Most health advice around glucose focuses entirely on plasma glucose concentration steady by continuous monitoring or steady on a tracker. While balancing blood sugar is vital, true metabolic health depends on how effectively your cells actually use<\/em> that sugar.<\/p>\n\n\n\n When your cells are hit with a wave of glucose, they rely on specific pathways to handle the workload. If those pathways are overwhelmed, your cellular machinery faces severe metabolic stress.<\/p>\n\n\n\n Here is a look at the exact science behind GlucoRegulate<\/strong> and how its dual-ingredient formula works to optimize your metabolic pathways before your day even begins.\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0<\/p>\n\n\n\n 1. Awakening Nrf2: Master Cytoprotective Regulator <\/strong><\/p>\n\n\n\n At the heart of GlucoRegulate’s formula\u2014a precise blend of trans-resveratrol<\/strong> and hesperetin<\/strong>\u2014is the activation of Nrf2<\/strong>. Nrf2 is a crucial transcription factor that acts as your body\u2019s master regulator of cellular defense and metabolic balance. As we age, Nrf2 can become sluggish. By awakening this master switch, GlucoRegulate restores your body’s natural blueprint for effective glucose control.<\/p>\n\n\n\n 2. Pacing the Pipeline: Normalising Hexokinase-2<\/strong><\/p>\n\n\n\n Once Nrf2 is activated, it goes to work optimizing your enzymes. When glucose enters a cell, an enzyme called Hexokinase<\/strong> acts as the main valve, pulling sugar into the pipeline to create energy. However, during times of high glucose, one type of hexokinase – hexokinase-2 (HK2), can become locked “open,” causing glycolytic overload<\/strong>. Nrf2 activation helps normalize HK2 levels, essentially installing a smart governor on the valve so fuel enters at a manageable, steady pace.<\/p>\n\n\n\n 3. The Great Detour: The Pentose Phosphate Pathway<\/strong><\/p>\n\n\n\n What happens to the excess sugar that gets kept out of the main engine? Rather than letting it build up and disrupt your glucose balance, GlucoRegulate safely diverts it into an alternative route called the Pentose Phosphate Pathway (PPP)<\/strong>.<\/p>\n\n\n\n The PPP is a highly protective alternative pathway. Instead of burning glucose for raw fuel (which creates cellular stress when overdone), the PPP uses that sugar to manufacture NADPH<\/strong>\u2014the fundamental building block your cells need to produce antioxidants and defend against aging. This is the definition of effective glucose use.<\/p>\n\n\n\n 4. Quietening the Cellular Distress Alarm<\/strong><\/p>\n\n\n\n When a cell is overstuffed with fuel, its internal factory gets overwhelmed. Proteins begin to misfold, which triggers an emergency distress signal called the Unfolded Protein Response (UPR)<\/strong>\u2014a primary driver of glucose-related cellular inflammation.<\/p>\n\n\n\n By activating Nrf2, GlucoRegulate also induces Glo1 (Glyoxalase 1)<\/strong>, a vital enzyme that acts like a pressure-relief valve. By boosting Glo1, the supplement calms the cellular environment, prevents the UPR alarm from firing, and stops metabolic inflammation before it starts.<\/p>\n\n\n\n GlucoRegulate supplement is available from GloVitality Ltd<\/a> and Amazon UK.<\/p>\n\n\n\n Paul J Thornalley, 16th July 2026<\/p>\n\n\n\n We have all been there. It\u2019s 2:00 PM. You enjoyed a perfectly normal lunch an hour ago – perhaps a sandwich or a bowl of pasta – and suddenly, a heavy wave of exhaustion hits. Your eyelids feel heavy, your brain feels foggy, and all you want is a nap or a third cup of coffee.<\/p>\n\n\n\n We might think this afternoon slump is just a natural part of aging. We assume our metabolism is naturally slowing down, and we simply accept the fatigue and loss of resilience.<\/p>\n\n\n\n But what if age isn’t the problem? What if you have simply lost optimal control over how your body processes fuel?<\/p>\n\n\n\n The Hidden Cause: Glycolytic Overload<\/strong><\/p>\n\n\n\n When we eat carbohydrates or sugars, our bodies break them down into glucose to use for fuel. This process is called glycolysis<\/em>.