Food Chemistry: Xinyan Bi, Joseph Lim, Christiani Jeyakumar Henry

Food Chemistry 217 (2017) 281293
Contents lists available at ScienceDirect
Food Chemistry
journal homepage: www.elsevier.com/locate/foodchem
Review
Spices in the management of diabetes mellitus

Xinyan Bi a,1, Joseph Lim a,1, Christiani Jeyakumar Henry a,b,
a
Clinical Nutrition Research Centre (CNRC), Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), 30 Medical Drive,
Singapore 117609, Singapore
b
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
a r t i c l e
i n f o
Article history:
Received 22 July 2015
Received in revised form 7 July 2016
Accepted 27 August 2016
Available online 29 August 2016
Keywords:
Spices
Diabetes mellitus
Antioxidant
Anti-inflammatory
Anti-diabetic
a b s t r a c t
Diabetes mellitus (DM) remains a major health care problem worldwide both in developing and
developed countries. Many factors, including age, obesity, sex, and diet, are involved in the etiology of
DM. Nowadays, drug and dietetic therapies are the two major approaches used for prevention and control
of DM. Compared to drug therapy, a resurgence of interest in using diet to manage and treat DM has
emerged in recent years. Conventional dietary methods to treat DM include the use of culinary herbs
and/or spices. Spices have long been known for their antioxidant, anti-inflammatory, and anti-diabetic
properties. This review explores the anti-diabetic properties of commonly used spices, such as cinnamon,
ginger, turmeric, and cumin, and the use of these spices for prevention and management of diabetes and
associated complications.
2016 Elsevier Ltd. All rights reserved.
Contents
1.
2.
3.
4.
5.
6.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Phenolic compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Diabetes mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Spices in the treatment of diabetes mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.
Cinnamon. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.
Ginger and turmeric . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3.
Cumin, coriander & anise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.4.
Fenugreek . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.5.
Garlic and onion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.6.
Cloves. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.7.
Mustards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.8.
Black pepper . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.9.
Curry leaves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Dietary intake and bioavailability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
282
282
282
284
285
287
288
288
289
289
289
289
290
290
290
Abbreviations: AMPK, 50 adenosine monophosphate-activated protein kinase; AGE, advanced glycation end-product; BP, blood pressure; CE, cinnamon extracts; CP,
cinnamon polyphenols; DM, diabetes mellitus; eNOS, endothelial nitric oxide synthase; FBG, fasting blood glucose; FDA, Food and Drug Administration; FFA, free fatty acid;
G6Pase, glucose-6-phosphatase; GLP-1, glucagon-like peptide 1; GLUT4, glucose transporter type 4; GPX, glutathione peroxidase; GRAS, Generally Recognized As Safe; HDL,
high-density lipoprotein; HbA1c, hemoglobinA1c; hsCRP, high-sensitivity C-reactive protein; IPF, insulin potentiating factor; IRS-1, insulin receptor substrate 1; IDDM,
insulin-dependent diabetes mellitus; JNK, c-Jun N-terminal kinase; LDL, low-density lipoprotein; NF-jB, nuclear factor-kappaB; NIDDM, non-insulin-dependent diabetes
mellitus; PEPCK, phosphoenolpyruvate carboxykinase; PKC, protein kinase C; PPAR-c, peroxisome proliferator-activated receptor gamma; PTP-1, protein tyrosine
phosphatase; ROS, reactive oxygen species; SBP, systolic blood pressure; SGLT1, sodium-glucose linked transporter 1; SOD, superoxide dismutase; STZ, streptozotocin; T1D,
type 1 diabetes; T2D, type 2 diabetes; VARC, volume regulated anion channel.
Corresponding author at: Clinical Nutrition Research Centre (CNRC), Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research
(ASTAR), 30 Medical Drive, Singapore 117609, Singapore.
E-mail address: jeya_henry@sics.a-star.edu.sg (C.J. Henry).
1
Equal contribution.
http://dx.doi.org/10.1016/j.foodchem.2016.08.111
0308-8146/ 2016 Elsevier Ltd. All rights reserved.
282
7.
X. Bi et al. / Food Chemistry 217 (2017) 281293
Future direction . . . .
Declaration of interest
Acknowledgements .
References . . . . . . . .
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1. Introduction
Diabetes mellitus (DM) is a chronic metabolic disorder of the
endocrine system that continues to be a major health care problem
worldwide. The prevalence of DM is expected to rise from the current 382 million individuals to 471 million by 2035 (IDF Diabetes
Atlas. Sixth edition., 2013). Diabetes is clinically characterized by
hyperglycemia (high blood glucose concentration) and the disturbance of carbohydrates, protein, and fat metabolism due to chronic
and/or relative insufficiency in insulin secretion and action
(Bastaki, 2005). Untreated, diabetes can cause many complications
and affect the eyes, nerves, kidneys, and blood vessels, and even
lead to premature death (Forbes & Cooper, 2013). It is believed that
hyperglycemia is also one of the most important factors in the
development of diabetes and associated complications. The
adverse effects of hyperglycemia may be derived from four metabolic pathways, including: activation of protein kinase C (PKC)
isoforms (Geraldes & King, 2010), increased hexosamine pathway
flux (James et al., 2002), increased advanced glycation endproduct (AGE) formation (Peppa, Uribarri, & Vlassara, 2004), and
increased aldose-reductase pathway flux (Rolo & Palmeira, 2006).
Drugs with anti-diabetic properties, coupled with insulin treatment, appropriate diet, and exercise, remain the main approach in
the treatment of diabetes. However, existing pharmaceutical treatments have toxic side effects and, sometimes, prolonged use leads
to diminished response (Hollander, 2007). In contrast, phenolic
compounds in commonly consumed plant-based foods have
attracted considerable attentions recently for being endowed with
compounds protective against diabetes (Perera & Handuwalage,
2015). Compared to synthetic drugs, the food components of plant
origin are natural, economical, and more appealing to consume.
Spices, in addition to fruits and vegetables, are the main dietary
sources of phenolic compounds. The polyphenols (one group of
the phenolic compounds) in 80 spices have been proven to exhibit
anti-glycation properties, which contribute to the prevention and
management of DM (Elosta, Ghous, & Ahmed, 2012). The spice
polyphenols may influence glucose metabolism via several mechanisms, such as glucose absorption in the intestine, stimulation of
insulin secretion from pancreatic b-cells, modulation of glucose
release from the liver, activation of insulin receptors and glucose
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290
291
291
291
uptake in the insulin-sensitive tissues, and modulation of hepatic

glucose output (Fig. 1). Therefore, the seasoning of foods with
spices has been suggested not only to increase the antioxidant content of meals, but also to have an anti-diabetic effect.
To date, various intact spices and spice extracts (as shown in
Tables 1a and 1b, respectively) have been used successfully to
manage type 2 diabetes (T2D), which makes up 90% of cases of
DM. Despite the beneficial effects of spices in reducing fasting
and postprandial glucose levels, interpretation of the actions of
bioactive compounds in spices still remains complicated. This is
due to the fact that each spice contains a wide range of phenolic
compounds and a synergistic effect may exist. Moreover, the daily
intake of individual spices differs between regions and the
bioavailability of the phenolic compounds in spices is affected by
various chemical and biological factors. Therefore, a better understanding of the anti-diabetic potential of the bioactive compounds
in common spices should help in the prevention of diabetes, and
associated complications and metabolic abnormalities. Herein,
we evaluate the beneficial effects of commonly consumed spices,
especially cinnamon, ginger, turmeric, cumin, coriander, aniseed,
fenugreek, garlic and onion, cloves, mustard, black pepper and
curry leaves for the management of DM. The bioactive compounds
and their bioavailability are also discussed.
2. Phenolic compounds
The positive effects of spices on health have been partly attributed to their complex mixture of phenolic compounds (Bower,
Marquez, & De Mejia, 2015). Phenolics refer to a large number of
compounds having one or more aromatic ring with at least one
hydroxyl groups attached. They range from small and single
aromatic-ringed compounds to large 110 polyphenols classified as
flavonoids (Pereira, Valentao, Pereira, & Andrade, 2009). Table 2a
shows some examples of phenolic compounds, including polyphenols, terpenes, vanilloids, and organosulfur compounds found in
commonly used spices. Among them, polyphenols are classified in
flavonoids (including flavanols, flavanones, flavones, and flavonols)
and non-flavonoids (such as phenolic acids). Flavonoids have been
reported to have antioxidant, anti-cancer, anti-allergic, antiinflammatory, and gastro-protective properties (Cook & Sammans,
1996). Emerging research has also suggested that terpenes, vanilloids, and organosulfur compounds possess antioxidant properties
and protect against chronic diseases like DM.
3. Diabetes mellitus
Fig. 1. The beneficial effects of spice polyphenols on glucose homeostasis and

