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Journal of Ethnic Foods 2 (2015) 36e43

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Journal of Ethnic Foods


journal homepage: http://journalofethnicfoods.net

Original article

Efficacy of ginger for treating Type 2 diabetes: A systematic review


and meta-analysis of randomized clinical trials
James W. Daily a, Mini Yang b, Da Sol Kim b, Sunmin Park b, *
a
Daily Manufacturing Inc., Vitamins and Supplements Store, Rockwell, NC, USA
b
Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan, South Korea

a r t i c l e i n f o a b s t r a c t

Article history: Background/Purpose: Few clinical trials have investigated the antidiabetic effects of ginger to date.
Received 13 January 2015 Several recent clinical trials published in 2013 and 2014, although small, have added contradictory but
Received in revised form compelling new evidence about the use of ginger in treating diabetes in humans. Therefore, a systematic
20 January 2015
review and meta-analysis was conducted to clarify the evidence for using ginger to treat diabetes.
Accepted 10 February 2015
Available online 26 February 2015
Methods: Five randomized clinical trials (RCTs) were identified and included in the meta-analysis. Four of
the RCTs were considered high quality and lasted 8 weeks; one lasted only 30 days and was considered
low quality. Outcomes measured included fasting blood glucose and insulin, homeostatic model
Keywords:
ginger
assessment (HOMA)-insulin resistance (IR), and hemoglobin A1c (HbA1c) levels, and were assessed as
hemoglobin A1c mean differences in the meta-analysis.
randomized clinical trials Results: Ginger supplementation significantly lowered fasting blood glucose concentrations and HbA1c
serum glucose levels levels, but did not significantly lower fasting blood insulin or HOMA-IR.
Type 2 diabetes Conclusion: Ginger root supplementation significantly lowers blood glucose and HbA1c levels. When
combined with dietary and lifestyle interventions it may be an effective intervention for managing Type
2 diabetes mellitus.
Copyright © 2015, Korea Food Research Institute, Published by Elsevier. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction global prevalence of diabetes was reported to be 382 million people


in 2013 and is expected to rise to 592 million by 2035. Type 2
Ginger, the rhizome of the plant Zingiber officinale, is indigenous diabetes makes up about 85% of cases of diabetes, with the other
to Southeast Asia where its cultivation dates back about 3,000 years 15% attributed to Type 1 diabetes mellitus and gestational diabetes
in India. Today its use has spread to most of the inhabited world [1]. [3]. Type 2 diabetes is a metabolic disorder that is characterized by
Ginger remains an integral part of Indian cuisine where it is hyperglycemia in the context of insulin resistance and relative lack
commonly used in many popular dishes. In Korea, ginger has been of insulin [4,5]. Several types of drugs such as sulfonylurea, thia-
used to season foods for the last 1,000 years approximately. Sliced zolidinedione, incretin, and dipeptidyl-peptidase 4 inhibitors have
ginger with sugar added is used to make tea, pickled ginger slices been prescribed for treating hyperglycemia in Type 2 diabetic pa-
(Gari) are frequently used as a condiment in Japan, and ginger is tients. These drugs work by reducing insulin resistance and
commonly used to flavor cookies and cakes in Western countries improving insulin secretion capacity [5]. However, each drug has
[2]. Almost simultaneous with its cultivation as a spice, ginger was adverse side-effects, so there is great interest in developing natural
incorporated into Indian traditional Ayurvedic medicine and today interventions for managing diabetes and its symptoms [5].
it is used a common herbal treatment for nausea in both Asian and Ginger contains various potentially bioactive substances such as
Western countries. gingerols, shogaols, zingerone and paradol. It also includes volatile
The prevalence of diabetes mellitus is high and rising worldwide oils such as sesquiterpenes [b-bisabolene and ()-zingiberene],
due to the global increases in obesity and unhealthy lifestyles. The geranial, and neral [6]. Among gingerols and shogaol the major
pungent components in the rhizome are 6-gingerol and 6-shogaol
[6]. Ginger has long been used as an herbal medicine to treat
* Corresponding author. Department of Food and Nutrition, Obesity/Diabetes various symptoms including vomiting, pain, and cold symptoms,
Research Centre, Hoseo University, 165 Sechul-Ri, BaeBang-Yup Asan-Si, Chung- and it has been shown to have anti-inflammatory, antidiabetic,
Nam-Do, 336e795, South Korea.
anticlotting and analgesic properties [7]. The data for the
E-mail address: smpark@hoseo.edu (S. Park).