<\/p>\n\n\n\n Think of glycolysis as a factory assembly line. When we are younger, this line moves efficiently, maintaining a perfect, healthy glucose balance. But as the decades pass, our cells can easily lose their natural pacing and become overwhelmed by a sudden influx of glucose. Instead of smoothly processing the fuel, the assembly line gets jammed.<\/p>\n\n\n\n Scientists call this glycolytic overload<\/strong>. When your cells are flooded with more fuel than they can handle, they experience a form of metabolic backpressure leading to multiple cellular stresses. Instead of giving you a burst of energy, that heavy, post-meal slump.<\/p>\n\n\n\n Restoring Effective Glucose Use<\/strong><\/p>\n\n\n\n The good news is that you don’t have to radically change your entire diet or give up your favorite foods to stay alert. You just need to restore your body\u2019s natural ability to manage glucose effectively.<\/p>\n\n\n\n By awakening a master internal switch that handles metabolic pressure, your body can smoothly re-route excess sugars before they overwhelm your system. Instead of jamming the engine and causing a mid-afternoon crash, that extra fuel is converted into steady, clean protection.<\/p>\n\n\n\n The Bottom Line:<\/strong> You don\u2019t have to accept afternoon fatigue as a permanent rule of getting older. By supporting your metabolic health first thing in the morning, you can restore a youthful glucose balance, take back control of your energy, and keep your momentum all day long. This is achieved with supplement GlucoRegulate by GloVitality Ltd<\/a>. <\/p>\n\n\n\n Paul J Thornalley 13th July 2026<\/p>\n\n\n\n Abnormal activation of astroglia cells in the brain, astrocytes and microglial cells, is linked to inflammation driving the development of cognitive impairment and increased risk of stroke. Inflammatory activation of astroglia cells in the brain can be assessed by magnetic resonance imaging (MRI). Increase in astrocyte and microglia cell inflammation correlated negatively with the marker of insulin resistance, oral glucose insulin sensitivity (OGIS) index. Increase in OGIS over one year in adults with obesity and normal glucose tolerance, impaired glucose tolerance, or type 2 diabetes was linked to decreased astroglia cell inflammatory activation (Diabetes Care<\/em> 45, 416\u2013424, 2022<\/a>). Dietary supplement GlucoRegulate (formerly called Glo1 inducer) increased OGIS in adults living with overweight and obesity to levels of healthy people with normal insulin sensitivity (Diabetes<\/em> 65, 2282\u20132294, 2016<\/a>). This holds the prospect that supplements like GlucoRegulate that correct OGIS to normal levels may decrease the risk of mild cognitive impairment and stroke in adults with overweight and obesity. Great to consider that we may have safe and effective supplements to decrease the risk of mild cognitive impairment and stroke – which is of increased prevalence in the elderly population. GlucoRegulate supplement is available from GloVitality Ltd<\/a>.<\/p>\n\n\n\n Paul J Thornalley, 1st<\/sup> July 2026<\/p>\n\n\n\n People with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and both impaired fasting glucose and impaired glucose tolerance had decrease insulin sensitivity – as judged by the oral glucose insulin sensitivity (OGIS) index. See Abdul-Ghani et al<\/em>., Diabetes 55, 1430\u20131435, 2006. In clinical trial, GlucoRegulate (trans<\/em>-resveratrol and hesperetin; previously known as Glo1 inducer) treatment of people living with overweight and obesity for 8 weeks corrected the OGIS index to the levels of people with normal glucose tolerance. See Xue et al<\/em>., Diabetes 65, 2282\u20132294, 2016.<\/a> Therefore, people living with impaired fasting glucose, impaired glucose tolerance and both impaired fasting glucose and impaired glucose tolerance may benefit from taking GlucoRegulate supplement.<\/p>\n\n\n\n For more on GlucoRegulate supplement see:<\/p>\n\n\n\n Xue, M., Rabbani, N. and Thornalley, P.J. (2025) Glyoxalase 1 inducer, trans<\/em>-resveratrol and hesperetin \u2013 dietary supplement with multi-modal health benefits. Antioxidants 14, 956.