Efficacy and Safety of Aronia, Red Ginseng, Shiitake Mushroom, and Nattokinase Mixture on Insulin Resistance in Prediabetic Adults: A Randomized, Double-Blinded, Placebo-Controlled Trial

We determined whether oral consumption of Aronia, red ginseng, shiitake mushroom, and nattokinase mixture (3.4: 4.1: 2.4: 0.1 w/w; AGM) improved glucose metabolism and insulin resistance in prediabetic adults in a 12-week randomized, double-blinded clinical trial. Participants with fasting serum glucose concentrations of 100-140 mg/dL were recruited and randomly assigned to an AGM or placebo group. Participants of the AGM group (n = 40) were given an AGM granule containing 4 g of freeze-dried Aronia, red ginseng, shiitake mushroom, and nattokinase (3.4: 4.1: 2.4: 0.1 w/w) twice daily for 12 weeks, and the placebo group participants (n = 40) were provided with corn starch granules identical in appearance, weight, and flavor for 12 weeks. Serum glucose and insulin concentrations were measured during oral-glucose tolerance tests (OGTT) after administering 75 g of glucose in a fasted state. HOMA-IR, liver damage, and inflammation indices were determined, and safety parameters and adverse reactions were assessed. As determined by OGTT, serum glucose concentrations were not significantly different between the AGM and placebo groups after the intervention. However, changes in serum insulin concentrations in the fasted state and Homeostatic model assessment-insulin resistance (HOMA-IR) index after the intervention were significantly lower in the AGM group than in the placebo group (-3.07 +/- 7.06 vs. 0.05 +/- 6.12, p = 0.043 for serum insulin; -0.85 +/- 2.14 vs. 0.07 +/- 1.92, p = 0.049 for HOMA-IR). Serum adiponectin concentrations were reduced by intervention in the placebo group but not in the AGM group. Changes in liver damage indexes, including serum activities of the gamma-glutamyl transferase, alanine aminotransferase, and aspartate aminotransferase, were lower in the AGM group and significantly reduced in the AGM group more than in the placebo group (p < 0.05). Changes in serum high sensitive-C-reactive protein concentrations in AGM and placebo groups were significantly different (-0.12 +/- 0.81 vs. 0.51 +/- 1.95, p = 0.06). In conclusion, AGM possibly improves insulin sensitivity and beta-cell function and reduces liver damage and inflammation in prediabetic adults.