Nicotinamide and Pyridoxine in Muscle Aging: Nutritional Regulation of Redox, Inflammation, and Regeneration

Abstract

Sarcopenia, the progressive loss of muscle mass, strength, and regenerative capacity with age, is driven by interconnected processes such as oxidative stress, chronic inflammation, mitochondrial dysfunction, and reduced activity of muscle stem cells. As the population ages, nutritional strategies that target these mechanisms are becoming increasingly important. This review focuses on nicotinamide (vitamin B3) and pyridoxine (vitamin B6), two essential micronutrients found in functional foods, which play complementary roles in redox regulation, immune balance, and muscle repair. Nicotinamide supports nicotinamide adenine dinucleotide (NAD⁺) metabolism, boosts mitochondrial function, and activates sirtuin pathways involved in autophagy and stem cell maintenance. Pyridoxine, via its active form pyridoxal 5'-phosphate (PLP), is key to amino acid metabolism, antioxidant defense, and the regulation of inflammatory cytokines. We summarize how these vitamins influence major molecular pathways such as Sirtuin1 (SIRT1), protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), Nuclear factor-κB (NF-κB), and Nrf2, contributing to improved myogenic differentiation and protection of the aging muscle environment. We also highlight emerging preclinical and clinical data, including studies suggesting possible synergy between B3 and B6. Finally, we discuss how biomarkers such as PLP, nicotinamide mononucleotide (NMN), and C-reactive protein (CRP) may support the development of personalized nutrition strategies using these vitamins. Safe, accessible, and mechanistically grounded, nicotinamide and pyridoxine offer promising tools for sarcopenia prevention and healthy aging.

Keywords: inflammaging; muscle regeneration; muscle stem cells; nicotinamide; nicotinamide adenine dinucleotide (NAD+) metabolism; nutritional intervention; pyridoxine; sarcopenia.

Figure 1

Multifactorial contributors to sarcopenia. Sarcopenia results from interconnected molecular and systemic factors, including mitochondrial dysfunction, hormonal dysregulation, chronic inflammation, neuromuscular and neurological impairment, as well as lifestyle-related contributors such as poor diet, obesity, and physical inactivity. Age-related decline and genetic predisposition further exacerbate muscle loss and functional impairment.

Figure 2

Structural organization of skeletal muscle and localization of satellite cells. This diagram illustrates the anatomical relationship between bones, joints, and skeletal muscles, emphasizing the microarchitecture of muscle fibers. Within the enlarged view, muscle fibers are shown alongside capillary networks (blood vessels) and quiescent satellite cells situated between the basal lamina and sarcolemma. Satellite cells are essential for muscle regeneration and respond to injury or metabolic stress by activating, proliferating, and differentiating into myogenic progenitors. This close spatial association with blood vessels ensures access to nutrients, oxygen, and signaling molecules, critical for regenerative responses in both physiological and pathological conditions such as aging and sarcopenia.

Figure 3

Cellular consequences of aging in muscle stem cells. This schematic compares a young muscle stem cell with an aged stem cell, highlighting the intracellular hallmarks of aging. In youthful cells, mitochondria, protein folding, and autophagy pathways are intact, enabling effective energy production, repair, and proteostasis. With aging, stem cells accumulate protein aggregates, exhibit impaired autophagy, and suffer mitochondrial damage. These changes lead to oxidative stress (↑ Reactive Oxygen Species ROS), DNA damage, and reduced regenerative capacity. Dysfunctional lysosomes and endoplasmic reticulum contribute to further metabolic decline. Collectively, these disruptions impair satellite cell homeostasis, contributing to sarcopenia and diminished muscle repair.

Figure 4

NAD⁺-dependent metabolic and regulatory pathways influenced by nicotinamide in aging skeletal muscle. Nicotinamide supports redox balance, energy metabolism, and gene regulation through its role in NAD⁺ homeostasis. NAD⁺ fuels dehydrogenase activity in key metabolic pathways, supports antioxidant regeneration via NADPH, and regulates sirtuin- and PARP-mediated cellular processes. Age-related NAD⁺ decline, driven by increased CD38 and reduced NAMPT levels, impairs mitochondrial function, increases inflammation, and reduces muscle regeneration.

Figure 5

Integrative framework for the role of nicotinamide (B3) and pyridoxine (B6) in skeletal muscle regeneration. This conceptual diagram illustrates a multifactorial strategy through which nicotinamide and pyridoxine support muscle regeneration and help counteract sarcopenia. Nicotinamide interacts synergistically with resistance exercise to enhance NAD⁺ synthesis via the SIRT1–NAMPT pathway, while pyridoxine acts in concert with amino acids and micronutrients to improve redox balance and metabolic regulation. Key factors such as the food matrix, timing of intake, and delivery form influence vitamin uptake and bioefficacy. Precision nutrition approaches, guided by biomarkers (e.g., PLP, NMN, and CRP) and individual phenotypic profiling, enable targeted intervention design. Integration with lifestyle factors such as resistance training, anti-inflammatory dietary patterns, and adequate protein intake further amplifies the regenerative impact. This framework highlights the importance of combining molecular, nutritional, and behavioral components for optimal muscle health in aging.