<\/a><\/p>\n\n\n\n GloVitality Ltd website<\/a><\/p>\n\n\n\n Paul J Thornalley, 29th<\/sup> May 2026<\/p>\n\n\n\n Happy to give a presentation on “Laboratory measurement of protein glycation in the era of precision medicine \u2013 biomarkers of metabolic dysfunction and health decline”. The conclusions of the presentation are given below.<\/p>\n\n\n\n Paul J Thornalley, 26th<\/sup> April 2026<\/p>\n\n\n\n Dietary supplements are often taken to support good health. It’s rare to see evidence of comparison with leading pharmaceuticals in clinical trial. An example is weight loss drug Tirzepatide<\/strong> (Zepbound<\/strong>) and supplement GlucoRegulate<\/strong>. Tirzepatide (5 mg, once weekly subcutaneous injection) for 72 weeks to subjects living with obesity improved insulin sensitivity, measured by the oral glucose insulin sensitivity (OGIS) index, by 75 units – including diet counselling to achieve 500 calories per day decrease and at least 150 min per week exercise; SURMOUNT-1 trial. Dietary supplement GlucoRegulate (once daily, oral capsule) for 8 weeks to subjects living with obesity improved OGIS index by 58 units – with no change in diet and exercise; HATFF trial. A similar improvement in metabolic health with GlucoRegulate as for Tirzepatide and achieved over a shorter period with minimal lifestyle change and low cost to consumer and healthcare provider. A remarkable comparison indeed!<\/strong> Increased insulin sensitivity in obesity is important to counter insulin resistance for improved metabolic, heart, liver, kidney and respiratory health. GlucoRegulate is a supplement by GloVitality (UK) Ltd <\/strong>(https:\/\/glovitality.com\/glucoregulate\/<\/a>).<\/p>\n\n\n\n Supporting papers: Mounjaro – Mari et al., Diabetes Care 2025; 48: 1622\u20131627; GlucoRegulate (then called Glo1 inducer) – Xue at al., Diabetes 2016; 65: 2282\u20132294.<\/p>\n\n\n\n Paul J Thornalley 19th March 2026<\/p>\n\n\n\n Insulin resistance is the impaired response to insulin of tissues that are normally insulin-responsive. It is increasingly recognized as impacting the liver, skeletal muscle, adipose tissue and also the brain. The mechanisms are distinct in different tissues. It is prevalent in obesity, prediabetes and type 2 diabetes and is often the primary initiator leading to type 2 diabetes development. <\/p>\n\n\n\n Hepatic insulin resistance<\/strong> is so-called “mixed” insulin resistance and is due to down regulation of insulin receptor substrate 2 (IRS-2). A major consequence of this is impaired down regulation of gluconeogenesis in the post-meal absorptive phase leading to hypersecretion of glucose from the liver. It is caused by overactivation of carbohydrate-response element binding protein (ChREBP) by a sugar rich diet, hyperinsulinaemia and also multilayered epigenetic and extrahepatic mechanisms, including regulation by the central nervous system and glucagon. Involvement of ChREBP is driven by glucokinase-linked glycolytic overload in hepatocytes. It is likely reversed by GlucoRegulate<\/strong> supplement, trans-resveratrol with hesperetin (Rabbani and Thornalley, Clinical Science 139, 1 \u2013 25, 2025).<\/p>\n\n\n\n Peripheral insulin resistance <\/strong>is the impaired response of skeletal muscle and adipose tissue to insulin. Normally in the absorptive phase insulin stimulates uptake of glucose into muscle for glycogen synthesis and uptake of glucose into adipose tissue for synthesis of lipids. Impaired recruitment of insulin-dependent GLUT4 glucose transporter appears to have a key role. We have described how hexokinase-2 linked glycolytic overload in the fasting period during impaired fasting glucose with increased fasting glucose concentration contributes to this. It is corrected by GlucoRegulate<\/strong> supplement (Rabbani and Thornalley, Front. Endocrinol. 14: 1268308, 2024).