Benefits
Smaller Post-Meal Rise in Blood Sugar
In placebo-controlled crossover trials in healthy adults, a DNJ-standardized leaf extract taken with maltodextrin, sucrose or a bread meal lowered the 2-hour glucose response by about 14 to 42%, depending on dose and meal. A pooled analysis of 13 randomized trials of Morus alba products found lower post-meal glucose at 30 to 90 minutes. Several trials were funded by or co-authored with the extract's maker.
Lower Post-Meal Insulin Response
In the same healthy-adult trials, the 2-hour insulin response was about 24 to 40% lower than placebo at effective doses. In adults with type 2 diabetes, a blend containing leaf extract lowered insulin versus the same blend without it only in the first hour after breakfast, not at 2 or 3 hours.
Post-Meal Glucose Over Weeks of Daily Use
In adults with raised fasting glucose, a DNJ-enriched extract before meals for 12 weeks raised 1,5-anhydroglucitol, a marker that improves when post-meal spikes are smaller, versus placebo, while fasting glucose and HbA1c did not differ. In a 3-month trial in type 2 diabetes, post-meal home readings were 18% lower than placebo but HbA1c did not differ.
Fasting Glucose and Insulin Markers
A 2023 pooled analysis of 12 trials (615 people) of leaf or leaf extract found lower fasting glucose, HbA1c and fasting insulin, with larger effects in subgroups using it for 8 weeks or more or starting with raised fasting glucose. An earlier pooled analysis of 13 trials found no difference in these fasting markers, and individual trials of 12 weeks to 3 months found no difference from placebo in fasting glucose or HbA1c.
Slower Breakdown of Dietary Sugars and Starch
DNJ, the leaf's main studied compound, blocks the gut enzymes that split sucrose, maltose and starch fragments, based on lab tests on human intestinal tissue. In a sucrose drink trial, peak glucose fell while the time to peak did not change. This is the main proposed reason for the lower post-meal glucose seen in trials.
Lower Oxidative Stress Marker (MDA)
In a single trial of 60 adults with type 2 diabetes, 300 mg of leaf extract twice daily for 12 weeks lowered malondialdehyde (MDA), a marker of lipid oxidation, versus placebo. No other trial cited here measured this outcome.
Higher HDL Cholesterol
In a single trial of 60 adults with type 2 diabetes, 12 weeks of leaf extract raised HDL cholesterol versus placebo, while other measured markers did not differ. A pooled analysis of 13 randomized trials of Morus alba products found no difference in total cholesterol, LDL, HDL or triglycerides.
Mechanism of action
α-Glucosidase Inhibition (DNJ)
1-Deoxynojirimycin (DNJ) is an iminosugar that resembles glucose. In lab tests on human small-intestine samples, a leaf extract (0.24% DNJ equivalent) diluted 1000-fold inhibited sucrase by 96%, maltase by 95% and isomaltase by 99%, and lactase and trehalase less (38% and 44%); in rat tissue the inhibition was competitive.
Flatter Post-Meal Glucose Curve
Slower splitting of sucrose and starch means glucose enters the blood more slowly. In a sucrose drink trial, peak glucose was 40% lower with no change in the time to peak, and a breakfast trial in type 2 diabetes found a lower glucose peak with the extract than without it.
Smaller Insulin Response
With less glucose absorbed in the first hour, less insulin is released, and trials measured lower insulin areas alongside lower glucose. In one breakfast trial the gut hormone GIP was also lower with the extract, while GLP-1 did not differ.
Oxidative Stress Marker
In one 12-week trial in type 2 diabetes, the extract lowered malondialdehyde (MDA), a lipid oxidation marker, versus placebo. How this happens in people is not established, and the trial did not measure post-meal glucose.
Clinical trials
Double-blind, randomized, placebo-controlled crossover trial at Oxford Brookes University. Capsules of Reducose (water extract of mulberry leaf standardized to 5% DNJ) at 125, 250 or 500 mg, or placebo, taken with 50 g maltodextrin. Funded by an Innovate UK grant; one author was an officer of Phynova, the developer of Reducose, which did not fund the study. (Lown et al. 2017, PLoS One)
37 healthy adults aged 19 to 59 with normal blood sugar and BMI 20 to 30.
Versus placebo, the 2-hour glucose response (positive iAUC) was 6% lower at 125 mg (not significant), 14% lower at 250 mg and 22% lower at 500 mg; the insulin response was about 24% lower at 250 and 500 mg. The odds of digestive symptoms did not differ from placebo.
Double-blind, randomized, placebo-controlled crossover trial: 250 mg Reducose stirred into a 75 g sucrose drink versus the sucrose drink alone. Funded by Phynova, the extract's maker; one author is a Phynova employee. Retrospectively registered (ISRCTN99601810). A published correction (PMID 34039387) changed one reference only. (Thondre et al. 2021, Nutr Metab (Lond))
38 healthy adults aged 20 to 58 enrolled; 37 completed and 36 had complete data.
Versus sucrose alone, the 2-hour glucose iAUC was 42% lower and the insulin iAUC 40% lower; peak glucose and peak insulin were also lower, while the time to peak did not change. No adverse events were reported.
