Bioequivalence of Mulberry Fruit Extract and 1-Deoxynojirimycin for Postprandial Blood Glucose Lowering: A Randomized Trial in Humans.

BACKGROUND

Mulberry extracts can reduce postprandial blood glucose (PPG) and insulin (PPI) responses by slowing rates of glucose uptake following carbohydrate-rich meals. The presumed mechanism is the inhibition of intestinal alpha-glucosidase, mainly attributed to 1-deoxynojirimycin (DNJ) in the extracts. However, other components including other iminosugars or polyphenols might also contribute to these effects.

OBJECTIVES

The primary objective was to test the bioequivalence of a mulberry fruit extract (MFE) and an equal dose of the DNJ component alone, for reducing the PPG positive incremental area under the curve over 2 h (+iAUC) following a carbohydrate-rich test meal. A secondary objective was to assess the efficacy of MFE and DNJ for reducing PPG and PPI relative to a placebo.

METHODS

Healthy adults (n = 84) participated in a balanced-order, double-blind, placebo-controlled study assessing PPG and PPI following the addition of MFE (0.75 g, containing 2.90 mg DNJ), pure DNJ (2.90 mg) or placebo to rice meals containing 50 g available carbohydrate. Using United States Food and Drug Administration guidance, bioequivalence was determined by whether the 90% confidence interval (CI) of the ratio of the geometric means of the effects of DNJ compared with MFE was between 0.80 and 1.25.

RESULTS

The ratio of the effect of DNJ relative to MFE was 0.903 (90% CI: 0.801, 1.019), meeting the prespecified criterion for bioequivalence. Although both MFE and DNJ produced absolute reductions in mean PPG and PPI relative to the control, these effects were more robust for MFE than DNJ. Mean plasma DNJ levels were also higher following MFE than DNJ.

CONCLUSIONS

This study confirms the bioequivalence of DNJ and MFE for reducing PPG responses in humans. However, although DNJ is largely responsible for this effect, other components of MFE, particularly 2-O-alpha-D-galactopyranosyl-deoxynojirimycin as a precursor of DNJ, may contribute to its observed efficacy for reducing PPG and PPI.

TRIAL REGISTRATION NUMBER

This trial was prospectively registered at clinicaltrials.gov as NCT02599740 (https://clinicaltrials.gov/study/NCT02599740).