Unlock better health with chiropractic restoration and metabolic health practices for improved metabolic function.
Table of Contents
Abstract
In modern clinical practice, conditions such as atherosclerotic cardiovascular disease, dilated cardiomyopathy, type 2 diabetes mellitus, and neurodegenerative disorders including Alzheimer’s disease share a common upstream driver rooted in mitochondrial bioenergetic failure and the progressive depletion of the essential coenzyme nicotinamide adenine dinucleotide (NAD+). This educational post, written from the clinical perspective of Dr. Alexander Jimenez, DC, APRN, FNP-BC, CFMP, IFMCP, ATN, CCST, synthesizes contemporary research on NAD+ biology with practical insights from integrative care. It examines how NAD+ functions both as a redox cofactor supporting ATP production through glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation, and as a consumable cosubstrate for sirtuins, poly(ADP-ribose) polymerases, and CD38. Landmark preclinical investigations from leading researchers, including work published between 2016 and 2020 in journals such as Nature Communications, the Journal of Neuroscience, and Cell, demonstrate that restoring NAD+ pools can mitigate plaque burden, reverse aspects of cardiomyopathy in animal models, improve insulin sensitivity, and support neuronal resilience. The discussion integrates these findings with the multidisciplinary approach at Injury Medical Clinic PA (also known as Mission Plaza Injury Medical Clinic) in El Paso, Texas, where Dr. Jimenez collaborates with Dr. Maria Guadalupe Cardenas, MD, Board Certified in Internal Medicine (NPI #1164426749, Texas MD License #J2933). With more than 40 years of experience as an internist, Dr. Cardenas serves as Medical Director and Collaborative Physician, providing medical oversight that complements chiropractic care, functional medicine strategies, rehabilitation, and personal injury protocols. The post explains the physiological rationale for non-surgical interventions that address spinal alignment, autonomic tone, inflammation, and cellular energy restoration to support patient outcomes.
Introduction to Integrative Care at Injury Medical Clinic PA
At Injury Medical Clinic PA in El Paso, Texas, patients presenting with musculoskeletal pain, fatigue, metabolic concerns, cardiovascular risk factors, or cognitive changes often reveal interconnected physiological disruptions when evaluated through a systems lens. Dr. Alexander Jimenez, DC, APRN, FNP-BC, CFMP, IFMCP, ATN, CCST, leads chiropractic and functional approaches focused on spinal integrity, biomechanical efficiency, and metabolic optimization. Dr. Maria Guadalupe Cardenas, MD, brings more than four decades of internal medicine expertise and works collaboratively. As Medical Director and Collaborative Physician, she provides medical direction, oversees complex cases, evaluates systemic inflammation and metabolic parameters, and ensures that integrative strategies remain aligned with established medical standards.
This multidisciplinary model is standard in many integrative and injury-focused clinics. Chiropractic care delivered by Dr. Jimenez addresses spinal subluxations, soft-tissue dysfunction, and autonomic imbalance that can perpetuate pain and elevate stress hormones. Dr. Cardenas’s medical oversight includes internal medicine evaluation of blood pressure, glycemic control, lipid profiles, and inflammatory markers. Functional medicine elements, including targeted nutrition and lifestyle modification, complement both. Rehabilitation protocols restore strength and mobility, while personal injury care includes thorough documentation for motor-vehicle or workplace incidents. The result is coordinated, patient-centered plans that prioritize non-surgical recovery by reducing mechanical stress, supporting tissue healing, and addressing underlying cellular energy deficits observed clinically at the practice and documented through perspectives available at Health Voice 360.
Clinical observations frequently show that patients with chronic soft-tissue inflammation or post-injury fatigue exhibit signs consistent with impaired mitochondrial ATP generation. Restoring foundational cellular physiology alongside structural care often accelerates functional gains. This post explores NAD+ dynamics as one pillar of that approach, drawing on evidence from leading researchers while staying grounded in practical, supervised clinical application.
The Dual Nature of NAD+ in Cellular Energy and Signaling
Every physiological process, from skeletal muscle contraction to DNA repair, depends on enzymes that accelerate biochemical reactions at body temperature. An inactive apoenzyme becomes a functional holoenzyme only after binding its cofactor. Among cofactors, NAD+ stands out for its versatility. British biochemists Arthur Harden and William John Young identified it in 1906 as a dialyzable factor that accelerates yeast fermentation (Harden & Young, 1906). Modern understanding recognizes two primary roles.