insulin resistance.
DM occurs when the body is unable to produce enough insulin

or use insulin effectively. There are two major forms of diabetes.
Type 1 diabetes (T1D) or insulin-dependent diabetes mellitus
(IDDM) results from the bodys failure to produce enough insulin.
The precise mechanism of IDDM is unknown, and hence there is
no known preventive measure for it. On the other hand, T2D or
non-insulin-dependent diabetes mellitus (NIDDM) is commonly
preceded by insulin resistance manifested by increased insulin
release to maintain glucose homeostasis (Kahn, Hull, &
Utzschneider, 2006).
The etiology of T2D has been suggested to be glucotoxicity,
lipotoxicity and inflammation, which lead to insulin resistance
Table 1a
Effectiveness of intact spices in the management of T2DM.
Spices
Family
Subject
number
Methodology
Effectiveness
References
Cinnamon
(Cinnamomum
zeylanicum)
Ginger (Zingiber
officinale)
Turmeric (Curcuma
longa)
Lauraceae
60
Randomized, double-blind, placebo-controlled trial

The dosage was 1, 3, 6 g/day in capsules
Cinnamon reduces serum glucose, triglyceride, total cholesterol, and LDL

cholesterol levels
Khan et al. (2003)
Zingiberaceae
88
Ginger reduces FBG and HbA1c as well as improves insulin resistance
Zingiberaceae
60
Randomized, double-blind, placebo-controlled trial

The dosage was 3 g/day in capsules
Standard metformin treatment with turmeric
supplementation (2 g)
Cumin (Cuminum
cyminum)
Coriander
(Coriandrum
sativum)
Anise (Pimpinella
anisum)
Fenugreek (Trigonella
foenum-graecum)
Onion (Allium cepa)
Apiaceae
94
The dosage of black cumin was 1, 2, 3 g/day
Apiaceae
60
The dosage of aniseed powder was 5 g/day

The dosage of coriander seed powder was 5 g/day
The daily consumption of 2 g of black cumin can significantly decrease

blood sugar levels
Both aniseeds and coriander seeds decreases FBG, serum lipids, and
lipoproteins, improves HDL, controls plasma lipid peroxidation
Mozaffari-Khosravi et al.
(2014)
Selvi, Sridhar,
Swaminathan, and
Sripradha (2015)
Bamosa et al. (2010)
Fabaceae
80
Amaryllidaceae
42
Mixed with water together with 2.5 g of Tulsi leaves

powder. The daily dosage was 25, 50, 75, and 100 g
100 g of the crude fresh slices of Allium cepa
Cloves (Eugenia
aromaticum)
Spice mix
Myrtaceae
36
Daily dosage was 0, 1, 2, and 3 g
22
Adding a spice mix to burger meat prior to cooking
Turmeric has a beneficial effect on blood glucose, oxidative stress and

inflammation
Mitra and Bhattacharya

(2006)
Eldin et al. (2010)
Khan et al. (2006)
Li et al. (2013)
Table 1b
Effectiveness of spice extracts in the management of T2DM.
Spice extract
Preparation method
Experimental model
Effectiveness
References
Cinnamon extract
112 mg of aqueous cinnamon extract was prepared by Finzelberg (Andernach, Germany)

from 1 g of cinnamon
T2D patients
(n = 79)
Mang et al. (2006)
Curcumin extract
Turmeric powder was extracted with ethanol and evaporated at low pressure to obtain
semisolid
extract containing oleoresin and curcuminoids. The oleoresin was removed to yield
curcuminoid
extract (total content between 75 and 85%)
Garlic powder tablets Allicor (INAT-Farma, Russia) containing 150 mg of dehydrated garlic
powder
T2D patients
(n = 240)
Cinnamon extract reduces fasting plasma

glucose
in diabetic patients with poor glycemic control
Curcumin improves function of b-cells
Garlic powder tablets

Allicor
T2D patients
(n = 60)
Allicor reduces FBG, serum fructosamine and

serum
triglyceride levels
Fenugreek decreases blood glucose and triglyceride levels when consumed

at higher doses
Ingestion of Allium cepa reduces FBG levels by 40 mg/dl, compared to
glibenclamide (81 mg/dl)
Cloves treatment reduced serum glucose, triglycerides, serum total
cholesterol and LDL
Spice mix decreases postprandial lipid oxidation and endothelial
dysfunction
Rajeshwari, Shobha et al.

(2011)
Chuengsamarn et al.
(2012)
Sobenin et al. (2008)
283
284
and islet b-cell failure (Giaccari, Sorice, & Muscogiuri, 2009). Glucotoxicity is a condition whereby there is prolonged high glucose
concentration circulating in the blood. The hyperglycemia causes
protein glycation; a sugar molecule covalently bonds to the amine
group of a protein or lipid to form reversible Schiff bases (Elosta
et al., 2012). These Schiff bases are converted into stable Amadori
products by intermolecular rearrangement, which undergo further
rearrangement and cross-linkage to form AGEs when accumulated
(Nawale, Mourya, & Bhise, 2006). AGEs play an important role in
the structural and functional alterations of proteins, which are
found in large amounts in poorly controlled or uncontrolled
diabetes (Bousova, Vukasovic, Juretic, Palicka, & Drsata, 2005).
Glycation is an unavoidable process of metabolism in human physiology. In a hyperglycemic state, protein glycation rate and AGEs
formation and accumulation are increased. The AGEs derived
cross-linking of structural proteins contributes to the complications of long-term diabetes, including nephropathy, retinopathy,
and neuropathy, and cardiovascular diseases (Forbes & Cooper,
2013).
Lipotoxicity is a condition where there is high circulating free
fatty acid (FFA) in blood, which has been associated with increased
interaction with NF-jB (nuclear factor-kappaB). NF-jB signals for
reactive oxygen species (ROS) production (Symons & Abel, 2013).
Previous cell culture and animal model studies have suggested that
ROS generated by high glucose concentration were able to activate
c-Jun N-terminal kinase (JNK) (Tsai et al., 2012). JNK deactivated
insulin receptor substrate 1 (IRS-1), which prevented the immobilization of glucose transporter type 4 (GLUT4) to the cell surface for
glucose uptake. Moreover, ROS disrupted endothelial nitric oxide
synthase (eNOS) dimer structure, and thus potentially reduced
blood flow to tissue for glucose uptake (Symons & Abel, 2013).
Inflammation is part of the immune response in the body. DM
has been reported to alter the components of the immune system,
with significant changes occurring in adipose tissue, pancreatic
islets, liver, vasculature and circulating leukocytes. The immuno-
logical changes include varied levels of specific cytokines and chemokins as well as increased apoptosis and tissue fibrosis. These
changes, when combined, suggest that inflammation plays an
important role in the pathogenesis of DM (Donath & Shoelson,
2011).
In the past few years, there has been an exponential growth in
the field of herbal medicine because of their natural origin and
reduced side effects. Spices such as cinnamon, cloves, oregano,
and allspice have been suggested to possess (1) anti-glycant (inhibit the formation of AGEs); (2) antioxidant (nullify the effects of
ROS); and (3) anti-inflammatory capacities (Dearlove, Greenspan,
Hartle, Swanson, & Hargrove, 2008) because of their high content
of phenolic compounds. Tables 1a and 1b show that both intact
spices and spice extracts have the potential to improve the condition of DM. The anti-diabetic properties of spices are, at least in
part, attributed to the presence of phenolic compounds
(Table 2a). Numerous mechanisms of action have been proposed
for these compounds, including their effects on pancreatic b-cells,
increasing insulin sensitivity, and their insulin-like property
(Dearlove et al., 2008). However, there are still many other active
compounds which have not been well characterized in some spices
such as coriander. Whether the protective effect of spices on management of DM is via antioxidant or other mechanisms, emerging
research strongly supports the positive relationship between
spices intake and the decreased risk of DM (Table 2b).
4. Spices in the treatment of diabetes mellitus