http://dx.doi.org/10.1016/j.jef.2015.02.007
2352-6181/Copyright © 2015, Korea Food Research Institute, Published by Elsevier. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/).
J.W. Daily et al. / Journal of Ethnic Foods 2 (2015) 36e43 37

bioavailability of ginger are limited. The major components of the participants had Type 2 diabetes for at least 2e10 years and had
ginger, 6-shogaol, 10-gingerol, 6-gingerol, and 8-gingerol, can be no serious diabetic complications. Furthermore, they did not have
detected in the plasma of rats and humans 1 hour after its oral acute inflammatory diseases, did not smoke or drink, and none
consumption [8,9]. At 48e60 hours after oral consumption of were pregnant or lactating. In all RCTs powder of dried ginger was
ginger, 6-gingerol and 6-shogaol are excreted, mainly into the bile orally consumed at different dosages (1.6e3 g/day) and for different
and some into the urine [8]. Thus, the components of ginger are durations (30e84 days).
absorbed into the body where they can exert various activities. The
safety of ginger has been investigated. Acute and chronic toxicity 2.5. Quality assessment of the articles
studies have demonstrated the broad safety of ginger [10e12]. The
LD50 of methanol and water extracts of ginger was 10.25 g/kg and The Cochrane tool was used to assess quality of the RCT articles
11.75 g/kg body weight by oral administration in mice [11]. included in this systematic review by determining the risk of bias
Administration of ginger powder up to 2 g/kg body weight/day did (ROB) [13]. This validated tool consisted of the following six cate-
not cause mortality or abnormal changes in hematological pa- gories: (1) random sequence generation; (2) allocation conceal-
rameters in rats [12]. Thus, if ginger is shown to be effective in ment; (3) blinding of participants; (4) incomplete outcome data;
alleviating hyperglycemia it can be safely used for its treatment. (5) selective outcome reporting; and (6) other bias. Each category
As several randomized clinical trials (RCTs) examining ginger was scored as high ROB, uncertain ROB, or low ROB. Three inde-
supplementation have been recently conducted in Type 2 diabetic pendent reviewers performed the quality assessment and dis-
patients, this study aims to carry out a systematic review of the use agreements on scores were resolved through discussion.
of ginger for alleviating hyperglycemia.
2.6. Data analysis
2. Methods
The mean difference (MD) was used with 95% confidence in-
2.1. Data sources and selection criteria tervals (CI) and standard deviation (SD). A meta-analysis was
conducted with simultaneous use of fixed-effect and random-effect
The following electronic databases were searched: PubMed, models. All statistical analyses were performed using RevMan V.5.1
EMBASE, the Cochrane Library, Korean database such as: DBpia, the (Cochrane Collaboration, Oxford, UK) software. The meta-analysis
Research Information Service System, and the Korean Studies Infor- included data from parallel-group design studies. Although the
mation Service System, Chinese medical databases such as: the China studies contained multiple time point observations and different
National Knowledge Infrastructure and the Chinese Scientific Jour- dosages, the intervention dosages were relatively similar: three
nals Database, the Indian Medical Journals, and Indian Journals. studies used 3 g/day and one study used 1.6 g/day. However, the
Dissertations were also included. The following search strategy was duration of studies was substantially different and the RCTs were
used: (“ginger” or “Zingiber officinale”) and (“diabetes” or “hyper- subdivided into shorter versus longer periods (30 days or > 30
glycemia” or “insulin”). All RCTs that studied the effects of ginger on days). Since the data used for the meta-analysis were continuous
diabetic symptoms including serum glucose and insulin levels, he- variables such as fasting serum glucose and insulin levels, HbA1c,
moglobin A1c (HbA1c), and homeostatic model assessment (HOMA)- and HOMA-IR, the MD and SD were used for meta-analysis. Het-
insulin resistance (IR) index in Type 2 diabetic patients were erogeneity of the included studies was tested with the Higgins I2
included. Studies that investigated the antidiabetic effects of complex test and meaningful heterogeneity was determined by 50% of the I2
herbal remedies that included ginger as an ingredient were excluded. value. When the I2 value was >50, a random-effect model was used
for the meta-analysis. Funnel plots were used to detect reporting
2.2. Data extraction, quality and validity assessment biases for this systematic review since the number of studies
induced was <10 studies.
The data search was conducted in English, Korean, and Chinese
language databases using the following keywords of mesh termi- 2.7. Subgroup analysis
nology: ginger, serum glucose levels, serum insulin levels, and Type
2 diabetes. Three independent reviewers screened the papers. In The duration of the studies was as follows: one study (30 days);
the first screening the related papers were identified by the titles two studies (8 weeks); and two studies (12 weeks). RCTs were
and abstracts of the papers and the relevant articles were retrieved subdivided into shorter versus longer periods (30 days
in full text and validated for inclusion in the systematic review. The versus > 30 days). However,  30 days was only one group;
fourth reviewer independently validated the selected the papers. therefore the analysis was conducted without the RCT of 30 days
duration.
2.3. Eligibility criteria for studies in this review
3. Results
All prospective RCT studies about using ginger consumption for
the treatment of hyperglycemia in Type 2 diabetic patients were 3.1. Summary of included studies
included in this systematic review. Although no language barriers
were imposed, all studies included in this review were written in An initial electronic search found a total of 869 studies. A total of
English. Dissertations were included. Case studies, case series, 853 studies were excluded (177 in vitro experiments, 376 animal
qualitative studies, and uncontrolled trials were excluded. experiments, and 300 ginger and similar plant related studies). Of
the remaining 15 studies five duplicate studies were removed.
2.4. Patients and intervention Finally, five RCTs met the inclusion criteria after removing two RCTs
not related to ginger and three RCTs in which participants did not
This systematic review included all RCTs that investigated the have Type 2 diabetes mellitus (Fig. 1). The five remaining RCTs were
effects of ginger powder on the treatment of hyperglycemia in Type used for meta-analysis [12e16]. The main data from the included
2 diabetic patients. The eligibility of participants was somewhat RCTs were summarized in Table 1. Surprisingly, four RCTs were
different among individual studies; however, in all of the studies conducted in Iran and one in India although ginger is commonly
38 J.W. Daily et al. / Journal of Ethnic Foods 2 (2015) 36e43

