{ "name": "Heretic", "url": "https://heretic.bio", "license": "All rights reserved; quote with attribution and a link.", "ratings": { "proven": { "name": "Proven", "meaning": "Replicated results in human randomized trials" }, "promising": { "name": "Promising", "meaning": "Some human trials, or consistent animal work with a clear mechanism" }, "early": { "name": "Early", "meaning": "Mostly animal or cell studies; few or uncontrolled human data" }, "speculative": { "name": "Speculative", "meaning": "Little primary evidence yet: mechanism, anecdote or tradition" } }, "count": 113, "entries": [ { "slug": "adaptogen-research", "name": "Adaptogens", "aliases": [], "type": "Compound", "rating": "promising", "fields": [ "soviet", "nootropics" ], "goals": [ "cog", "mind" ], "description": "Plant compounds coined in Soviet research to raise nonspecific stress resistance; RCTs best support rhodiola for fatigue and ashwagandha for anxiety.", "short_answer": "Adaptogens are a class of plant compounds, defined in Soviet-era research, claimed to increase the body's nonspecific resistance to stress via HPA-axis and stress-protein modulation. The strongest modern evidence is randomized-trial support for rhodiola in stress-related fatigue and ashwagandha for cortisol and anxiety. Other adaptogens rest on thinner or Soviet-era data, and extract standardization and trial heterogeneity are the main caveats.", "updated": "2026-08-06", "sources": 27, "url": "https://heretic.bio/articles/adaptogen-research.html", "markdown": "https://heretic.bio/articles/adaptogen-research.md" }, { "slug": "advanced-glycation-and-crosslink-breakers", "name": "Advanced glycation and crosslink breakers", "aliases": [], "type": "Mechanism", "rating": "speculative", "fields": [], "goals": [ "age" ], "description": "Sugar-protein end-products that crosslink and stiffen arteries, skin, and kidneys; every breaker or blocker program has failed and none is approved.", "short_answer": "Advanced glycation end-products are crosslinks formed when sugars modify long-lived proteins; the dominant one, glucosepane, accumulates for decades and no human enzyme removes it. Every drug program, alagebrium, aminoguanidine, pyridoxamine, azeliragon, failed or stalled in the clinic, and the reported glucosepane-cleaving enzyme activity could not be reproduced. No approved therapy removes existing crosslinks; only formation can be slowed, mainly through glycemic control.", "updated": "2026-08-06", "sources": 7, "url": "https://heretic.bio/articles/advanced-glycation-and-crosslink-breakers.html", "markdown": "https://heretic.bio/articles/advanced-glycation-and-crosslink-breakers.md" }, { "slug": "alpha-ketoglutarate-akg-the-metabolic-longevity-molecule", "name": "Alpha-ketoglutarate (AKG)", "aliases": [], "type": "Compound", "rating": "early", "fields": [], "goals": [ "age" ], "description": "A longevity metabolite that extends lifespan in worms, flies, and mice; human evidence is observational, with three randomized trials underway.", "short_answer": "Alpha-ketoglutarate is a TCA-cycle intermediate that declines with age and feeds the dioxygenase enzymes behind DNA and histone demethylation. It extends lifespan about 50% in C. elegans and ~12% with morbidity compression in mice; in humans, a 4,260-person observational study linked delayed-release CaAKG to lower methylation age, but no completed RCT exists. The ABLE trial and two other randomized trials are underway.", "updated": "2026-08-06", "sources": 6, "url": "https://heretic.bio/articles/alpha-ketoglutarate-akg-the-metabolic-longevity-molecule.html", "markdown": "https://heretic.bio/articles/alpha-ketoglutarate-akg-the-metabolic-longevity-molecule.md" }, { "slug": "autophagy", "name": "Autophagy", "aliases": [], "type": "Mechanism", "rating": "proven", "fields": [], "goals": [ "age" ], "description": "The cell's recycling system for damaged proteins and organelles; it declines with age and switches on with fasting, exercise, and caloric restriction.", "short_answer": "Autophagy is the cell's system for degrading and recycling damaged proteins, organelles, and pathogens; its discovery won the 2016 Nobel Prize. It is suppressed by mTORC1 and switched on by fasting beyond roughly 16 hours, exercise, caloric restriction, and compounds such as rapamycin and spermidine. Human evidence is strong for physiological activation; how much that drives longevity is extrapolated from animal models.", "updated": "2026-08-06", "sources": 7, "url": "https://heretic.bio/articles/autophagy.html", "markdown": "https://heretic.bio/articles/autophagy.md" }, { "slug": "biofilms-and-chronic-infection-overview", "name": "Biofilms and chronic infection", "aliases": [], "type": "Mechanism", "rating": "speculative", "fields": [], "goals": [ "inf" ], "description": "Microbes encased in a self-made matrix that tolerate antibiotic doses up to 1,000× higher than free cells; disruption protocols remain largely untested.", "short_answer": "Biofilms are organized microbial communities encased in a self-produced matrix, making them 10–1,000× more antibiotic-tolerant than free-floating cells and largely invisible to standard cultures. An NIH-cited estimate attributes about 65% of bacterial infections to biofilms. Disruption strategies, enzymes, chelators, quorum-sensing inhibitors, phages, rest mostly on in-vitro work and clinical reports, not controlled human trials.", "updated": "2026-08-06", "sources": 13, "url": "https://heretic.bio/articles/biofilms-and-chronic-infection-overview.html", "markdown": "https://heretic.bio/articles/biofilms-and-chronic-infection-overview.md" }, { "slug": "biohacking-and-optimization-overview", "name": "Biohacking and optimization", "aliases": [], "type": "Guide", "rating": "speculative", "fields": [], "goals": [ "age", "met", "cog" ], "description": "The optimization stack ranked by evidence: sleep, exercise, and nutrition do most of the work; modalities like IHHT, PEMF, and exosomes remain early.", "short_answer": "Biohacking here means deliberately pushing function above the statistical-normal baseline using biomarker feedback and hormetic stressors. The honest ledger: sleep, exercise, and nutrition account for roughly 80% of the benefit; sauna and cold exposure have real physiological effects; and hormone optimization helps the genuinely deficient. Peptides, PEMF, IHHT, and similar tools are promising but unproven extras.", "updated": "2026-10-14", "sources": 0, "url": "https://heretic.bio/articles/biohacking-and-optimization-overview.html", "markdown": "https://heretic.bio/articles/biohacking-and-optimization-overview.md" }, { "slug": "biological-age-clocks-measurement-and-interpretation", "name": "Biological age clocks", "aliases": [], "type": "Measure", "rating": "proven", "fields": [], "goals": [ "age" ], "description": "DNA-methylation algorithms estimating biological age; GrimAge and DunedinPACE predict disease and mortality in large cohorts, but readings are noisy.", "short_answer": "Epigenetic clocks are regression algorithms that read age-related DNA-methylation drift and output a biological age or aging rate. Three large 2025–2026 analyses, an 18,859-person head-to-head, a 24-year longitudinal study, and a NHANES mortality analysis, confirmed GrimAge-family and DunedinPACE as genuine risk stratifiers. The caveats: clocks disagree with each other, single measurements are noisy, and no intervention has yet proven that moving a clock changes lifespan.", "updated": "2026-10-14", "sources": 14, "url": "https://heretic.bio/articles/biological-age-clocks-measurement-and-interpretation.html", "markdown": "https://heretic.bio/articles/biological-age-clocks-measurement-and-interpretation.md" }, { "slug": "bpc-157-body-protection-compound", "name": "BPC-157", "aliases": [ "PL 14736", "PL-10", "PLD-116", "Bepecin", "PCO-02" ], "type": "Compound", "rating": "early", "fields": [ "peptides" ], "goals": [ "inj" ], "description": "A gastric-derived 15-amino-acid peptide with extensive rodent data on tendon and gut healing but no completed human trials. FDA Category 2; banned by WADA.", "short_answer": "BPC-157 is a synthetic fragment of a human gastric protein that survives gastric juice and shows protective effects across tendon, ligament, gut, and nerve tissue in rodent studies. Human evidence is nearly absent: one retrospective knee series (n=12), one small open-label IV safety pilot, and no published Phase II results. It sits in FDA Category 2, cannot be 503A-compounded, and is banned in competition by WADA.", "updated": "2026-10-15", "sources": 5, "url": "https://heretic.bio/articles/bpc-157-body-protection-compound.html", "markdown": "https://heretic.bio/articles/bpc-157-body-protection-compound.md" }, { "slug": "brainspotting", "name": "Brainspotting", "aliases": [], "type": "Therapy", "rating": "speculative", "fields": [], "goals": [ "mind" ], "description": "A trauma therapy using fixed eye positions to access subcortical processing; the evidence is small but consistently positive and large RCTs are missing.", "short_answer": "Brainspotting is a psychotherapy in which a client holds a fixed gaze on a 'brainspot' while processing distress, on the theory that eye position gates subcortical trauma networks. The published evidence is small, a few preliminary and comparative studies and case reports, all positive, with no large randomized trials. It is framed as a complement or fallback when EMDR stalls, not a proven equivalent.", "updated": "2026-08-06", "sources": 0, "url": "https://heretic.bio/articles/brainspotting.html", "markdown": "https://heretic.bio/articles/brainspotting.md" }, { "slug": "breathwork-and-somatic-release", "name": "Breathwork", "aliases": [], "type": "Therapy", "rating": "speculative", "fields": [], "goals": [ "mind" ], "description": "Conscious-breathing practices for regulation and trauma release; slow techniques carry trial-level support while intensive methods lean on case reports.", "short_answer": "Breathwork covers conscious-breathing practices used to shift autonomic state and, in intensive forms like holotropic breathwork, to process stored trauma. The strongest evidence is for slow regulated techniques, coherent breathing, box breathing, physiological sighs, supported by multiple RCTs for anxiety reduction and heart-rate variability. Claims about completing defensive responses or accessing pre-verbal trauma rest on clinical observation and case series.", "updated": "2026-08-06", "sources": 0, "url": "https://heretic.bio/articles/breathwork-and-somatic-release.html", "markdown": "https://heretic.bio/articles/breathwork-and-somatic-release.md" }, { "slug": "bromantane", "name": "Bromantane", "aliases": [], "type": "Compound", "rating": "speculative", "fields": [ "nootropics", "soviet" ], "goals": [ "cog" ], "description": "A Russian actoprotector approved there for asthenia that boosts dopamine-synthesis enzymes rather than blocking reuptake; Western replication is absent.", "short_answer": "Bromantane is a Russian adamantane actoprotector developed in the 1980s and approved there as Ladasten for neurasthenia and asthenia. Its distinctive mechanism is genomic: it raises tyrosine hydroxylase expression to increase dopamine synthesis rather than forcing release or blocking reuptake, which is why effects reportedly persist after discontinuation. The key trial was a 728-patient Russian multicenter study; independent Western replication is essentially absent, and it is sold elsewhere only as a research chemical.", "updated": "2026-08-06", "sources": 0, "url": "https://heretic.bio/articles/bromantane.html", "markdown": "https://heretic.bio/articles/bromantane.md" }, { "slug": "carnivore-diet", "name": "Carnivore diet", "aliases": [], "type": "Diet", "rating": "early", "fields": [], "goals": [ "met" ], "description": "An all-animal-food elimination diet backed by surveys and case series, not RCTs; documented concerns are LDL elevation, kidney stones, and nutrient gaps.", "short_answer": "The carnivore diet excludes all plant foods, functioning as a maximal elimination diet plus sustained ketosis. A 2026 scoping review found only nine qualifying human studies, mostly surveys and case series, with no RCTs on cardiovascular endpoints, and concluded reported benefits may reflect subjective perception and ketosis rather than the diet itself. Documented trade-offs include LDL elevation, calcium-oxalate kidney-stone risk, and shortfalls in vitamin C, magnesium, iodine, calcium, and fiber.", "updated": "2026-08-06", "sources": 19, "url": "https://heretic.bio/articles/carnivore-diet.html", "markdown": "https://heretic.bio/articles/carnivore-diet.md" }, { "slug": "cerebrolysin-porcine-neurotrophic-peptide-complex", "name": "Cerebrolysin", "aliases": [], "type": "Compound", "rating": "early", "fields": [ "peptides", "nootropics" ], "goals": [ "cog" ], "description": "A porcine brain-peptide mixture used for stroke, TBI, and dementia across ~40 countries; manufacturer trials are positive, two Cochrane reviews skeptical.", "short_answer": "Cerebrolysin is a standardized hydrolysate of pig-brain proteins, about 80% free amino acids and 20% small peptides, given IV for stroke, traumatic brain injury, and dementia in dozens of countries. The evidence is a genuine split: two EVER-funded RCTs report benefit in moderate-severe TBI, while Cochrane found weak, biased support in vascular dementia and no benefit plus a safety signal in acute stroke. There are zero controlled trials in healthy people.", "updated": "2026-08-06", "sources": 5, "url": "https://heretic.bio/articles/cerebrolysin-porcine-neurotrophic-peptide-complex.html", "markdown": "https://heretic.bio/articles/cerebrolysin-porcine-neurotrophic-peptide-complex.md" }, { "slug": "chronic-sinus-and-gut-biofilms", "name": "Chronic sinus and gut biofilms", "aliases": [], "type": "Condition", "rating": "speculative", "fields": [], "goals": [ "inf" ], "description": "Biofilms appear in 45–100% of chronic sinusitis cases and are implicated in SIBO resistance; disruption protocols against them are largely untested.", "short_answer": "This entry argues that biofilm-protected microbial communities explain why chronic rhinosinusitis and intestinal overgrowth recur despite treatment: biofilms tolerate antibiotics, harbor persister cells, and even shelter bacteria inside sinus epithelial cells. Detection studies find biofilms in 45–100% of CRS patients, and one cited 2023 study reported biofilm disruption improved SIBO antimicrobial outcomes. The layered disruption protocols described come mostly from clinical experience, not controlled trials.", "updated": "2026-08-06", "sources": 5, "url": "https://heretic.bio/articles/chronic-sinus-and-gut-biofilms.html", "markdown": "https://heretic.bio/articles/chronic-sinus-and-gut-biofilms.md" }, { "slug": "cold-and-heat-therapy", "name": "Cold