Although there are various spices that are used in flavouring
and preservation of food, only a few of them have been demonstrated in animals and human clinical trials to reduce the glycemic
response. The spices that were studied included cinnamon, ginger,
turmeric, cumin, coriander, anise, fenugreek, garlic, onion, cloves,
mustards, black pepper and curry leaves. In the following, a
Table 2a
Structures of phenolic compounds found in commonly used spices.
Category
Class
Sub-class
Polyphenols
Flavonoids
Flavanols (e.g. Catechin)
Nutmeg, Fennel, Cinnamon
Flavanones (e.g. Hesperetin, Eriodictyol)
Peppermint, Fennel, Onion
Flavones (e.g. Apigenin, Luteolin)
Aniseed, Peppermint, Onion, Oregano, Horseradish
Flavonols (e.g. Quercetin, Kaempferol,

Isorhamnetin)
Allspice, Aniseed, Coriander, Cumin, Fennel, Onion,

Black pepper, Red pepper, Oregano
Hydroxybenzoic acid derivatives
Allspice, Cloves, Saffron
Phenolic
acids
Terpenes
Vanilloids
Organosulfur
compounds
Structures/examples
of compounds
Gallic acid, Salicylic

acid
Hydroxycinnamic acid derivatives
Caffeic acid, pCoumaric acid
Limonene, Sesquiterpenes, Diterpenes, Triterpenes, Tetraterpenes
Curcumin, Gingerol, Capsaicin

Disulfides and Thiosulfinates
Examples of spices (Kaefer & Milner, 2008)
Coriander, Cumin, Nutmeg, Fennel, Onion, Peppermint,

Oregano, Saffron, Aniseed
Coriander, Cumin, Fennel, Fenugreek, Mustard, Turmeric,
Peppermint
Turmeric, Ginger, Mustard, Red pepper
Garlic, Onion
285

Table 2b
Major bioactive compounds of spices with potential beneficial effects for the management of DM.
Spices
Major bioactive compounds
Potential
beneficial effects
Potential mechanism for anti-diabetic characteristics
References
Cinnamon
Cinnamaldehyde
Hypoglycemic,
hypolipidemic
Antioxidant,
potentiate insulin
action
Hypoglycemic
Anti-diabetic
Up-regulate the expression of GLUT4
Subash Babu et al. (2007), Lu

et al. (2011)
A-type procyanidin
Ginger
B-type procyanidin
Gingerol
Shogaol
Zerumbone
Turmeric
Cumin
Curcumin
Cuminaldehyde, Cuminol
Coriander
Phenolics
Flavonoids
Anise
Trans-anethole
Fenugreek
Galactomannan soluble
fiber
Saponins
Antioxidant, antiinflammatory
Anti-diabetic
Insulinotropic
Antioxidant
Oxidative damage
protection
Anti-diabetic,
hypolipidemic
Hypoglycemic
Enhance the activity of insulin
Improve insulin sensitivity

Increase glucose uptake through promotion of GLUT4 translocation
Protect pancreatic b-cells
Improve glucose intolerance
a,b-Unsaturated ketone moiety to reduce free radicals
Attenuate reactive oxygen species
Improve functions of b-cells
The insulinotropic action was due to the closure of the ATPsensitive K channel and the increase in intracellular Ca2+
concentration
Reduce free radical formation and to scavenge free radicals
Increase release of insulin from the pancreatic b-cells
Chuengsamarn et al. (2012)

Patil, Takalikar, Joglekar,
Haldavnekar, and Arvindekar
(2013)
Wangensteen, Samuelsen, and
Malterud (2004)
Reduce cholesterol and lipid peroxidation
Shojaii and Fard (2012)
Increase secretion of insulin and utilization of glucose
Lu et al. (2008)
Increase utilization of glucose
Garlic
Allicin
Onion
Quercetin
Antioxidant,
hypoglycemic
Hypoglycemic
Mustards
Quercetin, Kaempferol
Hypoglycemic
Reverse proteinuria; reduce blood sugar, cholesterol and

triglycerides
Present as quercetin 3,40 -diglucoside and quercetin 40 monoglucoside to scavenge free radicals
Scavenge free radicals
Black
pepper
Cloves
Piperine
Anti-diabetic,
antioxidant
Hypoglycemic
Bioenhancer by inhibition of hepatic and intestinal

biotransformation
PPAR-c activation
Anti-diabetic
Increase secretion of insulin and utilization of glucose
Curry
Leaves
Dehydrodieugenol,
dehydrodieugenol B,
Oleanolic acid
Murrayacinine,
isomahanimbine,
mahanimboline
Rahman et al. (2014)
comprehensive discussion is given regarding the beneficial effects

of these spices on DM management. The bioactive compounds in
these spices are also discussed:
4.1. Cinnamon
Cinnamon is among the worlds most frequently consumed
spices and has been granted GRAS (Generally Recognized As Safe)
by the United States Food and Drug Administration (FDA).
Numerous studies have demonstrated that cinnamon is rich in
cinnamaldehyde, A-type procyanidin, and B-type procyanidin
(Table 2b), and, thus cinnamon possesses antioxidant
(Jayaprakasha, Ohnishi-Kameyama, Ono, Yoshida, & Jaganmohan,
2006), anti-microbial (Singh, Maurya, DeLampasona, & Catalan,
2007), anti-inflammatory (Tung, Chua, Wang, & Chang, 2008),
anti-pyretic (Kurokawa, Kumeda, Yamamura, Kamiyama, &
Shiraki, 1998), and anti-ulcer (Amr & Maysa, 2010) effects. The
potential use of cinnamon for treatment of diabetes was first
reported in 1990 when Khan, Bryden, Polansky, and Anderson
(1990) suggested that cinnamon had insulin potentiating factor
(IPF) as well as demonstrating that IPF might be involved in the
alleviation of diabetes symptoms and other diseases related to
insulin resistance. To date, Cinnamomum species identified as
showing some improvement in glycemic response include
Cinnamomum cassia, Cinnamomum burmannii, Cinnamomum
zeylanicum and Cinnamomum verum. Among these, Cinnamomum
Thomson, Al-Amin, Al-Qattan,

