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Abstracts:
Published Studies of Mulberry Leaf Extract Used in Glucocil


An extract of black, green, and mulberry teas causes malabsorption of carbohydrate but not of triacylglycerol in healthy volunteers*

Litao Zhong, MD, PhD
Julie K Furne, BS
Michael D. Levitt, MD

Background: In vitro studies suggest that extracts of black, green, and mulberry teas could interfere with carbohydrate and triacylclycerol absorption via their ability to inhibit alpha-amylase, alpha-glucosidase, sodium-glucose transporters, and pancreatic lipase.

Objective: We measured breath hydrogen and CO2 to investigate the ability of an extract of black, green, and mulberry tea leaves to induce malabsorption of carbohydrate and triacylglycerol in healthy volunteers.

Design: In a crossover design, healthy adult volunteers randomly ingested test meals with a placebo beverage or as a preparation containing an extract of black (0.1 g), green (0.1 g), and mulberry (1.0 g) teas. One test meal contained 50 g carbohydrate as white rice, 10 g butter, and 0.2 g [13 C]triolein, and the beverages contained 10 g sucrose. The calorie content of the second meal consisted entirely of lipid (30 g olive oil and 0.2 g [13 C]triolein). Breath-hydrogen and 13 CO2 concentrations were assessed hourly for 8 hours, and symptoms were rated on a linear scale.

Results: With the carbohydrate-containing meal, the tea extract resulted in a highly significant increase in breath-hydrogen concentrations, which indicated appreciable carbohydrate malabsorption. A comparison of hydrogen excretion after the carbohydrate-containing meal with that after the nonabsorbable disaccharide lactulose suggested that the tea extract induced malabsorption of 25% of the carbohydrate. The tea extract did not cause triacylglycerol malabsorption or any significant increase in symptoms.

Conclusion: This study provides the basis for additional experiments to determine whether the tea extract has clinical utility7 for the treatment of obesity or diabetes.

* Zhong L, Furne JK, Levitt MD. An extract of black, green, and
  mulberry teas causes malabsorption of carbohydrate but not
  of triacylglycerol in healthy volunteers. (The American Journal
  of Clinical Nutrition) Am J Clin Nutr 2006:84:551–5.


IInfluence of mulberry leaf extract on the blood glucose and breath hydrogen response to ingestion of 75 g of sucrose by subjects with type 2 diabetes and controls* (Unpublished Abstract)

Mitchell Mudra, BA
Nacide Ercan-Fang, MD
Litao Zhong, MD, PhD
Julie Furne, BS
Michael Levitt, MD

Background: Mulberry leaf is widely used in Asia for the treatment of diabetes.

Objective: The purpose of the present study was to determine if co-ingestion of mulberry leaf extract with 75 g of sucrose influenced the blood glucose response and sucrose absorption of controls and subjects with type II diabetes.

Design: In a double-blind crossover study, 10 healthy controls and 10 subjects with type II diabetes ingested 75 g of sucrose with 1.0 g of mulberry leaf extract or placebo. Blood glucose was assessed at intervals for 2 hours in controls and for 4 hours in subjects with diabetes. Breath samples were collected hourly for 8 hours for H2 determinations. Symptoms were monitored for approximately 10 hours after sucrose ingestion.

Results: Mulberry extract significantly reduced the blood glucose increase at 15, 30, and 45 minutes after sucrose ingestion in both controls and subjects with diabetes but increased blood glucose concentrations at the tail-end of the tolerance test. Area under the curve was not significantly altered by mulberry, but fluctuations in glucose concentrations were significantly reduced (p<0.01). Breath H2 analysis indicated that the extract caused malabsorption of 12 to 16 g of sucrose. The extract did not result in a significant increase in symptoms.

Conclusions: Co-ingestion of mulberry extract reduces both the increase and the fluctuation of blood glucose observed after ingestion of a 75 g dose of sucrose. Further studies of the clinical utility of this herbal product are indicated.

*Mudra R, Ercan-Fang N, Zhong L, Furne J, Levitt M. Influence
  of mulberry leaf extract on the blood glucose and breath
  hydrogen response to ingestion of 75 g of sucrose by subjects
  with type II diabetes and controls. Diabetes Care
  2007;30(5):1272–4.


The Relationship between Mulberry Leaf Extract and HbA1c Concentrations

[This subject is also discussed in the Post-meal sugar spikes section of Diabetes and Food.]

Re the Mudra et al. study (above), one might ask if the mulberry-induced diminution of blood glucose concentrations at early time points, but higher values at later time points, has clinical utility for subjects with diabetes. The common measure of efficacy of an anti-diabetic regimen is its influence on HbA1c, a time-averaged indicator of the mean glucose exposure of red cells (and the body) to glucose. Given that mulberry induced no significant differences in the area under the curve for changes in glucose concentration, the extract may have a minimal effect on HbA1c concentrations.

On the other hand, the findings of the Diabetes Control and Complications Trial1 indicate that a factor other than the integrated blood glucose concentration (as assessed by HbA1c) plays a role in the microvascular complications of diabetes. This factor may be the fluctuations in blood glucose concentration.2 Brownlee and Hirsch3 have proposed that generation of reactive oxygen species is the common pathway responsible for the complications observed in diabetes, and a variety of in vivo and in vitro studies have shown that fluctuations in blood glucose concentration (rather than hyperglycemia, per se) are associated with increased production of markers of oxidative injury.

As shown in the Mudra et al study (above), mulberry extract significantly reduced the fluctuation of blood glucose during the tolerance test. For example, the peak-to-trough difference in blood glucose concentration in subjects with Type II diabetes averaged 99 ± 11 mg /dl and 133 ± 12 mg/dl with mulberry versus placebo (p <0.01). Thus, mulberry extract might aid in the prevention of diabetic complications despite its presumed minimal effect on HbA1c concentrations.

References

1. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977-86.

2. Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C. Activation of oxidative stress by acute glucose fluctuations with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 2006;295:1681–7.

3. Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complication. JAMA 2006;295:1707–8.


Glucocil Formulation: Published Studies on Ingredients

Considerable research has been conducted on the ten ingredients (including mulberry leaf extract) contained in the Glucocil formulation. The citations for approximately 90 selected studies have been sorted into relevant sub-categories.
See References.

 


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