and heat therapy", "aliases": [], "type": "Therapy", "rating": "early", "fields": [], "goals": [ "inj", "met" ], "description": "Deliberate cold and heat exposure: strong observational data for frequent sauna, and trial evidence that post-workout cold immersion blunts muscle growth.", "short_answer": "Cold and heat exposure trigger hormetic responses: cold activates brown fat and norepinephrine, sauna induces heat-shock proteins and cardiovascular adaptation. The strongest data is observational, Finnish cohorts link frequent sauna to lower cardiovascular and dementia risk, plus a 2024 meta-analysis finding post-exercise cold immersion blunts hypertrophy at ~95.7% probability. Lifestyle confounding limits causal inference in both directions.", "updated": "2026-10-15", "sources": 9, "url": "https://heretic.bio/articles/cold-and-heat-therapy.html", "markdown": "https://heretic.bio/articles/cold-and-heat-therapy.md" }, { "slug": "creatine-monohydrate-muscle-brain-and-bone-evidence", "name": "Creatine monohydrate", "aliases": [], "type": "Compound", "rating": "promising", "fields": [ "nootropics" ], "goals": [ "cog", "inj" ], "description": "The most-studied ergogenic supplement: strong RCT evidence for muscle and strength, plus newer trials in cognition, depression, and postmenopausal bone.", "short_answer": "Creatine monohydrate refills the phosphocreatine energy buffer in muscle and brain. The evidence is strongest for muscle, more than a thousand trials supporting lean-mass and strength gains, including in older adults, while newer RCTs and meta-analyses support cognition under metabolic stress and depression augmentation, and 2-year data shows bone-geometry, not bone-density, benefits. Safety in healthy people is well supported over multi-year use; effects in rested young adults are minimal.", "updated": "2026-08-06", "sources": 4, "url": "https://heretic.bio/articles/creatine-monohydrate-muscle-brain-and-bone-evidence.html", "markdown": "https://heretic.bio/articles/creatine-monohydrate-muscle-brain-and-bone-evidence.md" }, { "slug": "darkfield-microscopy", "name": "Darkfield microscopy", "aliases": [], "type": "Method", "rating": "speculative", "fields": [ "soviet" ], "goals": [ "inf" ], "description": "Live-blood microscopy rooted in pleomorphism; the optics are valid and some findings match mainstream hematology, but the interpretation is unsupported.", "short_answer": "Darkfield microscopy illuminates unstained, living blood against a dark field, letting practitioners watch red-cell morphology, clotting behavior, and plasma particles in real time. The optics are legitimate and a few observations overlap mainstream hematology, rouleaux tracks fibrinogen, spherocytes mark hemolysis, but the interpretive framework of pleomorphism, terrain pH, and protits is not supported by modern biology, and live blood analysis is not a validated diagnostic.", "updated": "2026-10-15", "sources": 4, "url": "https://heretic.bio/articles/darkfield-microscopy.html", "markdown": "https://heretic.bio/articles/darkfield-microscopy.md" }, { "slug": "dental-biofilms-and-oral-systemic-health", "name": "Dental biofilms", "aliases": [], "type": "Condition", "rating": "promising", "fields": [], "goals": [ "inf" ], "description": "The mouth as a biofilm reservoir: periodontal therapy lowers HbA1c in RCTs, cardiovascular links are associative, and the Alzheimer's drug test failed.", "short_answer": "Dental plaque is the archetypal biofilm, and periodontitis is a chronic biofilm-protected infection affecting 10–15% of adults severely. The strongest systemic link is diabetes: periodontal therapy lowers HbA1c ~0.3–0.4% in meta-analyses of RCTs. Cardiovascular links are associative, the P. gingivalis–Alzheimer's hypothesis failed its direct drug test, and regular antiseptic mouthwash use measurably raises blood pressure by killing nitrate-reducing bacteria.", "updated": "2026-10-15", "sources": 6, "url": "https://heretic.bio/articles/dental-biofilms-and-oral-systemic-health.html", "markdown": "https://heretic.bio/articles/dental-biofilms-and-oral-systemic-health.md" }, { "slug": "dihexa-n-hexanoic-tyr-ile-6-aminohexanoic-amide", "name": "Dihexa", "aliases": [ "N-hexanoic-Tyr-Ile-(6) aminohexanoic amide", "NHex", "Dihexa" ], "type": "Compound", "rating": "speculative", "fields": [ "peptides", "nootropics" ], "goals": [ "cog" ], "description": "An angiotensin-IV-derived nootropic peptide built on retracted potency claims; no human studies exist, and its successor drug failed in Alzheimer's.", "short_answer": "Dihexa is an angiotensin-IV-derived oligopeptide sold to nootropic users on claims it is orders of magnitude more potent than BDNF. That foundation is compromised: the key papers are retracted or under expressions of concern, the related drug fosgonimeton failed its pivotal Alzheimer's trial, and no human study of dihexa exists. HGF/c-Met activation plus a multi-day half-life also raises a serious theoretical cancer risk.", "updated": "2026-10-15", "sources": 7, "url": "https://heretic.bio/articles/dihexa-n-hexanoic-tyr-ile-6-aminohexanoic-amide.html", "markdown": "https://heretic.bio/articles/dihexa-n-hexanoic-tyr-ile-6-aminohexanoic-amide.md" }, { "slug": "dmso-therapy", "name": "DMSO", "aliases": [], "type": "Compound", "rating": "speculative", "fields": [], "goals": [ "inj" ], "description": "A membrane-penetrating solvent used for pain and as a drug carrier; FDA-approved uses are narrow and systemic use remains unproven after 50+ years.", "short_answer": "DMSO is a small polar solvent that crosses skin, blocks pain fibers, reduces inflammation, and carries other compounds through tissue. FDA-approved uses are narrow: topical analgesia, interstitial cystitis, scleroderma. Systemic use is unapproved and controversial despite 50+ years of research. The carrier effect is both the appeal and the hazard: it potentiates whatever touches it.", "updated": "2026-08-06", "sources": 4, "url": "https://heretic.bio/articles/dmso-therapy.html", "markdown": "https://heretic.bio/articles/dmso-therapy.md" }, { "slug": "electromagnetic-therapies", "name": "Electromagnetic therapies (PEMF)", "aliases": [], "type": "Therapy", "rating": "early", "fields": [], "goals": [ "inj" ], "description": "Modalities from TENS to PEMF: FDA-approved for non-union fractures since 1979, RCT support for microcurrent wound healing, unproven frequency claims.", "short_answer": "Electromagnetic therapies span TENS, microcurrent, PEMF, and Rife. The proven core is PEMF, FDA-approved for non-union fractures since 1979 with growing evidence in osteoarthritis and post-surgical pain; microcurrent adds RCT support for wound healing. The contested fringe is frequency-specific and Rife-style claims, which the entry treats as unproven.", "updated": "2026-08-06", "sources": 6, "url": "https://heretic.bio/articles/electromagnetic-therapies.html", "markdown": "https://heretic.bio/articles/electromagnetic-therapies.md" }, { "slug": "emdr", "name": "EMDR", "aliases": [], "type": "Therapy", "rating": "proven", "fields": [], "goals": [ "mind" ], "description": "A structured trauma psychotherapy using bilateral stimulation, guideline-listed as first-line for PTSD; evidence is strongest for single-incident trauma.", "short_answer": "EMDR is a structured psychotherapy that pairs recall of traumatic memories with bilateral stimulation, usually guided eye movements, until the memory loses its charge. It is one of the most studied trauma therapies, listed as a first-line PTSD treatment by WHO, APA, NICE, and the DoD, with meta-analytic effect sizes around d = 0.84–1.27. It works best for single-incident trauma; mechanism debates and weaker complex-trauma data are the honest caveats.", "updated": "2026-10-15", "sources": 0, "url": "https://heretic.bio/articles/emdr.html", "markdown": "https://heretic.bio/articles/emdr.md" }, { "slug": "epitalon-aedg-tetrapeptide-telomerase-pineal-axis-and-geroprotective-evidence", "name": "Epitalon", "aliases": [ "Epithalon", "Epithalone", "Epithalamin (parent extract)" ], "type": "Compound", "rating": "early", "fields": [ "peptides", "bioregulators", "soviet" ], "goals": [ "age" ], "description": "A pineal tetrapeptide that activates telomerase and lengthens telomeres in human cells; human data is two small Russian trials without Western replication.", "short_answer": "Epitalon (AEDG) is a synthetic tetrapeptide modeled on the bovine pineal extract epithalamin, developed by Khavinson's St. Petersburg group. It activates telomerase and extends telomeres ~33% in human cell lines, with 2025 work adding a second route via ALT; animal lifespan data is positive. Human data is limited to two small, single-site Russian trials, retinitis pigmentosa (n=162) and circadian measures (n=75), with no Western replication.", "updated": "2026-08-06", "sources": 11, "url": "https://heretic.bio/articles/epitalon-aedg-tetrapeptide-telomerase-pineal-axis-and-geroprotective-evidence.html", "markdown": "https://heretic.bio/articles/epitalon-aedg-tetrapeptide-telomerase-pineal-axis-and-geroprotective-evidence.md" }, { "slug": "exercise-science-and-longevity", "name": "Exercise and longevity", "aliases": [], "type": "Guide", "rating": "promising", "fields": [], "goals": [ "age", "met" ], "description": "A longevity exercise framework built on VO2max and grip strength as mortality predictors, combining Zone 2 cardio, intervals, strength, and stability work.", "short_answer": "This guide frames exercise as the strongest longevity intervention: VO2max and grip strength predict all-cause mortality better than smoking, diabetes, or hypertension. Its program combines a Zone 2 aerobic base, high-intensity intervals, progressive resistance training, and stability work. The mortality associations are observational but large and consistent; the main 2025 caveat is that Zone 2's claimed superiority is contested.", "updated": "2026-10-15", "sources": 5, "url": "https://heretic.bio/articles/exercise-science-and-longevity.html", "markdown": "https://heretic.bio/articles/exercise-science-and-longevity.md" }, { "slug": "exosome-therapy", "name": "Exosome therapy", "aliases": [], "type": "Therapy", "rating": "early", "fields": [], "goals": [ "inj", "age" ], "description": "Acellular vesicle injections meant to deliver stem-cell repair signals without the cells; one small RCT is positive, and no product is FDA-approved.", "short_answer": "Exosome therapy injects small extracellular vesicles, the packets cells use for paracrine signaling, aiming to deliver stem-cell repair effects without transplanting cells. The human evidence is thin: one small double-blind RCT in severe COVID-19 reported lower mortality, while osteoarthritis and wound claims rest on animal meta-analyses. No exosome product is FDA-approved, and product characterization is the field's core problem.", "updated": "2026-08-06", "sources": 5, "url": "https://heretic.bio/articles/exosome-therapy.html", "markdown": "https://heretic.bio/articles/exosome-therapy.md" }, { "slug": "fasting-approaches", "name": "Fasting", "aliases": [], "type": "Diet", "rating": "promising", "fields": [], "goals": [ "met", "age" ], "description": "Structured abstention from calories, from 16:8 to multi-day fasts, triggering ketosis and autophagy; human outcome data trails the strong animal record.", "short_answer": "Fasting means structured abstention from calories, from 16:8 time-restricted windows to multi-day fasts and the fasting-mimicking diet. The metabolic switch to fat oxidation plus autophagy activation is well-described physiology, and human evidence is strong for weight loss and insulin sensitivity. Claims about immune reset, neuroprotection, and lifespan extension rest mostly on animal data, and the contraindication list is real.", "updated": "2026-10-15", "sources": 6, "url": "https://heretic.bio/articles/fasting-approaches.html", "markdown": "https://heretic.bio/articles/fasting-approaches.md" }, { "slug": "fasting-mimicking-diet", "name": "Fasting-mimicking diet", "aliases": [], "type": "Diet", "rating": "promising", "fields": [], "goals": [ "met", "age" ], "description": "A five-day, very-low-calorie protocol that mimics fasting with food; trials report less visceral fat, lower IGF-1, and ~2.6 years lower biological age.", "short_answer": "The fasting-mimicking diet is a 5-day, very-low-calorie, low-protein protocol designed to trigger fasting physiology while allowing some food, commercialized as ProLon. Randomized trials report reduced visceral and liver fat, lower IGF-1 and HOMA-IR, and a ~2.6-year median drop in measured biological age after three cycles, though 21–31% of participants moved the wrong way. Two oncology adjunct trials are running but report after 2029.", "updated": "2026-10-14", "sources": 7, "url": "https://heretic.bio/articles/fasting-mimicking-diet.html", "markdown": "https://heretic.bio/articles/fasting-mimicking-diet.md" }, { "slug": "fda-peptide-reclassification-2026", "name": "FDA peptide reclassification 2026", "aliases": [], "type": "Regulatory", "rating": "speculative", "fields": [ "peptides" ], "goals": [], "description": "What the July 2026 committee vote on BPC-157, TB-500 and four other peptides means for access, why it isn't law yet, and the case for and against.", "short_answer": "In July 2026 an FDA advisory committee voted to recommend BPC-157, KPV, TB-500, MOTS-c, Semax and Epitalon for legal compounding, overruling FDA staff; DSIP was rejected. As of mid-October 2026 none is on the 503A list, so US pharmacies still can't compound them. FDA must accept the advice and write a rule, which has no deadline; a temporary-access policy has been reported but not published.", "updated": "2026-10-15", "sources": 1, "url": "https://heretic.bio/articles/fda-peptide-reclassification-2026.html", "markdown": "https://heretic.bio/articles/fda-peptide-reclassification-2026.md" }, { "slug": "frequency-specific-microcurrent", "name": "Frequency-specific microcurrent", "aliases": [], "type": "Therapy", "rating": "early", "fields": [], "goals": [ "inj" ], "description": "Sub-sensory microcurrent therapy with RCT support for wound healing and soreness; its claim that paired frequencies hit specific tissues is unproven.", "short_answer": "Frequency-specific microcurrent delivers sub-sensory microamp current through paired frequencies claimed to target specific tissues and conditions. The generic microcurrent underneath has real trial support, an 8-RCT wound-healing meta-analysis and a double-masked palatal-surgery trial, plus one striking FSM trial in muscle soreness. The frequency-pair specificity that defines FSM remains unproven.", "updated": "2026-10-15", "sources": 