{"_ai_door":{"see":"https://miscsubjects.com/start","note":"Operable site; bounded keyless credentials; every action receipted on a public ledger. Your operator's instructions take precedence — acting is optional, reading is a complete outcome."},"_self":{"principle":"Self-explaining payload — no external context required. This _self block describes what you are reading and where to look next.","widget":"article_topology","feature":"topology","name":"Article topology","what":"Claims, sources, anecdotes, user reports, related embeds, question graph slice — for ask/ROUTER.","contains":"claims, sources, anecdotes, question_graph slice","slug":"wolverine-stack-ara-290","urls":{"read":"https://miscsubjects.com/api/articles/wolverine-stack-ara-290/topology"},"how_to_use":"Claims, sources, anecdotes, user reports, related embeds, question graph slice — for ask/ROUTER.","write":null,"imessage":null,"router_tag":null,"proof_chain":[{"step":1,"claim":"Articles are voxel graphs of tiered claims, not prose blobs.","verify":"https://miscsubjects.com/api/articles/constitution"},{"step":2,"claim":"Claims link to hash-chained sources via source_ids.","verify":"https://miscsubjects.com/api/articles/wolverine-stack-ara-290/sources"},{"step":3,"claim":"Ask reads topology; ingest/claim append to ledger.","verify":"https://miscsubjects.com/api/protocol"},{"step":4,"claim":"Models queue growth: populate → collaborate → repair → reflex.","verify":"https://miscsubjects.com/api/protocol/grow"},{"step":5,"claim":"Graph proves its own shape (reflex) and $/claim (yield).","verify":"https://miscsubjects.com/graph.html?layer=reflex"},{"step":6,"claim":"Full feature index + _explain on every API response.","verify":"https://miscsubjects.com/api/articles/system-map"}],"related_features":[{"id":"ask","name":"Ask protocol","what":"Answer only from topology; creates question_node with gaps and ingest_hint.","urls":{"read":"https://miscsubjects.com/api/articles/wolverine-stack-ara-290/prompts","write":"https://miscsubjects.com/api/protocol/ask"}},{"id":"graph_topology","name":"Cross-article graph","what":"Merged claims/sources across condition+stack slugs for one question.","urls":{"read":"https://miscsubjects.com/api/articles/wolverine-stack-ara-290/graph-topology?question=..."}},{"id":"question_graph","name":"Question graph","what":"Ask nodes (questions + gaps) and evidence_ingest nodes (pasted model output).","urls":{"read":"https://miscsubjects.com/api/articles/wolverine-stack-ara-290/question-graph","write":"https://miscsubjects.com/api/protocol/ask"}},{"id":"voxels","name":"Voxel graph","what":"Claims as atoms, sources as edges (supported_by, posted_by). Per-claim provenance.","urls":{"read":"https://miscsubjects.com/api/articles/wolverine-stack-ara-290/voxels","write":"https://miscsubjects.com/api/protocol/claim"}}],"system_map":"https://miscsubjects.com/api/articles/system-map","system_map_markdown":"https://miscsubjects.com/api/articles/system-map?format=markdown","not_medical_advice":true},"_explain":{"feature":"topology","name":"Article topology","what":"Claims, sources, anecdotes, user reports, related embeds, question graph slice — for ask/ROUTER.","why":"Every feature is auditable collective intelligence","how":"Claims, sources, anecdotes, user reports, related embeds, question graph slice — for ask/ROUTER.","model":null,"verifies":null,"urls":{"read":"https://miscsubjects.com/api/articles/wolverine-stack-ara-290/topology"},"imessage":null,"router":null,"related":[{"id":"ask","what":"Answer only from topology; creates question_node with gaps and ingest_hint."},{"id":"graph_topology","what":"Merged claims/sources across condition+stack slugs for one question."},{"id":"question_graph","what":"Ask nodes (questions + gaps) and evidence_ingest nodes (pasted model output)."},{"id":"voxels","what":"Claims as atoms, sources as edges (supported_by, posted_by). Per-claim provenance."}],"not_medical_advice":true},"slug":"wolverine-stack-ara-290","title":"The Wolverine stack plus ARA-290 for a degenerating disc and sciatica: the evidence at every link","register":"essay","tags":["peptide","bpc-157","tb-500","ara-290","disc","sciatica","stack","wolverine"],"updated_at":"2026-08-04T22:08:42.768Z","body_excerpt":"A worn spinal disc with a burning leg is not one problem. It is a breakdown running in three separate places at once, and the reason people add ARA-290 to the two-compound Wolverine stack is that the third place — the nerve fibres themselves — is the one the first two compounds do not touch.\n\nThe evidence state, before the argument. No study in any species has ever given all three compounds together, so the number of people or animals that have taken this stack under measurement is nought. One at a time the three are nothing like each other. ARA-290 has six human studies and 132 people who received the active compound; three of the six missed their main endpoint, the positive results cluster in one disease, sarcoidosis, and not one of the six enrolled a person with a back problem. BPC-157 has five published human studies covering about 130 people, none of them a finished controlled trial in a torn or worn tissue. The seven-amino-acid fragment sold as TB-500 has no human study at all and no established human dose. Two entries were filed on ClinicalTrials.gov in February 2026 by one sponsor, Hudson Biotech: NCT07437547, a 120-person randomised, double-blind, placebo-controlled hamstring trial marked recruiting, and NCT07487363, which names TB-500 and whose own public summary states that it is a fictional example of a registry record. Neither has reported anything. The animal record behind the disc argument is rats, mice and rabbits, and the one experiment that ever combined two of the three found the pair beat neither compound on its own. What has never been measured in a person: any of the three against a squeezed nerve root or a worn disc, and all three together in anything alive.