<\/p>\n\n\n\n Brain insulin resistance<\/strong> may be inferred from decreased response amplitudes to auditory and visual stimuli using electroencephalography and magneto-encephalography during a hyperinsulinemic euglycemic clamp. It is typically found in subjects living with obesity and type 2 diabetes which also have hepatic and peripheral insulin resistance. It is associated with decreased memory and improved cognitive performance and is thought to be mediated by inflammation and oxidative stress (Milstein, J.L., and Ferris, H.A. Mol Metab 52<\/em>, 101234, 2021). It is likely corrected by GlucoRegulat<\/strong>e supplement which is currently under consideration.<\/p>\n\n\n\n Paul J Thornalley, 15th March 2026<\/p>\n\n\n\n Happy New Year! Looking forward to working with in-house and collaborating international teams in 2026 to advance projects in biomedical research and commercialization – particularly of precision dietary\/food supplement GlucoRegulate (through Glovitality Ltd<\/a> and Glocentrica Ltd<\/a>) and screening blood test for autism (through iDiagnostix Ltd<\/a>).<\/p>\n\n\n\n \u201cCome, my friends, \u2018Tis not too late to seek a newer world<\/em>\u201d. From Ulysses, Alfred Lord Tennyson. <\/p>\n\n\n\n Paul J Thornalley, 1st January 2026<\/p>\n\n\n\n Still much more to discover in 2026!<\/p>\n\n\n\n Paul J Thornalley, 26th December 2025.<\/p>\n\n\n\n Naila Rabbani and Paul J Thornalley (2025) Molecular mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD): functional analysis of glucose and fructose metabolism pathways. Clinical Science 139, 1\u201325<\/strong>.<\/a><\/p>\n\n\n\n A pleasure to share this paper covering dietary glucose- and fructose-driven mechanisms of development of MASLD and in so doing, revealing the mechanism of development of insulin resistance and processes leading to peripheral insulin resistance and type 2 diabetes.<\/p>\n\n\n\n Summary points<\/strong><\/p>\n\n\n\n Figure 1: Unscheduled glycolysis and glycolytic overload in the initiation of metabolic dysfunction-associated steatotic liver disease.<\/strong> Key: pink back-filled metabolites, glycolytic intermediates increased in unscheduled glycolysis; red arrows \u2013 pathways of pathogenesis initiated by unscheduled glycolysis in hepatocytes; and blue metabolites and arrows \u2013 metabolism of fructose. Names of enzymes are given in italics. The nuclear translocation of GCK and GKRP is not shown for clarity.<\/p>\n\n\n\n Paul J Thornalley, 7th<\/sup> November 2025<\/p>\n\n\n\n <\/p>\n\n\n\n I saw a paper today<\/a> on a study finding that maintaining endothelial cell levels of NADPH is a strategy to counter vascular aging. Having found this, drug repurposing was explored for 1419 drugs. However, we already know that GlucoRegulate<\/a> supplement increases expression of glucose-6-phosphate dehydrogenase (G6PD) to increase NADPH and is well tolerated and safe. See our study of GlucoRegulate development<\/a>. This is an example where dietary supplements targeting activation of Nrf2 and increased expression of antioxidant response element-linked G6PD can be considered along with repurposed drugs as adjunct or even first line treatments – particularly as dietary supplements typically do not suffer the clinical adverse effects of synthetic drugs. The dietary supplements need to be clinically evidence-based, of course, and if used in special drug delivery format or out of the known safe and well-tolerated range, assessed for safety.<\/p>\n\n\n\n <\/p>\n\n\n\n Plasma Glycated and Oxidized Amino Acid-Based Screening Test for Clinical Early-Stage Osteoarthritis<\/p>\n\n\n\n Aisha Nasser J. M. Al-Saei, Usman Ahmed, Edward J. Dickenson, Kashif Rajpoot, Mingzhan Xue, Essam M. Abdelalim, Abdelilah Arredouani, Omar M. E. Albagha, Damian R. Griffin, Paul J. Thornalley and Naila Rabbani<\/p>\n\n\n\n The diagnosis of early-stage osteoarthritis (eOA) is important in disease management and outcomes. Herein we report the clinical validation of a blood test for the diagnosis of eOA in a large patient cohort using trace-level glycated and oxidized amino acid analytes. Subjects were recruited and enrolled in two study groups: subjects with eOA of the hip (n = 110) and asymptomatic controls (n = 120). Their plasma was analyzed for glycated and oxidized