5, "url": "https://heretic.bio/articles/frequency-specific-microcurrent.html", "markdown": "https://heretic.bio/articles/frequency-specific-microcurrent.md" }, { "slug": "ghk-cu-copper-tripeptide-gene-modulatory-regenerative-peptide", "name": "GHK-Cu", "aliases": [ "Copper peptide", "Gly-His-Lys-Cu", "Glycyl-L-Histidyl-L-Lysine-copper(II)", "Copper Tripeptide-1" ], "type": "Compound", "rating": "promising", "fields": [ "peptides" ], "goals": [ "inj", "age" ], "description": "A copper peptide backed by small human trials for skin aging and topical wound healing; systemic use has no human data. Injectable is FDA Category 2.", "short_answer": "GHK-Cu is a naturally occurring copper tripeptide whose plasma levels fall with age. Several small randomized and controlled trials support topical use for skin aging, and the first dedicated wound-healing RCT began recruiting in 2026. Hair, lung and systemic longevity claims rest on animal studies or confounded human data; no human trial has tested injected GHK-Cu.", "updated": "2026-08-06", "sources": 14, "url": "https://heretic.bio/articles/ghk-cu-copper-tripeptide-gene-modulatory-regenerative-peptide.html", "markdown": "https://heretic.bio/articles/ghk-cu-copper-tripeptide-gene-modulatory-regenerative-peptide.md" }, { "slug": "glp-1-muscle-preservation", "name": "GLP-1 drugs and muscle preservation", "aliases": [], "type": "Guide", "rating": "early", "fields": [ "peptides" ], "goals": [ "met" ], "description": "An evidence review of muscle loss on GLP-1 drugs: 25-45% of weight lost is lean tissue, and one phase 2 bimagrumab trial shows preservation.", "short_answer": "About 25-45% of weight lost on GLP-1 drugs is lean tissue, though 2026 analyses contest whether that is disproportionate to ordinary dieting. The strongest mitigation data is BELIEVE, a 507-person phase 2 trial where bimagrumab plus semaglutide cut fat mass 45.7% while losing only 2.9% lean mass at week 72. A five-arm trial in hypogonadal men found testosterone plus resistance training produced net lean-mass gain. Larger trials with MRI muscle endpoints read out in 2027.", "updated": "2026-10-14", "sources": 6, "url": "https://heretic.bio/articles/glp-1-muscle-preservation.html", "markdown": "https://heretic.bio/articles/glp-1-muscle-preservation.md" }, { "slug": "glp-1-peptides-semaglutide-tirzepatide-retatrutide", "name": "GLP-1 agonists", "aliases": [], "type": "Compound", "rating": "proven", "fields": [ "peptides" ], "goals": [ "met" ], "description": "GLP-1 drugs reviewed against the trials: 15-30% weight loss, proven cardiovascular benefit, and open questions on muscle loss, dependency and aging.", "short_answer": "GLP-1 receptor agonists are incretin-mimicking drugs with large randomized-trial evidence for weight loss: semaglutide about 15%, tirzepatide about 21%, and retatrutide up to about 30% in phase 3. Semaglutide also cut major cardiovascular events 20% in the 17,604-person SELECT trial. The caveats are lean-mass loss (25-39% of weight lost), rapid regain after stopping, and unproven claims such as slowed epigenetic aging, which rest on one small post-hoc analysis.", "updated": "2026-10-14", "sources": 21, "url": "https://heretic.bio/articles/glp-1-peptides-semaglutide-tirzepatide-retatrutide.html", "markdown": "https://heretic.bio/articles/glp-1-peptides-semaglutide-tirzepatide-retatrutide.md" }, { "slug": "glycine-glynac-and-glutathione-precursors-evidence-taxonomy", "name": "GlyNAC and glutathione precursors", "aliases": [], "type": "Compound", "rating": "promising", "fields": [], "goals": [ "age" ], "description": "A glycine-plus-NAC combination that restores glutathione; small trials show gains in oxidative stress, insulin sensitivity and physical function.", "short_answer": "GlyNAC pairs glycine and N-acetylcysteine, the two precursors needed to make glutathione, which declines with age. A 16-week randomized trial in 24 older adults corrected glutathione deficiency and improved oxidative stress, insulin resistance, inflammation and walking speed, with smaller pilots showing similar metabolic effects in diabetes. Nearly all human data comes from the Baylor/Sekhar group, and benefits faded within 12 weeks of stopping, so independent replication is the missing piece.", "updated": "2026-10-14", "sources": 8, "url": "https://heretic.bio/articles/glycine-glynac-and-glutathione-precursors-evidence-taxonomy.html", "markdown": "https://heretic.bio/articles/glycine-glynac-and-glutathione-precursors-evidence-taxonomy.md" }, { "slug": "gut-health-and-sibo", "name": "Gut health and SIBO", "aliases": [], "type": "Condition", "rating": "speculative", "fields": [], "goals": [ "inf", "met" ], "description": "An overview of SIBO and its methane, hydrogen-sulfide and fungal variants, where breath testing guides treatment and biofilms may explain failures.", "short_answer": "SIBO is an overgrowth of bacteria, archaea or fungi in the small intestine, diagnosed mainly by breath testing and treated with non-absorbed antibiotics such as rifaximin plus prokinetics. Relapse exceeds 50% within six months when the underlying motility or structural cause is not fixed, and the biofilm hypothesis is the leading explanation for treatment failures. Much of the biofilm evidence is indirect, so this entry stays speculative.", "updated": "2026-08-06", "sources": 0, "url": "https://heretic.bio/articles/gut-health-and-sibo.html", "markdown": "https://heretic.bio/articles/gut-health-and-sibo.md" }, { "slug": "gut-microbiome-and-postbiotics", "name": "Gut microbiome and postbiotics", "aliases": [], "type": "Mechanism", "rating": "early", "fields": [], "goals": [ "met" ], "description": "How the gut microbiome connects to metabolism and aging, with the strongest human data on pasteurized Akkermansia for insulin sensitivity, not lifespan.", "short_answer": "The gut microbiome acts like a metabolic organ, and centenarians share a characteristic microbial signature, though causation is unproven. The strongest human evidence is for pasteurized Akkermansia muciniphila: two randomized trials improved insulin sensitivity in metabolic patients, with benefit only in people who started with low levels. Fiber diversity remains the most reliable lever, while probiotics, postbiotics and FMT have narrower or weaker evidence.", "updated": "2026-08-06", "sources": 9, "url": "https://heretic.bio/articles/gut-microbiome-and-postbiotics.html", "markdown": "https://heretic.bio/articles/gut-microbiome-and-postbiotics.md" }, { "slug": "hallmarks-of-aging", "name": "Hallmarks of aging", "aliases": [], "type": "Mechanism", "rating": "early", "fields": [], "goals": [ "age" ], "description": "A consensus framework naming 12 biological processes that drive aging, from genomic instability to dysbiosis, used to organize longevity research.", "short_answer": "The Hallmarks of Aging is a consensus framework listing 12 interconnected processes, such as genomic instability, cellular senescence and inflammaging, that jointly drive aging. It was proposed in 2013 with nine hallmarks and expanded to twelve in 2023. It is a research scaffold built by expert agreement, not an empirical classification, and the evidence behind each hallmark differs.", "updated": "2026-08-01", "sources": 5, "url": "https://heretic.bio/articles/hallmarks-of-aging.html", "markdown": "https://heretic.bio/articles/hallmarks-of-aging.md" }, { "slug": "heavy-metal-burden-and-chelation", "name": "Heavy metals and chelation", "aliases": [], "type": "Therapy", "rating": "early", "fields": [], "goals": [ "inf" ], "description": "Chelation is proven for documented metal poisoning, failed its big cardiovascular test in 2024, and has no evidence behind wellness detox use.", "short_answer": "Chelation with drugs like DMSA or CaNa2EDTA is standard, evidence-based care for documented metal poisoning. For everything else the evidence is thin or negative: the 1,005-person TACT2 trial found EDTA chelation did not improve outcomes after heart attack, and the provoked-urine testing used to sell detox protocols has no validated reference ranges. Casual chelation also carries real risks, including mineral depletion and, with the wrong EDTA salt, fatal hypocalcemia.", "updated": "2026-08-06", "sources": 5, "url": "https://heretic.bio/articles/heavy-metal-burden-and-chelation.html", "markdown": "https://heretic.bio/articles/heavy-metal-burden-and-chelation.md" }, { "slug": "herniated-discs-lower-back-pain-non-surgical-regeneration", "name": "Herniated discs and low back pain", "aliases": [], "type": "Condition", "rating": "speculative", "fields": [], "goals": [ "inj" ], "description": "Non-surgical options for herniated discs: most herniations resorb on their own, while regenerative add-ons like BPC-157 rest on animal data.", "short_answer": "Many disc herniations resorb spontaneously within 6-12 months of conservative care, which is the strongest fact in this entry. Prolotherapy and PRP have moderate evidence for pain reduction, while the peptide therapies (BPC-157, TB-500) and exosomes that dominate regenerative marketing rest mostly on rodent disc models and case reports. No large randomized trial exists for peptides or exosomes in disc disease, so multimodal claims of 60-85% improvement are community estimates, not trial results.", "updated": "2026-08-06", "sources": 1, "url": "https://heretic.bio/articles/herniated-discs-lower-back-pain-non-surgical-regeneration.html", "markdown": "https://heretic.bio/articles/herniated-discs-lower-back-pain-non-surgical-regeneration.md" }, { "slug": "hormone-optimization-trt-hrt-perimenopause", "name": "Hormone optimization (TRT, HRT)", "aliases": [], "type": "Therapy", "rating": "promising", "fields": [], "goals": [ "age", "met" ], "description": "TRT and menopausal hormone therapy reviewed against the evidence: strong for symptoms, bone and body composition; timing and route decide safety.", "short_answer": "Hormone optimization spans TRT for hypogonadal men and menopausal hormone therapy for women. TRT has strong evidence for sexual function, lean mass, bone density and quality of life, with cardiovascular effects still contested. For women, the WHI's 2002 cancer scare has been substantially revised: starting therapy before 60 or within 10 years of menopause appears safe and possibly cardioprotective, with vasomotor relief and bone preservation the proven benefits, while transdermal estrogen and micronized progesterone carry lower clotting and breast-cancer risk than older oral and synthetic forms.", "updated": "2026-10-15", "sources": 18, "url": "https://heretic.bio/articles/hormone-optimization-trt-hrt-perimenopause.html", "markdown": "https://heretic.bio/articles/hormone-optimization-trt-hrt-perimenopause.md" }, { "slug": "hyperbaric-oxygen-therapy-hbot", "name": "Hyperbaric oxygen (HBOT)", "aliases": [], "type": "Therapy", "rating": "promising", "fields": [], "goals": [ "inj", "cog" ], "description": "Breathing pure oxygen under pressure is proven for wounds, CO poisoning and a dozen cleared uses, while anti-aging and brain claims lack trial support.", "short_answer": "HBOT means breathing 100% oxygen at raised pressure, which loads oxygen into plasma and reaches poorly perfused tissue. It is cleared for about a dozen indications including diabetic foot ulcers, carbon monoxide poisoning and radiation injury, with a meta-analysis showing 43% better ulcer healing. Off-label uses such as brain injury, longevity and anti-aging have no randomized trials and remain speculative.", "updated": "2026-08-06", "sources": 4, "url": "https://heretic.bio/articles/hyperbaric-oxygen-therapy-hbot.html", "markdown": "https://heretic.bio/articles/hyperbaric-oxygen-therapy-hbot.md" }, { "slug": "ifs-internal-family-systems", "name": "IFS (Internal Family Systems)", "aliases": [], "type": "Therapy", "rating": "speculative", "fields": [], "goals": [ "mind" ], "description": "A psychotherapy model treating the mind as protective and wounded parts around a core Self, supported by a few small randomized trials.", "short_answer": "Internal Family Systems is a therapy model developed by Richard Schwartz that treats the mind as naturally divided into protective managers and firefighters plus wounded exiles, ideally led by a core Self. Two small randomized trials found benefit for depression and for rheumatoid arthritis outcomes, and a 2025 scoping review catalogued consistent positive findings. The evidence base is still small, so the rating stays speculative despite its SAMHSA registry listing.", "updated": "2026-08-06", "sources": 4, "url": "https://heretic.bio/articles/ifs-internal-family-systems.html", "markdown": "https://heretic.bio/articles/ifs-internal-family-systems.md" }, { "slug": "immune-function", "name": "Immune function", "aliases": [], "type": "Mechanism", "rating": "speculative", "fields": [], "goals": [ "inf" ], "description": "How immune aging works and what might slow it, from Soviet-era thymic peptides to a trial where low-dose everolimus boosted vaccine response.", "short_answer": "Immunosenescence is the age-related remodeling of immunity: the thymus shrinks, naive T cells run out and latent CMV infection inflates the memory pool, leaving older adults over-inflamed and under-protected. This entry surveys countermeasures from Soviet thymic peptides to mTOR inhibitors; the most rigorous result is a trial where low-dose everolimus improved flu vaccine response about 20% in the elderly. Most of the rest rests on decades of Russian clinical reports rather than modern randomized trials.", "updated": "2026-08-06", "sources": 1, "url": "https://heretic.bio/articles/immune-function.html", "markdown": "https://heretic.bio/articles/immune-function.md" }, { "slug": "intermittent-hypoxia-hyperoxia-training-ihht", "name": "IHHT", "aliases": [], "type": "Therapy", "rating": "promising", "fields": [ "soviet" ], "goals": [ "age", "met" ], "description": "Alternating low-oxygen and high-oxygen air as a hormetic stressor, with controlled trials in cardiac and long-COVID rehab but no longevity endpoint data.", "short_answer": "IHHT alternates brief periods of low-oxygen and high-oxygen air at normal pressure, aiming for a hormetic HIF-1a and mitochondrial response. Controlled trials report improved exercise capacity, blood pressure and inflammation markers in cardiac rehab, long COVID and mild cognitive impairment, with a clean safety record. There are no large randomized trials and no mortality or aging endpoints, so it is a plausible rehabilitation tool, not a proven longevity intervention.", "updated": "2026-08-01", "sources": 6, "url": "https://heretic.bio/articles/intermittent-hypoxia-hyperoxia-training-ihht.html", "markdown": "https://heretic.bio/articles/intermittent-hypoxia-hyperoxia-training-ihht.md" }, { "slug": "ketogenic-approaches", "name": "Ketogenic