CaffeinevsNALT

Caffeine is a non-selective adenosine receptor antagonist with highest affinity for A1 and A2A subtypes. Adenosine accumulates during wakefulness and promotes sleepiness by binding to A1 receptors (inhibiting adenylyl cyclase and reducing neuronal excitability) and A2A receptors (modulating dopamine D2 receptor signaling in striatum). Caffeine competitively blocks these receptors, preventing the drowsiness signal. This disinhibition indirectly increases dopamine, norepinephrine, and acetylcholine neurotransmission via downstream pathways. Caffeine also inhibits phosphodiesterase (PDE) enzymes—particularly PDE4 in the brain—reducing cAMP degradation. Elevated intracellular cAMP amplifies catecholamine signaling through PKA-mediated phosphorylation of CREB and other transcription factors, enhancing alertness and cognitive performance.

NALT (N-acetyl L-tyrosine) is deacetylated by aryl acylamidase in the gut and liver to release L-Tyrosine. Tyrosine is hydroxylated to L-DOPA by tyrosine hydroxylase (TH) — the rate-limiting step in catecholamine synthesis, requiring tetrahydrobiopterin as cofactor. L-DOPA is decarboxylated by aromatic L-amino acid decarboxylase (AADC) to dopamine; dopamine is converted to norepinephrine by dopamine beta-hydroxylase (DBH), and norepinephrine to epinephrine by phenylethanolamine N-methyltransferase (PNMT). Under stress or sleep deprivation, catecholamine stores in noradrenergic and dopaminergic neurons deplete rapidly. Supplemental tyrosine provides substrate to maintain synthesis when demand exceeds supply, supporting prefrontal cortex function and working memory.