Carvalho GCN, Lira-Neto JCG, de Araújo MFM, Freitas RWJF, Zanetti ML, Damasceno MMC. Effectiveness of ginger in reducing metabolic levels in people with diabetes: a randomized clinical trial. Rev Lat Am Enfermagem. 2020;28:e3369.
Randomized, double-blind, placebo-controlled, parallel-group clinical trial
Adults aged 20 to 80 years (N=103) diagnosed with type 2 diabetes (T2D) for at least 2 years.
The study was conducted from December 2017 to June 2018 in public healthcare units (PHCUs) in Picos, Vale do Rio Guaribas, state of Piauí, Brazil. The PHCUs were chosen randomly from among those that operated in the morning and afternoon and had people registered and followed up with a T2D diagnosis. Researchers recruited 229 people and removed 85 according to exclusion criteria, leaving 144 to be randomized to treatment or placebo, 72 in each group. In the treatment group, 24 were lost; 22 left the study, 1 moved to another city and 1 had an adverse event. In the placebo group 15 were lost; 13 left the study, 1 traveled during the study, and 1 had an adverse event. The final subjects for analysis were 47 in the ginger group and 56 in the placebo group. The mean age was 58.64 years, 69.9% were female, 54.4% were brown-skinned (a Brazilian descriptor used in this paper), 61.2% were retired or unemployed, 60.2% were married or in a stable relationship, 43.7% had a mean of 9 years of education, 52.4% had a monthly income of less than or equal to the minimum wage of $243.00 US per month, 40.8% had been diagnosed with T2D for 2 to 5 years, 43.7% were followed up by nurses and doctors on a quarterly basis with lab tests occurring about twice per year, and 35.9% were physically active on a daily basis. Both treatment groups had high adherence to their treatment regime.
Participants were required to be undergoing treatment for T2D with oral drugs and have preserved cognitive function based on Mini-Mental State Examination (MMSE) and glycated hemoglobin (HbA1c) between 6% to 10% at baseline.
Exclusion was based on any of the following: use of alcohol and/or tobacco, use of natural products to control T2D, those on insulin therapy, and those with chronic changes to cardiovascular, liver, kidney, gastric, or mental systems. Pregnant and lactating women were also excluded.
Fasting glucose and HbA1c; lipid levels, total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and variation in homeostatic model assessment of insulin resistance (HOMA-IR) index (multiply blood glucose by insulin [µIU/mL] both after 10- to 12-hour fasting, and divide by 22.5 with a cutoff of 2.5). Other data collected included gender, skin color, schooling level, years of study, marital status, occupation, income, mean systolic and diastolic blood pressure, time of diagnosis with T2D, episodes of hypoglycemia and hyperglycemia in the 30 days prior to the trial, frequency of follow-up at the PHCU, and physical exercise.
Researchers placed powdered ginger (Zingiber officinale), of the family Zingiberaceae, weighing 600 mg, into capsules. Participants took 1 capsule 30 minutes before breakfast and 1 capsule 30 minutes before lunch for 90 days. Placebo capsules contained 600 mg of microcrystalline cellulose and were taken in the same manner. Each ginger capsule was from powdered rhizome containing 0.1% dried ginger, 33.51% water, 0.89% alcohol, and 0.36% total gingerols (6-gingerol, 10-gingerol, 6-shogaol). Subjects continued their same medications and same eating and exercise habits during the 90-day trial.
Fasting glucose dropped 29.55 mg/dL, P=0.001, in the treatment group vs 9.25 mg/dL, P=0.041, in the placebo group. LDL decreased more in the placebo group, P=0.001, than the treatment group, P=0.018. The change in triglycerides was not significant, and HOMA-IR increased more in the experimental group, but not significantly. HbA1c and total cholesterol decreased more in the experimental group, but the difference between groups was not significant. HDL rose in the experimental group and rose in the placebo group, but again the difference was not significant.
Adverse events included a single event in each of the 2 groups and were not severe.
In the treatment group, both fasting glucose and total cholesterol decreased significantly, while in the placebo group fasting glucose decreased significantly. LDL decreased significantly in both groups, with a greater decrease in the placebo group. Overall, the difference between the groups was not significant.
Ginger’s effects on T2D and related parameters have been the subject of 3 systematic reviews and meta-analyses. A 2015 systematic review and meta-analysis examined 5 trials, 4 of which it deemed high quality, and concluded that ginger lowered fasting glucose and HbA1c and, thus, may be effective for T2D management.1 A systematic review and meta-analysis from 2018 assessing T2D and metabolic syndrome identified 12 studies, 1 in India and 11 in Iran; included 10 of the studies for analysis; and concluded that ginger could significantly reduce fasting glucose and HbA1c, as well as insulin resistance, fasting insulin, and HOMA-IR, but had no significant effect on body mass index (BMI).2 This effect was deemed to be more prominent in patients with hyperglycemia, but the effect on dyslipidemia was inconsistent.2 The most recent systematic review and meta-analysis from 2019 included only 8 trials using 1,600 to 4,000 mg of ginger per day in capsules vs placebo over 8 to 12 weeks and involving 454 patients; it concluded that ginger had no effect on fasting glucose but that it significantly improved HbA1c and, thus, might impact fasting glucose over time.3 The authors graded all trials as “B” using Cochrane collaboration criteria and noted that ginger had been shown to be effective in patients with hypertension and coronary artery disease based on daily consumption in 4,628 adults, with data extracted from both interviews and their health records.3,4
Based on all of the ginger trials, a therapeutic trial of 1 g twice daily before meals should be considered in those with T2D, evidence of poor glucose control, and not treated with insulin.