diets", "aliases": [], "type": "Diet", "rating": "promising", "fields": [], "goals": [ "met", "cog" ], "description": "A high-fat, very-low-carb diet that is proven for drug-resistant epilepsy and type 2 diabetes, with early evidence in neurology and psychiatry.", "short_answer": "A ketogenic diet is high fat, moderate protein and very low carbohydrate, shifting metabolism toward ketones. It is proven in drug-resistant pediatric epilepsy, where 50-70% of children achieve major seizure reduction, and a one-year study reported diabetes reversal in 60% of patients. Evidence for Alzheimer's, psychiatric conditions, cancer adjunct use and longevity is early and mostly mechanistic, which is why the overall rating stays cautious.", "updated": "2026-10-15", "sources": 8, "url": "https://heretic.bio/articles/ketogenic-approaches.html", "markdown": "https://heretic.bio/articles/ketogenic-approaches.md" }, { "slug": "klotho-the-longevity-hormone", "name": "Klotho", "aliases": [], "type": "Mechanism", "rating": "early", "fields": [], "goals": [ "age" ], "description": "A kidney- and brain-derived longevity protein: overexpression extends mouse lifespan about 20-30%, yet no human has received it in a published trial.", "short_answer": "Klotho is a protein made mainly in kidney and brain that falls with age; low levels track higher mortality and cognitive decline in large cohorts. In animals the evidence is strong: overexpression extends mouse lifespan about 20-30%, and a single low-dose injection improved memory in aged monkeys. But no human has received klotho in a published trial, and the gene-therapy outfits selling it, including a non-placebo plasmid pilot, are running ahead of the science.", "updated": "2026-10-14", "sources": 14, "url": "https://heretic.bio/articles/klotho-the-longevity-hormone.html", "markdown": "https://heretic.bio/articles/klotho-the-longevity-hormone.md" }, { "slug": "lions-mane-and-mushroom-nootropics", "name": "Lion's mane and mushroom nootropics", "aliases": [], "type": "Compound", "rating": "promising", "fields": [ "nootropics" ], "goals": [ "cog" ], "description": "A medicinal mushroom whose compounds stimulate nerve growth factor; small trials show cognitive benefit in impairment but none acutely in healthy adults.", "short_answer": "Lion's mane contains hericenones and erinacines that stimulate nerve growth factor, a mechanism no common supplement shares. Human trials are small but real: a 16-week trial improved cognition in mild impairment and a 49-week pilot helped mild Alzheimer's, with gains fading after stopping, while a 2025 acute study in healthy young adults found nothing. A 2025 systematic review of registered trials found it safe, with benefits across cognition, mood and sleep in small, short studies.", "updated": "2026-08-06", "sources": 12, "url": "https://heretic.bio/articles/lions-mane-and-mushroom-nootropics.html", "markdown": "https://heretic.bio/articles/lions-mane-and-mushroom-nootropics.md" }, { "slug": "longevity-medicine-2026", "name": "Longevity medicine in 2026", "aliases": [], "type": "Guide", "rating": "early", "fields": [], "goals": [ "age" ], "description": "A map of the 2026 longevity clinic stack: biological-age tests, AI platforms and wearable clocks, and the evidence behind each pillar.", "short_answer": "Longevity medicine in 2026 runs on four pillars: multi-omic biological age testing, AI interpretation platforms, wearable aging clocks and physician oversight. The measurement science is real; third-generation epigenetic clocks predict mortality with AUCs of 0.80-0.87 and a wearable clock trained on 213,593 people estimates age within about 2.4 years. But no clinic has shown that acting on these scores improves outcomes, so the testing is informative while the intervention claims remain unproven.", "updated": "2026-08-06", "sources": 3, "url": "https://heretic.bio/articles/longevity-medicine-2026.html", "markdown": "https://heretic.bio/articles/longevity-medicine-2026.md" }, { "slug": "longevity-science-overview", "name": "Longevity science", "aliases": [], "type": "Guide", "rating": "speculative", "fields": [], "goals": [ "age" ], "description": "An overview of aging biology and interventions: lifestyle has the strongest evidence, while drugs like rapamycin show only surrogate-endpoint results.", "short_answer": "Longevity science targets the biological processes of aging itself, organized around the 12 hallmarks framework. The evidence pyramid is clear: exercise, sleep, diet and social connection have the strongest mortality data, while pharmaceuticals like rapamycin and metformin show safety and biomarker signals but nothing on human lifespan or healthspan endpoints. The best human trials so far, PEARL for rapamycin and TRIIM for epigenetic-age reversal, are small, short and surrogate-based.", "updated": "2026-10-14", "sources": 18, "url": "https://heretic.bio/articles/longevity-science-overview.html", "markdown": "https://heretic.bio/articles/longevity-science-overview.md" }, { "slug": "low-dose-naltrexone-ldn-evidence-taxonomy", "name": "Low-dose naltrexone (LDN)", "aliases": [], "type": "Compound", "rating": "speculative", "fields": [], "goals": [ "inf", "mind" ], "description": "Naltrexone at a tenth of the addiction dose, used off-label for pain, autoimmune and post-viral conditions, with one small Crohn's RCT as best evidence.", "short_answer": "LDN is naltrexone at about a tenth of the addiction dose, used off-label for fibromyalgia, Crohn's, MS, ME/CFS and long COVID. The best evidence is a single small randomized trial in Crohn's disease showing symptom improvement and mucosal healing; the long COVID data is four uncontrolled studies totaling 155 patients. It is safe and cheap, but every non-addiction use is unproven, largely because no sponsor funds trials of a generic drug.", "updated": "2026-08-06", "sources": 4, "url": "https://heretic.bio/articles/low-dose-naltrexone-ldn-evidence-taxonomy.html", "markdown": "https://heretic.bio/articles/low-dose-naltrexone-ldn-evidence-taxonomy.md" }, { "slug": "lyme-and-co-infections", "name": "Lyme and co-infections", "aliases": [], "type": "Condition", "rating": "speculative", "fields": [], "goals": [ "inf" ], "description": "Lyme disease and its co-infections, where persistence is proven in animal models but long-term antibiotic benefit in humans is contested.", "short_answer": "Lyme is the most common vector-borne disease in the Northern Hemisphere, and chronic cases sit at the center of a genuine scientific dispute. Borrelia's ability to form biofilms, encyst and persist after antibiotics is well documented in vitro and in monkeys, but whether that explains ongoing symptoms is unproven, and randomized trials of long-term antibiotics are mixed. Co-infections like Babesia and Bartonella are common, underdiagnosed and often untreated.", "updated": "2026-08-06", "sources": 5, "url": "https://heretic.bio/articles/lyme-and-co-infections.html", "markdown": "https://heretic.bio/articles/lyme-and-co-infections.md" }, { "slug": "magnesium-types", "name": "Magnesium forms", "aliases": [], "type": "Compound", "rating": "proven", "fields": [], "goals": [ "cog", "met" ], "description": "A guide to magnesium forms: glycinate and citrate absorb well, threonate is the only brain-targeted form with RCT data, and oxide is nearly useless.", "short_answer": "Magnesium is required for over 600 enzymatic reactions and deficiency is widespread, but the salt form changes everything: glycinate and citrate absorb well, oxide barely does, and threonate is the only form with randomized-trial evidence for brain effects. Sleep trials are positive but modest; in one 155-person study 81% saw no clinically meaningful benefit, and meta-analyses show no lipid effect beyond a small HDL rise. A proven nutrient with real but modest trial effects.", "updated": "2026-10-14", "sources": 11, "url": "https://heretic.bio/articles/magnesium-types.html", "markdown": "https://heretic.bio/articles/magnesium-types.md" }, { "slug": "metabolic-health-and-insulin", "name": "Metabolic health and insulin", "aliases": [], "type": "Mechanism", "rating": "speculative", "fields": [], "goals": [ "met" ], "description": "The insulin-centric model of chronic disease: chronically high insulin drives obesity, diabetes and beyond, and fasting insulin reveals it a decade early.", "short_answer": "This entry presents the insulin-centric model: chronic carbohydrate excess keeps insulin elevated, cells become resistant, and the resulting hyperinsulinemia is proposed to drive obesity, diabetes, cardiovascular disease and related conditions years before glucose or HbA1c move. Fasting insulin and HOMA-IR are the early markers discussed for tracking risk. The framework is mechanistically coherent and useful for risk detection, though insulin-as-root-cause remains a contested model rather than settled consensus.", "updated": "2026-08-06", "sources": 3, "url": "https://heretic.bio/articles/metabolic-health-and-insulin.html", "markdown": "https://heretic.bio/articles/metabolic-health-and-insulin.md" }, { "slug": "metformin-and-rapamycin", "name": "Metformin and rapamycin", "aliases": [], "type": "Compound", "rating": "early", "fields": [], "goals": [ "age", "met" ], "description": "The two flagship anti-aging drugs compared: rapamycin extends mouse lifespan, metformin has decades of safety data, and neither is proven in humans.", "short_answer": "Metformin and rapamycin are the best-known pharmaceutical longevity candidates. Rapamycin robustly extends lifespan in mice, including when started late in life, while metformin's case rests on diabetes outcomes and confounded observational data. Neither drug has a completed human lifespan trial, and the definitive metformin trial, TAME, is still not recruiting, so both sit at promising rather than proven.", "updated": "2026-10-15", "sources": 7, "url": "https://heretic.bio/articles/metformin-and-rapamycin.html", "markdown": "https://heretic.bio/articles/metformin-and-rapamycin.md" }, { "slug": "methylene-blue", "name": "Methylene blue", "aliases": [], "type": "Compound", "rating": "speculative", "fields": [ "nootropics" ], "goals": [ "cog" ], "description": "A 170-year-old dye turned mitochondrial drug: approved for methemoglobinemia, with small fMRI trials for cognition and contested phase 3 Alzheimer's data.", "short_answer": "Methylene blue is an old synthetic dye that donates electrons in the mitochondrial transport chain at low doses and inhibits MAO at high doses. It is FDA-approved for methemoglobinemia, and recent randomized trials show a pressor-sparing benefit in septic shock without proven mortality benefit. For cognition, two small fMRI trials show acute effects but no chronic-dosing trial exists, and the phase 3 Alzheimer's program is contested because it lacked a true placebo arm.", "updated": "2026-08-06", "sources": 7, "url": "https://heretic.bio/articles/methylene-blue.html", "markdown": "https://heretic.bio/articles/methylene-blue.md" }, { "slug": "mitochondrial-health", "name": "Mitochondrial health", "aliases": [], "type": "Mechanism", "rating": "promising", "fields": [ "light" ], "goals": [ "age", "met", "cog" ], "description": "How mitochondria are maintained and measured: exercise is the strongest proven lever, and urolithin A is the first mitophagy inducer with a human RCT.", "short_answer": "Mitochondrial health is the cell's capacity to produce ATP and recycle damaged mitochondria, and its decline tracks fatigue, metabolic disease and aging. Exercise is the only intervention with multi-system human evidence; urolithin A became the first mitophagy inducer with a randomized trial in 2025, and CoQ10 has the strongest supplement data. A 2026 review states plainly that no mitochondrial intervention has been shown to slow aging in healthy humans.", "updated": "2026-10-14", "sources": 13, "url": "https://heretic.bio/articles/mitochondrial-health.html", "markdown": "https://heretic.bio/articles/mitochondrial-health.md" }, { "slug": "modafinil-and-eugeroics", "name": "Modafinil and eugeroics", "aliases": [], "type": "Compound", "rating": "promising", "fields": [ "nootropics" ], "goals": [ "cog" ], "description": "A wakefulness drug approved for narcolepsy and shift work that modestly enhances higher-order cognition in healthy adults, with low abuse risk.", "short_answer": "Modafinil is a wakefulness-promoting drug approved for narcolepsy, sleep apnea and shift-work disorder, used off-label as a cognitive enhancer. A systematic review of 24 placebo-controlled studies found it improves executive function, learning and memory in healthy non-sleep-deprived adults, but effects are modest and largest when users are tired, tasks are hard or baseline performance is low. Dependence risk is low, though it carries a rare Stevens-Johnson risk and reduces the effectiveness of hormonal birth control.", "updated": "2026-10-15", "sources": 8, "url": "https://heretic.bio/articles/modafinil-and-eugeroics.html", "markdown": "https://heretic.bio/articles/modafinil-and-eugeroics.md" }, { "slug": "mold-illness-mycotoxins-and-cirs", "name": "Mold illness and CIRS", "aliases": [], "type": "Condition", "rating": "speculative", "fields": [], "goals": [ "inf" ], "description": "Damp-building illness is well documented; the CIRS framework for it rests on one research group and its urine mycotoxin tests are contested.", "short_answer": "CIRS is a proposed multisystem illness in which genetically susceptible people (about 25% by HLA type) fail to clear biotoxins from water-damaged buildings, driving chronic innate inflammation. The solid part: damp buildings cause illness across 112 of 114 epidemiological studies and mycotoxins are demonstrably toxic. The contested part: the diagnostic biomarker panel, urine mycotoxin testing and the 12-step Shoemaker treatment protocol come almost entirely from one research group, and toxicology bodies question the commercial testing.", "updated": "2026-10-15", "sources": 8, "url": "https://heretic.bio/articles/mold-illness-mycotoxins-and-cirs.html", "markdown": "https://heretic.bio/articles/mold-illness-mycotoxins-and-cirs.md" }, { "slug": "mots-c-mitochondrial-open-reading-frame-of-12s-rrna-type-c", "name": "MOTS-c", "aliases": [ "Mitochondrial ORF of the 12S rRNA Type-C", "Mitochondrial-derived peptide MOTS-c" ], "type": "Compound", "rating": "early", "fields": [ "peptides" ], "goals": [ "met", "age" ], "description": "A mitochondrial-encoded peptide with strong rodent metabolic data; the only completed human trial used an analog. A Phase 2 of native MOTS-c is recruiting.", "short_answer": "MOTS-c is a 16-amino-acid peptide encoded by mitochondrial DNA that acts like an exercise signal, activating AMPK and improving glucose handling in rodents. Human evidence is thin: the only completed trial