\n\nOne disclosure, because it should change how you read the rest. The operator of this site has a commercial interest in compounds described here. That is a reason to weigh what is on this page against the sources it cites rather than against its tone, and every claim below carries the source that supports it for exactly that reason.\n\nThis page sets out what is breaking down, what makes it break down faster, what each of the three compounds is proposed to build back, and how strong the evidence is at every single link. The grades differ enormously between links, and the strongest evidence in the whole stack sits on the compound most people leave out.\n\n## Three things break down in a worn disc, and they break down in order\n\n**The disc dries out.** The soft centre of a spinal disc is mostly water, held there by a large sugar-and-protein molecule called aggrecan that acts like a sponge. At birth that centre is about 90% water. By 60 it is closer to 70%, because the aggrecan gets chopped up and washed out. Less water means less pressure inside, and a disc that cannot hold pressure cannot spread load.\n\n**The outer ring tears.** As the centre flattens, load transfers to the tough fibrous ring around it. That ring is not built to take the load directly, so it splits — small cracks first, then tears that run through to the outside. That is how a worn disc becomes a bulging or herniated one.\n\n**The chemistry turns hostile, and nerves grow in.** Disc cells under load start pumping out two inflammatory signals, TNF-alpha and IL-1beta. Those signals do three things at once. They raise the enzymes that chew up the disc's own scaffolding while lowering the proteins that block those enzymes, so breakdown outruns building. They irritate any nerve root nearby. And they coax pain nerve fibres to grow into a disc that normally has none in its centre at all.\n\nThat third step is why worn and painful are different conditions. Plenty of badly degenerated discs never hurt. What makes a worn disc a painful one is chemistry, not the wear.\n\n[[embed:degenerative-disc-disease]]\n\n## The reason the disc cannot fix any of it\n\nThe spinal disc is the largest structure in the body with no blood supply of its own. Nothing feeds it directly. Nutrients seep in slowly through the bony end ","ranking":"safety-first (interaction_risk/limitations), then quote-gated effective_weight","claims":[{"id":"c3","text":"A 4 mg subcutaneous dose of ARA-290 peaks at about 3 ng/mL and clears in roughly twenty minutes, yet is dosed once daily and produces effects lasting days, because receptor binding starts an intracellular repair programme that continues after the compound has cleared.","tier":"human","section":"The nerve is the only link with randomised human evidence behind it","slot":"limitations","interaction_risk":false,"status":"active","source_ids":["s2"],"why_material":"Explains the apparent contradiction between a twenty-minute half-life and daily dosing.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c4","text":"Culver 2017 (NCT02039687), a Phase 2b randomised placebo-controlled trial in 64 people with sarcoidosis-associated small fibre neuropathy, 16 per arm, 28 days: corneal nerve fibre area rose 697 square micrometres above placebo at 4 mg per day (p = 0.012), while 1 mg (109) and 8 mg (431) did not reach significance, and pain in the moderate-to-severe group did not separate (p = 0.157).","tier":"human","section":"ARA-290's trials were real, and not one of them enrolled a back","slot":"limitations","interaction_risk":false,"status":"active","source_ids":["s1","s3"],"why_material":"The single strongest human result on the page, and its dose response is non-monotonic — 4 mg worked and 8 mg did not.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c1","text":"The stack is built on four separable links — no blood supply reaching damaged tissue (BPC-157), repair cells not arriving or not organising (TB-500), nerve fibres damaged and dying back (ARA-290), and the nerve root chemically irritated by TNF-alpha (BPC-157 and TB-500, weakly) — and no compound in the stack is claimed to move displaced tissue off a nerve.","tier":"mechanistic","section":"Three compounds, three different parts of the problem, graded link by link","slot":"limitations","interaction_risk":false,"status":"active","source_ids":["s21","s22"],"why_material":"The page grades each link separately; a reader who conflates them cannot tell which part of the claim is supported.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.3,"quote_gated":false},{"id":"c10","text":"Four named reasons the combination null may not transfer to a disc, each specifying the experiment that would settle it: wrong tissue (tendon has blood supply, a disc has essentially none), one dose level of each compound tested, a possible measurement ceiling because TB-500 alone already saturated the model, and a four-week readout when collagen keeps reorganising for months.","tier":"mechanistic","section":"Four ways that result could be wrong for a disc","slot":"limitations","interaction_risk":false,"status":"active","source_ids":["s5"],"why_material":"Distinguishes a limitation that names its own test from a hedge.