Shaban, and Ali (2007)
Caridi et al. (2007)
Cartea, Francisco, Soengas, and
Velasco (2011)
Arcaro et al. (2014)
Kuroda et al. (2012a)
Ganesan, Phaiphan, Murugan,

and Baharin (2013)
cassia (or Chinese cinnamon) has the most favourable profile for
treating hyperglycemia in T2D (Howard & White, 2013). There
are several proposed mechanisms through which cinnamon
decreases blood glucose and lipid levels. These mechanisms
include stimulating insulin secretion or insulin mimetic, increasing
glucagon-like peptide 1 (GLP-1), delaying gastric emptying,
inhibiting glucosidase activity, as well as increasing GLUT4
expression.
Table 3 shows that extensive studies, conducted both in vitro
and in vivo, have reported the anti-diabetic properties of cinnamon.
In vitro studies done by Imparl-Radosevich et al. (1998) have
shown that the polyphenol compounds (i.e. A-type procyanidin)
extracted from cinnamon had insulin-like properties, which could
inhibit PTP-1 (protein tyrosine phosphatase) activity or serine
phosphorylation of IRS-1. Thus, it was suggested that cinnamon
may be useful in the treatment of diseases related to insulin
resistance and metabolic syndrome. To compare the insulinpotentiating or insulin-like activity (Broadhurst, Polansky, &
Anderson, 2000), extracts from 49 common herbs, spices, and
medicinal plants were tested in vitro using a rat epididymal adipocyte assay. It was found that cinnamon extracts (CE) potentiated
insulin activity, which was 20-fold higher than other spice and
herb extracts.
Besides in vitro studies, insulin-potentiating effects of cinnamon
were also reported in animal and human trials (as summarized in
Table 3). For example, Qin et al. (2004) observed that administration
286
Table 3
Role of cinnamon in the management of DM.
In vitro
Methodology
Proposed mechanism/significant effects
References
Protein tyrosine phosphatases (PTP) assay: 32P-RCMlysozyme as substrate

Autophosphorylation assays: kinase domain 1 mM [c-32P]ATP as substrate
Rat epididymal fat cell assay: [U-14C]-glucose as substrate
and Wortmannin as PI0 3 Kinase inhibitor
Glucose production assay: H4IIE hepatoma cells in glucose
free medium
PECK and G6Pase gene expression: H4IIE hepatoma cells
Both assay was treated with control (water), insulin,
metformin or cinnamon extract
Carbohydrase inhibition assay
Enzyme used: pancreatic a-amylase, maltase, sucrose
Stimulate autophosphorylation of insulin receptor and inhibit PTP-1
Imparl-Radosevich et al. (1998)
Inhibit hepatic glucose production via suppression of gene expression (PEPCK and G6Pase)
Cheng et al. (2012)
Cinnamon bark extracts inhibit intestinal a-glucosidase and pancreatic a-amylase
Adisakwattana, Lerdsuwankij, Poputtachai,

Minipun, & Suparpprom, 2011
Experimental model
References
T2D mice
T1D rats
STZ-induced diabetic rats
Improve insulin sensitivity or slow absorption of carbohydrates in the small intestine

Cinnamaldehyde has antihyperglycemic and hypolipidemic effects
Cinnamon extracts potentiate insulin in serum or increase the pancreatic secretion of insulin from b-cells or
release from the bound form
Cinnamon works as a hypocholesterolemic and hepatoprotective agent; it improves cardiovascular function
through modulation of oxidative stress, nitric oxide, and homocysteine
Kim et al. (2006)

Subash Babu et al. (2007)
Jia et al. (2007)
Diabetic animals
Amin and Abd El-Twab (2009)
Human studies
Experimental
model
Subject Number
Form and Dose
References
Healthy
subjects
14 (8 men + 6 women)
Whole cinnamon, 6 g
30 (15 men + 15 women)

60 (30 men + 30 women)
3 placebo groups
3 treatment groups
10 (5 men + 5 women) each group
57 (Placebo group: 28 Treatment group: 29)
Whole C. cassia powder, 6 g

Whole C. cassia powder, 1, 3, and 6 g
for 40 days
Inclusion of cinnamon in diet lowers the postprandial glucose

response and reduces the gastric empty rate
Reduce blood glucose concentration and enhance insulin sensitivity
Decrease FBG and increase insulin sensitivity
Hlebowicz, Darwiche, Bjrgell, and Almer

(2007)
Magistrelli and Chezem (2012)
Khan et al. (2003)
Whole C. cassia powder, 1 g for

90 days
Aqueous C. cassia extract, 120 mg
and 360 mg for 91 days
No significant reduction in HbA1c and FBG

Effects of cinnamon differ by population
Reduce FBG and HbA1c; improve glucose uptake
Blevins et al. (2007)
Aqueous C. cassia extract, 500 mg for

84 days
Reduce FBG in pre-diabetics
Ziegenfuss et al. (2006)

84 days
Reduce FBG and HbA1c
Akilen et al. (2010)
Reduce HbA1c
Crawford (2009)
21 (placebo group: 10, treatment group: 11)

90 days
Aqueous extract, 500 mg for 84 days
25 postmenopausal women (Placebo group:

13, treatment group: 12)

42 days
Reduce FBG and malondialdehyde

Increase plasma thiol group
No significant reduction in HbA1c and FBG
Roussel, Hininger, Benaraba, Ziegenfuss, and

Anderson (2009)
Vanschoonbeek, Thomassen, Senden, Wodzig,
and van Loon (2006)
T2D patients
69 (25 men + 41 women)