tested an analog (CB4211) in a Phase 1 study, where liver enzymes improved but the liver-fat imaging endpoint did not beat placebo. A Phase 2 trial of native MOTS-c in prediabetes started recruiting in 2026. Everything else is rodent data and observational correlations.", "updated": "2026-10-14", "sources": 10, "url": "https://heretic.bio/articles/mots-c-mitochondrial-open-reading-frame-of-12s-rrna-type-c.html", "markdown": "https://heretic.bio/articles/mots-c-mitochondrial-open-reading-frame-of-12s-rrna-type-c.md" }, { "slug": "mtor-and-ampk-pathways", "name": "mTOR and AMPK", "aliases": [], "type": "Mechanism", "rating": "speculative", "fields": [], "goals": [ "age" ], "description": "The cell's two metabolic switches: mTOR builds, AMPK repairs. Mechanistic evidence is strong; human longevity trials are still pending.", "short_answer": "mTOR and AMPK are the cell's two master metabolic switches: mTOR drives growth and protein synthesis, AMPK drives repair, autophagy and fat burning. The mechanistic evidence is strong and chronic mTOR activation is now classed as a hallmark of aging, but human proof is thin. Rapamycin healthspan data rests on surveys and off-label use, and metformin's lifespan benefit awaits the unfinished TAME trial. The working model is cycling between the two states, not blocking either.", "updated": "2026-08-06", "sources": 11, "url": "https://heretic.bio/articles/mtor-and-ampk-pathways.html", "markdown": "https://heretic.bio/articles/mtor-and-ampk-pathways.md" }, { "slug": "muse-cell-therapy-evidence-taxonomy-and-clinical-translation", "name": "Muse cell therapy", "aliases": [], "type": "Therapy", "rating": "early", "fields": [], "goals": [ "inj" ], "description": "A pluripotent-like cell therapy with small Japanese disease trials; the anti-aging claims marketed to longevity patients rest on a two-person case series.", "short_answer": "Muse cells are stress-enduring, pluripotent-like cells discovered by Mari Dezawa's group, infused without HLA matching. Small academic Japanese trials report improved heart function after heart attack, faster ulcer healing in epidermolysis bullosa, and a roughly 40% responder rate in subacute stroke versus 10% on placebo. The anti-aging claims marketed by Eterna Health rest on a two-patient case series measured by an epigenetic clock. No large randomized trial exists for any indication.", "updated": "2026-10-15", "sources": 0, "url": "https://heretic.bio/articles/muse-cell-therapy-evidence-taxonomy-and-clinical-translation.html", "markdown": "https://heretic.bio/articles/muse-cell-therapy-evidence-taxonomy-and-clinical-translation.md" }, { "slug": "nad-and-sirtuin-activators", "name": "NAD+", "aliases": [], "type": "Compound", "rating": "promising", "fields": [], "goals": [ "age" ], "description": "A metabolic cofactor; NR and NMN precursors reliably raise blood NAD+ in human trials, but functional benefits are unproven.", "short_answer": "NAD+ is a cofactor every cell needs for energy production, DNA repair and sirtuin signaling. Multiple randomized trials show the oral precursors NR and NMN reliably raise blood NAD+, and a 2026 crossover trial showed NR raises brain NAD+ in humans. The caveats are large: whole-blood NAD+ does not actually decline with age (2026 Nature Metabolism), 24 weeks of high-dose NMN produced no functional benefit, and no trial shows lifespan extension. IV NAD+ rests on anecdotes and small uncontrolled reports.", "updated": "2026-10-14", "sources": 21, "url": "https://heretic.bio/articles/nad-and-sirtuin-activators.html", "markdown": "https://heretic.bio/articles/nad-and-sirtuin-activators.md" }, { "slug": "natural-nootropics", "name": "Natural nootropics", "aliases": [], "type": "Compound", "rating": "promising", "fields": [ "nootropics" ], "goals": [ "cog" ], "description": "Plant and nutrient-based cognitive enhancers with several real randomized trials; effects are genuine but modest and domain-specific.", "short_answer": "Natural nootropics are plant- and nutrient-derived compounds taken for cognition. A few have credible human data: bacopa improves memory after 8 to 12 weeks, L-theanine with caffeine improves attention, alpha-GPC and citicoline show benefits in dementia and mild cognitive impairment, and a 2026 trial showed single-dose creatine protects cognition during sleep deprivation. Effects are generally modest and strongest in people with deficits or under stress, not in healthy young adults.", "updated": "2026-08-06", "sources": 19, "url": "https://heretic.bio/articles/natural-nootropics.html", "markdown": "https://heretic.bio/articles/natural-nootropics.md" }, { "slug": "nootropic-combinations", "name": "Nootropic combinations studied", "aliases": [], "type": "Guide", "rating": "speculative", "fields": [ "nootropics" ], "goals": [ "cog" ], "description": "A guide to combining cognitive enhancers by mechanism; only the caffeine plus L-theanine pairing has direct human trial support.", "short_answer": "Nootropic stacking means combining compounds that hit different cognitive pathways at once. The logic is mechanistically sound, but almost no stack has been tested as a combination. The exception is caffeine plus L-theanine, which improved speed, accuracy and resistance to distraction in human trials. Everything else rests on single-ingredient evidence plus mechanism reasoning, such as pairing racetams with a choline donor to cover increased acetylcholine demand.", "updated": "2026-10-15", "sources": 15, "url": "https://heretic.bio/articles/nootropic-combinations.html", "markdown": "https://heretic.bio/articles/nootropic-combinations.md" }, { "slug": "nootropics-and-smart-drugs-overview", "name": "Nootropics and smart drugs", "aliases": [], "type": "Guide", "rating": "early", "fields": [ "nootropics" ], "goals": [ "cog" ], "description": "An overview of cognitive enhancers from caffeine and theanine to modafinil, ranked by evidence; the strongest data cover narrow domains and impaired users.", "short_answer": "Nootropics are compounds meant to improve cognition without significant side effects; by Giurgea's original 1972 criteria, few marketed products qualify. The evidence is uneven: modafinil works for wakefulness and executive function but is prescription-only, while caffeine plus L-theanine, citicoline, bacopa, lion's mane, rhodiola and ashwagandha each have human trials showing modest, domain-specific effects. The field's own honest assessment is that no compound compensates for poor sleep, inactivity or bad nutrition.", "updated": "2026-10-14", "sources": 9, "url": "https://heretic.bio/articles/nootropics-and-smart-drugs-overview.html", "markdown": "https://heretic.bio/articles/nootropics-and-smart-drugs-overview.md" }, { "slug": "optimal-human-nutrition-overview", "name": "Human nutrition", "aliases": [], "type": "Guide", "rating": "speculative", "fields": [], "goals": [ "met" ], "description": "A first-principles guide to the diet paradigms, from keto to carnivore to Mediterranean, with the evidence graded and industry conflicts flagged.", "short_answer": "This is the site's framework for reading nutrition science: humans evolved as omnivores, hormones rather than raw calories drive metabolic outcomes, and dietary guidelines carry documented industry influence. The strong consensus points are that ultra-processed food is harmful (a controlled feeding trial showed it drives excess calorie intake), adequate protein matters, and time-restricted eating has real metabolic benefits. Most paradigm-level claims, including the carnivore and seed-oil positions, rest on weaker or contested evidence.", "updated": "2026-08-06", "sources": 7, "url": "https://heretic.bio/articles/optimal-human-nutrition-overview.html", "markdown": "https://heretic.bio/articles/optimal-human-nutrition-overview.md" }, { "slug": "organ-meats-and-nose-to-tail-eating", "name": "Organ meats", "aliases": [], "type": "Diet", "rating": "speculative", "fields": [], "goals": [ "met" ], "description": "The case for liver, heart and other organs as the most nutrient-dense foods, built on nutrient analysis and anthropology rather than clinical trials.", "short_answer": "Organ meats are the most nutrient-dense foods in the comparison data: beef liver supplies many times the recommended intake for vitamin A, B12, folate, copper and choline per serving, and heart is the richest food source of CoQ10. The broader claims, that traditional cultures prized organs and that 'like supports like' through tissue-specific peptides, rest on anthropology and plausibility rather than trials. Safety is reasonable with caveats: organs can concentrate toxins and very high liver intake risks vitamin A toxicity.", "updated": "2026-08-06", "sources": 0, "url": "https://heretic.bio/articles/organ-meats-and-nose-to-tail-eating.html", "markdown": "https://heretic.bio/articles/organ-meats-and-nose-to-tail-eating.md" }, { "slug": "ozone-therapy", "name": "Ozone therapy", "aliases": [], "type": "Therapy", "rating": "early", "fields": [], "goals": [ "inf", "inj" ], "description": "Medical ozone (O2-O3 mixture) for wounds, disc herniation and joint pain, with several RCTs locally but no FDA approval and poor protocol standardization.", "short_answer": "Medical ozone is a controlled oxygen-ozone mixture proposed to work through hormesis: a mild oxidative pulse that activates Nrf2 and antioxidant defenses. Evidence is condition-specific. Systematic reviews and randomized trials support it as an adjunct for chronic wounds, diabetic foot ulcers and lumbar disc herniation pain, with weaker data for knee osteoarthritis. It is not FDA-approved, protocols vary widely, and the systemic detox and longevity claims outrun the evidence. Ozone must never be inhaled.", "updated": "2026-08-06", "sources": 9, "url": "https://heretic.bio/articles/ozone-therapy.html", "markdown": "https://heretic.bio/articles/ozone-therapy.md" }, { "slug": "pain-management", "name": "Pain management", "aliases": [], "type": "Guide", "rating": "speculative", "fields": [], "goals": [ "inj" ], "description": "An integrative pain framework covering topical analgesics, DMSO as carrier and agent, peptides and nervous-system downregulation, sorted by pain type.", "short_answer": "This guide sorts pain by mechanism (nociceptive, neuropathic, nociplastic) and matches tools to each. The best-documented agent here is topical DMSO, a transdermal carrier with anti-inflammatory properties: one controlled trial supports it in complex regional pain syndrome, and it is FDA-approved for interstitial cystitis. Other options range from moderate-evidence topical NSAIDs to preclinical peptides. The framework's claim that root-cause treatment beats symptom suppression is a position, not a tested outcome.", "updated": "2026-08-06", "sources": 2, "url": "https://heretic.bio/articles/pain-management.html", "markdown": "https://heretic.bio/articles/pain-management.md" }, { "slug": "partial-epigenetic-reprogramming", "name": "Partial epigenetic reprogramming", "aliases": [], "type": "Mechanism", "rating": "speculative", "fields": [], "goals": [ "age" ], "description": "Resetting cellular age with transient Yamanaka-factor (OSK) expression; the first human trial began dosing in June 2026 for optic neuropathies.", "short_answer": "Partial epigenetic reprogramming uses short pulses of three Yamanaka factors (OSK, without c-Myc) to reset epigenetic age markers while keeping cell identity. The evidence is preclinical: mouse studies show restored function and lifespan effects, and a primate model showed restored methylation patterns. The first human trial, Life Biosciences' ER-100 for optic neuropathies, dosed its first patient in June 2026. It is a small open-label safety study (n=18) with initial results expected in late 2026.", "updated": "2026-08-06", "sources": 1, "url": "https://heretic.bio/articles/partial-epigenetic-reprogramming.html", "markdown": "https://heretic.bio/articles/partial-epigenetic-reprogramming.md" }, { "slug": "peptide-bioregulation-khavinson", "name": "Peptide bioregulators (Khavinson)", "aliases": [], "type": "Compound", "rating": "speculative", "fields": [ "peptides", "bioregulators", "soviet" ], "goals": [ "age" ], "description": "Fifty years of Soviet research into short peptides claimed to regulate gene expression, with six Russian-approved drugs but little independent replication.", "short_answer": "Khavinson's peptide bioregulators are ultrashort peptides (2-7 amino acids) claimed to regulate gene expression by binding DNA promoter regions, developed over 50 years of Soviet and Russian research. Six are registered medicines in Russia and observational studies claim large mortality reductions in the elderly. The caveats are fundamental: nearly everything comes from one research group, the mortality claims rest on non-Western trial methods, and the flagship Epitalon telomerase claim got its first independent replication only in 2025. A Hopkins-Harvard review calls Epitalon biologically active but clinically unproven.", "updated": "2026-08-06", "sources": 12, "url": "https://heretic.bio/articles/peptide-bioregulation-khavinson.html", "markdown": "https://heretic.bio/articles/peptide-bioregulation-khavinson.md" }, { "slug": "peptide-evidence-grading-framework", "name": "Peptide evidence grading", "aliases": [], "type": "Method", "rating": "speculative", "fields": [ "peptides" ], "goals": [], "description": "A proposed framework scoring peptides on a five-tier evidence scale plus a regulatory tier, applied to the 2026 FDA compounding reviews.", "short_answer": "This is a method note, not a therapy: a five-tier evidence scale running from human randomized trials down to anecdote, combined with a regulatory tier running from FDA-approved to prohibited. Applied to mid-2026 examples, most gray-market peptides land at Tier 3-4, meaning animal or mechanistic data only, while their regulatory status shifted with the April 2026 Category 2 removal and the July 2026 PCAC reviews. It is a proposed framework for sorting claims, not a clinical tool.", "updated": "2026-08-06", "sources": 0, "url": "https://heretic.bio/articles/peptide-evidence-grading-framework.html", "markdown": "https://heretic.bio/articles/peptide-evidence-grading-framework.md" }, { "slug": "peptide-sciences-shutdown-us-gray-market-collapse-fda-enforcement-wave", "name": "Peptide gray-market enforcement", "aliases": [], "type": "Regulatory", "rating": "early", "fields": [ "peptides" ], "goals": [], "description": "The 2026 collapse of the US research-peptide gray market: Peptide Sciences' shutdown, 50+ FDA warning letters, and the PCAC vote for compounding.", "short_answer": "Peptide Sciences, the largest US gray-market peptide vendor, shut down in March 2026 amid 50+ FDA warning letters and DOJ pleas. In July an FDA committee