Double-blind, randomized, placebo-controlled crossover trial: capsules with 200, 225 or 250 mg Reducose or placebo before a meal of 150 g white bread with egg mayonnaise filling. Two authors are employees of Phynova, which helped conceive and design the study. (Thondre et al. 2024, Nutrients)
37 healthy adults completed the study.
Versus placebo, the 2-hour glucose iAUC was 30%, 33% and 32% lower and the insulin iAUC 31%, 34% and 38% lower at 200, 225 and 250 mg.
Two randomized, double-blind trials: a placebo-controlled crossover test of single doses (3, 6 or 9 mg DNJ) before 200 g boiled white rice, and a 12-week parallel trial of 6 mg DNJ three times daily before meals versus placebo tablets. Three authors were employees or the chief executive of Project M and Minato Pharmaceutical, the extract's manufacturers. (Asai et al. 2011, J Diabetes Investig)
Adults with fasting glucose of 100 to 140 mg/dL (single-dose test: 12 enrolled, 10 analyzed) or 110 to 140 mg/dL (12-week trial: 76 enrolled, 65 analyzed).
Single doses lowered the post-rice glucose rise in a dose-dependent way versus placebo. Over 12 weeks, 1,5-anhydroglucitol (a blood marker that rises when post-meal glucose spikes are smaller) increased versus placebo, but fasting glucose, HbA1c and glycated albumin did not differ between groups.
Randomized, double-blind, placebo-controlled pilot trial: 2-week placebo run-in, then standardized mulberry leaf extract 1,000 mg or matching placebo three times daily with meals for 3 months. Primary outcomes were HbA1c and home glucose readings. Registered NCT00795704. (Riche et al. 2017, Complement Ther Med)
24 adults with type 2 diabetes on stable oral medication enrolled; 17 completed.
HbA1c did not differ from placebo (7.30% to 6.94% within the extract group, not significant). Post-meal home glucose readings were 18.2% lower than placebo at 3 months. Serum creatinine rose 15% versus baseline and placebo; weight, fasting home readings, low-glucose events and other safety markers did not differ.
Randomized controlled study in two parts: a dose-finding test of leaf powder equal to 0 (control), 6, 12 or 18 mg DNJ taken with a sucrose drink in healthy adults, then a 12-week trial of 12 mg DNJ three times daily versus a control group. No competing interests declared. (Thaipitakwong et al. 2020, Complement Ther Med)
Healthy adults (dose-finding part) and adults with obesity and borderline-high blood sugar (12-week part).
Versus the 0 mg control, 12 mg DNJ was the lowest dose that reduced the post-sucrose glucose rise. In the 12-week trial, glucose tolerance did not improve; fasting plasma glucose fell 3.86 mg/dL and HbA1c 0.11% compared with baseline levels (the abstract reports these changes against baseline, not against the control group), and insulin resistance showed a nonsignificant trend (p = 0.057). Bloating, flatulence and loose stools were the common side effects.
Randomized, double-blind, placebo-controlled trial: Morus alba leaf extract 300 mg or placebo twice daily for 12 weeks; fasting blood samples only, no post-meal testing. Registered IRCT2016081312438N21; no conflicts declared. (Taghizadeh et al. 2022, Clin Nutr ESPEN)
60 adults with type 2 diabetes (30 per group).
Versus placebo, the extract lowered fasting insulin (P = 0.026) and malondialdehyde (MDA), an oxidative stress marker (P < 0.001), and raised HDL cholesterol (P = 0.001). Other measured metabolic profiles did not differ from placebo.
Randomized, double-blind trial of blood glucose after rice meals in women with impaired glucose tolerance and in healthy adults. The coating (SEMA) was 20% Morus alba leaf 50% ethanol extract, 58.6% onion water extract, 20% deep sea water and 0.5% sodium alginate, so the effect of mulberry alone is not isolated. Participants ate 75 g of coated or plain rice; cooked coated rice held about 11.7 mg DNJ per 100 g. The paper also reports lab enzyme tests and animal toxicity tests. (Hwang et al. 2016, Evid Based Complement Alternat Med)
Women aged 50 to 70 in the impaired-tolerance group (16 per group) and 14 healthy adults aged 22 to 45 (7 per group); 46 of 70 enrolled completed.
Because onion extract made up more of the coating than mulberry extract, this result belongs to the blend. In the women, the 30-minute reading after breakfast was 142 versus 173 mg/dL with plain rice and the 2-hour area was 49% lower (P < 0.001). In the healthy group, the 30-minute reading was about 11 mg/dL lower, which was not significant.
Randomized controlled exploratory crossover trial at two centers (USA, Singapore): a 2 g blend with 250 mg leaf extract (12.5 mg DNJ), fiber, vitamin D3 and chromium versus the same blend without the extract, sprinkled on a 350 kcal breakfast with 55.4 g carbohydrate. Funded by Nestlé Health Science, which employed several authors. Registered NCT04877366. (Mohamed et al. 2023, Diabetes Ther)
30 adults of Asian origin with type 2 diabetes (mean age 59, HbA1c 7.1%).
Versus the blend without extract, glucose iAUC was 20%, 17% and 15% lower at 1, 2 and 3 hours, and peak glucose was 0.8 mmol/L lower. Insulin iAUC was 24% lower at 1 hour only; GLP-1 did not differ.