In redox reactions, NAD+ accepts a hydride ion to become NADH. This cycle powers glycolysis at the glyceraldehyde-3-phosphate dehydrogenase step, supports pyruvate dehydrogenase activity that converts pyruvate to acetyl-CoA, drives oxidative decarboxylation steps in the tricarboxylic acid cycle, and enables beta-oxidation of fatty acids. NADH then donates electrons to Complex I of the electron transport chain. The resulting proton gradient drives ATP synthesis at Complex V. Without adequate NAD+/NADH cycling, cells cannot efficiently extract energy from carbohydrates, fats, or proteins.
In non-redox signaling, NAD+ is cleaved. Sirtuins (SIRT1 through SIRT7) use NAD+ to deacetylate proteins that regulate mitochondrial biogenesis, oxidative stress resistance, and metabolic gene expression. Poly(ADP-ribose) polymerases, especially PARP1, consume large amounts of NAD+ to recruit DNA repair machinery after single-strand breaks. CD38 and related ectoenzymes generate cyclic ADP-ribose and other messengers that influence calcium flux and immune signaling. Because these pathways destroy NAD+ rather than recycle it, high activity under chronic inflammation or DNA damage can rapidly deplete the pool.
Targeted restoration strategies are explored for one reason: when NAD+ falls, both ATP production and sirtuin-mediated protection decline, and DNA repair becomes inefficient. Clinical observations at the practice often link patient reports of persistent fatigue or slow recovery after injury to this dual impairment.
NAD+ Biosynthetic Pathways and Age-Related Decline
Mammalian cells maintain NAD+ through three main routes. The salvage pathway predominates in most tissues. Nicotinamide released after sirtuin or PARP activity is converted by the rate-limiting enzyme nicotinamide phosphoribosyltransferase (NAMPT) to nicotinamide mononucleotide (NMN), which is then adenylated by NMNAT enzymes localized in the nucleus, cytosol, or mitochondria. The Preiss-Handler pathway incorporates dietary nicotinic acid. The de novo kynurenine pathway begins with tryptophan and converges on the same downstream intermediates.
Steady-state NAD+ levels decline substantially with chronological age, often by 50 percent or more across tissues. Two mechanisms drive this: reduced NAMPT expression due to chronic low-grade inflammation and circadian disruption, and increased consumption by CD38 on aging macrophages and by PARP1 in response to accumulated DNA damage (Camacho-Pereira et al., 2016; Covarrubias et al., 2021). The physiological consequence is progressive loss of metabolic flexibility. Cells produce more reactive oxygen species, mitophagy falters, and genomic maintenance slows.
Researchers have therefore tested whether replenishing the pool with precursors or directly administering NAD+ can interrupt this trajectory. The rationale is that restoring substrate availability reactivates sirtuin-mediated protection and improves redox balance without requiring perfect upstream conditions.
Atherosclerotic Cardiovascular Disease and NAD+ Restoration
Atherosclerosis remains the leading cause of premature cardiovascular death. It begins with endothelial dysfunction under shear stress, oxidized low-density lipoprotein, or inflammatory cytokines. Endothelial nitric oxide synthase (eNOS) normally produces nitric oxide from L-arginine, using tetrahydrobiopterin as a cofactor. When NAD+ is low, SIRT1 cannot efficiently deacetylate eNOS at key lysine residues. The enzyme becomes uncoupled, transfers electrons to oxygen, and generates superoxide instead of nitric oxide. Superoxide reacts with nitric oxide to form peroxynitrite, which further oxidizes tetrahydrobiopterin and locks the endothelium into a dysfunctional state.
Circulating monocytes then adhere via upregulated VCAM-1 and ICAM-1, enter the intima, and differentiate into macrophages. These cells internalize oxidized LDL through scavenger receptors, become foam cells, secrete matrix metalloproteinases that weaken the fibrous cap, and undergo defective clearance. A necrotic core forms and plaque instability increases.
A 2016 study showed that administering a systemic NAD+ precursor reduced plaque volume and inflammatory burden in hyperlipidemic models (Braidy et al., 2016). Mechanistically, restored macrophage SIRT1 suppressed NF-?B activity, lowered cytokine production, and improved reverse cholesterol transport through ABCA1. SIRT3-mediated deacetylation of superoxide dismutase 2 reduced mitochondrial reactive oxygen species. Researchers study these interventions because they simultaneously address endothelial uncoupling, macrophage inflammation, and oxidative stress at the vessel wall—processes that conventional lipid-lowering strategies do not fully reverse.
In the clinic, Dr. Jimenez integrates chiropractic care to optimize spinal alignment and reduce excessive sympathetic tone that can elevate systemic cortisol and inflammatory signaling. Dr. Cardenas provides medical oversight of lipid subfractions, high-sensitivity C-reactive protein, and blood pressure, ensuring that any supportive strategies align with established cardiovascular risk management.
