestyle such as suitable diet and exercise programs along with pharmacotherapy and education of patients are beneficial therapies for patients with type 2 diabetes. The ethnopharmacological use of herbal medicines, many of them part of our diet as spices, vegetables and fruits, has been developed for the treatment of diabetes due to inexpensiveness, easy availability and few side effects. Aim of the study: Our aim is to present a review for researchers who are interested in the biologically active dietary plants traditionally utilized in the treatment of diabetes. Materials and methods: Information was obtained from a literature search of electronic databases such as Google Scholar, Pubmed, Sci Finder and Cochrane. Common and scientific name of the fruits, vegetables, beverages, oils and spices and the words 'antidiabetic', 'hypoglycemic', 'anti-hyperglycemic', 'type 2 diabetes' were used as keywords for search. Results: Certain fruits and vegetables are functional foods and their consumption reduces the incidence of type 2 diabetes. Hypoglycemic effects of fruits and vegetables may be due to their inducing nature on pancreatic β-cells for insulin secretion, or bioactive compounds such as flavonoids, alkaloids and anthocyanins, which act as insulin-like molecules or insulin secretagogues. Conclusion: This write-up covers hypoglycemic, anti-hyperglycemic and anti-diabetic activities of some dietary fruits, vegetables, beverages, oils and spices and their active hypoglycemic constituents. Including such plant species in the diet might improve management of type 2 diabetes.