Placebo group: 8 men + 12 women
120 mg group: 8 men + 15 women
360 mg group: 9 men + 14 women
22 (10 men + 12 women)
Treatment group: 7 men + 4 women
58 (26 men + 32 women)
Treatment group: 11 men + 19 women
54 men + 55 women
Lu et al. (2012)
Hypercholesterolimic rats
of CE improved glucose utilization in normal rats fed a high fructose diet. CE potentiated the action of insulin and helped to
improve glucose metabolism. Moreover, CE-treated rats had higher
glucose infusion rates than controls. Cinnamon had also been
shown to effectively lower blood glucose, total cholesterol, and
triglyceride levels while raising HDL (high-density lipoprotein)
cholesterol levels in diabetic mice (Kim, Hyun, & Choung, 2006).
The anti-diabetic and hypolipidemic effects of cinnamon were
probably attributed to the presence of cinnamaldehyde (Subash
Babu, Prabuseenivasan, & Ignacimuthu, 2007). It was observed that
the administration of cinnamaldehyde to streptozotocin (STZ)induced diabetic rats significantly decreased plasma glucose, total
cholesterol, and triglyceride levels.
Several other studies indicated that cinnamon oil or polyphenolic oligomer rich extracts had anti-hyperglycemic, hypolipidemic,
and antioxidant effects in diabetic rats (Jia et al., 2007; Talpur,
Echard, Ingram, Bagchi, & Preuss, 2005). It was reported that cinnamon polyphenols (CP) exhibited insulin-like and insulinindependent activities on the regulation of gene expression
involved in insulin signal transduction pathway using mouse adipocytes (Cao, Graves, & Anderson, 2010). CP increased the amount
of insulin receptor b, GLUT4 and tristetraprolin in the cells. It
increased glycogen synthase activity and glycogen accumulation
with decreased glycogen synthase kinase-3b activity. All of these
activities led to glucose transportation and utilization. Among
them, the accumulation of tristetraprolin by CP might provide
the molecular basis for cinnamon to improve diabetes by down
regulating the synthesis of pro-inflammatory cytokines, as it bound
to and then promoted the degradation of those mRNAs encoding
pro-inflammatory cytokines.
In 2003, Khan, Safdar, Khan, Khattak, and Anderson (2003)
conducted the first randomized, double-blind, placebo-controlled
clinical trial to evaluate the effects of cinnamon on individuals
with T2D (Table 3). In the short-term study, sixty T2D patients
(30 men and 30 women) received either placebo or 3 different
doses of cinnamon powder (1, 3, 6 g/day, respectively) for 40 days.
It was found that cinnamon reduced fasting blood glucose (FBG).
Moreover, the change in doses did not lead to any further reduction
in FBG beyond 1 g/day. After the withdrawal of treatment, the lowering effect of FBG was not observed (20 days after completing the
study) except for group receiving 1 g of cinnamon powder. It was
also found that cinnamon reduced triglyceride, LDL (low-density
lipoprotein) cholesterol, and total cholesterol levels in the diabetic
patients. The effects of cinnamon on glucose and blood lipids might
be due to its ability to activate glycogen synthase, increase glucose
uptake, as well as inhibit glycogen synthase kinase-3b, and
dephosphorylation of the insulin receptor. However, the treatment
of T2D by cinnamon was found to differ between populations.
Blevins et al. (2007) did not observe significant improvements in
hemoglobinA1c (HbA1c) in 43 diabetic patients and thus it was
not generally suggested in the American population.
Table 3 shows that, in another study, Lu et al. (2012) demonstrated the reductions of FBG and HbA1c by CE in a dose response
manner. It was noted that participants at the start of experiment
had similar HbA1c. But they had different starting FBG, which
was a confounding factor in the study. It was uncertain whether
the placebo was not showing any observable effect due to the relatively low starting FBG. Although the changes of FBG and HbA1c
suggested that cinnamon helped in lowering HbA1c in diabetic
patients, the FBG results needed to be evaluated with caution. Similar effects were observed in pre-diabetic patients (Ziegenfuss,
Hofheins, Mendel, Landis, & Anderson, 2006). In the study, both
the placebo and treatment arm had similar starting FBG, and there
was an observable reduction FBG by 0.54 mmol/L. In addition, the
treatment group had a reduction in systolic blood pressure (SBP)
from 133 to 128 mmHg, which was not observed in the placebo
287
group. However, this study was making an unequal gender representation of each group. Given the unequal gender representation
and small sample size, a more balanced and larger number of participants needed to be recruited to verify the effects in FBG reduction. Another study (Akilen, Tsiami, Devendra, & Robinson, 2010)
showed that treatment with 2 g of cinnamon was found to lower
HbA1c and BP of T2D patients. The reduction of BP by cinnamon
indicated that the reduction in glycemia might be related to
improvement in eNOS function.
Mang et al. (2006) investigated the effects of CE on plasma
glucose, HbA1c, and serum lipids in patients with T2D. It was concluded that CE had a moderate effect in reducing FBG in diabetic
patients with poor glycemic control. Crawford (Crawford, 2009)
reported that cinnamon decreased HbA1c in 109 patients with
T2D. The effects of cinnamon on HbA1c values were only slightly
less than the placebo-adjusted reductions. All of these results,
taken together, suggested that cinnamon, regardless whole or the
aqueous extract, has the potential to lower HbA1c and/or FBG. In
addition, cinnamon is without known side effects. Therefore,
cinnamon may be helpful as a supplement to regulate diabetes
treatment in people with T2D. Further research is needed to confirm how the bioactive compounds in cinnamon lead to these
anti-diabetic benefits.
4.2. Ginger and turmeric
Ginger and turmeric have the same scientific classification and
are reported to have anti-hyperglycemic and many other therapeutic effects (Al-Suhaimi, Al-Riziza, & Al-Essa, 2011). The three
biologically active components of ginger include gingerol, shogaol
and zerumbone, while turmeric contains curcumin, demethoxycurcumin, and bisdemethoxycurcumin (Table 2b).
It is generally suggested that gingerol is the most prominent
component to promote glucose uptake and exhibits anti-diabetic
potential (Li, Tran, Duke, & Roufogalis, 2012a). The action modes
of ginger on glycemic control include: (1) inhibition of enzymes,
i.e. a-amylase and a-glucosidase in carbohydrate digestion, (2)
increase of insulin release and sensitivity, and (3) lipid profiles
improvement. To date, a number of studies have examined the
efficacy of ginger in hyperglycemia control (Li, Tran, Duke, &
Roufogalis, 2012b). For example, a study conducted on patients
with T2D (Mozaffari-Khosravi, Talaei, Jalali, Najarzadeh, &
Mozayan, 2014) suggested that daily consumption of three onegram capsules of ginger powder for 8 weeks could reduce FBG
and HbA1c as well as improve insulin resistance.
Besides gingerol, the phenolic compounds present in ginger
include the hydroxyl positional isomers of gingerol and curcumin
(Yeh et al., 2014). The cell culture study on L6 myotubes treated
with 6-gingerol confirmed the glucose uptake in the absence of
insulin stimulation (Son, Miura, & Yagasaki, 2015). L6 myoblast
transfected with HaloTag-GLUT4 revealed that, when treated with
6-gingerol, GLUT4 was immobilized to the cell surface, and thus
the treated cells showed increased phosphorylated AMPK (50
adenosine monophosphate-activated protein kinase). These results
suggest that glucose uptake by ginger could be due to 6-gingerol
stimulating the activation of AMPK to signal for translocation of
GLUT4 to cell surface (Nagendran, Waller, & Dyck, 2013). Ginger
may regulate plasma glucose through a variety of mechanisms
such as activation of GLUT4 translocation for glucose uptake;
inhibition of enzymes associated with gluconeogenesis and
glycogenolysis. Therefore, it is plausible to use ginger to manage
DM. However, more studies are needed to evaluate the bioavailability of the bioactive components, e.g. gingerol, at its site of
action to further confirm its mechanism and determine its efficacy.
Researchers in Thailand (Chuengsamarn, Rattanamongkolgul,
Luechapudiporn, Phisalaphong, & Jirawatnotai, 2012) found that
288
curcumin may lower the risk of T2D in people with pre-diabetes.

Curcumin is the principal active component of turmeric, the spice
that gives curry dishes their characteristic flavour and yellow colour. Cell culture studies (Best, Elliott, & Brown, 2007) using rat bcells suggested that cells treated with curcumin demonstrated
activation in volume regulated anion channel (VARC) leading to
increase insulin secretion. The activation of VARC led to intracellular efflux of chloride resulting in cell membrane depolarization
which stimulated calcium influx into b-cells. High intracellular calcium concentration signals for exocytosis of insulin granules and as
a result, insulin secretion. These effects could potentially be used to
manage diabetic patients by increasing insulin secretion and glucose uptake.
Another cell culture study (Kim et al., 2010) using rat L6 normal
and insulin resistant myotubes treated with curcumin was also
conducted. It was found that curcumin activated AMPK and
increased glucose uptake. In the absence of insulin, radio-labeled
glucose assay showed increase glucose uptake into normal myotubes after being treated with curcumin in a dose response manner. Both AMPK inhibition assay and radio-labeled glucose assay
demonstrated that the treatment of curcumin on inhibited cells
did not increase AMPK phosphorylation and glucose uptake. The
same effect was observed in with AMPK expression down regulated L6 myotubes. The results from these cell culture studies suggested that curcumin increased glucose uptake in myotubes
through the activation of AMPK pathway. The effects of AMPK
phosphorylation were reproducible in rat model studies. The
administration of curcumin to both healthy and diabetic rats
increased the phosphorylation of AMPK in rat muscles (Na et al.,
2011). Therefore, it is highly possible that curcumin activates
AMPK in the muscles which signal for GLUT4 translocation for glucose uptake.
In an in vitro study (Lekshmi, Arimboor, Indulekha, & Menon,
2012), both fresh and dried turmeric volatile oil extracts were
found to inhibit a-glucosidase and a-amylase activity, which was
proposed as one of the possible mechanisms for turmeric to reduce
plasma glucose and HbA1c levels in diabetic patients. Moreover, it
has been demonstrated that turmeric had a synergistic effect with
metformin (an oral anti-diabetic drug) in diabetics in lowering FBG
(Selvi et al., 2015). When T2D patients received turmeric supplementation with metformin, both FBG and HbA1c levels were significantly reduced as compared to those received metformin
alone. These results suggested that turmeric had a beneficial effect
on blood glucose, oxidative stress and inflammation. It was known
that turmeric reduced oxidative stress through a list of oxidative
stress markers. There was an increase in antioxidant glutathione
and a reduction in plasma lipid peroxidation and high-sensitivity
C-reactive protein (hsCRP). Therefore, it is possible to use turmeric
to help maintain plasma glucose level through stimulating increase
expression for antioxidant and reducing inflammation and ROS
that inhibits eNOS and GLUT4 translocation for glucose uptake.
4.3. Cumin, coriander & anise
Cumin is a spice that flavours many Mediterranean, Indian,
North African and Middle Eastern dishes. Traditionally speaking,
cumin seeds have been used for the treatment of dyspepsia, diarrhea, and jaundice due to the active ingredient, cuminaldehyde
(Lee, 2005). Recently, anti-obese and anti-diabetic effects of cumin
seeds were observed in normal rats (Iyer, Panchal, Poudyal, &
Brown, 2009). Additionally, cumin supplementation was found to
be more effective than glibenclamide (an anti-diabetic drug) in
the treatment of DM (Ismail, Assem, & Zakriya, 2010). The antihyperglycemic effect of cumin may be due to the protection of surviving pancreatic b-cells, increase in insulin secretion and glycogen
storage (Jagtap & Patil, 2010). Modern scientific research (Bamosa,
Kaatabi, Lebda, Elq, & Al-Sultanb, 2010) indicates that therapeutic