amino acids by quantitative liquid chromatography\u2013tandem mass spectrometry. Algorithms were developed using plasma hydroxyproline and 12 glycated and oxidized amino acid analyte features to classify the subjects with eOA and asymptomatic controls. The accuracy was defined as the percentage of the subjects correctly classified in the test set validation. The minimum number of analyte features required for the optimum accuracy was five glycated amino acid analytes: N\u03c9-carboxymethyl-arginine, hydroimidazolones derived from glyoxal, methylglyoxal and 3-deoxyglucosone, and glucosepane. The classification performance metrics included an accuracy of 95%, sensitivity of 96%, specificity of 94%, area under the curve of the receiver operating characteristic curve of 99%, and positive and negative predictive values of 94% and 97%. We concluded that an assay of five trace-level glycated amino acids present in plasma can provide a simple blood test for the screening of eOA. This is predicted to improve the case identification for expert referral 9-fold.<\/p>\n\n\n\n Antioxidants 2025, 14, 1146. https:\/\/doi.org\/10.3390\/antiox14101146<\/a><\/p>\n\n\n\n Published 23rd<\/sup> September 2025.<\/p>\n\n\n\n Glyoxalase 1 Inducer, trans-Resveratrol and Hesperetin\u2013Dietary Supplement with Multi-Modal Health Benefits Abstract<\/p>\n\n\n\n A dietary supplement, trans-resveratrol and hesperetin (tRES+HESP)\u2014also known as GlucoRegulate\u2014induces increased expression of glyoxalase 1 (Glo1) by activation of transcription factor Nrf2, countering accumulation of the reactive dicarbonyl glycating agent, methylglyoxal. tRES+HESP corrected insulin resistance and decreased fasting and postprandial plasma glucose and low-grade inflammation in overweight and obese subjects in a clinical trial. The aim of this study was to explore, for the first time, health-beneficial gene expression other than Glo1 induced by tRES+HESP in human endothelial cells and fibroblasts in primary culture and HepG2 hepatoma cell line and activity of cis-resveratrol (cRES) as a Glo1 inducer. We measured antioxidant response element-linked gene expression in these cells in response to 5 \u00b5M tRES+HESP by the NanoString method. tRES+HESP increases gene expression linked to the prevention of dicarbonyl stress, lipid peroxidation, oxidative stress, proteotoxicity and hyperglycemia-linked glycolytic overload. Downstream benefits were improved regulation of glucose and lipid metabolism and decreased inflammation, extracellular matrix remodeling and senescence markers. The median effective concentration of tRES was ninefold lower than cRES in the Glo1 inducer luciferase reporter assay. The GlucoRegulate supplement provides a new treatment option for the prevention of type 2 diabetes and metabolic dysfunction\u2013associated steatotic liver disease and supports healthy aging.<\/p>\n\n\n\n Keywords: methylglyoxal; oxidative stress; lipid peroxidation; ER stress; proteotoxicity; insulin resistance; diabetes; MASLD; aging; resveratrol<\/p>\n\n\n\n
\n\n\n\nWhy Your Lunch is Making You Tired (And How to Restore Healthy Glucose Control)<\/strong><\/h2>\n\n\n\n
\n\n\n\nProspect of improved brain health with supplements that increase oral glucose insulin sensitivity (OGIS) index <\/strong> <\/h1>\n\n\n\n
\n\n\n\nBenefit of GlucoRegulate supplement in impaired fasting glucose and impaired glucose tolerance<\/strong> <\/h2>\n\n\n\n
\n\n\n\nPresentation at the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Strategic Conference 2026, Prague, Czechia, 24th – 25th April<\/strong><\/h2>\n\n\n\n
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\n\n\n\nHappy New Year 2026<\/strong><\/h2>\n\n\n
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\n\n\n\nWhat have we discovered in 2025?<\/strong><\/h2>\n\n\n\n
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by Mingzhan Xue, Naila Rabbani and Paul J. Thornalley<\/strong><\/p>\n\n\n\n![\"\"](\"https:\/\/pjthornalley.com\/wp-content\/uploads\/2025\/09\/Graphical-abstract-1024x629.jpg\")
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