Fig. 1. Selection process of the randomized clinical trials (RCTs).

consumed worldwide (Table 1). Four RCTs had a two-arm parallel not significantly different in meta-analysis (p ¼ 0.07). However, the
design (ginger powder and placebo groups) and one RCT adopted a MDs were significantly lower in the ginger group for all five RCTs
four-arm parallel design including ginger powder, two other herbs, (n ¼ 131) than the placebo group (n ¼ 128) (p ¼ 0.009).
and a placebo group. HbA1c levels in the circulation of Type 2 diabetic patients were
significantly decreased in all four RCTs in which the levels were
3.2. Risk of bias measured. The 95% CI of MDs of four RCTs were [2.04, 1.29]
(p < 0.001) (Fig. 2C). This indicated that there was a significant
The ROB assessment for the included RCTs is presented in difference between the ginger (n ¼ 123) and placebo (n ¼ 120)
Table 2. Of the five RCTs identified for analysis in this study, four groups, suggesting that ginger had a long-term serum glucose
were classified as high quality and one as low quality [12e16]. Four lowering effect.
studies used a proper randomization of participants such as coin When pooling the three RCTs that measured fasting serum in-
flipping and computer generated random numbers [12e14,16] but sulin levels, the MDs were not significantly different between the
one study was considered low quality as it did not describe how the ginger (n ¼ 101) and placebo groups (n ¼ 101) (p ¼ 0.17) (Fig. 2D).
participants were randomized [15]. In addition, four RCTs used Furthermore, the MDs of HOMA-IR, when pooling three RCTs were
blinding of participants and practitioners [14e16,18], blinding was also not significantly different between the ginger and placebo
not mentioned in the one low quality RCT. Drop-out rates were not groups (p ¼ 0.17) (Fig. 2F). Ginger supplementation may prevent
high in any of the RCTs, four RCTs recorded the reasons for with- increased fasting serum insulin levels and HOMA-IR, this could be
drawal where applicable [14e16,18]. determined if the sample size was as large as it was for fasting
serum glucose levels. Therefore, it is possible, but not well estab-
3.3. Outcomes lished, that ginger improves fasting serum glucose levels
and HbA1c by decreasing insulin resistance in Type 2 diabetic
Type 2 diabetes statuses were determined by fasting serum patients.
levels of glucose, HbA1c (the index of long-term serum glucose
control), insulin, and HOMA-IR (the index of insulin resistance). 3.4. Adverse events
Three RCTs determined all four variables [14e16,18] and one RCT
measured fasting serum glucose levels and HbA1c in Type 2 dia- Four RCTs did not report any adverse effects; one RTC did report
betic patients [17]. In the one remaining RCT, only fasting serum an adverse event. Arablou et al [14] reported that one patient out of
glucose levels were measured. The pooled summary effects of 33 in the ginger treated group had heartburn after taking the
fasting serum glucose levels for all five RCTs and then for the four supplement.
RCTs with longer periods are provided in Fig. 2A and Fig. 2B. Four
RCTs reported lower fasting serum glucose levels in the ginger 4. Discussion
supplemented group in comparison to the placebo group. However,
RCTs showed no improvement in the glucose levels in the ginger This review found that studies administering 1,600e3,000 mg of
group. The MDs of the levels observed tended to be lower in the ginger powder per day for 8e12 weeks lowered fasting serum
ginger group (n ¼ 123) than the placebo group (n ¼ 120) but it was glucose levels and HbA1c levels in patients with Type 2 diabetes.
Table 1
The Summaries of Five Randomized Clinical Trials to Investigate the Effects of Ginger Supplementation on Type 2 Diabetic patients.