doses of cumin may have an effect on blood sugar levels, especially
in people with diabetes. A daily 2 g dose of black cumin (Nigella
sativa), was given to T2D patients, who consumed cumin along
with their regular medications. After 12 weeks, the patients experienced a significant drop in their blood sugar levels, leading to
conclude that cumin might be an effective treatment option for
diabetic patients.
Coriander is a well-known herb, used as fresh and dried fruit,
and leaves to flavour meals and as an ingredient in curry powder.
Coriander seeds were shown to be effective as an anti-diabetic
agent in STZ-induced diabetic mice (Gray & Flatt, 1999). In vitro
studies have demonstrated that coriander seed powder increased
the glucose transport and incorporation into muscle glycogen
and also increased the insulin secretion in pancreatic b-cells
(Gray & Flatt, 1997). The anti-diabetic, hypolipidemic and antioxidant activities of coriander seeds were recently assessed in vivo by
the administration of coriander seed powder (5 g/day) to T2D
patients for 60 days (Rajeshwari, Shobha, & Andallu, 2011). It
was found that the coriander seeds (1) decreased blood sugar
(anti-hyperglycemic); (2) decreased serum lipids, lipoproteins
and improved HDL (hypolipidemic); and (3) controlled lipid peroxidation (anti-oxidative). These activities were the results of the
synergistic effects of various bioactive compounds present in
coriander seeds (Rajeshwari, Shobha et al., 2011).
Anise, a native to the eastern Mediterranean, is one of the oldest
known spice plants. Anise seed (or aniseed) promotes health and
helps the body fight off diseases. For example, it aids digestion
and enhances brain health. It may also strengthen the pancreas
and lessen the possibility of pancreatic dysfunction (Valussi,
2012). Both in vitro and in vivo experiments have shown that aniseeds could effectively decrease FBG, lipid peroxidation, and protein oxidations in diabetic patients (Rajeshwari, Abirami, &
Andallu, 2011). The blood sugar lowering effect exhibited by aniseeds was probably attributed to the phytochemicals, e.g. caffeic
acid, camphene, eugenol, mannitol, vitamins, and minerals present
in aniseeds (Tables 2a and 2b).
4.4. Fenugreek
Fenugreek is a strongly scented herb that is widely used in
cooking and as a traditional medicine for diabetes in Asia. It has
been reported that fenugreek seeds have potential hypoglycemic
and hypolipidaemic effects (Neeraja & Rajyalakshmi, 1996). Active
compounds of fenugreek include soluble fiber, saponins, trigonelle,
diosgenin, and 4-hydroxyisoleucine (Neelakantan, Narayanan,
Souza, & Dam, 2014). Among them, the anti-diabetic activities of
fenugreek are mainly attributed to the presence of galactomannan
soluble fiber and saponins (Table 2b).
Human studies have shown that co-ingestion of fenugreek seed
extracts with carbohydrates reduced glycemic response in a dose
response manner (Faqih & Al-Nawaiseh, 2006). In addition, fenugreek seeds reduced the plasma glucose level in diabetic patients
(Sharma, 1986). The possible mechanisms include: (1) fenugreek
increases viscosity in the gastrointestinal tract, which limits carbohydrases mobility to hydrolyse carbohydrates and glucose mobility
to be absorbed by the intestine (Srichamroen, Thomson, Field, &
Basu, 2009), and (2) Galactomannan soluble fiber is one of the
active ingredients in fenugreek seeds responsible for the glycemic
lowering effect (Sharma, 1986).
Interestingly, for the diabetic patients on the sulfonylurea (an
anti-diabetic drug) treatments, when supplemented with fenugreek saponin extracts, both FBG and HbA1c levels were reduced
(Lu et al., 2008). These results suggested that saponin increased
antioxidant enzymes SOD (superoxide dismutase), GPX
(glutathione peroxidase) and catalase in liver; and reduced lipid
peroxidation in liver. The reduction in peroxidation implies a possibility of reduction in inflammation, which means lower inhibition
in insulin signalling and increases glucose uptake. Therefore, fenugreek helps to increase glucose uptake from the circulatory system
and reduce plasma glucose level. Results from clinical trials
(Neelakantan et al., 2014) support the potential beneficial effects
of fenugreek in the management of DM. Nonetheless, in order to
provide more conclusive evidence, clinical trials with more diabetic
patients (e.g. 100) and longer duration (e.g. 3 months) are required.
4.5. Garlic and onion
Allium species, such as garlic and onion, have been used as
important dietary constituents worldwide and have attracted particular attention of modern medicine (Otunola & Afolayan, 2015).
Garlic and onion are rich in sulphur containing compounds
(Table 2a), which possess anti-diabetic, anti-biotic, hypocholesterolemic, and various other biological effects. As a result, they
have been used to protect against cardiovascular disease, respiratory concerns, diabetes, and a variety of cancers.
Allicin is the active ingredient in garlic, which has the potential
to lower blood glucose. Animal studies have shown that garlic was
able to reduce blood glucose levels (Jelodar, Maleki, Motadayen, &
Sirus, 2005). Additionally, it might alleviate liver and renal damage
caused by allexan-induced diabetes (El-Demerdash, Yousef, & ElNaga, 2005). In humans, the timed-release garlic powder, Allicor,
was found to lower FBG and triglyceride levels more successfully
than a placebo (Sobenin et al., 2008).
Table 2a shows that onion is rich in flavonoids (e.g. quercetin)
and sulphur compounds which benefit human health. Quercetin
has been reported to lower glycemic response (Cermak, Landgraf,
& Wolffram, 2004). The studies of brush border membrane vesicle
from pigs suggested that cells treated with quercetin-3-Oglycosides inhibited sodium-glucose linked transporter 1 (SGLT1),
which prevented glucose absorption (Cermak et al., 2004). Moreover, it was noteworthy that in the absence of insulin, onion
extract stimulated glucose uptake in a dose response manner in
a L6 myotube cell culture study (Noipha, Ratanachaiyavong, &
Ninla-Aesong, 2010). Animal studies showed that the aqueous
extract of onion (Jevas, 2011) reduced FBG level in a dose response
manner and lowered glycemic response in T1D rats. The aqueous
onion peel extract (Jung, Lim, Moon, Kim, & Kwon, 2011) increased
liver and muscle glycogen levels of the diabetic rats, and as a result,
increased glucose uptake. The onion extract also regulated GLUT4
expression and insulin receptor in skeletal muscle while reducing
the inflammatory markers.
The anti-diabetic activity of onion has also been demonstrated
in several clinical studies. The addition of onion to the diet for
T2D patients (Bhushan, 1984) decreased the dose of anti-diabetic
medication required to control the disease. It was also found that
ingestion of crude Allium cepa caused a significant reduction in
FBG levels and induced hyperglycemia in both T1D and T2D
patients (Eldin, Ahmed, & Abd, 2010). These results, when combined, suggested that onion acted as an anti-diabetic agent, which
could reduce glycemic response through increased glucose uptake
from the systemic circulation and inhibited external glucose
absorption from the intestinal tract. Therefore, onion improved
glucose uptake through stimulating GLUT4 and insulin receptor
expression, and reduced inflammation.
4.6. Cloves
Cloves are the aromatic flower buds of a tropical evergreen tree
(Eugenia aromatica), which have many useful medicinal and spicing
purposes. A recent animal study provided new evidence on the
beneficial effects of cloves as an anti-hyperglycemic, hypolipi-
289
demic, hepatoprotective and antioxidant agent (Adefegha, Oboh,

