Medications, label and off-label. Honest context.

Activates AMPK and suppresses hepatic gluconeogenesis, primarily reducing fasting glucose without stimulating insulin secretion.

Long-acting glucagon-like peptide-1 receptor agonist that augments glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite via central pathways.

Single-molecule dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, producing additive effects on insulin secretion, glucagon suppression, gastric emptying, and central appetite regulation.

Reversibly inhibits intestinal alpha-glucosidase enzymes, delaying carbohydrate absorption and blunting postprandial glucose excursions.

Selectively inhibits sodium-glucose cotransporter 2 in the proximal renal tubule, producing glucosuria, mild osmotic diuresis, modest weight loss, and natriuresis with downstream cardiorenal benefit.

Canagliflozin selectively inhibits sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubule, causing urinary glucose excretion of 60-100 g/day. This produces glycemic improvement, mild weight loss, blood pressure reduction, uric acid lowering, and — increasingly clearly — cardiorenal protection independent of glycemic effect. The Interventions Testing Program (ITP, Miller 2020) found canagliflozin extended median lifespan in male UM-HET3 mice by 14%, making it one of the most robust longevity signals ever reported in the program. Mechanism for the lifespan effect remains unclear; hypotheses include caloric restriction mimicry, reduced glycemic excursions, ketone elevation, and renal preservation.

Same mechanism as standard rapamycin (FKBP12-mTORC1 allosteric inhibition) but at intermittent low doses designed to preferentially inhibit mTORC1 while sparing mTORC2. Hypothesized to capture autophagy and senescence-clearance benefits without the metabolic and immune costs of continuous high-dose immunosuppression. Protocol is associated with Blagosklonny's "rapamycin for everyone" framework and Peter Attia's clinical practice.

Selectively inhibits phosphodiesterase type 5, increasing cyclic GMP and producing vasodilation primarily in pulmonary, penile, and possibly cerebral vasculature.

Forms a complex with intracellular FKBP12 that allosterically inhibits mechanistic Target Of Rapamycin Complex 1 (mTORC1). Reduces cap-dependent protein translation, ribosomal biogenesis, and lipogenesis while activating autophagy and lysosomal biogenesis. Extends lifespan across yeast, worms, flies, and mice. In humans, intermittent dosing is hypothesized to inhibit mTORC1 selectively without suppressing immune-relevant mTORC2.

Finasteride inhibits 5-alpha reductase type II, the enzyme that converts testosterone to dihydrotestosterone (DHT) in the scalp, prostate, and skin. Lower DHT slows androgenic hair loss and shrinks the prostate. Serum DHT is reduced roughly 65–70%.

Exogenous bioidentical testosterone restores serum androgen levels in men with confirmed hypogonadism. Binds the androgen receptor in muscle, bone, CNS, and adipose tissue. Suppresses LH/FSH via negative feedback, reducing endogenous production and spermatogenesis.

Anastrozole reversibly binds aromatase (CYP19A1), blocking the conversion of androgens (testosterone, androstenedione) into estrogens (estradiol, estrone). In men this lowers serum estradiol and slightly raises testosterone via reduced negative feedback.

Clomiphene is a mixture of two isomers: enclomiphene (antagonist) and zuclomiphene (weak agonist). The antagonist component blocks estrogen receptors in the hypothalamus, removing the negative feedback brake on GnRH — which raises LH and FSH, which stimulates the testes to produce more testosterone and sperm.

Enclomiphene is the trans-isomer of clomiphene — a pure estrogen receptor antagonist at the hypothalamus. It blocks negative feedback, raising GnRH, LH, FSH, and consequently endogenous testosterone, without the weak agonist activity of zuclomiphene.

HCG structurally mimics luteinizing hormone (LH) and binds the LH receptor on Leydig cells in the testes, directly stimulating intratesticular testosterone production and preserving spermatogenesis — independent of the hypothalamic-pituitary axis.

Modafinil is a wakefulness-promoting agent whose precise mechanism is incompletely understood. It weakly inhibits dopamine reuptake, increases histamine, orexin, and norepinephrine tone, and modulates GABA/glutamate in cortical and hypothalamic circuits. Unlike classical stimulants it produces alertness without the sympathomimetic intensity or addiction profile of amphetamines.

Armodafinil is the pure R-enantiomer of racemic modafinil. The R-isomer has a longer half-life (~15 hours vs ~4 hours for the S-isomer), producing more sustained plasma levels through the afternoon. Mechanism is otherwise identical to modafinil: weak dopamine reuptake inhibition, increased orexin/histamine tone, modulation of cortical glutamate-GABA balance.

Methylene blue accepts electrons from NADH and donates them directly to cytochrome c, bypassing damaged complexes I-III of the mitochondrial electron transport chain. At low doses (<2 mg/kg) it acts as an alternative electron carrier and antioxidant; at higher doses it becomes a pro-oxidant. It is also a potent reversible monoamine oxidase A inhibitor (MAOI) — the source of its most dangerous interaction.