First author (y) [Ref.] Study design No. & characteristics Eligibility criteria of Exclusion criteria Included Experimental Control FPG result Effect size Author's Adverse
(country to conduct of patients / FPG subjects of subjects intervention / use intervention / use 1. FPG 1. FPG conclusions events
the study) level / treatment level / treatment 2. HbA1c 2. HbA1c
duration duration 3. Insulin 3. insulin
4. HOMA 4. HOMA

Arablou et al (2014) RCT with two 70 DM2 patients / Treated with oral Ginger (n ¼ 2) 1. Ginger Ginger powder Wheat flour 1. (p ¼ 0.02) 1. 9.1 Ginger can reduce (n ¼ 1)
[14] (Iran) parallel groups FPG 88.5~191.2 mg/dL hypoglycemic agents, Heartburn (n ¼ 1) (n ¼ 33) capsule before powder capsule 2. (p ¼ 0.001) 2. 1.0 blood glucose and heartburn
30e70 y HbA1c between 7% and Unwilling to 2. Placebo lunch & dinner before lunch & 3. (p ¼ 0.001) 3. 3.7 insulin levels and
10%, BMI between cooperate (n ¼ 1) (n ¼ 30) 800 mg 12 wks dinner 4. (p ¼ 0.001) 4. 1.7 improve insulin
20 kg/m2 and 35 kg/m2, Placebo (n ¼ 5) 800 mg 12 wks sensitivity in DM2
no pregnancy or 1. Unwilling to patients.
lactation, no use of cooperate (n ¼ 3)
tobacco or alcohol, no 2. Pregnancy
renal, liver, thyroid and(n ¼ 1)
parathyroid disorders, 3. Recurrence of
cancer, infection, disease and the
inflammation and fever need for insulin
therapy (n ¼ 1)
Mozaffari-Khosravi RCT with two 88 DM2 patients / Having DM2 for at least Ginger 1. Ginger Ginger powder Microcrystalline 1. (p < 0.005) 1 .18.17 Ginger lowered FBS nr