voted to allow compounding of BPC-157, TB-500 and four others, but as of October 2026 FDA has not listed them, so buyers face a shrinking gray market and no legal pharmacy route yet.", "updated": "2026-10-15", "sources": 3, "url": "https://heretic.bio/articles/peptide-sciences-shutdown-us-gray-market-collapse-fda-enforcement-wave.html", "markdown": "https://heretic.bio/articles/peptide-sciences-shutdown-us-gray-market-collapse-fda-enforcement-wave.md" }, { "slug": "peptide-sources-and-quality", "name": "Peptide sources and quality", "aliases": [], "type": "Guide", "rating": "speculative", "fields": [ "peptides" ], "goals": [], "description": "How to vet gray-market peptide suppliers: COAs, HPLC purity, mass-spec checks, cold chain, and the red flags that mark counterfeits.", "short_answer": "The research-peptide market has essentially no regulatory oversight, so quality verification falls on the buyer. This guide lays out the mechanics: batch-specific certificates of analysis showing HPLC purity above 98% and mass-spec confirmation, third-party lab testing, cold-chain shipping, and red flags from missing COAs to implausibly low prices. It is practical guidance, not proof a product is safe or effective. Most of these peptides are unapproved for human use and several are WADA-banned.", "updated": "2026-08-06", "sources": 0, "url": "https://heretic.bio/articles/peptide-sources-and-quality.html", "markdown": "https://heretic.bio/articles/peptide-sources-and-quality.md" }, { "slug": "peptide-therapy-for-injuries", "name": "Peptides for injury", "aliases": [], "type": "Guide", "rating": "early", "fields": [ "peptides" ], "goals": [ "inj" ], "description": "Peptides like BPC-157 and TB-500 for tissue repair, where 2025-2026 reviews found abundant animal data but almost no human orthopedic trials.", "short_answer": "Peptides such as BPC-157, TB-500 and GHK-Cu are promoted for tissue repair, and the preclinical data are genuinely strong across tendon, bone, muscle and gut models. The human orthopedic evidence is nearly absent: a 2025 systematic review of 544 articles found one human study, a retrospective series of 12 knee-pain patients, and a 2026 scoping review found zero human interventional TB-500 studies in musculoskeletal use. The strongest human signal for thymosin beta-4 is a 2025 cardiac trial, not injury.", "updated": "2026-10-14", "sources": 3, "url": "https://heretic.bio/articles/peptide-therapy-for-injuries.html", "markdown": "https://heretic.bio/articles/peptide-therapy-for-injuries.md" }, { "slug": "peptide-therapy-for-trauma", "name": "Peptides for trauma", "aliases": [], "type": "Guide", "rating": "speculative", "fields": [ "peptides" ], "goals": [ "mind" ], "description": "A guide pairing trauma's biological sequelae (gut, nerve, immune, tissue) with peptides like BPC-157; evidence is almost all preclinical.", "short_answer": "This guide maps peptides onto the biological sequelae of trauma: BPC-157 for gut and tissue repair, TB-500 and GHK-Cu for tissue and inflammation, Cortexin and Semax for nervous-system recovery, Selank for anxiety. The rationale is mechanistically coherent, but the evidence is almost entirely preclinical or from Russian clinical tradition; only one animal study addresses PTSD-like behaviors directly. No peptide is FDA-approved for any trauma application, and sourcing quality is the main practical risk.", "updated": "2026-08-06", "sources": 2, "url": "https://heretic.bio/articles/peptide-therapy-for-trauma.html", "markdown": "https://heretic.bio/articles/peptide-therapy-for-trauma.md" }, { "slug": "phage-therapy", "name": "Phage therapy", "aliases": [], "type": "Therapy", "rating": "promising", "fields": [ "soviet" ], "goals": [ "inf" ], "description": "Viruses that kill specific bacteria, used for a century in Georgia and Russia; modern trials confirm safety, with efficacy best for isolate-matched cases.", "short_answer": "Phage therapy uses bacteriophages, viruses that infect specific bacteria, to treat infections. It is established medicine in Georgia and Russia and has documented US compassionate-use cures, including the landmark 2017 Patterson case. The honest modern evidence: 13 recent trials found it generally safe but efficacy inconsistent, and the one placebo-controlled trial found a commercial UTI cocktail non-inferior to antibiotics but not better than placebo irrigation. The strongest use case is personalized phage matching for drug-resistant infections.", "updated": "2026-10-15", "sources": 9, "url": "https://heretic.bio/articles/phage-therapy.html", "markdown": "https://heretic.bio/articles/phage-therapy.md" }, { "slug": "plasmalogens-and-membrane-health", "name": "Plasmalogens", "aliases": [], "type": "Compound", "rating": "promising", "fields": [], "goals": [ "cog", "age" ], "description": "Vinyl-ether membrane lipids that decline steeply with age and track cognitive decline; supplements raise blood levels, but no placebo trial exists.", "short_answer": "Plasmalogens are membrane phospholipids whose vinyl-ether bond makes them sacrificial antioxidants; they concentrate in brain and heart and fall steeply after age 50. Low blood levels robustly predict cognitive decline in cohort data including Framingham. The intervention evidence is much thinner: one open-label trial of a DHA precursor (n=22) raised blood plasmalogens dose-dependently and 41% of participants improved on the CDR scale, but there is no placebo-controlled trial, and the FDA warned the lead researcher's clinic in 2025 for studying supplements without an IND.", "updated": "2026-08-06", "sources": 6, "url": "https://heretic.bio/articles/plasmalogens-and-membrane-health.html", "markdown": "https://heretic.bio/articles/plasmalogens-and-membrane-health.md" }, { "slug": "polyvagal-theory", "name": "Polyvagal theory", "aliases": [], "type": "Mechanism", "rating": "speculative", "fields": [], "goals": [ "mind" ], "description": "Stephen Porges' three-tier model of the autonomic nervous system, widely used in trauma therapy to explain fight, flight, freeze and safety states.", "short_answer": "Polyvagal theory, developed by Stephen Porges, proposes a three-tier autonomic hierarchy: a ventral vagal state for social engagement and safety, a sympathetic state for fight-or-flight, and a dorsal vagal state for freeze and shutdown. Trauma, in this model, leaves the nervous system miscalibrated, reading safe situations as threats. It is influential in somatic and trauma therapy and gives a coherent frame for interventions like co-regulation and vagal stimulation. The cited support is the originator's own books and clinical organizations, not controlled trials.", "updated": "2026-08-06", "sources": 0, "url": "https://heretic.bio/articles/polyvagal-theory.html", "markdown": "https://heretic.bio/articles/polyvagal-theory.md" }, { "slug": "prolotherapy", "name": "Prolotherapy", "aliases": [], "type": "Therapy", "rating": "promising", "fields": [], "goals": [ "inj" ], "description": "Dextrose injections that restart the healing cascade in ligaments and tendons, with multiple trials for knee osteoarthritis and an excellent safety record.", "short_answer": "Prolotherapy injects a mild irritant, usually hyperosmolar dextrose, into ligament and tendon insertions to trigger controlled inflammation and new collagen growth. It is one of the better-evidenced regenerative injections: a systematic review found moderate evidence for safety and symptom control in knee osteoarthritis, with positive trials in tendinopathy and sacroiliac dysfunction. Serious adverse events are essentially absent from the literature. Caveats: it is rarely covered by insurance, and the evidence is still small trials rather than large definitive ones.", "updated": "2026-10-15", "sources": 3, "url": "https://heretic.bio/articles/prolotherapy.html", "markdown": "https://heretic.bio/articles/prolotherapy.md" }, { "slug": "prp-and-stem-cell-therapies", "name": "PRP and stem cells", "aliases": [], "type": "Therapy", "rating": "promising", "fields": [], "goals": [ "inj" ], "description": "Autologous platelet concentrates and mesenchymal stem cells for joints and tendons; PRP has multiple positive trials, stem cells are mostly unapproved.", "short_answer": "PRP concentrates your own platelets to deliver growth factors to damaged tissue; stem cell therapy delivers progenitor cells that work mainly through paracrine signaling. PRP has real trial support: multiple randomized trials show it beating hyaluronic acid and saline in knee osteoarthritis, plus positive data in tendinopathy and hair loss, with an excellent safety profile as an autologous product. Stem cell evidence is weaker and most orthopedic stem cell treatments are not FDA-approved, with unregulated clinics a real hazard.", "updated": "2026-10-15", "sources": 2, "url": "https://heretic.bio/articles/prp-and-stem-cell-therapies.html", "markdown": "https://heretic.bio/articles/prp-and-stem-cell-therapies.md" }, { "slug": "psychedelic-assisted-therapy", "name": "Psychedelic-assisted therapy", "aliases": [], "type": "Therapy", "rating": "promising", "fields": [], "goals": [ "mind" ], "description": "MDMA, psilocybin and ketamine combined with psychotherapy for PTSD and depression; Phase 3 data exist for MDMA, and ketamine is FDA-approved.", "short_answer": "Psychedelic-assisted therapy pairs a supervised drug session with preparation and integration psychotherapy. The evidence is promising but uneven: MDMA-assisted therapy reduced PTSD symptoms versus placebo-plus-therapy in Phase 2 and 3 trials with benefits held at 12 months, psilocybin has its strongest data in treatment-resistant depression and end-of-life anxiety, and ketamine is the only FDA-approved option. Key caveats are strict exclusion criteria, near-impossible blinding, and limited long-term safety data. MDMA and psilocybin remain Schedule I federally.", "updated": "2026-10-15", "sources": 0, "url": "https://heretic.bio/articles/psychedelic-assisted-therapy.html", "markdown": "https://heretic.bio/articles/psychedelic-assisted-therapy.md" }, { "slug": "racetams", "name": "Racetams", "aliases": [], "type": "Compound", "rating": "early", "fields": [ "nootropics" ], "goals": [ "cog" ], "description": "A class of synthetic nootropics led by piracetam; a 2024 pooled analysis found no memory benefit, though narrow medical uses are proven.", "short_answer": "Racetams are synthetic nootropics built on a pyrrolidone core, modulating AMPA glutamate and cholinergic signaling. The honest verdict: piracetam has real, narrow clinical wins (cortical myoclonus, dyslexia adjunct, post-stroke and post-ECT cognitive recovery), but the 2024 AAN meta-analysis of 18 randomized trials found no significant memory benefit versus placebo. The newer racetams (aniracetam through noopept) rest mostly on older European and Russian trials never replicated in the West. None are FDA-approved for cognition; phenylpiracetam is WADA-banned.", "updated": "2026-10-14", "sources": 7, "url": "https://heretic.bio/articles/racetams.html", "markdown": "https://heretic.bio/articles/racetams.md" }, { "slug": "rapamycin-mtor-inhibition-pearl-trial-evidence-and-clinical-translation", "name": "Rapamycin", "aliases": [], "type": "Compound", "rating": "early", "fields": [], "goals": [ "age" ], "description": "An immunosuppressant repurposed off-label for longevity; it extends mouse lifespan but human trials show modest, mixed signals.", "short_answer": "Rapamycin (sirolimus) is an FDA-approved transplant drug now prescribed off-label at low intermittent doses for longevity. The animal data are the best in geroscience, with 9-30% mouse lifespan extension, but no human trial has shown a lifespan benefit. The two key human trials are PEARL (n=114, safe, modest lean-mass and pain signals in women) and RAPA-EX-01 (n=40, weekly dosing attenuated exercise training gains in sensitivity analyses). The open question has shifted from safety to dosing interval.", "updated": "2026-10-15", "sources": 5, "url": "https://heretic.bio/articles/rapamycin-mtor-inhibition-pearl-trial-evidence-and-clinical-translation.html", "markdown": "https://heretic.bio/articles/rapamycin-mtor-inhibition-pearl-trial-evidence-and-clinical-translation.md" }, { "slug": "red-light-therapy", "name": "Red light therapy", "aliases": [], "type": "Therapy", "rating": "promising", "fields": [ "light" ], "goals": [ "inj", "cog" ], "description": "Photobiomodulation with red and near-infrared light; trials support it for neck pain, knee arthritis and wounds, while brain claims remain early.", "short_answer": "Photobiomodulation uses red (630-680 nm) and near-infrared (810-1100 nm) light to relieve nitric-oxide inhibition of mitochondrial cytochrome c oxidase, raising ATP output. It is one of the few alternative therapies with hundreds of randomized trials behind it: strong evidence for chronic neck pain, knee osteoarthritis, wound healing and chemotherapy-induced oral mucositis. Brain and longevity claims are early, transcranial light penetration is small, and the dose response is biphasic, so more is not better.", "updated": "2026-08-06", "sources": 9, "url": "https://heretic.bio/articles/red-light-therapy.html", "markdown": "https://heretic.bio/articles/red-light-therapy.md" }, { "slug": "regenerative-medicine-overview", "name": "Regenerative medicine", "aliases": [], "type": "Guide", "rating": "speculative", "fields": [], "goals": [ "inj" ], "description": "A map of regenerative therapies for orthopedic injury, from trial-backed options (PRP, PEMF, HBOT) to experimental ones (stem cells, peptides).", "short_answer": "Regenerative medicine aims to repair tissue rather than suppress symptoms, and the evidence varies enormously by modality. The randomized-trial-backed options are PRP for tendinopathy, PEMF for fracture non-union and HBOT for diabetic wounds; prolotherapy and shockwave sit at moderate. Stem cell therapy is early, with bone marrow concentrate the best-studied source and birth-tissue products often containing no viable cells; peptides like BPC-157 are preclinical. Almost all of it is out of pocket.", "updated": "2026-08-06", "sources": 5, "url": "https://heretic.bio/articles/regenerative-medicine-overview.html", "markdown": "https://heretic.bio/articles/regenerative-medicine-overview.md" }, { "slug": "russian-pharmacology", "name": "Russian pharmacology", "aliases": [], "type": "Guide", "rating": "early", "fields": [ "soviet" ], "goals": [ "cog" ], "description": "A guide to Soviet and Russian pharmacology: adaptogens, peptide nootropics, meldonium and phenibut, and evidence that rarely meets modern RCT standards.", "short_answer": "Soviet and Russian pharmacology built a distinct drug culture around performance, resilience and state institutes, producing compounds like