NAD+ Cream

NAD ⁺ exhibits cell specificity and regional differential distribution in the brain, with the highest concentration in the core functional area
Neurons: Neurons in the cortex, hippocampus, thalamus, and cerebellar granule layer have the highest NAD ⁺ content, especially in the presynaptic membrane and mitochondria, which directly support synaptic transmission and energy supply.
Glial cells: Astrocytes and microglia have moderate NAD ⁺ levels and are mainly involved in the regulation of neuroinflammation, metabolic support, and injury repair; Oligodendrocytes rely on NAD ⁺ to maintain myelin synthesis and integrity.

Vascular endothelial cells: Brain microvascular endothelial cells highly express NAMPT (NAD ⁺ synthesis rate limiting enzyme), which is the main source of NAD ⁺ in the blood-brain barrier (BBB) and regulates BBB permeability and substance transport.
Regional differences: The concentration of NAD ⁺ in the CA1-CA3 area of the hippocampus and the prefrontal cortex is significantly higher than in other brain regions, and is highly correlated with learning, memory, and executive function; The concentration in the brainstem and spinal cord is low, with a focus on basic nerve conduction.

NAD ⁺ in the brain cannot penetrate the blood-brain barrier and relies entirely on in situ synthesis, with remedial pathways accounting for over 95%. Neurons and glial cells form a metabolic synergy network:
Remedial synthesis pathway (core): Using nicotinamide (NAM) as a precursor, NMN is generated through NAMPT catalysis, and then converted to NAD ⁺ through NMNAT; Neurons highly express NAMPT, but their activity drops sharply during aging or injury, leading to NAD depletion.
Neuron astrocyte metabolic coupling: Neuronal activity releases NAM, which is taken up by astrocytes to synthesize NMN, which is then transported back to neurons to generate NAD+, forming the NAD ⁺ cycle and maintaining neuronal energy homeostasis.

De novo synthesis pathway (secondary): using tryptophan as raw material, synthesized in the liver and glial cells with extremely low efficiency, only activated in severe deficiency.
Degradation pathways: CD38, PARP, Sirtuins are the main consuming enzymes: PARP activation (DNA damage) can rapidly deplete NAD ⁺; CD38 increases with age and accelerates NAD ⁺ hydrolysis; Sirtuins consume NAD ⁺ to generate NAM and return to the remedial cycle.

Neurons are high energy consuming and lack energy reserves. The brain consumes 20% of the body's oxygen and energy, relying entirely on NAD ⁺ - mediated mitochondrial oxidative phosphorylation to generate ATP, which is the fundamental guarantee for the survival of neurons.
Glucose metabolism coupling: Neurons take up glucose, which undergoes glycolysis to produce pyruvate, which enters mitochondria and undergoes the tricarboxylic acid cycle to produce NADH; NADH transfers electrons through the electron transfer chain (ETC), driving a proton gradient and ultimately generating ATP -1 molecule of NADH generates 2.5 molecules of ATP, with NAD ⁺ levels directly determining neuronal productivity efficiency.

Synaptic energy supply: ATP is required for presynaptic membrane neurotransmitter release, postsynaptic membrane receptor activation, and ion channel transport; When NAD ⁺ is insufficient, synaptic transmission efficiency decreases, neurotransmitter synthesis decreases, leading to a decline in learning and memory abilities and delayed responses.
Mitochondrial function maintenance: NAD+ Cream activates SIRT3, deacetylates mitochondrial complexes I-III and ATP synthase, enhances ETC efficiency, reduces electron leakage and ROS generation; During aging, NAD ⁺ decreases, mitochondrial structure is disrupted, ATP production is insufficient, ROS bursts occur, leading to neuronal energy depletion and apoptosis.

Neuronal terminal differentiation and inability to divide, DNA damage cannot be repaired through cell division, relying on PARP enzyme mediated repair mechanism; NAD ⁺ is the only substrate of PARP, providing "fuel" for DNA repair and maintaining neuronal genome integrity.
DNA single strand break repair: Oxidative stress, radiation, and neurotoxic substances (such as A β) cause DNA single strand breaks, and PARP is rapidly activated, consuming NAD ⁺ to generate poly ADP ribose (PAR). Repair proteins such as XRCC1 and DNA ligase are recruited to complete the repair; Each repair consumes 1 molecule of NAD ⁺, and when the damage is severe, NAD ⁺ is greatly depleted.

DNA double strand break repair: PARP collaborates with BRCA1/2 to repair double strand breaks. When NAD ⁺ is insufficient, repair fails, causing gene mutations, chromosomal abnormalities, and accelerating neuronal aging and death.
Telomere protection: NAD ⁺ activates SIRT1/SIRT6, inhibits telomerase reverse transcriptase (TERT) degradation, and maintains telomere length; During aging, NAD ⁺ decreases, telomeres shorten rapidly, and neurons enter the aging/apoptosis program.
RNA splicing error correction (new mechanism): Research in 2025 has confirmed that NAD ⁺ corrects RNA splicing errors by regulating the EVA1C protein, reversing neuronal damage and memory loss caused by tau protein aggregation; In the brain tissue of early AD patients, the level of EVA1C is significantly reduced, and supplementing NAD ⁺ can restore its expression and repair RNA splicing defects.