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.3,"quote_gated":false},{"id":"c11","text":"No study in any species, at any dose, by any route has given BPC-157, TB-500 and ARA-290 together; there is no animal experiment, no case series and no registry entry for the three-compound combination.","tier":"mechanistic","section":"All three together has never been tested in anything","slot":"limitations","interaction_risk":false,"status":"active","source_ids":[],"source_status":"GAP: this is an absence claim. It is supported by the absence of any record in the registry and literature searches described on the page, not by a positive source.","why_material":"The page's headline configuration has zero experimental record of any kind, and that must be stated as an absence rather than implied.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.3,"quote_gated":false},{"id":"c19","text":"At vendor list prices read 4 August 2026, twelve weeks of all three at reachable doses costs 984 US dollars in materials including consumables (11.71 dollars a day); running ARA-290 at the 4 mg dose that was actually trialled raises that to 2,234 dollars (26.60 dollars a day).","tier":"mechanistic","section":"Twelve weeks of all three, priced to the dollar","slot":"limitations","interaction_risk":false,"status":"active","source_ids":["s15","s16"],"why_material":"The dose with randomised human evidence behind it costs more than twice the whole rest of the stack combined.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.3,"quote_gated":false},{"id":"c20","text":"BPC-157 and TB-500 both appear on FDA's list of bulk drug substances nominated but withdrawn, in category 2 for possible significant safety risks; ARA-290 appears nowhere on those lists because it was never nominated for compounding, which means no regulator has published any safety assessment of it as a compounding ingredient.","tier":"mechanistic","section":"Where United States law puts all three","slot":"limitations","interaction_risk":false,"status":"active","source_ids":["s17"],"why_material":"ARA-290's absence from the list is a thinner status, not a cleaner one, and is commonly misread as the opposite.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.3,"quote_gated":false},{"id":"c21","text":"No pharmacy can lawfully compound any of the three; none is on the 503A or 503B lists. On 23 to 24 July 2026 FDA's Pharmacy Compounding Advisory Committee voted 8 to 6 with one abstention in favour of allowing BPC-157 and TB-500 to be compounded, against FDA's own written recommendation, and that vote binds nothing.","tier":"mechanistic","section":"Where United States law puts all three","slot":"limitations","interaction_risk":false,"status":"active","source_ids":["s17","s18"],"why_material":"Determines that there is no lawful supply channel today, and that the position is moving.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.3,"quote_gated":false},{"id":"c22","text":"TB-500 is named on the WADA 2026 Prohibited List under S2.3 as a thymosin-beta-4 derivative and BPC-157 under S0, both prohibited at all times; ARA-290 is not named but S0 covers any substance with no current approval by any government health authority, which ARA-290 lacks, so it should be treated as covered.","tier":"mechanistic","section":"One of the three ends a tested athlete's season","slot":"limitations","interaction_risk":false,"status":"active","source_ids":["s19"],"why_material":"Decisive for any tested athlete regardless of efficacy, and ARA-290's unnamed status is not an exemption.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.3,"quote_gated":false},{"id":"c23","text":"On the page's own grading scale ARA-290 holds a B (randomised placebo-controlled human trial in a different condition with the target tissue measured directly), BPC-157 and TB-500 both hold a D (controlled animal experiment in a related tissue), the inflammation link holds an E, and the three-way combination holds an F — so the compound with the strongest evidence is the one usually treated as the optional add-on.","tier":"mechanistic","section":"The grades explained","slot":"limitations","interaction_risk":false,"status":"active","source_ids":["s1","s2","s5","s21","s22"],"why_material":"The evidence ordering is the inverse of the purchasing ordering, which is the page's central argument.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.3,"quote_gated":false},{"id":"c24","text":"The disc cannot repair itself because the adult nucleus has no blood supply and depends on diffusion across cartilage end plates that stiffen with age; every compound in the stack is therefore aimed at a tissue that is the hardest possible target for a systemically dosed agent.","tier":"speculative","section":"Three things break down in a worn disc","slot":"limitations","interaction_risk":false,"status":"active","source_ids":["s22"],"why_material":"If delivery to the disc fails, every mechanism claim above it is moot regardless of the compound's activity elsewhere.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.12,"quote_gated":false},{"id":"c2","text":"ARA-290 (cibinetide) is an eleven-amino-acid fragment of erythropoietin retaining the tissue-repair activity and omitting the red-cell activity; the two functions run through different receptors, and the repair receptor pairing appears on tissue only after injury and is absent from healthy tissue.","tier":"human","section":"The nerve is the only link with randomised human evidence behind it","slot":"what_is_known","interaction_risk":false,"status":"active","source_ids":["s2","s1"],"why_material":"The design rationale for why ARA-290 does not thicken blood the way erythropoietin does.