Semax, Selank, meldonium, phenibut and cortexin. The evidence is mostly regional comparative studies, mechanistic work and institutional experience rather than blinded randomized trials, so the leads are real but most efficacy claims are unproven. Some entries carry serious risks, above all phenibut's dependence and withdrawal.", "updated": "2026-08-06", "sources": 14, "url": "https://heretic.bio/articles/russian-pharmacology.html", "markdown": "https://heretic.bio/articles/russian-pharmacology.md" }, { "slug": "seed-oils-and-inflammation", "name": "Seed oils and inflammation", "aliases": [], "type": "Diet", "rating": "speculative", "fields": [], "goals": [ "met" ], "description": "The case against seed oils rests on linoleic-acid oxidation mechanisms and recovered trial data; short-term human RCTs find no inflammatory signal.", "short_answer": "Seed oils are rich in linoleic acid, which critics say drives oxidative damage, membrane fragility and inflammatory signaling through oxidized metabolites (OXLAMs). The direct human evidence cuts both ways: two recent randomized crossover trials found no rise in inflammatory markers or oxidized LDL, and an 11-RCT review found some seed oils improve lipids in diabetics, while recovered-data reanalyses of older trials found higher mortality on linoleate-rich diets. The unresolved issue is chronic exposure, since tissue linoleic acid has a 600-800 day half-life that short trials cannot probe.", "updated": "2026-10-15", "sources": 14, "url": "https://heretic.bio/articles/seed-oils-and-inflammation.html", "markdown": "https://heretic.bio/articles/seed-oils-and-inflammation.md" }, { "slug": "selank-tuftsin-derived-anxiolytic-peptide", "name": "Selank", "aliases": [], "type": "Compound", "rating": "promising", "fields": [ "peptides", "nootropics", "soviet" ], "goals": [ "mind", "cog" ], "description": "A tuftsin-derived anxiolytic peptide approved in Russia; small trials show benzodiazepine-comparable anxiety relief, but no Western trials exist.", "short_answer": "Selank is a synthetic heptapeptide analog of the immune peptide tuftsin, developed in Moscow and approved in Russia for generalized anxiety since 2009. Small Russian randomized trials (n=60-70) found anxiolysis comparable to medazepam and phenazepam without sedation, dependence or cognitive impairment, and a 2024 open-label cohort (n=64) reported benefit in post-COVID asthenia. There are no Western randomized trials and no FDA approval, so the signal is promising but geographically narrow.", "updated": "2026-10-14", "sources": 17, "url": "https://heretic.bio/articles/selank-tuftsin-derived-anxiolytic-peptide.html", "markdown": "https://heretic.bio/articles/selank-tuftsin-derived-anxiolytic-peptide.md" }, { "slug": "semax-acth4-7-pgp-neurotrophic-peptide", "name": "Semax", "aliases": [ "Semax® (0.1% and 1% solutions)", "Heptapeptide ACTH(4-7)-PGP" ], "type": "Compound", "rating": "promising", "fields": [ "peptides", "nootropics", "soviet" ], "goals": [ "cog" ], "description": "An ACTH-derived heptapeptide approved in Russia for stroke; evidence is Russian clinical studies and preclinical work, with no double-blind Western RCTs.", "short_answer": "Semax is a synthetic ACTH(4-7) analog developed at Moscow's Institute of Molecular Genetics in 1982 and approved in Russia for stroke, encephalopathy and optic nerve disease. Human evidence is Russian-language: a stroke study (n=110) reported raised plasma BDNF, and a pilot fMRI study (n=24) found default-mode-network effects in healthy volunteers. A 2023-2026 wave of animal and molecular studies identified new targets, but no English-language double-blind RCT exists.", "updated": "2026-08-06", "sources": 16, "url": "https://heretic.bio/articles/semax-acth4-7-pgp-neurotrophic-peptide.html", "markdown": "https://heretic.bio/articles/semax-acth4-7-pgp-neurotrophic-peptide.md" }, { "slug": "senolytics", "name": "Senolytics", "aliases": [], "type": "Compound", "rating": "early", "fields": [], "goals": [ "age" ], "description": "Drugs that selectively kill senescent cells; small human pilots show dasatinib plus quercetin clears them, but lifespan benefit is animal data only.", "short_answer": "Senolytics are compounds that selectively eliminate senescent cells, which accumulate with age and drive inflammation through the SASP. Human evidence is early: small open-label pilots of dasatinib plus quercetin (n=9 in diabetic kidney disease, n=14 in pulmonary fibrosis) reduced senescent-cell burden and improved physical function, and foselutoclax posted positive phase 2b results in diabetic macular edema. Mouse studies show lifespan extension, but no human trial has tested hard aging outcomes.", "updated": "2026-08-06", "sources": 18, "url": "https://heretic.bio/articles/senolytics.html", "markdown": "https://heretic.bio/articles/senolytics.md" }, { "slug": "sglt2-inhibitors-as-senotherapeutics-evidence-taxonomy", "name": "SGLT2 inhibitors", "aliases": [], "type": "Compound", "rating": "early", "fields": [], "goals": [ "age", "met" ], "description": "A diabetes drug class proven for heart and kidney outcomes; its senolytic case rests on animal and cell data plus one small telomere RCT.", "short_answer": "SGLT2 inhibitors are approved diabetes drugs that unexpectedly engage aging biology: AMPK and SIRT1 activation, SASP suppression, and immune-mediated clearance of senescent cells shown in cell and mouse studies. The human evidence is large but indirect: EMPA-REG showed a 32% reduction in all-cause mortality in diabetics with cardiovascular disease, and one small RCT found leukocyte telomere lengthening at 26 weeks. No trial has tested senescence or healthspan endpoints in healthy people, and canagliflozin shortened female mouse lifespan in the ITP dataset.", "updated": "2026-10-14", "sources": 12, "url": "https://heretic.bio/articles/sglt2-inhibitors-as-senotherapeutics-evidence-taxonomy.html", "markdown": "https://heretic.bio/articles/sglt2-inhibitors-as-senotherapeutics-evidence-taxonomy.md" }, { "slug": "sleep-optimization", "name": "Sleep", "aliases": [], "type": "Guide", "rating": "promising", "fields": [], "goals": [ "cog", "mind" ], "description": "A guide to sleep physiology and optimization: sleep stages, glymphatic clearance, circadian cues, supplements, prescription drugs and tracking metrics.", "short_answer": "Sleep drives memory consolidation, hormone regulation and glymphatic clearance of amyloid-beta and tau; even one night of poor sleep measurably reduces insulin sensitivity. Evidence strength varies by lever: light, temperature and schedule have solid circadian rationale, magnesium and glycine have randomized-trial support, and orexin-antagonist drugs have phase III data. Closed-loop acoustic stimulation is promising for boosting slow-wave sleep in older adults but is not yet standard of care.", "updated": "2026-10-14", "sources": 13, "url": "https://heretic.bio/articles/sleep-optimization.html", "markdown": "https://heretic.bio/articles/sleep-optimization.md" }, { "slug": "somatic-experiencing", "name": "Somatic Experiencing", "aliases": [], "type": "Therapy", "rating": "speculative", "fields": [], "goals": [ "mind" ], "description": "Peter Levine's body-based trauma therapy; two small RCTs and meta-analyses show reduced PTSD symptoms, but evidence certainty is rated very low.", "short_answer": "Somatic Experiencing is Peter Levine's body-based trauma therapy, built on completing interrupted fight-flight-freeze responses rather than retelling the trauma. Controlled evidence is thin: a waitlist-controlled RCT (n=63) found large PTSD symptom reductions and a second RCT (n=91) found large effects in chronic pain patients with comorbid PTSD, but a 2020 meta-analysis rated the certainty very low and ISTSS lists it as emerging, not first-line.", "updated": "2026-08-06", "sources": 15, "url": "https://heretic.bio/articles/somatic-experiencing.html", "markdown": "https://heretic.bio/articles/somatic-experiencing.md" }, { "slug": "soviet-medical-research-overview", "name": "Soviet medical research", "aliases": [], "type": "Guide", "rating": "speculative", "fields": [ "soviet" ], "goals": [], "description": "A survey of Soviet medical research, from peptide bioregulators to phage therapy, adaptogens and space medicine, and what the West has since validated.", "short_answer": "The USSR ran a parallel, state-funded medical tradition that produced peptide bioregulators, bacteriophage therapy, adaptogen pharmacology and space medicine, much of it never absorbed by the West. Validation is uneven: phage therapy is now NIH- and EU-funded mainstream research and adaptogens have modern randomized trials, while Khavinson's longevity peptide claims have never been tested in a registered Western RCT. Most primary literature is Russian-only, so each claim has to be individually traced rather than adopted or dismissed wholesale.", "updated": "2026-08-06", "sources": 4, "url": "https://heretic.bio/articles/soviet-medical-research-overview.html", "markdown": "https://heretic.bio/articles/soviet-medical-research-overview.md" }, { "slug": "soviet-space-medicine", "name": "Soviet space medicine", "aliases": [], "type": "Guide", "rating": "early", "fields": [ "soviet" ], "goals": [], "description": "A survey of Soviet space medicine, from microgravity countermeasures to adaptogens and peptides, and which parts translate to terrestrial health.", "short_answer": "Soviet space medicine was a whole-system survival science built to keep humans functional under microgravity, radiation and isolation, producing decades of long-duration physiology data. What transfers well is mechanical loading and autonomic reconditioning; what does not is pharmacology, since adaptogen and peptide claims rest mostly on historical use, patents and animal work. With bone loss near 1-2% per month and 20% muscle atrophy in 11 days, spaceflight works as a rough accelerated-aging model, not a perfect one.", "updated": "2026-08-06", "sources": 5, "url": "https://heretic.bio/articles/soviet-space-medicine.html", "markdown": "https://heretic.bio/articles/soviet-space-medicine.md" }, { "slug": "spermidine-autophagy-and-longevity", "name": "Spermidine", "aliases": [], "type": "Compound", "rating": "early", "fields": [], "goals": [ "age" ], "description": "A polyamine that induces autophagy; lifespan extension is shown in mice and flies, while human evidence is early cognitive and cardiovascular signals.", "short_answer": "Spermidine is a natural polyamine that induces autophagy through EP300 inhibition and eIF5A hypusination, and it extends lifespan across yeast, flies, worms and mice (about 10% in mice). Human evidence is early: small trials show cognitive and cardiovascular signals, and observational data link higher dietary intake to lower all-cause mortality. The catch is dose: a 2024 exploratory RCT found 40 mg/day barely moved circulating polyamine levels, so whether oral dosing raises tissue levels is unresolved.", "updated": "2026-10-14", "sources": 11, "url": "https://heretic.bio/articles/spermidine-autophagy-and-longevity.html", "markdown": "https://heretic.bio/articles/spermidine-autophagy-and-longevity.md" }, { "slug": "ss-31-elamipretide-cardiolipin-targeted-mitochondrial-peptide", "name": "SS-31 (elamipretide)", "aliases": [ "Elamipretide®", "Bendavia®", "MTP-131", "FORZINITY™ (FDA-approved for Barth syndrome)", "SS-31" ], "type": "Compound", "rating": "promising", "fields": [ "peptides" ], "goals": [ "age" ], "description": "A cardiolipin-targeting mitochondrial peptide, FDA accelerated-approved for Barth syndrome in 2025 on open-label data after primary endpoints missed.", "short_answer": "SS-31 (elamipretide, FORZINITY) is a pentapeptide that binds cardiolipin on the inner mitochondrial membrane to stabilize electron transport and reduce ROS. It received FDA accelerated approval in September 2025 for Barth syndrome in patients weighing at least 30 kg, the first approval of its kind, but the basis was narrow: the randomized trial's co-primary endpoints were negative and approval rested on strength gains in a 168-week open-label extension with 8 completers. A confirmatory randomized trial is required by 2029-2030, and a phase 3 in mitochondrial myopathy previously failed.", "updated": "2026-10-14", "sources": 5, "url": "https://heretic.bio/articles/ss-31-elamipretide-cardiolipin-targeted-mitochondrial-peptide.html", "markdown": "https://heretic.bio/articles/ss-31-elamipretide-cardiolipin-targeted-mitochondrial-peptide.md" }, { "slug": "stealth-pathogens", "name": "Stealth pathogens", "aliases": [], "type": "Condition", "rating": "speculative", "fields": [], "goals": [ "inf" ], "description": "A framework for chronic infections that evade immunity via biofilms, L-forms and intracellular persistence; mechanisms solid, clinical reach contested.", "short_answer": "Stealth pathogens are microbes that persist by shedding their cell walls (L-forms), hiding inside host cells, forming biofilms, or entering dormant persister states, which defeats standard cultures and cell-wall-targeting antibiotics. The underlying biology is well established: biofilm organisms are 10-1000x more resistant to antimicrobials, and the NIH has estimated over 80% of chronic infections involve biofilms. The weaker link is broad disease attribution: associations with chronic fatigue, MS and ALS exist, but causation is unproven.", "updated": "2026-08-06", "sources": 12, "url": "https://heretic.bio/articles/stealth-pathogens.html", "markdown": "https://heretic.bio/articles/stealth-pathogens.md" }, { "slug": "sulforaphane-nrf2-activation-and-clinical-evidence", "name": "Sulforaphane", "aliases": [], "type": "Compound", "rating": "early", "fields": [], "goals": [ "age", "inf" ], "description": "A broccoli-sprout isothiocyanate and the best-studied natural Nrf2 activator, with a human RCT ledger containing real positives and real nulls.", "short_answer": "Sulforaphane is an isothiocyanate generated from glucoraphanin in cruciferous vegetables, richest in broccoli sprouts, and the most-studied natural activator of the Nrf2 defense pathway. Its human RCT ledger is real but mixed: small trials show a replicated benefit on schizophrenia negative symptoms and clean pollutant-detoxication data, while prediabetes and lung-chemoprevention trials missed their primary endpoints. The practical catch is conversion: glucoraphanin supplements only work if your gut microbes or an added enzyme supply myrosinase.", "updated": "2026-10-15", "sources": 31, "url": "https://heretic.bio/articles/sulforaphane-nrf2-activation-and-clinical-evidence.html", "markdown": "https://heretic.bio/articles/sulforaphane-nrf2-activation-and-clinical-evidence.md" }, { "slug": "supplements-and-nutraceuticals", "name": "Supplements and