The brain has a high oxygen environment, high lipid content, and low expression of antioxidant enzymes, making it highly susceptible to attacks from reactive oxygen species (ROS); NAD ⁺ constructs a neuronal "antioxidant barrier" through a triple mechanism of direct antioxidant activity, activation of the antioxidant system, and inhibition of ROS generation.
NADPH mediated reduction antioxidant: NAD ⁺ is converted into NADPH through the pentose phosphate pathway (PPP), which acts as a glutathione reductase coenzyme to reduce oxidized glutathione (GSSG) to reduced glutathione (GSH) - the strongest antioxidant in neurons. It clears free radicals, lipid peroxides, and toxic metabolites, protecting cell membranes, proteins, and DNA from oxidative damage.

Inhibition of ROS generation: NAD ⁺ activates SIRT3, deacetylates mitochondrial complexes I/III, reduces electron leakage, and lowers ROS production; During aging, NAD ⁺ decreases, ROS accumulates, leading to oxidative stress cascade damage, resulting in neuronal membrane lipid peroxidation, protein carbonylation, and DNA breakage.
Anti neurotoxic substance oxidation: NAD ⁺ inhibits the oxidative aggregation of A β and tau proteins, reducing the formation of toxic oligomers; A β oligomers can induce ROS bursts, further depleting NAD ⁺ and forming a toxic cycle. Supplementing NAD ⁺ can block this cycle.

Chronic neuroinflammation is the core pathological feature of neuroaging, cognitive decline, and neurodegenerative diseases; NAD ⁺ regulates the polarization of microglia, inhibits pro-inflammatory signals, promotes the secretion of anti-inflammatory factors, balances central immune responses, and reduces inflammatory damage.

Polarization regulation of microglia: Microglia are central "immune sentinels" that can polarize into M1 type (pro-inflammatory, cytotoxic) and M2 type (anti-inflammatory, reparative);

NAD ⁺ activates the SIRT1/NF - κ B pathway, inhibits M1 polarization (reduces TNF - α, IL-1 β, IFN - γ release), promotes M2 polarization (increases IL-10, TGF - β secretion), alleviates neuroinflammation, and accelerates tissue repair.

Inhibition of astrocyte inflammation: NAD ⁺ inhibits the release of pro-inflammatory cytokines and overexpression of glial fibrillary acidic protein (GFAP) in astrocytes, reduces glial scar formation, and maintains stable neuronal microenvironment.
Blood brain barrier (BBB) inflammation protection: NAD ⁺ protects brain microvascular endothelial cells through the CX43-PARP1-NAD ⁺ pathway, inhibits BBB leakage induced by inflammatory factors, reduces peripheral immune cell and toxic substance invasion into brain tissue, and alleviates neuroinflammation.

The blood-brain barrier (BBB) is a selective barrier in the brain that prevents the invasion of peripheral toxins, maintains ion balance in the brain, and regulates nutrient transport; BBB leakage during aging and neurological disorders can lead to neuroinflammation, neuronal damage, and cognitive decline.
Maintenance of endothelial cell function: NAD ⁺ activates SIRT1, promotes nitric oxide (NO) synthesis, dilates cerebral blood vessels, and improves cerebral microcirculation; Inhibit endothelial cell apoptosis and maintain BBB structural integrity.

Regulation of tight junction proteins: NAD ⁺ upregulates the expression of tight junction proteins (ZO-1, occludin, claudin-5), enhances BBB tight junction, and reduces leakage; During aging, NAD ⁺ decreases, tight junction proteins degrade, and BBB permeability increases.
Pericytes protection: NAD ⁺ protects brain microvascular pericytes (key cells maintaining BBB stability), inhibits apoptosis and fibrosis of pericytes, and ensures normal BBB function.

The increase and decrease in neuronal apoptosis are the direct causes of cognitive decline and neurodegenerative diseases; NAD ⁺ promotes neuronal survival by regulating the apoptotic pathway, activating survival signals, inhibiting autophagy abnormalities.
Activation of anti apoptotic signals: NAD ⁺ activates SIRT1, deacetylates apoptotic proteins such as p53 and FoxO3a, inhibits the expression of pro apoptotic factors (Bax, caspase-3), upregulates anti apoptotic factor (Bcl-2), blocks mitochondrial apoptosis pathway, and reduces neuronal apoptosis.

Autophagy regulation: NAD+ Cream  activates the SIRT3/AMPK pathway, promoting physiological autophagy (clearing damaged mitochondria and toxic proteins), inhibiting pathological autophagy (excessive autophagy leading to neuronal death), and maintaining neuronal homeostasis.
Neurotrophic factor promotion: NAD ⁺ upregulates the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), activates TrkB/PI3K/Akt survival signals, and promotes neuronal survival, proliferation, and differentiation.