Liu Y, Zhang J, Guo H, et al. Effects of mulberry leaf and white kidney bean extract mix on postprandial glycaemic control in pre-diabetic subjects aged 45–65 years: a randomized controlled trial. J Funct Foods. 2020;73:104117.
To determine the acute and chronic effects of 2 plants—mulberry leaf and white kidney bean—containing different antihyperglycemic constituents on glucose control in subjects with prediabetes
A randomized, single-blinded control study at the Department of Nutrition and Food Hygiene, School of Public Health, in Beijing
The study included 66 participants, all with prediabetes, ranging from 45 to 65 years of age. One person was excluded because they were not able to attend part of the study. The researchers recruited participants through flyers, posters, and the internet and selected them during a 1-month period between July and August 2018.
Researchers screened participants using 2 criteria methods: a questionnaire and laboratory testing.
The researchers adopted the prediabetes diagnostic criteria from the American Diabetes Association (ADA): glycohemoglobin (ie, hemoglobin A1C) between 5.7% to 6.4%; fasting plasma glucose (FPG) of 100 mg/dL to 125 mg/dL; or an oral glucose tolerance test (OGTT) result ranging from 140 mg/dL to 199 mg/dL.
Subjects were excluded if they had any of the 5 following criteria:
- Existing diagnosis of any disease that could affect glucose metabolism. This included diabetes, digestive disorders, thyroid issues, kidney disease, liver disease, or cancer
- Long-term use of food supplements or pharmaceuticals that impact glucose metabolism
- Allergic reactions to study products
- Inability to participate in the interview process because of issues relating to sight, hearing, or mental disability
- Pregnancy or lactation
Study Parameters Assessed
Researchers conducted the laboratory tests 2 weeks before the study began, including tests on fasting blood glucose and hemoglobin A1C (HbA1c).
The participants were separated into 2 groups of 33 participants each, with 1 acting as the control group and the other the intervention group.
Researchers used 3 stages to assess the acute and chronic effects of mulberry leaf and white kidney bean extract mix on the after-meal glucose control.
Stage 1 (Baseline)
Stage 1 is the baseline for the study. Researchers took a fasting venous blood draw and asked participants to consume 100 grams of white bread and drink 200 mL of water in a 10-minute period of time. Blood was drawn 30, 60, and 120 minutes after consumption.
Stage 2 (Acute Effect Test)
One week after the baseline blood draw, both the test group and the control group again consumed 100 grams of white bread and 200 mL of water within 10 minutes. The test group also received mulberry leaf and white kidney bean extract mix (1.5 grams) with this test meal. The control group did not receive anything additional. Again, blood was drawn at 30, 60, and 120 minutes after consumption.
Stage 3 (Chronic Effect Test)
After stage 2, the test group consumed 1.5 grams of mulberry leaf and white kidney bean extract mix with each meal, 3 times per day with their normal diets over a period of 4 weeks. Therefore, the test-group participants received a total of 4.5 grams of the supplement each day. The control group did not receive any dietary supplementation, and they also consumed their normal diets.
Researchers contacted participants 3 times per week to help them stay compliant with the protocols for the study. Twice during Stage 3 (on day 15 and day 29), participants received a meal of 100 grams of white bread and 200 mL of plain water to consume in 10 minutes, and their blood sugar levels were checked 30, 60, and 120 minutes after they started to eat the meal.
Using both substances together is thought to have a greater potential to lower postprandial glucose levels by combining active antiglycemic agents in each plant.
During the entire study, participants were asked to avoid mulberry leaf, white kidney beans, and any substances that contained mulberry leaves or white kidney beans, as well as anything that may alter their glucose metabolism. The participants were asked to maintain their normal exercise and dietary habits.
Two days before each visit for a blood draw, participants received instructions to avoid strenuous exercise, heavy meals, caffeine, alcohol, and tobacco; to eat the same meal each time before they went to get blood drawn; and to fast for 10 to 14 hours before they came in. They were asked to come in before 9:00 a.m. on the morning of the blood draw and were given instructions about the research process.
Primary Outcome Measures
Stage 2 (Acute Effects)
- Postprandial glucose levels were decreased from baseline after 30 minutes (P<0.001) and after 60 minutes (P=0.006).
- Postprandial insulin levels were decreased from baseline after 30 minutes (P=0.002), and after 60 minutes (P=0.010).
- Postprandial C-peptide levels were decreased from baseline after 30 minutes (P=0.010), and after 60 minutes (P=0.002).
The last measure looked at the area under the curve depicting 120 minutes after taking the mulberry leaf and white kidney bean extract mix and showed significant decreases from the baseline for glucose, insulin, and C-peptide.
Stage 3 (Chronic Effects)
Supplementation with mulberry leaf and white kidney bean extract mix did not result in any significant changes as measured by the area under the curve (120 minutes) for levels of glucose, insulin, or C-peptide on days 15 and 29.
The homeostatic model assessment—insulin resistance (HOMA-IR), the hemoglobin A1c, and the glycated serum proteins (GSP) showed no significant change at days 15 and 29.
For Stage 1, the baseline stage of the study, there was no significant difference between the test group and the control group even after adjusting for body mass index (BMI).
However, in the acute-effects stage of the study, the test group had significantly lower postprandial glucose, postprandial insulin, and postprandial C-peptide at the 30-minute and 60-minute timeframes. These measures were also lower after adjusting for BMI. At the 120-minute timeframe, the percent change in the intervention group for postprandial glucose, postprandial insulin, and postprandial C-peptide was more significant (versus baseline) than in the 30- and 60-minute timeframes.
In the chronic-effects stage of the study, the test group did not show any significant effects.
This is the first study that looked at the combination of mulberry leaf and white kidney bean extract to lower glucose levels.
Using both substances together is thought to have a greater potential to lower postprandial glucose levels by combining active antiglycemic agents in each plant. White kidney beans contain an active α-amylase inhibitor, and the 1-deoxynojirimycin (DNJ) found in mulberry leaf also blocks α-amylase activity. The flavonoids and polysaccharides in the mixed extract also exhibit alpha-glucosidase inhibitory activities.
Alpha-amylase and α-glucosidase are 2 brush border enzymes responsible for the metabolism of starches in the proximal small intestine. By blocking enzymes that break down carbohydrates, the carbohydrates are left intact, and are too large to be absorbed. This has implications for prediabetic and diabetic populations because lower absorbency is a key factor in reducing blood glucose levels and may affect longer-term HbA1c levels.1
Adding foods high in α-amylase inhibitors may be indicated for prediabetic patients to incorporate into their dietary plans to help reduce postprandial glucose levels. Alpha-amylase inhibitors are found in many common beans beyond white kidney beans, especially in red kidney beans and black kidney beans.2 Eating foods that limit the digestion and absorption of starches may be a good means to gently modify blood glucose levels, and further research should give us better guidance as we learn the best food combinations to control glucose.