J.W. Daily et al. / Journal of Ethnic Foods 2 (2015) 36e43


et al parallel groups FPG 95.64~226.21 10 y, Fasting blood 1. Lost to follow- (n ¼ 40) capsule cellulose capsule 2. (p < 0.005) 2. 0.4 and HbA1c mean
(2014) [15] (Iran) mg/dL glucose <180 mg/dL up (n ¼ 2) 2. Placebo Three meals / Three meals / 3. (p < 0.005) 3. 7.4 values as well as
and 2h blood-sugar 2. Discontinued (n ¼ 41) 1,000 mg 8 wks 1,000 mg 8 wks 4. (p < 0.005) 4. 1.02 variation in fasting
<250 mg/dL, no intervention insulin, insulin
pregnancy or lactation, (n ¼ 2) resistance, increase
no autoimmune Placebo of sensitivity to
disorder, no cardiac 1. Lost to follow- insulin and the
ischemic or renal up (n ¼ 2) QUICKI
diseases, no thyroid and 2. Discontinued
chronic inflammatory intervention
diseases, peptic ulcer (n ¼ 1)
and infection, no
regular consumption of
ginger or other herbal
drugs, no sensitivity to
ginger, BMI <40 kg/m2,
no consumption of
triglycerides or
cholesterol-, estrogen-,
or progesterone-
lowering drugs, and no
consumption of any
supplements such as
vitamin C, vitamin E,
and omega 3 for 2 m
before starting the
research.
Mahluji et al (2013) RCT with two 64 DM2 patients / Insulin therapy at Ginger Ginger Ginger powder Cornstarch tablet. 1. (p ¼ 0.425) 1. 6.1 Oral ginger nr
[16] (Iran) parallel groups FPG 106~200 mg/dl baseline or throughout Treatment failure (n ¼ 28) capsule. Three Three 2. (p ¼ 0.664) 2. 3.5 supplementation
38e65 y the study, no smoking, (n ¼ 2) 2. Placebo meals / 1,000 mg meals / 1,000 mg 3. (p ¼ 0.001) 3. 13 decreased the
pregnancy or Travel (n ¼ 1) (n ¼ 30) 8 wks 8 wks 4. (p ¼ 0.002) 4. 8.1 levels of insulin in
breastfeeding, no Medication patients with DM2
taking any herbal changing (n ¼ 1) without a
plants as a home Placebo significant effect on
remedy or as a 1. Treatment fasting plasma
supplement within the failure (n ¼ 1) glucose and HbA1c.
previous 3 w or 2. Travel (n ¼ 1)
throughout the study,

39
(continued on next page)
Table 1 (continued )

40
First author (y) [Ref.] Study design No. & characteristics Eligibility criteria of Exclusion criteria Included Experimental Control FPG result Effect size Author's Adverse
(country to conduct of patients / FPG subjects of subjects intervention / use intervention / use 1. FPG 1. FPG conclusions events
the study) level / treatment level / treatment 2. HbA1c 2. HbA1c
duration duration 3. Insulin 3. insulin
4. HOMA 4. HOMA

no acute illnesses or
having kidney, liver,
gallbladder or thyroid
disorders,
inflammatory intestinal
diseases and
immunodeficiency
diseases.
Andallu et al (2001) RCT with four 32 DM2 Diabetics and nr 1. Ginger Ginger powder Six corn starch 1. p < 0.01 1. 12 Aswagandha, nr
[17] parallel groups hypercholesterolemic hypercholesterolemic (n ¼ 8) capsules. Six capsules (two ginger and
(India) patients / FPG 2. Placebo capsules (two after a meal)/ mulberry appear to
106~200 mg/dL (n ¼ 8) after a meal) / 500 mg/30 d be effective in
40e60.5 y 500 mg/30 d lowering blood
glucose and serum

J.W. Daily et al. / Journal of Ethnic Foods 2 (2015) 36e43


lipid levels.
Khandouzi et al RCT with two 64 DM2 patients / Disease duration at Ginger 1. Ginger Per 1g Ginger Per 1g Lactose p ¼ 0.000 1. 19 Ginger nr
(2015) [18] (Iran) parallel groups FPG 73.17~237.3 mg/dL least 2 y, HbA1c level of 1. Lost to follow- (n ¼ 22) powder capsule / powder capsule / p ¼ 0.000 2. 0.77 supplementation
20e60 y 6e8%, taken with no up (n ¼ 1) 2. Placebo twice daily / 12 w twice daily / 12 w significantly
antioxidant 2. Discontinued (n ¼ 19) reduced the levels
supplements such as intervention of FBS, HbA1c,
selenium, zinc and (n ¼ 1) Apo B, Apo B /
beta-carotene for at 3. Excluded from Apo A-I and
least 3 m prior to the analysis (n ¼ 1) malonyldialdehyde
study, no smoking or Placebo (MDA), and
drinking. 1. Lost to follow- increased the level
up (n ¼ 1) of Apo A-I in DM2
2. Discontinued patients.
intervention
(n ¼ 2)
3. Excluded from
analysis (n ¼ 3)