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c5","text":"Brines 2015 (NTR3858), randomised double-blind placebo-controlled, 49 enrolled and 48 analysed, type 2 diabetes with painful neuropathy, 4 mg subcutaneous daily for 28 days: HbA1c fell 0.16% against 0.01% for placebo (p = 0.002), pain score improved significantly, and nerve fibre density rose 2.6 plus or minus 1.0 fibres per mm in the 18 people whose baseline was genuinely abnormal (p = 0.02).","tier":"human","section":"ARA-290's trials were real, and not one of them enrolled a back","slot":"what_is_known","interaction_risk":false,"status":"active","source_ids":["s2"],"why_material":"The second randomised human trial with a measured structural nerve endpoint.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c6","text":"Not one ARA-290 trial enrolled a person with a compressed lumbar nerve root; every positive result comes from small fibre neuropathy in sarcoidosis or diabetes, which is a different disease of the same tissue.","tier":"human","section":"ARA-290's trials were real, and not one of them enrolled a back","slot":"what_is_known","interaction_risk":false,"status":"active","source_ids":["s1","s2","s3"],"why_material":"The read-across from small fibre neuropathy to nerve root compression is the load-bearing and untested assumption of the whole page.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c7","text":"Etanercept, a direct TNF-alpha blocker, delivered at the nerve root against epidural steroid in subacute lumbar nerve pain, lost: steroid beat saline by 1.26 points on leg pain without reaching significance, and etanercept did worse than steroid on function by a margin that did reach significance.","tier":"human","section":"The chemical-irritation link is the weakest one, and it has been tested hard","slot":"what_is_known","interaction_risk":false,"status":"active","source_ids":["s4"],"why_material":"The most potent available block of the exact target the anti-inflammatory argument rests on produced a null; this sets the ceiling for the peptide version of that argument.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c8","text":"A separate randomised trial of transforaminal epidural etanercept in 49 patients with symptomatic lumbar disc herniation found separation only at the lowest of three doses (0.5 mg), with the 2.5 mg and 12.5 mg arms not separating, at a loose significance threshold.","tier":"human","section":"The chemical-irritation link is the weakest one, and it has been tested hard","slot":"what_is_known","interaction_risk":false,"status":"active","source_ids":["s24"],"why_material":"An upside-down dose response in the one positive trial weakens rather than supports the inflammation link.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c12","text":"NCT07437547 is a Phase 2 randomised, double-blind, placebo-controlled trial of BPC-157 in 120 planned participants with MRI-confirmed Grade II hamstring strain, subcutaneous once daily for 14 days, started 2 February 2026, measuring days to unrestricted return to sport at 8 weeks and blinded MRI injury volume at day 14.","tier":"human","section":"Two randomised human trials began enrolling in February 2026","slot":"what_is_known","interaction_risk":false,"status":"active","source_ids":["s20"],"why_material":"The first design capable of producing a blinded imaging measurement of BPC-157 in a person.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c13","text":"NCT07487363 is a Phase 1/2 randomised, double-blind, placebo-controlled stepped dose-escalation trial of TB-500 in 80 planned adults with stable atherosclerotic heart disease, started 5 February 2026, measuring side events at 12 weeks, serious events at 28 days, and absorption and clearance.","tier":"human","section":"Two randomised human trials began enrolling in February 2026","slot":"what_is_known","interaction_risk":false,"status":"active","source_ids":[],"source_status":"GAP: the NCT07487363 registry record is cited in the body but is not registered as a source object on this article; only NCT07437547 (s20) is attached.","why_material":"It will produce the first human safety and clearance numbers for the TB-500 fragment and will say nothing about tendon or disc.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c14","text":"A 2024 meta-analysis pooling 31 studies and 2,233 people with a lumbar disc herniation treated without surgery found a spontaneous resorption rate of 70.39% overall: 87.77% for sequestrated fragments, 66.91% for extrusions, 37.53% for protrusions and 13.33% for bulges — the more displaced the herniation, the more likely the body removes it.","tier":"human","section":"The number any protocol has to beat is the disc's own recovery rate","slot":"what_is_known","interaction_risk":false,"status":"active","source_ids":["s23"],"why_material":"This is the base rate any uncontrolled protocol must beat, and it makes single-person before-and-after reasoning uninformative.