Diabetes mellitus is characterized by chronic hyperglycemia resulting from impaired insulin action/secretion (
). The prevalence of type 2 diabetes is high in the Middle East; the rate of 7.7% has been reported for Iran (
). The prevalence of this disorder is progressively increasing around the world (
). About 6.4% or 285 million individuals in the adult population (20–79 years) were affected by diabetes in 2010. It is estimated that by 2030, this rate will increase by 7.7% or 439 million persons, and during 2010–2030, about 69% of the increase will be allocated to developing countries and 20% to developed ones (
). A wide variety of therapeutic agents in modern medicine are available against these diseases such as antihypertensive (Angiotensin converting enzyme inhibitors, beta blockers, diuretics, calcium channel blockers etc.) but most of these drugs have potentially serious side effects and high costs, and if the therapy is not regularly monitored, it can lead to toxicity and non-compliance. Most of these drugs are not suitable to be used as a preventive measure against these risk factors (
Virtually about 3/4 of the people of the world trust in traditional treatments especially herbal treatments; until the mid-19
th century at least 80% of the medicines were herbal derivatives (
Gilani, 2005). The use of herbal medicines including ginger is among different strategies for preventing and controlling diabetes complications (
Mozaffari-Khosravi et al., 2013).
Ginger (
Zingiber officinale) a well-known spices plant, sweet, pungent, heating appetizer has been used in traditional oriental medicines for a long time. Its extract and major pungent principles
have been shown to exhibit a variety of biological activities (
Ghayur and Gilani, 2005,
Wei et al., 2005).
Ginger is reported to possess anti-inflammatory, analgesic, antipyretic, antimicrobial, hypoglycemic, antimigraine, molluscicidal, antischistosomal,
anti–motion sickness, antioxidant, hepatoprotective, hypocholesterolemic, and antithrombic activities (
Langner et al., 1997). Because of the antithrombic potential of ginger, it may interact with blood-thinning drugs such as warfarin and must be used carefully in patients with blood clotting disorders (
Ghayur and Gilani, 2005). The use of ginger in cardiovascular diseases has long been known. Ginger is known to have a diuretic and blood pressure (BP)-lowering effect (
Ghayur and Gilani, 2004,
Miller and Murray, 1998). In the traditional medicine practice of Pakistan, herbalists prescribe ginger to hypertensive patients to be taken after dinner. Interestingly, a few studies have been carried out to explore the BP-lowering potential of ginger extract and its active constituents; however, conflicting results were obtained (
Ghayur and Gilani, 2005,
Langner et al., 1997) and the precise mode of action remained to be elucidated (
Suekawa et al., 1986,
Suekawa et al., 1984,
Weidner and Sigwart, 2000).
Ginger has now a high potential for treating many aspects of cardiovascular disease. Reviewing recent trials show that ginger has considerable
anti-inflammatory, antioxidant, anti-platelet, hypotensive and hypolipidemic effects in vitro
and animal studies (
Nicoll and Henein, 2009).
When ginger was used in combination with other herbs, it caused significant physiological changes, including reduction of body weight, skin thickness, and waist/hip circumference (
Paranjpe et al., 1990).
In a study accomplished by Arablouet, et al. (2014) in Iran, the effect of ginger consumption on some cardiovascular risk factors in patients with type 2 diabetes mellitus was investigated. The results represented no significant difference in systolic and diastolic blood pressure (
Arablou et al., 2014). In another study conducted by Sanghal, et al. (2012) in India, an experimental study was investigated to evaluate the preventive effect of
Zingiber officinale (ginger) on hypertension and hyperlipidaemia and its comparison with
Allium sativum (garlic) in rats. In this study, ginger have shown significant preventive effect on systolic blood pressure and lipid level in comparison to control group (
Sanghal et al., 2012). Furthermore, in a study done by Ghayur, et al. (2005) in Pakistan, it was found that ginger reduces blood pressure through blockage of voltage-dependent calcium channels. The results of this study showed that the intravenous administration of fresh ginger extract reduces blood pressure effect in anaesthetized rats. In the isolated tissue preparations, ginger extract exhibited a negative inotropic and chronotropic effect while also showing a vasodilator effect through a specific blockade of the voltage dependent Ca
2+ channels. The vasodilator effect was found to be independent of endothelium (
Ghayur and Gilani, 2005).
Despite different scientific evidences there was no agreement regarding various ginger effects and few studies have been conducted on ginger and its relation with BP in patients with diabetes. This study was, therefore, carried out to determine the effect of ginger on BP patients with type 2 diabetes.
Materials and Methods
Design and participants: The present study is a randomized, double-blind, placebo-controlled trial with the participation of 88 patients with type 2 diabetes supported by Yazd Diabetes Research Center between January to July 2013.
Inclusion criteria: Having type 2 diabetes for at least 10 years, fasting blood glucose (FBG)
< 180 mg/dL and 2h-blood-sugar < 250 mg/dL, no pregnancy or lactation, no autoimmune disorder, no cardiac ischemic or renal diseases, no thyroid and chronic inflammatory diseases, no peptic ulcer and infection, no regular consumption of ginger or other herbal drugs, no sensitivity to ginger, body mass index (BMI)
< 40 kg/m
2, no consumption of triglyceride
or cholesterol, estrogen, progesterone-lowering drugs, and no consumption of any supplements such as vitamin C, E, and omega-3 during 2 months before starting the study.
Exclusion criteria: Any sensitivity due to ginger consumption reported by the patient or noticed after starting the study, consumption of vitamin, mineral or other nutritional supplements, consumption of alcohol or narcotic drugs, and any variation in patients' routine treatment according to physicians' resolution (i.e., variation in type and dose of the drugs to be consumed, and treatment with insulin).
