Early Online (Volume - 10 | Issue - 1)

NAD⁺ Biology in Ageing and Chronic Disease: Mechanisms and Evidence across Skin, Fertility, Osteoarthritis, Hearing and Vision Loss, Gut Health, Cardiovascular–Hepatic Metabolism, Neurological Disorders, and Muscle

Published on: 26th January, 2026

Background: Nicotinamide adenine dinucleotide (NAD⁺) is a pivotal coenzyme and signaling substrate that integrates redox balance with mitochondrial energy production, DNA repair, epigenetic control, and cellular stress resilience. Declines in NAD⁺ availability—frequently observed with ageing, chronic inflammation, and metabolic stress—have intensified interest in NAD⁺ restoration as a potential strategy to influence disease biology across multiple organ systems.Objective: This narrative review summarizes contemporary mechanistic and translational evidence on NAD⁺ biosynthesis and turnover, highlighting the de novo kynurenine pathway and vitamin B3–dependent salvage routes (nicotinic acid, nicotinamide, nicotinamide riboside, and nicotinamide mononucleotide). We also examine how major NAD⁺ consumers and sensors, sirtuins, poly(ADP-ribose) polymerases (PARPs), and CD38 link NAD⁺ status to inflammation, oxidative stress, and tissue dysfunction in diverse clinical contexts.Methods: Peer-reviewed literature on NAD⁺ metabolism, NAD⁺-dependent signaling, and preclinical/clinical studies of NAD⁺ precursors was evaluated and organized into: (i) core biochemical functions in cellular energetics, (ii) NAD⁺ consumption in genome maintenance and immune signaling, and (iii) organ-focused evidence relevant to skin disorders, infertility and reproductive health, osteoarthritis, hearing loss, vision decline, gut barrier dysfunction, cardiovascular and renal metabolism, hepatic steatosis, neurological diseases, and skeletal muscle health.Results: NAD⁺ supports glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation, while acting as an essential substrate for PARP-driven DNA repair and sirtuin-mediated deacylation programs that shape mitochondrial fitness, inflammatory tone, and metabolic flexibility. Across experimental models, impaired NAD⁺ homeostasis repeatedly associates with mitochondrial dysfunction, heightened oxidative injury, and dysregulated immune–barrier responses, features shared by intestinal inflammation, neurodegeneration and ischemic injury, cardiometabolic disease, kidney injury, and fatty liver disease. Supplementation with NAD⁺ precursors (notably NR and NMN) reliably elevates NAD⁺ in preclinical systems and increases circulating NAD⁺ metabolites in humans, with early signals of pathway engagement; however, clinical outcomes remain heterogeneous across populations, dosing regimens, and endpoints. Evidence for intravenous NAD⁺ “drip” therapy is comparatively limited and insufficiently standardized, with constraints related to tolerability, dose consistency, and cost, underscoring the need for controlled trials.Conclusion: NAD⁺ occupies a central position at the interface of energy metabolism, genome integrity, and immunometabolic signaling, providing a coherent framework for understanding how cellular stress can propagate multisystem dysfunction. Although NAD⁺-boosting strategies are biologically plausible and mechanistically supported, definitive clinical benefit across skin, fertility, osteoarthritis, sensory decline, gut disorders, cardiovascular and hepatic disease, neurological conditions, and muscle health will require well-designed human studies with standardized biomarkers, safety surveillance, and clinically meaningful endpoints.
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Analysis and Control of a Glucose-insulin Dynamic Model

Published on: 29th January, 2026

The dynamics of the glucose-insulin regulatory system are highly nonlinear and must be understood to be controlled effectively. Bifurcation analysis and multiobjective nonlinear model predictive control (MNLMPC) are performed on a glucose-insulin dynamic model. MATCONT was used for the bifurcation analysis, and for the MNLMPC calculations, the optimization language PYOMO is used in conjunction with the solvers IPOPT and BARON. The bifurcation analysis revealed a Hopf bifurcation point and a limit point. A Hopf bifurcation point is a tipping point where a system that was behaving steadily suddenly starts to oscillate or cycle on its own, like a machine that begins to vibrate instead of staying still. A limit point is a tipping point at which pushing a system a little further suddenly causes it to jump to a completely different state, rather than changing smoothly. MNLMC converged on the Utopia solution. The Hopf bifurcation point, which leads to an unwanted limit cycle, is eliminated by an activation factor. A limit cycle is a repeating pattern of behavior that a system naturally settles into over time, like a steady heartbeat or a clock that keeps ticking. The limit point (which causes multiple steady-state solutions from a singular point enables the Multiobjective nonlinear model predictive control calculations to converge to the Utopia point (the best possible solution) in the model. A Utopia solution in multi-objective nonlinear model predictive control is an ideal operating point at which all goals are simultaneously perfectly optimized.
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Sustainable Weight Loss and Body Composition Improvement through Intensive Lifestyle Modification with Meal Replacement: A 12-Case Series with International Perspectives

Published on: 13th April, 2026

Background: Obesity is one of the most pressing global health challenges, with over one billion people now living with the condition worldwide. In Southeast Asia, nearly 40% of the population is projected to be overweight or obese by 2035, with Thailand reporting prevalence exceeding 42%. Intensive Lifestyle Modification (ILM) combined with Meal Replacement (MR) has emerged as a promising strategy for achieving sustainable weight loss, supported by landmark trials including the Diabetes Prevention Program, Look AHEAD, and DiRECT.Objective: To illustrate the clinical effectiveness of ILM combined with MR through detailed case presentations documenting anthropometric outcomes at baseline, 8 weeks, and 52 weeks, contextualized within international obesity management guidelines and comparative research across diverse populations. We hypothesized that selected participants undergoing the ILM+MR intervention would demonstrate clinically significant weight loss (≥5% of initial body weight) sustained through 52 weeks, with concurrent improvements in waist circumference indicating reduced central adiposity.Methods: Twelve participants (9 female, 3 male) from the ILM+MR arm of a previously published retrospective cohort study (n = 702) were selected based on complete longitudinal data and representativeness. The intervention comprised structured nutritional counseling, soy-based MR (220 kcal per serving, twice daily for 8 weeks), behavioral modification with group therapy, and physical activity guidance aligned with the 2013 AHA/ACC/TOS guidelines. Body weight and waist circumference were measured at baseline, 8 weeks, and 52 weeks.Results: Mean total weight loss was 38.2 kg (35.3% of initial body weight), with mean waist circumference reduction of 13.0 inches (33.0 cm) over 52 weeks. All 12 participants achieved clinically significant weight loss (>5%), substantially exceeding the 5–10% threshold recommended by international guidelines. Weight loss occurred in two phases: a rapid intensive phase (mean 14.0 kg during weeks 0–8) followed by continued loss during maintenance (mean 24.2 kg during weeks 8–52). All participants completed the 52-week follow-up.Conclusion: This case series demonstrates the potential for substantial, sustained weight loss through ILM+MR intervention, supporting findings from the larger Thai cohort study and international research including the DiRECT trial and systematic meta-analyses. These results reaffirm the foundational role of comprehensive lifestyle programs and highlight their relevance as scalable, culturally adaptable interventions for obesity management across diverse populations.
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