trans-Resveratrol and hesperetin combination (tRES+HESP)
Glyoxalase 1 (Glo1) is an enzyme and protective agent in all cells and tissues. It metabolizes the potentially reactive and damaging compound formed from glucose metabolism, methylglyoxal (MG). Levels of Glo1 may decline with age and MG exposure may increase in overnutrition and obesity. Glo1 inducer increases expression of Glo1 every time you take it, restoring normal level protective against MG.
Our Chief Executive Led The Discovery
Professor Paul J Thornalley led the research project in 2012 – 2015 that discovered and optimized Glo1 inducer, trans-Resveratrol and hesperetin combination (tRES+HESP), and its evaluation in the clinical trial “Healthy Aging Through Functional Food” (HATFF or Hats-off) study. Based on this research and our related experience and expertise in allied techniques, Glocentrica Ltd was founded for commercial development of Glo1 inducer. It holds ownership of the patent of RES+HESP and related Glo1 inducer combinations.
Glo1 inducer tRES+HESP increases Glo1, decreases methylglyoxal (MG) and increases insulin sensitivity, as measured the oral glucose insulin sensitivity index (OGIS) – correcting insulin resistance. Research suggests overweight and obese people are exposed to higher levels of MG which causes increased protein misfolding and increased low level inflammation and insulin resistance. Decreasing MG levels to those of lean healthy subjects corrected insulin resistance in overweight and obese subjects. This is expected to prevent the development of type 2 diabetes. Some scientists think this may also prevent obesity in overweight subjects and help with weight loss.
In experimental models, increased Glo1 has also been found to slow the aging process. So, Glo1 inducer may also support healthy aging.
Changes in overweight and obese subjects after 8 weeks treatment by tRES+HESP capsule, once daily. Placebo had no effect. Abbreviations: PBMC, peripheral blood mononuclear cells; OGIS, oral glucose insulin sensitivity index. Source: HATFF study (Xue et al., (2016) Improved glycemic control and vascular function in overweight and obese subjects by glyoxalase 1 inducer formulation. Diabetes 65, 2282 – 2294).
Glo1 inducer was developed to increase expression of Glo1 via activation of Nrf2 through a functional antioxidant response element (ARE). The is a consequent decrease of MG and related protein glycation and formation of the major physiological advanced glycation endproduct (AGE). A major beneficial effect of this is prevention of activation of the unfolded protein response (UPR) and downstream inflammatory signalling (Xue, M., Rabbani, N. and Thornalley, P.J. (2024) Increased cellular protein modification by methylglyoxal activates three sensors of the unfolded protein response. Redox Biol. 65, 103025).
Glo1 inducer also increases expression of glucose-6-phosphate dehydrogenase, thereby decreasing glucose-6-phosphate (G6P) and G6P/Mondo A/Mlx transcriptional signalling – including decrease of expression of hexokinase-2. This contributes to prevention of peripheral insulin resistance and indirectly pancreatic beta-cell glucotoxicity (Rabbani, N. and Thornalley, P.J. (2024) Hexokinase-linked glycolytic overload and unscheduled glycolysis in hyperglycemia-induced pathogenesis in insulin resistance, beta-cell glucotoxicity and diabetic vascular complications. Frontiers in Endocrinology 14 doi.org/10.3389/fendo.2023.1268308)
Main health benefits of Glo1 inducer
→ Improves fasting and post-meal blood glucose levels
→ Corrects insulin resistance
→ Safe, effective and highly-tolerated
Overall, a strong boost to improve glycemic health
Combination of Resveratrol with hesperetin is more effective than Resveratrol alone because:
● Hesperetin improves uptake of resveratrol into the body, overcoming problems of limited absorption, poor bioavailability and poor effectiveness of resveratrol alone
● Resveratrol and hesperetin act synergistically together to increase protective gene expression, up to 79-fold greater response than by resveratrol alone
● Resveratrol and hesperetin together correct “glycolytic overload” to restore good glucose balance in the body
Quotes
“Glo1 inducer increased insulin sensitivity to that of lean, healthy subjects. We know of no other supplement that has achieved this in robust, randomized placebo-controlled crossover studies in overweight and obese subjects”
– Paul J Thornalley, Ph.D.
“Subsequent studies show Glo1 inducer also corrects abnormally high levels of glucose metabolism in hyperglycemia or glycolytic overload and unscheduled glycolysis that also contributes to health benefits”
– Naila Rabbani, Ph.D.