Adefegha, Boligon, & Athayde, 2014). When diabetic rats were
fed with clove powder over the course of 14 days, the FBG was
lowered in a dose response manner. Since the blood glucose could
be lowered through a-glucosidase inhibition, the intestinal
a-glucosidase activity was reduced in the diabetic rats; thus limiting glucose availability for absorption. A related cell culture study
on rat liver cells treated with aqueous clove extract (Prasad,
Herzog, Boone, Sims, & Waltner-Law, 2005) showed that cloves
could regulate the expression of the key gluconeogenic enzymes
PEPCK (phosphoenolpyruvate carboxykinase) and G6Pase
(glucose-6-phosphatase). The down regulation of gluconeogenesis
enzyme could be due to the clove extracts acting as PPAR-c (Peroxisome proliferator-activated receptor gamma) agonist (Kuroda
et al., 2012b). The chromatographic fractions of clove extracts that
bound to PPAR-c had been identified as dehydrodieugenol, dehydrodieugenol B and oleanolic acid (Kuroda et al., 2012b).
The effects of cloves on diabetic patients were also investigated.
Earlier studies (Khan, Qadir, & Khattak, 2006) have shown that
clove extracts could improve the function of insulin and lower glucose, total cholesterol, LDL and triglycerides in people with T2D.
Thirty-six people with T2D were divided into four groups and
given capsules containing 0, 1, 2, or 3 g of cloves per day for
30 days followed by a 10-day washout period. There were no significance differences in responses among the three levels of cloves
used, but there were marked differences between those who took
cloves and those who did not. At the end of the 30 days, the diabetic patients who had been taking some levels of clove supplementation showed a decrease in serum glucose, triglycerides,
serum total cholesterol, and LDL. The diabetic patients who had
not been taking clove supplementation showed no differences.
4.7. Mustards
Brassica nigra (black mustard) and Brassica juncea (Indian mustard) are commonly used as food supplement in various food items.
Mustards have also been used in traditional medicine to treat
arthritis and rheumatism. Table 2b shows that mustard seeds
contain various chemical constituents including carotenes and
phenolic compounds. Preliminary studies have shown that both
black and Indian mustard possess anti-diabetic and antihyperlipidemic effects in diabetic rats (Thirumalai, Therasa,
Elumalai, & David, 2011). The anti-diabetic effect of mustard was
attributed to the release of insulin from the pancreas and change
of glucose metabolizing enzyme activities to normal levels, hence
stabilizing glucose homeostasis in the liver and kidney (Anand,
Murali, Tandon, Murthy, & Chandra, 2009).
4.8. Black pepper
Black pepper is known as the king of spices and it is among
the most widespread and most used spice in various food preparations for its taste and carminative properties. Black pepper has
been reported to possess anti-cancer, anti-microbial, antiinflammatory and anti-glycant properties (Ahmad et al., 2012). Scientists from the National Institute of Nutrition in India (Saraswat,
Reddy, Muthenna, & Reddy, 2009) evaluated the ability of black
pepper extracts to prevent the accumulation of AGEs and found
that black pepper can effectively block complications from diabetes. Piperine, the active phenolic compound in black pepper
extract, was studied to determine its glucose regulatory efficacy
in alloxan-induced diabetic mice (Atal, Agrawal, Vyas, Phadnis, &
Rai, 2012). It was observed that subacute administration of piperine at dose of 20 mg/kg significantly lowered blood glucose concentrations, whereas acute administration at high doses (40 mg/
kg) raised blood glucose. Therefore, further investigations are
290
necessary to consider black pepper as a prospective anti-diabetic

agent at an appropriate dosage.
Although black pepper has shown anti-glycant property in vitro
and anti-hyperglycemic activity in animal studies, it has not yet
shown significant anti-diabetic effects in diabetic patients.
Nonetheless, black pepper might enhance the anti-diabetic and
antioxidant properties of other spices due to the potential synergistic effects. For example, the combination of black pepper and
turmeric powder led to an increase in antioxidant activity and thus
the decrease in lipid peroxidation during food preparation (Zhang
et al., 2015). The decrease in lipid peroxidation reduced postprandial changes such as oxidative damage and inflammatory processes
and might be beneficial in reducing the development of DM. Since
piperine strongly enhances the bioavailability of phytochemicals,
the potential synergistic effects of black pepper on the antidiabetic activity of other spices deserve further investigation.
4.9. Curry leaves
Curry leaf is often used as a culinary spice due to its aromatic
nature. It is a rich source of biologically active carbazole alkaloids
and possesses pharmacological activities such as antioxidant, antiinflammatory, hepatoprotective, and anti-tumor. The curry leaf
extract has been reported to decrease blood cholesterol and glucose concentrations in diabetic animals (Kesari, Gupta, & Watal,
2005; Xie et al., 2006). Yadav, Vats, Dhunnoo, and Grover (2002)
reported that feeding a diet containing various doses of curry
leaves (5, 10 and 15%) to normal rats for 7 days as well as
alloxan-induced mild diabetic and STZ-induced moderate diabetic
rats for 5 weeks showed varying hypoglycemic effects. In normal
rats, reduction in blood glucose was almost negligible. In mild
and moderate diabetic rats, feeding of 15% diet caused a maximal
reduction in blood sugar by 21.4% and 8.21%, respectively. In
another animal study (Khan, Abraham, & Leelamma, 1995), 10%
of curry leaf administration in food to normal rats increased hepatic glycogen concentration and glycogenesis, while decreased
glycogenolysis and gluconeogenesis.
Curry leaves are rich in many minerals and trace elements,
which are important for maintaining normoglycemia. This is done
by the activation of pancreatic b-cells, which are responsible for
the creation of insulin. While the nutrients in curry leaves account
for only about 12% of the required daily intake for the elements,
they are bio-available, or readily usable by the body. Therefore, it
has been suggested that curry leaves may be useful for the management of DM (Arulselvan & Subramanian, 2007). However, the
dry powder of curry leaf consumed for 15 days by T2D patients
did not provide any beneficial effects (Iyer & Mani, 1990). More
clinical research is hence needed to further confirm the real efficacy of curry leaves in the management of DM.
5. Dietary intake and bioavailability
The potential health effects of spices depend on the amount
consumed and their bioavailability. Spices are normally used in
small quantities for flavouring foods and form an integral part of
our diets. Moreover, the intake of individual spices varies considerably between different regions and between different dietary cuisines. Therefore, more studies are required when recommending
spices in combinations of foods for their medicinal benefits. On
the other hand, spices contain high concentrations of bioactive
compounds, e.g. flavonoids and phenolics, which contribute to
their beneficial health effects. However, these compounds have a
low bioavailability, which are affected by various chemical and
biochemical factors. For example, the maximum concentration of
a single polyphenol compound in plasma rarely exceeds 1 lM after
the consumption of 10100 mg of the compound (Scalbert &

