1. Blood Glucose Regulation: The 1-DNJ Mechanism
The most established benefit of MLE is the suppression of postprandial (post-meal) blood glucose spikes.
- Mechanism of Action: 1-DNJ is a structural analog of glucose.It competitively inhibits α-glucosidase enzymes in the small intestine, specifically sucrase and maltase. By preventing the breakdown of complex carbohydrates into simple sugars, it delays glucose absorption into the bloodstream.
- Human Clinical Data: A double-blind, randomized crossover trial (Lown et al., 2017) demonstrated that a single dose of 250mg MLE (standardized to 5% DNJ) reduced the glucose area under the curve (AUC) by 42% and insulin spikes by 40% after carbohydrate ingestion.
- Long-term Efficacy: In a 12-week study on subjects with impaired glucose metabolism, 12mg of 1-DNJ three times daily significantly improved serum 1,5-anhydroglucitol (a marker for postprandial control) and lowered HbA1c levels without causing hypoglycemia.
2. Blood Lipid Health: Flavonoid-Mediated Lipid Lowering
Mulberry flavonoids and DNJ work synergistically to modulate lipid metabolism via the liver and adipose tissue.
- Lipid Profile Improvements: Clinical studies show that MLE supplementation (approx. 280mg, 3x daily) can lead to:
- Triglycerides (TG): Reduction of 10%–16%
- LDL-C (“Bad” Cholesterol): Reduction of 5%–8%
- HDL-C (“Good” Cholesterol): Increase of up to 19%
- Animal Efficacy Data: Studies in high-fat diet (HFD) mice indicate that MLE activates the AMPK signaling pathway, which inhibits fatty acid synthesis and promotes β-oxidation (fat burning) in the liver, effectively preventing non-alcoholic fatty liver disease (NAFLD).
3. Cardiovascular Protection & Anti-Atherosclerosis
Beyond glucose and lipids, MLE exerts direct protective effects on the vascular system
- Endothelial Function: Total flavonoids in mulberry leaves possess potent antioxidant properties that reduce the oxidation of LDL (ox-LDL). Since ox-LDL is a primary trigger for arterial plaque formation, MLE effectively slows the progression of atherosclerosis.
- Blood Pressure: Preclinical models show that MLE can induce vasodilation by increasing Nitric Oxide (NO) production and inhibiting Angiotensin-Converting Enzyme (ACE) activity
| Health Marker | Component | Effect Size (Human) | Primary Mechanism |
| Postprandial Glucose | 1-DNJ | -25% to -42% | α-glucosidase inhibition |
| HbA1c | 1-DNJ / Flavonoids | -0.5%to-0.8% | Improved insulin sensitivity |
| Triglycerides | Flavonoids | -10% to -15% | AMPK pathway activation |
| LDL Cholesterol | Flavonoids | -5% to -12% | Inhibition of cholesterol synthesis |
| Oxidative Stress | Quercetin/Phenolics | Significant reduction | Scavenging of ROS / NO promotion |
Safety and Dosage Synthesis
- Standardized Dosage: Most clinical benefits are observed at dosages of 250-1000mg of extract per meal, standardized to at least 1%-5% 1-DNJ
- Safety Profile: MLE is generally well-tolerated. Minor gastrointestinal side effects (bloating, gas) may occur due to the delayed carbohydrate fermentation in the lower gut, similar to the drug Acarbose but usually milder.
Conclusion
Mulberry leaf extract, characterized by 1-DNJ and total flavonoids, is a high-potential therapeutic agent for metabolic syndrome. It effectively bridges the gap between dietary intervention and pharmacological treatment for pre-diabetes and dyslipidemia.
Selected References
Chung HI, et al. (2013). Improvement of lipid profiles with mulberry leaf extract in moderately hypercholesterolemic patients. Nutrition Research and Practice.
Lown M, et al. (2017). Mulberry-extract improves glucose tolerance and decreases insulin concentrations in normoglycaemic adults. PLoS ONE.
Asano N, et al. (2001). Polyhydroxylated alkaloids isolated from mulberry trees and silkworms. Journal of Agricultural and Food Chemistry.
Thaipitakwong T, et al. (2018). Mulberry leaves and their potential effects against cardiometabolic risks. Pharmaceutical Biology.
Mudra M, et al. (2007). Influence of mulberry leaf extract on the postprandial glycemic response of healthy volunteers. Diabetes Care.