Cardiac Bioenergetics and Dilated Cardiomyopathy
The adult myocardium consumes roughly 6 kg of ATP daily. Mitochondria occupy 30 to 40 percent of cardiomyocyte volume. Under normal conditions, the heart flexibly oxidizes fatty acids (60–90 percent) and glucose or ketones. In dilated cardiomyopathy, the myocardium shifts toward inefficient glycolysis, Complex I destabilizes and leaks electrons, SERCA2a fails to reuptake calcium under energy shortage, and the mitochondrial permeability transition pore opens, releasing cytochrome c and triggering apoptosis.
Karamanlidis, Lee, and colleagues (2019) showed in Nature Communications that myocardial NAD+ depletion, driven by reduced NAMPT and elevated CD38/PARP activity, produces hyperacetylation of Complex I subunits and superoxide dismutase 2. Subcutaneous NAD+ precursor administration normalized pools, reactivated SIRT3, restored electron transport, reduced fibrosis, reversed left-ventricular dilation, and improved ejection fraction in animal models. The physiological rationale is that correcting the NAD+/NADH ratio re-enables sirtuin-dependent quality control and antioxidant defense precisely where energy demand is highest.
Clinical observations frequently note that patients with cardiac risk factors or post-injury deconditioning also report musculoskeletal fatigue consistent with systemic bioenergetic strain. Non-surgical chiropractic adjustments improve biomechanical efficiency and can lower resting sympathetic drive, thereby reducing an additional stressor on cardiac workload while rehabilitation rebuilds aerobic capacity under medical supervision.
Type 2 Diabetes as a Mitochondrial and NAD+ Disorder
Type 2 diabetes is increasingly recognized as a disease of impaired mitochondrial fuel switching and NAD+ depletion rather than solely peripheral carbohydrate intolerance. In pancreatic beta cells, glucose enters, undergoes glycolysis, and generates NADH that drives ATP production. The rising ATP/ADP ratio closes ATP-sensitive potassium channels, depolarizes the membrane, opens voltage-gated calcium channels, and triggers insulin exocytosis. When NAD+ is low, this coupling fails, and oxidative stress increases beta-cell apoptosis.
In skeletal muscle and adipose tissue, insulin normally activates the insulin receptor, phosphorylates IRS-1 on tyrosine residues, and promotes GLUT4 translocation through PI3K/Akt. Under nutrient excess, mitochondrial electron leakage generates reactive oxygen species; incomplete fatty-acid oxidation accumulates diacylglycerols and ceramides. These activate PKC-? and JNK, which phosphorylate IRS-1 on serine residues, blocking downstream signaling so that GLUT4 remains sequestered. Hepatic gluconeogenesis becomes dysregulated when SIRT1 cannot deacetylate FOXO1.
A 2019 Nature Communications report showed that subcutaneous NAD+ repletion restored SIRT1 and SIRT3 activity, improved PGC-1?-driven mitochondrial biogenesis, cleared toxic lipid intermediates, suppressed stress kinases, and normalized glucose-stimulated insulin secretion and peripheral sensitivity in diabetic models (Lee et al., 2019). The reasoning is that correcting the upstream bioenergetic deficit removes the triggers for serine phosphorylation and inflammatory transcription rather than merely forcing glucose uptake.
In practice, continuous glucose monitoring and HOMA-IR assessment under Dr. Cardenas’s medical direction identify metabolic inflexibility. Chiropractic care and structured rehabilitation reduce physical stress that can elevate cortisol and further impair insulin action, while nutritional strategies support endogenous NAD+ salvage.
Alzheimer’s Disease as Bioenergetic Failure and Type 3 Diabetes
The brain accounts for about 2 percent of body weight yet consumes more than 20 percent of resting glucose and oxygen. Neurons in the hippocampus and neocortex require continuous ATP to maintain membrane potential, support synaptic transmission, and enable plasticity. When neuronal NAD+ declines, mitochondrial electron transport uncouples, reactive oxygen species rise, BACE1 is upregulated, and amyloid precursor protein is processed toward toxic amyloid-beta oligomers. Concurrently, SIRT1 inactivation and GSK-3? activation drive tau hyperphosphorylation, microtubule destabilization, and neurofibrillary tangle formation. Defective mitophagy allows damaged mitochondria to accumulate and propagate inflammation.
Cheng and colleagues (2018) in the Journal of Neuroscience demonstrated that NAD+ repletion activated mitochondrial SIRT3, deacetylated superoxide dismutase 2 and isocitrate dehydrogenase 2, reduced reactive oxygen species, preserved synaptic architecture, and protected hippocampal neurons from apoptosis in Alzheimer’s models. Fang and colleagues (2020) in Cell showed that subcutaneous NAD+ administration restored PINK1/Parkin-mediated mitophagy and SIRT1-PGC-1? biogenesis, reversed cognitive deficits, and halted structural neurodegeneration in preclinical systems. The rationale is that amyloid and tau pathology are downstream consequences of energy failure; restoring mitochondrial quality control interrupts the cascade earlier than plaque-clearing approaches alone have achieved.