Selegiline selectively inhibits monoamine oxidase B (MAO-B) at low doses (5-10 mg/day), sparing MAO-A and avoiding the dietary tyramine restrictions of older MAOIs. MAO-B preferentially metabolizes dopamine and phenylethylamine; inhibition raises striatal dopamine and may protect dopaminergic neurons. At higher doses (>20 mg/day) selectivity is lost and full dietary precautions apply.

Competitive inhibition of HMG-CoA reductase, the rate-limiting enzyme of hepatic cholesterol synthesis. Upregulates LDL receptors, lowering circulating ApoB-containing particles (LDL-C, VLDL remnants). Pleiotropic effects include endothelial stabilization and reduction in hsCRP.

Prodrug activated to bempedoyl-CoA in the liver (not muscle) by very long-chain acyl-CoA synthetase 1. Inhibits ATP-citrate lyase, an enzyme upstream of HMG-CoA reductase in cholesterol biosynthesis. Reduces hepatic cholesterol production, upregulates LDL receptors, lowers LDL-C and ApoB. Lack of skeletal muscle activation explains absence of myopathy.

Selectively inhibits intestinal absorption of dietary and biliary cholesterol at the Niemann-Pick C1-Like 1 (NPC1L1) transporter on enterocytes. Reduces hepatic cholesterol delivery, upregulating LDL receptors and lowering circulating LDL-C and ApoB. Synergistic with statins.

Monoclonal antibody that binds and inactivates circulating PCSK9, the protein that normally degrades LDL receptors after they recycle to the cell surface. Inhibition increases hepatic LDL receptor density, dramatically lowering LDL-C and ApoB. Unlike statins, also lowers Lp(a) by 20-30% via partially understood mechanisms.

Selectively blocks the AT1 angiotensin II receptor while uniquely acting as a partial PPAR-gamma agonist, combining blood pressure reduction with insulin-sensitizing metabolic effects.

Fenbendazole binds parasitic beta-tubulin, blocking microtubule polymerization in helminths. Preclinical work suggests similar microtubule disruption in some cancer cell lines in vitro and in mouse xenografts — a mechanism overlapping with the chemotherapy drug class taxanes/vinca alkaloids. Human pharmacokinetic and efficacy data for cancer indications is absent.

Ivermectin binds glutamate-gated chloride channels in invertebrate nerve and muscle cells, causing paralysis and death in parasites. The 2015 Nobel Prize in Medicine recognized Campbell and Omura for ivermectin's impact on global parasitic disease. In vitro, ivermectin has shown antiviral activity against SARS-CoV-2 at supraphysiologic concentrations — concentrations not achievable at human safe doses. Human RCTs (TOGETHER, PRINCIPLE) showed no clinically meaningful benefit for COVID-19.

At standard doses (50 mg), naltrexone is a competitive opioid receptor antagonist used in alcohol and opioid use disorder. At low doses (1.5–4.5 mg), it is hypothesized to produce transient opioid receptor blockade that triggers compensatory upregulation of endogenous opioids and modulates microglial TLR4 signaling — translating into reduced neuroinflammation and possible immunomodulation in autoimmune conditions.

NMN is a direct precursor of nicotinamide adenine dinucleotide (NAD+), a coenzyme essential to mitochondrial respiration, sirtuin activity, and DNA repair via PARP enzymes. NAD+ levels decline with age. Oral NMN is rapidly converted to nicotinamide riboside (NR) in the gut, then taken up by cells and phosphorylated back to NMN before conversion to NAD+. Human bioavailability and tissue distribution of oral NMN remain incompletely characterized.

17-alpha-estradiol is the C17-epimer of 17-beta-estradiol (the body's primary estrogen). The alpha configuration binds estrogen receptors very weakly and produces no significant feminizing effects in male mammals — yet in the NIH Interventions Testing Program it extended median lifespan in male UM-HET3 mice by 12-19% across three independent cohorts (Harrison 2014, 2021). The female-mouse lifespan effect was absent. Proposed mechanisms include hypothalamic AMPK activation, modulation of inflammation via ERα in non-reproductive tissues, and metabolic effects independent of classical estrogen signaling.

NAD+ IV therapy delivers nicotinamide adenine dinucleotide directly into the bloodstream, bypassing first-pass metabolism. Typical infusions are 250-1000 mg over 1-4 hours. The biochemical rationale is that intravenous delivery achieves higher and more rapid NAD+ availability than oral precursors (NR or NMN). However, plasma NAD+ does not equal intracellular tissue NAD+, and the molecule's ability to cross cell membranes intact is debated. Most likely the infused NAD+ is degraded extracellularly into nicotinamide and other precursors which are then taken up.