Dose, type of supplement, and intervention duration: The patients randomly received ginger capsules (3g/day in 3 divided dose; ginger group (GG)) or cellulose microcrystalline (3g/day in 3 divided dose; placebo group (PG)) for 8 weeks. The dried rhizome of ginger was purchased from a valid marker (Bou-Ali Sina herbal drug Researchers Corporation, Ghom, Iran).
Contacting with patients, in order to control their consumption of capsules, response to the relevant questions, and prevention of sample loss, was performed weekly by calling them and every other week via monitoring the patients' referring to Yazd Diabetes Research Center to receive capsules for the next few weeks.
It is worth mentioning that supplements were not totally delivered to the participants. In order to ensure the supplement consumption and placebo by the participants and calculate the rate of capsule consumption, the participants were asked to deliver the empty boxes of capsules first and then receive the new ones needed for next two weeks. The participants were also advised not to change their usual diet, to stop self-reliant changes of their supplements doses, and to stop physical activities during the intervention.
Measurements: General information including age, weight, height, gender, marital status, occupation, education, disease duration , type and dose of the drugs required for diabetes control, were accessed and recorded through interviews with the patients. Height was recorded by a standard clinical stadiometer with an accuracy of 0.1 cm. Weight was measured with light clothes and without shoes and a balance with 100g accuracy. Both were done at the beginning of 8
th week of the intervention. BMI was calculated as weight in kilograms, divided by height per square meter.
The participants’ systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and mean arterial pressure (MAP) were measured in the morning before the intervention, 2
nd week, 4
th week, 6
th week and at the end of study (8
th week) with an accuracy of 2 mmHg; furthermore, the patients were sitting on a chair and, rested for 5 min, and they were tested by their right arm using a mercury sphygmomanometer (Samsung, Japan). In order to record blood pressure, mean measurement was calculated twice. The PP and the difference between the SBP and the DBP were also measured. The following calculation formula is for the MAP : MAP = DP + 0.333 (SBP − DBP) or [SBP + (2DBP)]/3 (
MEANEY et al., 2000).
To study the patients' diet in terms of daily intake of energy, carbohydrate, protein, fiber, and total fat, a 24h-dietary-recall questionnaire was used both at the beginning and the end of the intervention. Nutritionist IV software (Nutritionist IV Diet Analysis, First Data Bank Division, Hearst Corp., San Bruno, CA) was utilized to analyze the 24h-dietary-recall data.
Ethical Considerations: The study aims and methods were explained to patients and the informed written consent was received from them if they seemed to be interested in participation. Furthermore,, the research was approved by Ethics Commission of Deputy for Research in Shahid Sadoughi University of Medical Sciences. This study was also registered at the Iranian registry of clinical trials (www.irct.ir) with IRCT 201111306278N2 code.
Data Analysis: The data were analyzed by SPSS version 11 (SPSS Inc., Chicago, IL, USA). Kolmogorov–Smirnov test was used to determine quantitative data distribution, paired t-test to compare normal distribution variables mean in two groups before and after the intervention, and Student t-test to compare the variables mean between two groups. The results of quantitative data with normal distribution were reported as mean±SD. The significance level was set at
P-value equal or less than 0.05.
Results
Out of 88 patients who participated in the study, the following cases were excluded from the intervention: 4 patients who had no tendency to continue the study, 1 for her husband's death, and 2 due to travel, the remaining 81 participants were all investigated to the end of the study (
Figure 1). None of participants in both groups reported any adverse effects.
All the patients received oral hypoglycemic agents, 50 (61.7%) of which were female and 31 (38.3%) male. The mean age of the patients in GG and PG showed to be 49.83 ± 7.23 year and
51.05 ± 7.70 year, respectively. The baseline characteristics of patients did not differ significantly between both groups (
Table 1). In addition, BMI did not significantly change within each group during the study.
There were no significant differences in daily dietary intake of total energy and some nutrients between two groups at baseline and the end of the intervention (
Table 2).
The comparison among SBP and DBP, PP and MAP before and after the intervention in GG and PG are given in
Table 3.
As it is shown in
Table 3, the SBP was significantly decreased in the GG (
P = 0.001)
group at the end of the 8
th week and at the end of the study compared to the beginning of the
study (126.50 ± 13.50 to 109.00 ± 11.27 mmHg).
No significant changes were observed in the
PG (118.65 ± 13.32 to 117.31 ± 12.70,
P = 0.54), however, its mean was statistically different between both groups at the end of the intervention (
P = 0.003) (
Table 3).
The DBP was significantly decreased in the GG (
P = 0.001) group at the end of 8
th week and at the ± 7.08 to 66.37 ± 6.20 mmHg). There was no significant change in the PG (72.31 ± 8.37 to 70.24 ± 6.51,
P = 0.11), however its mean was statistically different between both groups at the end of the intervention (
P = 0.008) (
Table 3).
The PP was significantly decreased in the GG
(
P = 0.001) group at the end of the 8
th weekand at the end of the study compared to the beginning of the study, 52.50 ± 10.31 to 42.62 ± 8.91 mmHg. No significant changes were observed in the PG (46.34 ± 7.66 to 47.07 ± 9.61,
P = 0.66). However, its mean was statistically different between both groups at the end of the intervention (
P = 0.034) (
Table 3).
The MAP was decreased significantly in the GG (
P = 0.001) group at the end of the 8
th week and at the end of the study compared to the beginning of the study, 97.66 ± 8.94 to 86.11 ± 7.56 mmHg. No significant changes were observed in the PG (93.79 ± 10.31 to 91.78. ± 8.34,
P = 0.99). However, its mean score was statistically different between both groups at the end of the intervention (
P = 0.002) (
Table 3). Furthermore, regarding the BMI mean score, no significant difference was observed between both groups at the beginning and at the end of the study.