Effect of supplementation with n-trans caffeoyltyramine and n-trans feruloyltyramine on glycemia in prediabetic individuals:Randomized, double-blind, placebo-controlled trial

Resumo

Background: The global prevalence of elevated blood glucose levels is at an all-time high. For many people, reversal to normoglycemia is possible with diet and lifestyle modification. Dietary bioactives, in the form of functional food formulations or supplements, have attracted interest for their potential to improve glycemic control. In silico prediction, validated by preclinical research, has identified novel bioactives, N-trans-Caffeoyltyramine (NCT) and N-trans- Feruloyltyramine (NFT), as potent HNF4α agonists with gluco-regulatory effects. While promising, clinical studies are needed to validate these findings in humans.

Objective: To evaluate the effects of a proprietary dietary supplement containing 120 mg of NCT/NFT on fasting blood glucose and other biomarkers of glycemia in an otherwise healthy population with prediabetes.

Methods: A randomized, double-blind, placebo-controlled parallel arm trial was conducted in Asian Indian adults (Age: 18-50 years; BMI: 25-30 kg/m2) with prediabetes (fasting blood glucose >100 mg/dL and <126 mg/dL) and abdominal adiposity (waist circumference >80 cm for females and >90 cm for males). A total of 126 participants were randomized to receive either 120 mg/d NCT/NFT (n=63) or placebo (n=63) for 4 weeks. Outcomes were measured at day 0 and day 28. The primary endpoint was fasting blood glucose. Secondary endpoints included fasting insulin, postprandial glucose response, and time spent within and outside of the ideal glucose range (<140 mg/dL) as assessed by continuous glucose monitoring (CGM). Additional outcomes related to CGM will be presented in a subsequent publication. Glycated hemoglobin (HbA1c), serum lipids, and anthropometrics were also measured.

Results: Supplementation with a proprietary sustained-release formula of 120 mg/d NCT/NFT for 4 weeks resulted in significant improvements in the primary outcome measure, fasting blood glucose (NCT/NFT: -4.1 ± 7.1 mg/dL vs. Placebo: -0.7 ± 7.0 mg/dL; p=0.0026). Fasting insulin, postprandial glucose response, and time spent outside of the ideal glucose range were also significantly improved with treatment (p=0.0147, p=0.0036, and p=0.0138, respectively). No changes were observed in other markers of glycemia, lipid profile, or anthropometric measures.

Conclusions: Naturally occurring bioactive compounds, NCT and NFT, act as potent HNF4 α agonists for the part that they play in blood glucose regulation and should be considered as part of a comprehensive approach to support glycemic and overall metabolic health.

Novelty of the Study: This study is among the first randomized, double-blind, placebo-controlled clinical trials to evaluate the effects of N-trans caffeoyltyramine (NCT) and N-trans feruloyltyramine (NFT) supplementation on blood glucose regulation in prediabetic adults. While prior research has focused on outcomes that provide a snapshot in time (e.g. fasting glucose or insulin), this study uniquely integrates both cross-sectional (fasting levels) and continuous endpoints (continuous glucose monitoring), providing a comprehensive assessment of bloglucose regulation through novel bioactive compounds. The findings introduce a new direction for bioactive supplementation targeting individuals with looking to maintain healthy blood glucose regulation.

This trial was registered at clinicaltrials.gov as NCT06417840.

Keywords: dietary supplements, N-trans caffeoyltyramine, N-trans feruloyltyramine, prediabetes, Type 2 Diabetes, glucose regulation, HNF4α, NCT, NFT