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c9","text":"In the only experiment ever to put BPC-157 and TB-500 in the same animals against each alone — 32 rats, Achilles tendon cut and repaired, four weeks of daily intraperitoneal dosing, four groups of eight — TB-500 alone raised breaking strength against control (p < 0.05) and improved both tissue scores (p = 0.016 and p = 0.017), BPC-157 alone was numerically better without reaching significance, and the combination did not confer additional benefits compared to either agent alone.","tier":"preclinical","section":"Two of the three have been tested together once","slot":"what_is_known","interaction_risk":false,"status":"active","source_ids":["s5"],"why_material":"The only direct experimental test of stacking, and it found stacking bought nothing.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.5,"quote_gated":false},{"id":"c18","text":"ARA-290 in a 10 mg vial reconstituted with 1.25 mL gives 8,000 micrograms per mL and 80 micrograms per mark on a U-100 syringe, so 1 mg is 12.5 marks; reconstituted with 2.0 mL it gives 5,000 micrograms per mL and 50 micrograms per mark, so 1 mg is 20 marks and the 4 mg trial dose is 80 marks or 0.80 mL.","tier":"mechanistic","section":"Reconstituting three vials, one arithmetic at a time","slot":"what_it_is","interaction_risk":false,"status":"active","source_ids":[],"source_status":"Arithmetic derived in-page from stated vial mass and diluent volume; checkable by recomputation.","why_material":"The trial dose of ARA-290 is eight times the commonly used dose, and the arithmetic is what makes that visible on a syringe.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.3,"quote_gated":false},{"id":"c15","text":"Filtering the self-report record to people describing a back, disc or sciatic problem specifically yields seven usable reports: 4 said it helped, 2 said nothing changed, 1 said something got worse.","tier":"anecdotal","section":"Seven people with a back problem wrote down what happened","slot":"who_claims_what","interaction_risk":false,"status":"active","source_ids":["s6","s7","s8","s9","s10","s11","s12"],"why_material":"Seven reports against a 70.39% spontaneous resorption base rate cannot distinguish treatment from natural course, and the page says so.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.3,"quote_gated":false},{"id":"c16","text":"Four ARA-290 self-reports were located and only one states an outcome; no report was found on any platform of a person running all three compounds together.","tier":"anecdotal","section":"What people report on ARA-290","slot":"who_claims_what","interaction_risk":false,"status":"active","source_ids":["s13","s14"],"why_material":"The three-compound stack has no human record at all — not a trial, not a case, not a forum post.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.3,"quote_gated":false},{"id":"c17","text":"Whether repair signalling accomplishes anything while a nerve is still being mechanically compressed has no published answer; nobody has tested repair signalling against an ongoing mechanical squeeze.","tier":"speculative","section":"What people report on ARA-290","slot":"what_is_unknown","interaction_risk":false,"status":"active","source_ids":["s14"],"why_material":"The sharpest objection in the record, raised by a skeptic rather than the author, and it is unanswered.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.12,"quote_gated":false}],"sources":[{"id":"s1","type":"source","url":"https://pubmed.ncbi.nlm.nih.gov/28475703/","title":"Culver DA et al. Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain. Phase 2b, NCT02039687. PMID 28475703","quote":"64 subjects, 16 per arm, 1, 4 or 8 mg subcutaneous daily for 28 days. Placebo-corrected change in corneal nerve fibre area: 109 µm² at 1 mg (not significant), 697 µm² at 4 mg (p = 0.012), 431 µm² at 8 mg (not significant). GAP-43+ regenerating skin fibres rose in the 4 mg arm, p = 0.035. Pain severity in the moderate-to-severe subgroup, p = 0.157.","claim_ids":[],"hash":"e7c1ac3117f7d289546481084e44be89a72ada246837f6f3abdaabf0c5d5ba4f"},{"id":"s2","type":"source","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4365069/","title":"Brines M et al. ARA 290 in type 2 diabetes with painful neuropathy — randomised double-blind placebo-controlled trial, NTR3858, full text with pharmacokinetics and adverse events","quote":"49 enrolled, 48 analysed, 4 mg subcutaneous daily self-injected for 28 days with 56-day follow-up. HbA1c fell 0.16% at day 28 and 0.21% at day 56 versus 0.01% and +0.21% for placebo, p = 0.002. Corneal nerve fibre density rose 2.6 ± 1.0 fibres/mm² in the abnormal subgroup (n = 18, p = 0.02) against +0.7 for placebo.","claim_ids":[],"hash":"4d71c539dc7ee609679a31cd53c301043cf842058b576fa72d62116b46f70ede"},{"id":"s3","type":"source","url":"https://clinicaltrials.gov/study/NCT02039687","title":"ClinicalTrials.gov NCT02039687 — Study of Efficacy of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms of Subjects With Sarcoidosis. Completed","quote":"Phase 2, randomised, double-blind, placebo-controlled dose-ranging study of ARA 290 in sarcoidosis-associated small nerve fibre loss. Primary outcome: change in corneal nerve fibre area at day 28.","claim_ids":[],"hash":"35feb0d834ded8821dbc2f5517e34a60b0f6e647427b9fbd0949457aaefff9f4"},{"id":"s4","type":"source","url":"https://pubmed.ncbi.nlm.nih.gov/22508732/","title":"Cohen SP et al. Epidural steroids, etanercept, or saline in subacute sciatica: a multicenter, randomized trial. Ann Intern Med 2012. PMID 22508732","quote":"Steroids beat saline by 1.26 points on the leg pain measure, which did not reach significance. Etanercept fared worse than steroids on functional capacity, by a margin that did.","claim_ids":[],"hash":"5b248f0615085f0a2e4fc3f736aa7122ca2d243cab972b53f087d59b097036f2"},{"id":"s5","type":"source","url":"https://pubmed.ncbi.nlm.nih.gov/42542926/","title":"Biçer O, Adanir O, Güleryüz Y, Balci EC. Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study. Jt Dis Relat Surg, 23 July 2026. PMID 42542926","quote":"32 rats, Achilles transection and repair, four arms of eight, four weeks intraperitoneal: control, BPC-157 10 µg/kg/day, TB-500 60 µg/kg/day, or both. TB-500 alone raised maximum load to failure (p<0.05), Bonar score (p=0.016) and Movin score (p=0.017). The combination did not confer additional benefits compared to either agent alone.","claim_ids":[],"hash":"29dc106f0202e36088b0a2bc6c80a97ffe5a5f26b63796a8a8e01e17c0e78cd8"},{"id":"s6","type":"source","url":"https://x.com/MuroCrypto/status/2083184469956059529","title":"X — @MuroCrypto, 31 July 2026 — anecdotal, positive, herniated lumbar disc, ran both compounds","quote":"My lowest disc in the lower back is dried out, almost no fluid left, classic herniated disc. Flared up hard in March, could barely sit or stand without pain. Went on for 3 months with zero improvement. In June I ran BPC-157 and TB-500 for about 6 weeks. After 3-4 weeks it already felt better.","claim_ids":[],"hash":"798edfd4dca7fccf4a88df9a8fc3212d325a48fb377567f620929b991ed7e873"},{"id":"s7","type":"source","url":"https://www.reddit.com/r/Sciatica/comments/1rnicr5/pinched_sciatic_nerve/","title":"Reddit r/Sciatica — u/kunukxathletix, 7 March 2026 — anecdotal, positive, sciatic pain","quote":"I tried ever and eventually decided to try injectable BPC 157 and within a few weeks pain started to ease, well this could be random so I continued use after about 6-7 weeks sciatic pain was almost all the way gone","claim_ids":[],"hash":"efaf906fd92f029f2741a58434b24abaf1710d93ba4b0d0e188852d2bf2eab12"},{"id":"s8","type":"source","url":"https://x.com/drmarlonperalta/status/2062565899714925044","title":"X — @drmarlonperalta, 4 June 2026 — anecdotal, positive, ten years of low back pain from a herniated disc","quote":"I've suffered for 10+ years with lower back pain from a herniated disc. I would constantly reposition myself for relief while working. A 6-week cycle removed this distraction permanently.","claim_ids":[],"hash":"0fe317c19f1f02569a1c89fe9e82c2f82559895ba1fc7184f5a18b3f2a3a84a9"},{"id":"s9","type":"source","url":"https://x.com/AJA_Cortes/status/1794522474702336108","title":"X — @AJA_Cortes, 26 May 2024 — anecdotal, positive, L5-S1 flare, writer flags placebo himself","quote":"Decided to try to taking oral BPC157 at 2000mcg daily. Also got two deep tissue massages, and a chiro adjustment. 7 days later, pain free. Did the BPC157 help? Maybe, maybe not. Im always open to possibility of placebo.","claim_ids":[],"hash":"270188080870ba811474a2d3685ab95b9e292e4fda20f127b1b011f4f3ce367b"},{"id":"s10","type":"source","url":"https://www.reddit.com/r/backpain/comments/1mu96us/hlab27_sacroiliitis_on_mri_vs_disc_obliteration/","title":"Reddit r/backpain — u/ImNotSchema, 19 August 2025 — anecdotal, no effect, ran both compounds","quote":"I also experimented with TB500 and BPC-157 peptides, but saw no improvement. The one thing that actually helped was Prednisone.","claim_ids":[],"hash":"ccd316586ec1303e18c8f304031783816e6fc2f65e2f75f9df7c70caaa610602"},{"id":"s11","type":"source","url":"https://www.reddit.com/r/backpain/comments/1ccysh4/chronic_onesided_thoracic_pain/","title":"Reddit r/backpain — u/Dizzy-Breakfast-9405, 25 April 2024 — anecdotal, no effect after a month","quote":"I even tried peptides (BPC-157) for a month, no results.","claim_ids":[],"hash":"aaf124740bf0586e55a79ea6ad0dd300c1cdd306875c7032e774f7bc0b3358e0"},{"id":"s12","type":"source","url":"https://www.reddit.com/r/backpain/comments/1fi50ar/bpc_157_and_tb_500_for_herniated_disc/","title":"Reddit r/backpain — u/Miserable_Fan1984, 16 September 2024 — anecdotal, got worse, herniated disc, ran both compounds","quote":"I started taking bpc 157 and tb 500 and 500mcg a day to help with healing but I have started to feel worse and have pain going down my leg again.","claim_ids":[],"hash":"719e140ed0baf5ec101cce5e11729977e5cf00bcc37020c9068749ad323a4860"},{"id":"s13","type":"source","url":"https://x.com/NewsDeskOne/status/2077929820760019113","title":"X — @NewsDeskOne, 17 July 2026 — anecdotal, positive, ARA-290 for nerve symptoms in the feet","quote":"Did a run of ara 290, seemed to make a difference in neuropathy and sensitivity in my feet. This was after a couple months of bpc and 500","claim_ids":[],"hash":"cc8bf50af5e15cbaa53716ba33071d3b43006edb79fd22d02e045efc6889881d"},{"id":"s14","type":"source","url":"https://x.com/vedichi_/status/2077787145238913472","title":"X — @vedichi_, 16 July 2026 — anecdotal, skeptical, names the read-across problem directly","quote":"most of the ARA-290 data is small-fiber neuropathy, not compression. does the repair signalling do anything while the tunnel is still squeezing the nerve?","claim_ids":[],"hash":"1d5f383bd30ac36c910ace8adb964036dfe906e9638d97861195d704528f8810"},{"id":"s15","type":"source","url":"https://www.nationwidepeptides.com/products/ara-290-cibinetide-peptide/","title":"Nationwide Peptides — ARA-290 (cibinetide), BPC-157 and TB-500 research-chemical listings, prices read 4 August 2026","quote":"ARA-290 (Cibinetide) Peptide $43.00. BPC-157 Peptide price range: $42.00 through $63.00. TB-500 Peptide (TB4) price range: $38.00 through $61.00. For Research Use Only. Not for human use.","claim_ids":[],"hash":"6f06a5349984cc1ed9af7fb65811960b4e74fb65c593e494bc6366da8e963716"},{"id":"s16","type":"source","url":"https://luxepeptides.is/ara-290/","title":"Luxe Peptides — ARA-290 peptide listing, prices read 4 August 2026","quote":"ARA-290 Peptide — 10 mg at $50.00, 16 mg at $70.00. Research use only.","claim_ids":[],"hash":"1a54fbbaebf65a91598a3b9c97a879106a9bc140c141d46d404b1218a9c731ad"},{"id":"s17","type":"source","url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"FDA — Certain Bulk Drug Substances for Use in Compounding That May Present Significant Safety Risks, current as of 22 April 2026","quote":"Bulk drug substances nominated but withdrawn. This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators. Thymosin beta-4, fragment (LKKTETQ), also known as TB-500: FDA has not identified any human exposure data drug products containing Thymosin Beta-4, Fragment. Cibinetide and ARA-290 appear nowhere on this page.","claim_ids":[],"hash":"cec8b1b9b360f879a004568911def6808bd1f32b52ef8740192099aa378e9141"},{"id":"s18","type":"source","url":"https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026","title":"FDA — 23-24 July 2026 meeting of the Pharmacy Compounding Advisory Committee","quote":"Committee considered whether BPC-157, KPV and TB-500 should be placed on the 503A bulks list. The vote is advisory; FDA is not bound by it and no rulemaking has completed.","claim_ids":[],"hash":"05e8b89d58fad32942135a3ca47d08d1bdf5c6c6198e71d1fb92bfa67bb8849d"},{"id":"s19","type":"source","url":"https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf","title":"World Anti-Doping Code International Standard — Prohibited List 2026, effective 1 January 2026","quote":"S2.3 Growth Factors and Growth Factor Modulators: Thymosin-ß4 and its derivatives e.g. TB-500. S0 Non-Approved Substances: any pharmacological substance with no current approval by any governmental regulatory health authority for human therapeutic use. Prohibited at all times.","claim_ids":[],"hash":"bd8985579bba951e1e5bedd7e682c37223a2fc357019830cf528892322892e1a"},{"id":"s20","type":"source","url":"https://clinicaltrials.gov/study/NCT07437547","title":"NCT07437547 — A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of Pentadecapeptide BPC 157 for Accelerated Repair of Acute Grade II Hamstring Strain Confirmed by MRI. Hudson Biotech. Recruiting, started 2 February 2026","quote":"120 participants planned. Subcutaneous injection once daily for 14 days versus placebo. Primary outcomes: time to return to unrestricted sport participation at 8 weeks, and change from baseline to day 14 in MRI-assessed hamstring injury volume by blinded central radiology review.","claim_ids":[],"hash":"17f5eef8fb243c07e58658c897b30d427be8467f263f90195ba2f05162f139dd"},{"id":"s21","type":"source","url":"https://pubmed.ncbi.nlm.nih.gov/41966639/","title":"Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance. Sports Med, 12 April 2026. PMID 41966639","quote":"Independent 2026 review of the peptide musculoskeletal literature, covering BPC-157 and thymosin beta-4 products.","claim_ids":[],"hash":"e073cb454b965c1891f9525270a76028f6c173e3dec4603500afa4bb4d421ec7"},{"id":"s22","type":"source","url":"https://pubmed.ncbi.nlm.nih.gov/41490200/","title":"Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions. J Am Acad Orthop Surg Glob Res Rev, 1 January 2026. PMID 41490200","quote":"Independent 2026 orthopaedic review of therapeutic peptides, their applications and the state of the evidence.","claim_ids":[],"hash":"f0f525fdf54cd1dc9a95c0e34be3a2d11655ca8fd4e3b623176921b96a195545"},{"id":"s23","type":"source","url":"https://pubmed.ncbi.nlm.nih.gov/37559207/","title":"Incidence of Spontaneous Resorption of Lumbar Disc Herniation: A Meta-analysis. Clin Spine Surg, 2024. PMID 37559207","quote":"31 studies, 2,233 conservatively treated patients. Overall spontaneous resorption rate 70.39%: 87.77% for sequestration, 66.91% for extrusion, 37.53% for protrusion, 13.33% for bulging.","claim_ids":[],"hash":"41705da420faf1e9228f0eebebe5c3f967c30ac13f0f98ff8f9c6adbcb21eda4"},{"id":"s24","type":"source","url":"https://pubmed.ncbi.nlm.nih.gov/24165696/","title":"Randomized, double-blind, placebo-controlled trial of transforaminal epidural etanercept for symptomatic lumbar disc herniation. PMID 24165696","quote":"49 patients across three doses. Separation from placebo appeared only at the lowest dose, 0.5 mg; the 2.5 mg and 12.5 mg arms did not separate, at a significance threshold of P < 0.1.","claim_ids":[],"hash":"1c38666d780e4c40f98651f00f53a4f642005e33966bbf7b9ef78551682e5d35"}],"anecdotal_sources":[],"scientific_sources":[],"user_reports":[],"related_articles":[{"slug":"wolverine-stack","title":"The Wolverine stack: BPC-157 and TB-500, the evidence, the dosing arithmetic and the eight-week cost","claims":[{"id":"c1","text":"BPC-157 is thought to work on the blood supply step of repair, growing new vessels into damaged tissue by switching on VEGF and the nitric oxide system that widens vessels.","tier":"mechanistic"},{"id":"c2","text":"TB-500 is a seven-amino-acid fragment of thymosin beta-4, covering residues 17 to 23 with the front end capped, and the stretch it copies is the part that grabs actin.","tier":"mechanistic"},{"id":"c400","text":"Grabbing actin frees up the internal scaffolding a repair cell uses to crawl into a wound.","tier":"mechanistic"},{"id":"c3","text":"Tendon, ligament and the adult disc between two vertebrae