Effectiveness of ginger in reducing metabolic levels in people with diabetes: a randomized clinical trial

Objective: to evaluate the effectiveness of ginge (Zingiber officinale) in reducing blood sugar and lipid levels in people with type 2 diabetes. Method: a randomized and double-blind clinical trial conducted with people with type 2 diabetes in primary care facilities. The study included individuals aged between 20 and 80 years old, using oral antidiabetic drugs and with HbA1c levels between 6.0% and 10%. The participants were paired 1:1, allocated in two distinct groups, and randomized in blocks, based on their HbA1c levels. In the experimental group, the participants used 1.2g of ginger and, in the control group, 1.2g of placebo, daily for 90 days. The primary outcome was a reduction in fasting blood sugar and HbA1c, and the secondary outcome was a reduction in lipids and HOMA-IR. 103 individuals completed the study, 47 in the experimental group and 56 in the control group. Results: the participants in the experimental group showed a greater reduction in the blood glucose and total cholesterol values compared to the control group. Conclusion: the use of ginger can help in the treatment of people with diabetes, and data support the inclusion of this herbal drug in the clinical practice of nurses. RBR-2rt2wy


Introduction
The control of type 2 Diabetes Mellitus (T2DM) has been one of the main challenges for health professionals, researchers, and people with the disease (1) . Factors such as clinical inertia and lack of adherence to the prescribed therapeutic regimen appear as strong obstacles in the treatment of the disease, leading to important metabolic dysregulation (2)(3)(4) .
As a result, the worldwide interest in research involving the use of alternative and complementary practices has been increasing. This interest is due to factors such as the search for affinities for the use of natural products; the high price of private medical assistance, together with the high cost of the medications; precarious public assistance; and the attempt to mitigate complications related to chronic diseases, such as T2DM (5)(6)(7)(8)(9) . In this sense, ginger appears as a promising adjuvant for the treatment of T2DM, mainly acting in the regulation of lipid metabolism, in the improvement of anti-inflammatory activities, and in the modulation of insulin release and response, with minimal adverse events and increasingly effective results (10)(11)(12)(13) .
Given the above, it was established as a hypothesis that the use of ginger is effective in decreasing glycemic and lipid biomarkers in people with T2DM, compared to a placebo. However, studies analyzing the effect of ginger in the treatment of people with T2DM are still scarce and so far no publications have been found on the subject in Brazil, indicating the need for more evidence to legitimize and subsidize the inclusion of this product in the clinical practice of health professionals, mainly in Primary Health Care, as a way to facilitate the control of T2DM (12)(13) . This study aimed at assessing the effectiveness of ginger (Zingiber officinale) in reducing blood sugar and lipid levels in people with T2DM.  The study included people diagnosed with T2DM for   at least two years, aged between 20 and 80 years old,   with preserved cognitive functions -according to the Mini Mental State Examination (MMSE) (14) , and undergoing treatment with oral antidiabetic drugs and glycated hemoglobin (HbA1c) between 6.0% and 10.0% in the baseline. The cut-off point established for HbA1c is justified since, with levels below 6.0%, people with T2DM already have good control of this biomarker; and, above 10.0%, these patients would already have important dysregulation, making the research unfeasible (15) .

Method
In turn, the exclusion criteria used were the following: people using alcohol or tobacco, using any natural product to control diabetes, on insulin therapy, with the presence of chronic changes (cardiovascular, liver, kidney, gastric, or mental disorders diagnosed), and pregnant or lactating women. Chronic changes and mental disorders were assessed through information provided by the participants themselves, during assessment of the eligibility criteria, and confirmed with the health professionals in the PHCU where they were monitored. The individuals could be discontinued from the study if they experienced any adverse events. All the data was previously checked during the nursing appointments.
The study had as primary outcome the reduction in blood sugar levels (fasting glucose and HbA1c) of people with T2DM and, as secondary outcomes, the reduction in lipid levels (total cholesterol, triglycerides, LDL-cholesterol, and HDL-cholesterol) and the variation of the HOMA-IR index. In Picos there were no records on the number of people with T2DM and HbA1c levels between 6.0% and 10.0%, monitored in the PHCUs. Therefore, the sample was calculated using the mean difference between two groups using the G*Power 3.1.9.2 software, in which a significance level of 5% and a test power of 80% were set, based on a previous study (16)(17) , which resulted in the need to include 102 individuals. However, considering potential losses, a percentage of 40% was added. Guideline for Hypertension (18) . The laboratory data corresponded to the levels established by the Brazilian Society of Diabetes (15) , and by the V Brazilian Guideline on Dyslipidemias and Prevention of Atherosclerosis (19) . Blood samples (10 mL) were taken after 10 to 12 hours of fasting.   (Table 1).  There was also a better outcome in the HDL levels of the EG when compared to the CG, although not statistically significant. The LDL values showed a better result in those who received a placebo. In the intergroup analysis, however, no outcome variable was significant. It is highlighted that the studied groups were homogeneous regarding the outcome variables (Table 3).    that found women to be more vulnerable to higher levels for this marker (28) .
A systematic review that investigated the effects of ginger on the lipids of people with diabetes showed that, in addition to TC and LDL, the product was able to reduce TG levels when in doses of 1 to 3 g/day (23) .  (9,29) . It is noted that, in this study, the homogeneity of the groups regarding the socioeconomic and clinical variables reduced possible biases in differential and confounding information.
Although R 2 (53.2%) did not attain a very high level in the adjustment model, some predictor variables proved to be statistically significant when associated with the outcome variables. Even so, it is still possible to draw conclusions about the influence of these predictor variables on the studied outcomes. It is highlighted that, during the intervention period, only two participants reported some adverse event, one in the EG and the other in the CG. Data from two systematic reviews were unanimous regarding the safety of this product, and they minimize the occurrence of toxicity from the use of ginger (13,25) .
From observation and interpretation, it is possible to say that ginger has therapeutic potential to be used in the treatment of T2DM, increasing the chances of normal levels of blood sugar and lipids in people with the disease.
Thus, the most relevant contribution of this research is to make it evident that the use of ginger is viable as an adjuvant herbal drug in the treatment of T2DM, especially because it is an easily accessible and low-cost spice, which can serve as a complementary technology to be offered in the clinical practice of nurses, supporting the work of these professionals, and encouraging equitable, integral, and resolute practices also by the multidisciplinary team that works in Primary Health Care (30) . Furthermore, this clinical trial is a pioneering initiative in the country, since it fills not only a knowledge gap, but also elucidates possible limitations that can be adjusted in future research studies.

Conclusion
This study demonstrated that the daily consumption