Clinical observations note that patients with chronic pain or post-concussive symptoms often describe cognitive fog consistent with impaired cerebral energetics. Spinal care that improves autonomic balance and reduces systemic inflammation, combined with medical evaluation of metabolic contributors, forms part of a non-surgical supportive framework.
The Unified Triad of Inflammation, Insulin Resistance, and Mitochondrial Dysfunction
Chronic degenerative conditions converge on a triad. Systemic inflammation sustains NF-?B and NLRP3 activity, elevates CD38, and accelerates NAD+ consumption. Insulin resistance generates lipid intermediates and reactive oxygen species that further impair mitochondrial function. Damaged mitochondria release mitochondrial DNA that activates cGAS-STING and amplifies inflammasome signaling. NAD+ depletion sits at the center: sirtuins cannot maintain quality control, PARP cannot complete DNA repair, and mitophagy fails.
Addressing any single node in isolation yields incomplete results. The clinical rationale for multimodal care is that spinal alignment and reduced mechanical pain lower sympathetic drive and cortisol, reducing one driver of CD38 upregulation; medical oversight manages glycemic and inflammatory markers; and targeted support for NAD+ pathways restores the enzymatic capacity needed for repair.
Clinical Translation of Bioenergetic Support in Non-Surgical Care
In practice, evaluation begins with advanced biomarkers: lipoprotein particle number and ApoB, high-sensitivity C-reactive protein, fasting insulin and HOMA-IR, organic acid testing of tricarboxylic acid cycle intermediates, and, when accessible, NAD+/NADH ratios. Dr. Cardenas’s medical team interprets these data to guide personalized plans.
Restorative strategies include evidence-informed NAD+ precursor or subcutaneous protocols tailored to tolerance, polyphenolic sirtuin activators such as resveratrol or quercetin, CD38 inhibition with compounds such as apigenin, time-restricted eating that activates AMPK and upregulates NAMPT, Zone 2 training that drives PGC-1?-mediated biogenesis, and high-intensity intervals that challenge respiratory capacity. Chiropractic adjustments correct segmental dysfunction, improve proprioceptive input, and reduce nociceptive drive that would otherwise maintain elevated sympathetic tone and inflammatory signaling. Rehabilitation rebuilds muscular efficiency so that daily activities no longer impose disproportionate energetic cost. Each element is included because it either increases NAD+ supply, decreases unnecessary consumption, restores mitochondrial quality control, or removes an extrinsic stressor that accelerates decline.
Outcome monitoring uses continuous glucose profiles, cardiopulmonary exercise metrics, and functional mobility scores. Clinical observations recorded in Health Voice 360 consistently show that patients who combine structural care with metabolic support report improved energy, reduced pain, and greater resilience during recovery from injury or chronic conditions.
Summary of Molecular Interventions and Clinical Implications
Targeted NAD+ repletion has been shown in preclinical models to reduce atherosclerotic plaque burden and stabilize fibrous caps by restoring eNOS coupling and macrophage efflux pathways; to reverse established dilated cardiomyopathy by deacetylating Complex I and superoxide dismutase 2 while normalizing calcium handling; to restore insulin-receptor tyrosine phosphorylation and GLUT4 translocation in type 2 diabetes models; and to support mitophagy, suppress amyloidogenic processing, and recover cognitive performance in neurodegeneration models. These findings, drawn from leading research groups, provide a mechanistic foundation for considering cellular bioenergetics within comprehensive, supervised care.
The decline of NAD+ with age is not merely a passive byproduct; it actively contributes to metabolic, cardiovascular, and neurological vulnerability. Integrating chiropractic care that optimizes biomechanical and autonomic function with medical oversight of systemic parameters and functional strategies that support endogenous and exogenous NAD+ pathways offers a coherent, non-surgical framework for promoting cellular repair and functional resilience.
References
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Medical Disclaimer
The information in this educational post is for informational purposes only and does not constitute medical advice, diagnosis, or treatment. Individual circumstances vary. Any consideration of NAD+ support, nutritional changes, fasting protocols, or rehabilitative strategies must be reviewed and supervised by a qualified healthcare professional. Dr. Alexander Jimenez, DC, APRN, FNP-BC, CFMP, IFMCP, ATN, CCST, Dr. Maria Guadalupe Cardenas, MD, and Injury Medical Clinic PA expressly disclaim liability for any loss or risk incurred from the use of material presented here.
