Taurine

Cheap, broad-spectrum amino acid with A-tier evidence for cardiovascular function (BP, heart rate, LVEF in heart failure), B-tier for endurance and mild calm. Subjective effects are subtle — this is insurance, not stimulation. The 2023 Yadav longevity paper is now contested by a 2025 NIA reanalysis, but cardiovascular/metabolic benefits do not depend on the longevity claim. For Dylan: STRONG-CANDIDATE at 1-2g/day pre-workout or pre-bed.

Taurine is a sulfur-containing amino acid synthesized endogenously from cysteine via two enzymes — CDO1 (cysteine dioxygenase, rate-limiting) and CSAD (cysteine sulfinic acid decarboxylase). Humans synthesize less than mice, making dietary intake more functionally relevant. It is the most abundant free amino acid in heart, retina, white blood cells, and skeletal muscle.

It does not work through one receptor — it has a portfolio of distinct mechanisms:

1. Cellular osmolyte and membrane stabilizer. Regulates cell volume in brain, retina, muscle, and white blood cells. Stabilizes membrane potential by interfering with Na+/K+-ATPase. This is its most fundamental and oldest-evolved role.

2. Weak GABA-A receptor agonist (extrasynaptic δ-subunit). Lower affinity than GABA itself but produces real chloride influx and tonic inhibition in thalamic relay neurons. This is the basis of its mild calming/anxiolytic profile. Chronic taurine intake also upregulates GAD (glutamate decarboxylase), increasing endogenous GABA synthesis.

3. Cardiac calcium handling. Modulates L-type calcium channels, ryanodine receptors, and Na+/Ca2+ exchangers. Prevents calcium overload during ischemia-reperfusion. Taurine-transporter knockout mice develop cardiomyopathy — proof-of-concept that taurine is structurally required for cardiac function.

4. Mitochondrial protection. Conjugates with uridine on mitochondrial tRNAs (5-taurinomethyluridine), required for proper translation of mitochondrial-encoded proteins (especially ETC complex I subunits). Loss of mitochondrial taurine = MELAS-syndrome-like respiratory chain failure. Also scavenges hypochlorous acid (HOCl) to form N-chlorotaurine, reduces superoxide, and inhibits mitochondrial-permeability-transition-pore opening.

5. Bile acid conjugation. Conjugates with cholic and chenodeoxycholic acid in the liver to form taurocholate / taurochenodeoxycholate. In humans, glycine conjugation dominates ~3:1, but taurine conjugates are more water-soluble at low pH and resist deconjugation by gut bacteria better.

6. Anti-inflammatory. Suppresses NF-kB; reduces pro-inflammatory cytokines (IL-6, TNF-α); attenuates inflammaging in animal models.