Apo, apolipoprotein; BMI, body mass index; bw, body weight; DM2, type 2 diabetes mellitus; FBS, fasting blood sugar; FPG, Fasting plasma glucose; HbA1c, hemoglobin A1c; HOMA, homeostatic model assessment; MDA; nr, not
reported; QUICKI, quantitative insulin sensitivity check index; RCT, randomized controlled trial.
J.W. Daily et al. / Journal of Ethnic Foods 2 (2015) 36e43 41

Table 2
Risk of Bias in Included Trials.

Random Allocation Patient & Assessor Reporting Intention-to Selective Other potential
sequence concealment practitioner blinding drop-out or treat analysis outcome bias
generation blinding withdrawal reporting

Arablou et al (2014) [14] L L L L L U U U


Mozaffari-Khosravi et al (2014) [15] L L L L U L U U
Mahluji et al (2013) [16] L L L L U L U L
Andallu et al (2001) [17] H H H H U U U U
Khandouzi et al (2015) [18] L L L U L L U U

H, high risk of bias; L, low risk of bias, U, uncertain risk of bias.

Fig. 2. Forest plot of ginger showing its effectiveness in treating Type 2 diabetes mellitus. (A) For fasting serum glucose levels with short-term study. (B) For fasting serum glucose
levels without short-term study. (C) For hemoglobin A1C levels in four studies. (D) For fasting serum insulin levels in three studies. (E) For HOMA-IR in three studies.
42 J.W. Daily et al. / Journal of Ethnic Foods 2 (2015) 36e43

The supplementation of ginger tended to lower fasting serum in- participants in each trial. However, that was offset by the consis-
sulin levels and HOMA-IR, an index of insulin resistance, but they tency of the results in which, regardless of the statistical signifi-
were not significantly different in Type 2 diabetic patients. Thus, cance of the individual studies, none of them showed an increase in
ginger supplementation improves glucose homeostasis in Type 2 blood glucose levels due to ginger consumption and all of them
diabetic patients possibly by lowering insulin resistance although showed a least a modest decrease in blood glucose levels. The po-
the mechanism remains uncertain since neither the decreased in- wer of the combined data clearly demonstrated that ginger can
sulin levels nor HOMA-IR reached statistical significance. This could lower blood glucose and HbA1c levels in humans. Also of impor-
be due to insufficient power of the meta-analysis since only four tance was the demonstration that a manageable dose of ginger
relatively small studies were available. powder can be effective. However, further studies carefully evalu-
The studies included in the meta-analysis were quite homoge- ating dose-dependency are needed to clearly establish what dosage
neous. All studies were conducted in Iran and all participating pa- provides the greatest efficacy for the treatment of diabetes. The
tients had Type 2 diabetes. Most of studies were conducted for safety of long-term ginger consumption may need to be further
8e12 weeks and one study was conducted over 30 days. In this evaluated; however, the safety of ginger use for treating nausea
study, only fasting serum glucose levels were measured so this during pregnancy has been evaluated in human studies at doses up
study was not included with longer duration studies, only fasting to 2,500 mg/day, and demonstrated to be safe for use during
serum glucose levels were reviewed and reported. The Andallu et al pregnancy [10,26].
[17] study supports the current evidence base from the human, In conclusion, this meta-analysis provides convincing evidence
animal, and cellular studies that suggest a therapeutic benefit of to support the efficacy of ginger in the management of Type 2
ginger for lowering fasting serum glucose levels in Type 2 diabetic diabetes.
patients. The mechanism by which ginger improves glucose toler-
ance remains uncertain and even which bioactive compound in
Conflicts of interest
ginger is responsible for its antidiabetic efficacy is unknown,
although it likely that 6-gingerol, the predominant pungent com-
The authors have no conflicts of interest.
pound in ginger, is responsible for its benefits [2,6]. Some studies
have also shown that Type 2 diabetic rats fed ginger or gingerol
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