nutraceuticals", "aliases": [], "type": "Guide", "rating": "promising", "fields": [], "goals": [ "age", "met" ], "description": "A framework for supplement use built on testing and evidence tiers, covering vitamin D, magnesium, omega-3 and creatine data plus what to avoid.", "short_answer": "This is a tiered framework: test first, supplement for confirmed deficiencies or increased demand, and insist on third-party quality certification. The top tier has real RCT meta-analyses, including vitamin D3 cutting all-cause mortality 6% across 56 trials and omega-3 cutting MI risk 28% in VITAL, while condition-specific and longevity tiers get progressively thinner. Some popular products are actively harmful, such as high-dose beta-carotene in smokers and iron taken without testing.", "updated": "2026-10-14", "sources": 10, "url": "https://heretic.bio/articles/supplements-and-nutraceuticals.html", "markdown": "https://heretic.bio/articles/supplements-and-nutraceuticals.md" }, { "slug": "taurine-the-aging-amino-acid", "name": "Taurine", "aliases": [], "type": "Compound", "rating": "early", "fields": [], "goals": [ "age" ], "description": "An amino acid that extends mouse lifespan 10-12%; human trials show modest cardiometabolic benefit, and the age-decline premise was refuted in 2025.", "short_answer": "Taurine is one of the body's most abundant free amino acids. A 2023 Science paper showed supplementation extends mouse lifespan 10-12% and improves healthspan in monkeys, but two 2025 studies overturned its core premise: blood taurine does not reliably decline with age. Human randomized trials show modest but real cardiometabolic benefits on blood pressure, glucose and lipids, and the dedicated TauAge aging trial finished primary completion in November 2025 with results pending.", "updated": "2026-10-15", "sources": 12, "url": "https://heretic.bio/articles/taurine-the-aging-amino-acid.html", "markdown": "https://heretic.bio/articles/taurine-the-aging-amino-acid.md" }, { "slug": "tb-500-and-bpc-157-combination", "name": "TB-500 and BPC-157 together", "aliases": [], "type": "Guide", "rating": "early", "fields": [ "peptides" ], "goals": [ "inj" ], "description": "The 'Wolverine Stack' pairs two gray-market repair peptides; BPC-157 has five small uncontrolled human studies, TB-500 has none, and the stack is untested.", "short_answer": "The Wolverine Stack combines BPC-157 and TB-500 for injury recovery. BPC-157 has extensive rodent data and five small uncontrolled human reports totaling under 80 subjects, all from one research group; TB-500 has zero published human trials as of September 2026. No study has tested the combination against either peptide alone. Neither is FDA-approved, both are WADA-prohibited, and a July 2026 FDA advisory vote recommending 503A compounding inclusion is non-binding pending rulemaking.", "updated": "2026-10-14", "sources": 8, "url": "https://heretic.bio/articles/tb-500-and-bpc-157-combination.html", "markdown": "https://heretic.bio/articles/tb-500-and-bpc-157-combination.md" }, { "slug": "tb-500-thymosin-beta-4", "name": "TB-500 (thymosin beta-4)", "aliases": [ "Thymosin β4", "Tβ4", "TB4", "TB-500" ], "type": "Compound", "rating": "early", "fields": [ "peptides" ], "goals": [ "inj" ], "description": "A synthetic fragment of thymosin beta-4; full-length T-beta-4 has phase II wound, eye and cardiac trials, but the TB-500 fragment has no human studies.", "short_answer": "TB-500 is the research-market name for an active fragment (amino acids 17-23) of thymosin beta-4, a natural actin-binding peptide involved in cell migration and wound repair. Full-length T-beta-4 has real human data, including phase II/III trials in dry eye and dermal wounds and a phase II cardiac RCT reporting ejection-fraction improvement, but the TB-500 fragment itself has no published human studies. A 2026 scoping review of 80 papers makes this distinction explicit. It is also flagged as unsafe in active malignancy because it promotes migration and angiogenesis.", "updated": "2026-10-14", "sources": 9, "url": "https://heretic.bio/articles/tb-500-thymosin-beta-4.html", "markdown": "https://heretic.bio/articles/tb-500-thymosin-beta-4.md" }, { "slug": "telomere-science", "name": "Telomeres", "aliases": [], "type": "Mechanism", "rating": "promising", "fields": [], "goals": [ "age" ], "description": "Telomeres shorten with cell division and age; recent RCTs show a drug and exercise can lengthen them in humans, but the anti-aging payoff is unproven.", "short_answer": "Telomeres are the protective caps on chromosome ends that shorten with each cell division, and their length is one of the more reliable biological aging markers. Elongation was long considered one-directional in adults, but a 2025 RCT showed the SGLT2 inhibitor henagliflozin lengthened leukocyte telomeres in 26 weeks, a 2026 RCT showed combined physical and cognitive training lengthened them in MCI patients, and hTERT mRNA therapy produced sustained elongation in telomere-disorder patients. Whether lengthening telomeres slows human aging is unproven, and the cancer question remains open.", "updated": "2026-10-14", "sources": 8, "url": "https://heretic.bio/articles/telomere-science.html", "markdown": "https://heretic.bio/articles/telomere-science.md" }, { "slug": "therapeutic-peptides", "name": "Therapeutic peptides", "aliases": [], "type": "Guide", "rating": "early", "fields": [ "peptides" ], "goals": [ "inj", "age" ], "description": "A landscape guide to therapeutic peptides: repair compounds like BPC-157, Russian bioregulators, cognitive peptides and GLP-1s, each graded by evidence.", "short_answer": "Peptides are short amino-acid chains (2-50 residues) sitting between small molecules and biologics: highly target-specific, cheap to synthesize, but mostly not orally bioavailable. The evidence is bimodal: GLP-1 agonists are approved drugs with huge phase 3 programs and elamipretide won accelerated FDA approval for Barth syndrome in 2025, while BPC-157, TB-500 and the Russian bioregulators rest on animal data or Russian clinical literature. The dominant practical risk is sourcing, because research peptides have no standardized quality control.", "updated": "2026-10-14", "sources": 8, "url": "https://heretic.bio/articles/therapeutic-peptides.html", "markdown": "https://heretic.bio/articles/therapeutic-peptides.md" }, { "slug": "therapeutic-plasma-exchange-tpe", "name": "Therapeutic plasma exchange", "aliases": [], "type": "Therapy", "rating": "promising", "fields": [], "goals": [ "age" ], "description": "Plasma exchange is FDA-cleared for autoimmune and blood disorders; for longevity, one small RCT found a transient 2.6-year drop in measured biological age.", "short_answer": "Therapeutic plasma exchange removes plasma containing pro-aging factors and replaces it with albumin or donor products. It is an established, FDA-cleared treatment for conditions like Guillain-Barre and TTP; for longevity, the evidence is one 2025 randomized placebo-controlled trial (n=44) in which TPE plus IVIG cut composite biological age by 2.6 years across 36 epigenetic clocks. Effects waned within months, the trial had no IVIG-only arm, and sicker participants benefited most. Long-term safety of repeated use is unknown.", "updated": "2026-10-15", "sources": 6, "url": "https://heretic.bio/articles/therapeutic-plasma-exchange-tpe.html", "markdown": "https://heretic.bio/articles/therapeutic-plasma-exchange-tpe.md" }, { "slug": "thymalin", "name": "Thymalin", "aliases": [], "type": "Compound", "rating": "speculative", "fields": [ "peptides", "bioregulators", "soviet" ], "goals": [ "inf", "age" ], "description": "A calf-thymus peptide complex approved in Russia; claimed mortality reductions in elderly cohorts are dramatic but rest on Russian non-randomized research.", "short_answer": "Thymalin is a calf-thymus polypeptide complex developed by Vladimir Khavinson and approved in Russia as an immunomodulator. The flagship claim, a 266-person elderly cohort reporting two- to four-fold mortality reductions over six years, comes from non-randomized Russian research, and a single-blind COVID-19 trial (n=80) reported halved hospital mortality in severe cases. No independent Western RCT exists, and the effect sizes are large enough that replication is the whole question.", "updated": "2026-08-06", "sources": 4, "url": "https://heretic.bio/articles/thymalin.html", "markdown": "https://heretic.bio/articles/thymalin.md" }, { "slug": "thymosin-alpha-1-immune-modulation-and-longevity-translation", "name": "Thymosin alpha-1", "aliases": [], "type": "Compound", "rating": "early", "fields": [ "peptides" ], "goals": [ "inf" ], "description": "A thymic peptide approved in 35+ countries for hepatitis and cancer adjuvant use; the landmark sepsis trial was null and longevity claims are extrapolated.", "short_answer": "Thymosin alpha-1 (thymalfasin, Zadaxin) is a 28-amino-acid thymic peptide approved in more than 35 countries for hepatitis B/C and as a cancer adjuvant, with a 2024 review covering over 11,000 subjects. The sepsis and longevity-clinic story is weaker: the largest randomized trial, TESTS (n=1,106), found no mortality benefit in sepsis, and a 2025 meta-analysis found earlier positive signals erode in high-quality trials. The live edge is oncology, where small studies position it as an immune-checkpoint-inhibitor adjunct.", "updated": "2026-10-14", "sources": 10, "url": "https://heretic.bio/articles/thymosin-alpha-1-immune-modulation-and-longevity-translation.html", "markdown": "https://heretic.bio/articles/thymosin-alpha-1-immune-modulation-and-longevity-translation.md" }, { "slug": "trauma-and-somatic-therapies", "name": "Trauma and the body", "aliases": [], "type": "Guide", "rating": "speculative", "fields": [], "goals": [ "mind" ], "description": "A guide to body-based trauma therapy: how trauma dysregulates the nervous system, the ACE evidence on disease risk, and which modalities have real trials.", "short_answer": "This guide covers somatic and body-based trauma therapies, grounded in the finding that childhood adversity predicts adult disease in a dose-response way (the 17,000-person ACE study). The neurobiology is solid, but modality evidence varies sharply: EMDR, prolonged exposure and cognitive processing therapy have strong randomized-trial support, Somatic Experiencing and IFS are a tier down, and Brainspotting or TRE rest on limited data. The claim that the body stores trauma is plausible, while the causal details remain unsettled.", "updated": "2026-08-06", "sources": 1, "url": "https://heretic.bio/articles/trauma-and-somatic-therapies.html", "markdown": "https://heretic.bio/articles/trauma-and-somatic-therapies.md" }, { "slug": "urolithin-a-mitophagy-inducer-and-geroprotectant", "name": "Urolithin A", "aliases": [], "type": "Compound", "rating": "promising", "fields": [], "goals": [ "age" ], "description": "A gut-microbiome-derived postbiotic that induces mitophagy; four small RCTs show muscle and immune benefits, all short and industry-funded.", "short_answer": "Urolithin A is a postbiotic made by gut bacteria from ellagitannins in pomegranate and walnuts, and the first compound shown to induce mitophagy in human trials. Four randomized trials (n=50-88) found better muscle strength or endurance, improved mitochondrial markers, and a remodeled T-cell profile; lifespan data are animal-only. Caveats: no trial ran longer than 4 months, most were funded by the manufacturer, and about a third of people cannot produce it from food at all.", "updated": "2026-10-15", "sources": 10, "url": "https://heretic.bio/articles/urolithin-a-mitophagy-inducer-and-geroprotectant.html", "markdown": "https://heretic.bio/articles/urolithin-a-mitophagy-inducer-and-geroprotectant.md" }, { "slug": "vitamin-d-optimization", "name": "Vitamin D", "aliases": [], "type": "Compound", "rating": "promising", "fields": [ "sun" ], "goals": [ "inf", "age" ], "description": "A fat-soluble vitamin deficient in ~42% of US adults; mortality benefits appear mainly in deficient people, while large trials in the replete were null.", "short_answer": "Vitamin D deficiency affects about 42% of US adults and far more in dark-skinned populations, and this entry argues the 30 ng/mL threshold marks adequacy against rickets rather than optimal health. The evidence splits by baseline status: meta-analyses find lower cancer and all-cause mortality mainly in deficient or older subgroups, while VITAL and D-Health found no benefit in largely replete populations. Mendelian randomization supports a causal role for low vitamin D in MS, type 1 diabetes and mortality.", "updated": "2026-08-06", "sources": 6, "url": "https://heretic.bio/articles/vitamin-d-optimization.html", "markdown": "https://heretic.bio/articles/vitamin-d-optimization.md" }, { "slug": "vitamin-k2", "name": "Vitamin K2", "aliases": [], "type": "Compound", "rating": "speculative", "fields": [], "goals": [ "age" ], "description": "The vitamin that directs calcium into bone via osteocalcin and blocks arterial calcification via MGP; large Western outcome trials are still missing.", "short_answer": "Vitamin K2 activates osteocalcin, which deposits calcium into bone, and matrix Gla protein, which blocks calcium deposition in arteries. Observational cohorts link high K2 intake to 50% lower CHD mortality and Japanese data show fewer vertebral fractures, but the controlled evidence is thinner: a slowed coronary-calcification signal in one RCT sub-group and a null trial in hemodialysis patients. The entry concedes that large Western RCTs proving reduced events or fractures are still lacking.", "updated": "2026-08-06", "sources": 1, "url": "https://heretic.bio/articles/vitamin-k2.html", "markdown": "https://heretic.bio/articles/vitamin-k2.md" }, { "slug": "what-36000-nootropic-ratings-actually-tell-us", "name": "What 36,000 nootropic ratings show", "aliases": [], "type": "Guide", "rating": "speculative", "fields": [ "nootropics" ], "goals": [ "cog" ], "description": "An analysis of 36,000 self-reported nootropic ratings: useful for hypotheses, but self-selection and no blinding make it weak efficacy evidence.", "short_answer": "The Nootroflix dataset holds about 36,000 ratings from 2,802 users of the Slate Star Codex nootropics surveys. Weightlifting, sleep and meditation rank alongside prescription stimulants at the top, but the data are unblinded, uncontrolled and self-selected, so high ratings describe reported experience, not causal efficacy, and the safety model is weaker still. Its real value is flagging which claims deserve controlled testing.", "updated": "2026-10-14", "sources": 0, "url": "https://heretic.bio/articles/what-36000-nootropic-ratings-actually-tell-us.html", "markdown": "https://heretic.bio/articles/what-36000-nootropic-ratings-actually-tell-us.md" } ] }