Many of the trials to date have had compelling results. In a 12-week trial, 70 T2D patients received 1,600 mg per day of ginger vs placebo in capsules, leading to a significant reduction in fasting glucose, HbA1c, insulin, HOMA, triglycerides, total cholesterol, C-reactive protein (CRP), and prostaglandin E2 (PGE2).5 In an 8-week trial, investigators gave 3 1,000 mg capsules of ginger vs placebo to 88 patients who had been diagnosed with 2D for at least 10 years without medication, and they found statistical significance in median fasting insulin, HOMA-IR, and quantitative insulin sensitivity check index.6 Fasting glucose decreased 10.5% in the treatment group and increased 21% in the placebo group, P=0.003.6 Oral ginger powder for 12 weeks at 1,000 mg twice daily in 41 T2D patients caused a significant reduction in fasting glucose, HbA1c, apolipoprotein B (apo B), apo AI, apo B/apo AI, and malondialdehyde (MDA), and increased the level of apo AI compared to placebo.7 A trial of 1,000 mg of ginger vs placebo 3 times daily for 3 months in 20- to 60-year-old T2D patients not on insulin yielded a significant reduction in glucose, HbA1c, insulin, insulin resistance, high-sensitivity CRP, paraoxonase-1, total antioxidant capacity, and MDA in the ginger group.8 In a 2016 trial, 1,000 mg of ginger powder in capsules vs placebo was taken twice daily for 10 weeks by 50 T2D patients diagnosed 1 to 10 years prior, not on insulin, and with a BMI of 18.5 to 35.0 kg/m2 with the result that fasting glucose, HbA1c, and the LDL/HDL ratio were significantly reduced in the ginger group.9
In a 12-week trial of obese women aged 18 to 45 years, 1,000 mg of ginger vs placebo twice daily led to a significant reduction in serum glucose, total cholesterol, triglycerides, cholesterol/HDL, LDL/HDL, and increased HDL in both groups, with the decrease in triglycerides significant in the ginger group.10 In a 12-week trial of obese (BMI 30-40 kg/m2) females, treatment with 1,000 mg of ginger powder twice daily vs placebo yielded a significant reduction in BMI, insulin, and HOMA-IR index, and increased quantitative insulin sensitivity check index (QUICKI) in the ginger group.7 There was also a significant reduction in leptin, adiponectin, resistin, and glucose in both groups.11
The probable mechanism for the beneficial effects of ginger may involve inhibition of alpha-glucosidase and alpha-lipase, key enzymes for digestion and absorption of carbohydrates.2 A mouse study found that 6-shogaol and 6-paradol stimulated glucose utilization; 6-paradol was utilized in a high-fat mouse diet, and it decreased blood glucose, cholesterol, and body weight, and thus, 6-paradol, which is formed when Zingiber is dried, stored, or cooked, may be the active antihyperglycemic constituent of ginger.12 Another possible mechanism is increased expression and translocation of GLUT-4 glucose transport to the cell’s plasma membrane.9 Ginger may also inhibit cholesterol biosynthesis through elevation of hepatic cholesterol 7 alpha-hydroxylase, and it also contains small amounts of niacin.13 It is worth noting that Curcuma longa is in the same family, is also a rhizome, is used in cooking, has been the subject of extensive medical research, and probably originated in Vietnam or India, while Zingiber officinale originated in maritime Southeast Asia.14
Zingiber doses in human clinical trials have ranged from 1,200 to 4,000 mg per day, usually given over 2 or 3 doses before meals. Usually the ginger was dried, ground, and placed in capsules, except for 1 study that used steamed ginger. Both methods of preparation are supported in the above mouse study.12 None of the trials reviewed reported on whether subjects correctly guessed if they were in the treatment or placebo group; only a few reported on side effects, generally gastrointestinal upset; and the maximum trial length was 12 weeks. Based on all of the ginger trials, a therapeutic trial of 1 g twice daily before meals should be considered in those with T2D, evidence of poor glucose control, and not treated with insulin.
This article was easy to read, though the extraction of the independently prepared ginger extract was not well described. This study used a lower dose than those from Iran and India, but it was the maximum permissible dose under Brazilian regulations in a trial to assess its potential benefit in PHCUs when administered by nurses. This article was extracted from the doctoral dissertation of the first author in the Department of Nursing, Federal University of Ceará, Fortaleza, Brazil.