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. 2023 Sep 19;11(11):7283-7295.
doi: 10.1002/fsn3.3654. eCollection 2023 Nov.

Lemon flavonoids nutraceutical (Eriomin®) attenuates prediabetes intestinal dysbiosis: A double-blind randomized controlled trial

Fernanda M M Ramos  1 , Carolina B Ribeiro  1 , Thais B Cesar  1 , Dragan Milenkovic  2 , Lucélia Cabral  3 , Melline F Noronha  4 , Katia Sivieri  1
Affiliations

Lemon flavonoids nutraceutical (Eriomin®) attenuates prediabetes intestinal dysbiosis: A double-blind randomized controlled trial

Fernanda M M Ramos et al. Food Sci Nutr. .

Abstract

Eriocitrin (eriodictyol 7-O-β-rutinoside), a citrus flavonoid from lemon juice and peel, reduces hyperglycemia and improves diabetes-related biomarkers in prediabetes patients. Eriocitrin is first metabolized by gut microbiota, producing energy for gut cells and short chain fatty acids that play a relevant role in glycemic control. The aim of this study was to assess the effect of Eriomin®, a nutraceutical composed of 70% eriocitrin, 5% hesperidin, and 4% naringin, on the microbiota of prediabetic patients. Patients were randomly divided into two groups and received unlabeled capsules of Eriomin® (200 mg/day) or placebo during 12 weeks. After treatment with the nutraceutical, it was a 6% decrease of hyperglycemia and 22% increase of GLP-1 blood levels of (p < .05). The profile of intestinal microorganisms, obtained by 16S rRNA sequencing of the patients' feces extract, showed changes in microbiota composition, such as lower growth of Firmicutes and less abundance of the Lachnospiraceae family. The family Ruminococcaceae increased and Blautia genus reduced with Eriomin® supplementation. In additional, Blautia was positively correlated with hyperglycemia reduction. In conclusion, the nutraceutical Eriomin® moderately reduced the growth of microorganisms associated with intestinal dysbiosis and increased the abundance of beneficial bacteria. Changes promoted mainly by the flavonoid eriocitrin in the microbiota were related to a lower glycemic level and increased production of GLP-1 in patients with prediabetes.

Keywords: Eriomin®; clinical trial; eriocitrin nutraceutical; intestinal dysbiosis; lemon flavonoid; microbiota (16S rRNA); pre‐diabetes.

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Conflict of interest statement

The authors declare no conflicts of interest. The sponsors had no role in the design, execution, interpretation, or writing of the study.

Figures

FIGURE 1
FIGURE 1
Experimental design of a 12‐week, double‐blind, randomized, placebo‐controlled, two‐arm parallel study. Of the 62 eligible candidates, 45 subjects were selected and separated randomly into two groups: Placebo (n = 20) and Eriomin® (n = 25). For 12 weeks they received a daily dose of the designated supplement, and after subtracting the dropouts, 29 subjects participated in the final analysis of the study.
FIGURE 2
FIGURE 2
Course of (a) blood serum glucose (mg/dL) and (b) GLP‐1 over 12 weeks of treatment (Week 0 and Week 12) with 200 mg/day of Eriomin versus Placebo in prediabetes patients. Circular points represent individual measurements of Glucose (a) and GLP‐1 (b). Dash line represents the average trend line over time.
FIGURE 3
FIGURE 3
Distribution of intestinal bacterial phyla: Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria before (week 0) and after (12 weeks) treatment with Eriomin® or placebo. Data are expressed as percentage of relative abundance by group mean in each experimental period.
FIGURE 4
FIGURE 4
(a) Distribution of the main microbial families before (week 0) and after (week 12) treatment with Eriomin® or Placebo. Data are expressed as percentage of relative abundance by group mean (Eriomin® or Placebo) in each experimental period. (b) Changes in the abundance of the Ruminococcaceae family after 12 weeks of Eriomin® treatment. Values are expressed in OTU. The increment of Ruminococcaceae with Eriomin® versus the decrease after Placebo is statistically significant (p ≤ .035).
FIGURE 5
FIGURE 5
(a) Distribution of the main microbial genera before (week 0) and after (week 12) treatment with Eriomin® or Placebo. Data are expressed as percentage of relative abundance by group mean in each experimental period (week 0 and week 12). (b) Changes in the abundance of Blautia genus after 12 weeks of Eriomin® treatment. Values are expressed in OTU. The increment of Blautia with Eriomin® versus the decrease after Placebo is statistically significant (p ≤ .014).
FIGURE 6
FIGURE 6
Heatmap of Pearson's correlation analysis between gut microbiota and glucose, after 0 and 12 weeks of Eriomin® treatment.
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