Williamson, 2000). In addition, the bioavailability always differs
between one compound and another, such that the most abundant
polyphenols of spices in the diet are not necessarily those leading
to the highest concentrations of metabolites in target tissues.
Therefore, more studies are required to investigate the bioavailability of bioactive compounds in spices to correlate the spice
intake with the potential health effects observed from epidemiological studies.
6. Conclusion
Overall, this review suggests that adding spice to our life may
serve as a delicious and sensible way to maintain a healthy body.
Spices are rich in antioxidant compounds and have potential pharmacological effects in the management of diabetes and its complications. The well-recognized anti-diabetic action of spices seems to
be mediated through stimulation of pancreas to secrete insulin, or
interference with glucose absorption, or insulin-sparing action of
the bioactive compounds (i.e. phenolic compounds). Although various spices have been intensively investigated for their health
improvement effects in recent years, the mechanisms of action of
individual phenolic compounds remain unknown by the fact that
each spice usually contains a wide range of phenolic compounds.
In the future, further investigation needs to be carried out to evaluate the anti-diabetic benefit of single phenolic compound present
in spices to clarify the exact mechanisms.
Understanding the daily intake of spices and the bioavailability
of their bioactive compounds is a prerequisite to understand the
mechanism of their pharmacological effects in the management
of DM. Research is also needed on the metabolism of bioactive
compounds in spices to propose recommendations on dietary
intake, effective dosage, and dietary guidelines. On the other hand,
most of the evidence presented has been based on cell culture or
animal models instead of human model studies. Hence, there is
an urgent need to carry out further studies in humans with spices
that had been suggested to reduce glycemic response. It is imperative to confirm its effects and efficacy in human trials. Thus, spices
may form a novel category of functional ingredients in the management and treatment of DM.
7. Future direction
As functional foods, the benefits of including spices in diet
emerge with a better understanding of their attributes of health,
and in methodological developments addressing the evidence base
for their effects. Currently, recommendations are warranted to
support the consumption of spices which are rich in bioactive components for seasoning of foods at low-dosage. However, caution
should be exercised when recommending high-dose spices to all
consumers for long-term use due to the potential adverse effects
(Table 4). In future, a greater body of scientific evidence supporting
the benefits of spices in the overall maintenance of health and
protection from diseases will be expected. The increasing global
prevalence of diabetes makes the management of DM and related
complications a major challenge. A better understanding of the
pathogenesis of DM may make successful treatment possible.
Anti-diabetic drugs have been successfully used to treat DM.
The mechanisms include (1) stimulating insulin release by inhibiting the KATP channel; (2) reducing gluconeogenesis by acting on the
liver and reducing insulin resistance by increasing AMPK signalling; (3) reducing insulin resistance by activating PPAR-c in
fat and muscle; and (4) reducing glucose absorbance by acting
on small intestine. Although synthetic drugs are effective treatments for DM, they have various side effects, including the
291

Table 4
Potential adverse effects of high-dose spices for long-term use.
Spices
Potential adverse effects
References
Cinnamon
Interaction between cinnamon supplement and statin. Case had been reported to cause acute hepatitis. User may
experience abdominal pain, diarrhea and vomiting
Results on rat model suggested that extracts of turmeric may be hepatotoxic
High doses of fenugreek reduced the bioavailability of calcium, zinc, iron, and potassium, may produce laxative
effect on users, case had been reported to enhance the effects of with diuretics and hypokalemic agents resulting in
hypokalemia
Reduced thromboxane levels in humans. Case had been reported that consumption of garlic supplement enhanced
the effects of anticoagulant, resulting in increased risk of bleeding
Accidental ingestion of clove essential oil had been reported to demonstrate eugenol poisoning. Effects included
intravascular coagulation and renal failure
When black pepper or piperine was co-administered with drugs which had narrow therapeutic ranges, it was
possible to exert the unexpected adverse effects via the altered systemic exposure of drugs
Brancheau, Patel, and Zughaib

(2015)
Balaji and Chempakam (2010)
Pandey and Awasthi (2015)
Turmeric
Fenugreek
Garlic
Clove
Black
pepper
increased risk of hypoglycemia, gastrointestinal problems, and

heart failure. On the other hand, spices are natural products containing high concentrations of antioxidant compounds, which have
been studied for their potential anti-diabetic effects. These include
anti-glycation, anti-inflammation, and anti-hyperglycemia. More
research is needed to identify the phytochemical compounds in
spices, their targets and their modes of action on DM and complications, as well as the combination therapy of spices with the synthetic drugs.
Seasoning of foods with spices may increase the daily intake of
antioxidants and provide a possible means of decreasing the risk
for developing diabetic complications and metabolic abnormalities.
However, few clinical trials have been carried out on spices and
thus there is insufficient evidence to determine their effectiveness.
In addition, spices are generally used in seasoning of recipes in
small amounts, and the chemical composition and bioavailability
of antioxidant compounds may be affected during food preparation.
As a result, their therapeutic potential may be limited. In future,
more clinical research is needed to confirm the real efficacy of
including spices in diet to aid in diabetes prevention and treatment.
Declaration of interest
The authors have no relevant interests to declare.
Acknowledgements
The authors greatly acknowledge the financial support from
Singapore Institute for Clinical Sciences, Agency for Science,
Technology, and Research (A*STAR) Singapore.
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Food Chemistry 217 (2017) 281293

Contents lists available at ScienceDirect

Spices in the management of diabetes mellitus

X. Bi et al. / Food Chemistry 217 (2017) 281293

uptake in the insulin-sensitive tissues, and modulation of hepatic

Fig. 1. The beneficial effects of spice polyphenols on glucose homeostasis and

DM occurs when the body is unable to produce enough insulin

Randomized, double-blind, placebo-controlled trial

Cinnamon reduces serum glucose, triglyceride, total cholesterol, and LDL

Khan et al. (2003)

Ginger reduces FBG and HbA1c as well as improves insulin resistance

Randomized, double-blind, placebo-controlled trial

The dosage of black cumin was 1, 2, 3 g/day

The dosage of aniseed powder was 5 g/day

The daily consumption of 2 g of black cumin can significantly decrease

Mixed with water together with 2.5 g of Tulsi leaves

Daily dosage was 0, 1, 2, and 3 g

Adding a spice mix to burger meat prior to cooking

Turmeric has a beneficial effect on blood glucose, oxidative stress and

Mitra and Bhattacharya

112 mg of aqueous cinnamon extract was prepared by Finzelberg (Andernach, Germany)

Mang et al. (2006)

Cinnamon extract reduces fasting plasma

Garlic powder tablets

Allicor reduces FBG, serum fructosamine and

X. Bi et al. / Food Chemistry 217 (2017) 281293

Fenugreek decreases blood glucose and triglyceride levels when consumed

Rajeshwari, Shobha et al.

Sobenin et al. (2008)

X. Bi et al. / Food Chemistry 217 (2017) 281293

4. Spices in the treatment of diabetes mellitus

Flavanols (e.g. Catechin)

Nutmeg, Fennel, Cinnamon

Flavanones (e.g. Hesperetin, Eriodictyol)

Peppermint, Fennel, Onion

Flavones (e.g. Apigenin, Luteolin)

Aniseed, Peppermint, Onion, Oregano, Horseradish

Flavonols (e.g. Quercetin, Kaempferol,

Allspice, Aniseed, Coriander, Cumin, Fennel, Onion,

Hydroxybenzoic acid derivatives

Allspice, Cloves, Saffron

Gallic acid, Salicylic

Curcumin, Gingerol, Capsaicin

Examples of spices (Kaefer & Milner, 2008)

Coriander, Cumin, Nutmeg, Fennel, Onion, Peppermint,

X. Bi et al. / Food Chemistry 217 (2017) 281293

Major bioactive compounds

Potential mechanism for anti-diabetic characteristics

Up-regulate the expression of GLUT4

Subash Babu et al. (2007), Lu

Enhance the activity of insulin

Improve insulin sensitivity

Chuengsamarn et al. (2012)

Reduce cholesterol and lipid peroxidation

Shojaii and Fard (2012)

Increase secretion of insulin and utilization of glucose

Increase utilization of glucose

Reverse proteinuria; reduce blood sugar, cholesterol and

Bioenhancer by inhibition of hepatic and intestinal

Increase secretion of insulin and utilization of glucose

Rahman et al. (2014)

comprehensive discussion is given regarding the beneficial effects

Thomson, Al-Amin, Al-Qattan,