all heal slowly because blood barely reaches them.","tier":"mechanistic"},{"id":"c401","text":"The centre of an adult disc has no vessels in it at all. It is fed by seepage across cartilage end plates that stiffen and calcify as a person gets older.","tier":"mechanistic"},{"id":"c4","text":"In a rat Achilles tendon repair, TB-500 at 60 micrograms per kilogram per day raised the maximum load the tendon took before failing, against control, at p < 0.05.","tier":"preclinical"},{"id":"c402","text":"That experiment ran 32 rats, 8 to a group, with a daily injection into the belly for four weeks.","tier":"preclinical"},{"id":"c5","text":"In that same experiment TB-500 improved the Bonar tissue score at p = 0.016 and the Movin score at p = 0.017.","tier":"preclinical"}]},{"slug":"bpc-157","title":"BPC-157: Body Protection Compound","claims":[{"id":"c1","text":"BPC-157 is a made-in-a-lab chain of 15 amino acids, copied from a stretch of a protein found in stomach juice.","tier":"human"},{"id":"c2","text":"More than 100 studies in animals and in cells report faster healing — better-organised collagen, and blood vessels growing into the wound — across tendon, gut, muscle, bone and nerve.","tier":"preclinical"},{"id":"c3","text":"A 2025 pilot study dripped up to 20 mg of BPC-157 into the veins of two healthy adults. Nothing went wrong with their vital signs, their blood tests, or how they said they felt.","tier":"human"},{"id":"c4","text":"The proposed explanation is that BPC-157 encourages new blood vessel growth at the injury and works on the body’s nitric oxide system. That is a proposal drawn from animal work, not something measured in a person.","tier":"mechanistic"},{"id":"c6","text":"One person reported feeling sick within two weeks of starting BPC-157 and stopped taking it. That is one person. The same account was then ingested 25 more times from other copies of the same thread, and each copy is listed below so the count is visible rather than hidden.","tier":"anecdotal"},{"id":"c8","text":"The second copy of that same single nausea report, ingested again from another copy of the same thread. It is the same one person, not 2 people.","tier":"anecdotal"},{"id":"c10","text":"The third copy of that same single nausea report, ingested again from another copy of the same thread. It is the same one person, not 3 people.","tier":"anecdotal"},{"id":"c11","text":"Ten of the sources catalogued on this page are vendors and clinics selling BPC-157. That is marketing material, and it is listed here as marketing material rather than as evidence.","tier":"human"}]},{"slug":"tb-500","title":"TB-500 (Thymosin Beta-4)","claims":[{"id":"c1","text":"TB-500 is sold as a made-in-a-lab version of thymosin beta-4, a small protein your own cells already make.","tier":"mechanistic"},{"id":"c300","text":"Thymosin beta-4 is the body's main handler of loose actin, the building material a cell uses to change shape and crawl.","tier":"mechanistic"},{"id":"c301","text":"Holding that building material is how thymosin beta-4 sets the pace at which cells move into an injury, and cells moving into an injury is what repair is.","tier":"mechanistic"},{"id":"c2","text":"The same seven amino acids that let thymosin beta-4 grip actin also make new blood vessels grow.","tier":"mechanistic"},{"id":"c302","text":"Those seven amino acids also make the cells that line blood vessels crawl, so new blood vessel growth is not a side effect of the repair. It is part of it.","tier":"mechanistic"},{"id":"c3","text":"In controlled animal wound experiments, thymosin beta-4 made skin grow back across the wound 42 to 61% faster than in untreated animals.","tier":"preclinical"},{"id":"c303","text":"Those same animal wounds laid down more collagen and grew more new blood vessels.","tier":"preclinical"},{"id":"c4","text":"Thymosin beta-4, the full protein rather than the fragment in the vial, was tested in people with pressure sores and long-standing leg ulcers in proper randomised, double-blind, placebo-controlled trials.","tier":"human"}]},{"slug":"ara-290","title":"ARA-290 (cibinetide): a fragment of erythropoietin that acts on nerves, not on blood","claims":[{"id":"c1","text":"ARA-290 (cibinetide) is an 11-amino-acid peptide from EPO's helix-B surface that activates the innate repair receptor (EPOR/beta-common heterocomplex) to drive tissue repair, distinct from EPO's erythropoietic receptor.","tier":"mechanistic"},{"id":"c2","text":"Because it engages the innate repair receptor rather than the homodimeric EPO receptor, ARA-290 does not stimulate erythropoiesis or raise hematocrit, avoiding EPO's thrombotic risk.","tier":"mechanistic"},{"id":"c3","text":"The mechanism was defined by Michael Brines and Anthony Cerami, who showed EPO's tissue protection runs through an EPOR/beta-common-receptor heterocomplex.","tier":"mechanistic"},{"id":"c4","text":"In a randomized, double-blind, placebo-controlled pilot in sarcoidosis patients with small-fiber neuropathy, ARA 290 significantly improved neuropathy symptom scores versus placebo.","tier":"human"},{"id":"c5","text":"In a Phase 2b RCT (n=64), 4 mg/day cibinetide significantly increased corneal nerve fiber area and raised GAP-43+ regenerating intraepidermal nerve fibers, an objective structural sign of nerve regeneration.","tier":"human"},{"id":"c6","text":"In type 2 diabetics, ARA 290 improved neuropathic symptoms alongside HbA1c and lipids over 56 days without safety issues.","tier":"human"},{"id":"c7","text":"In nerve-injury models, ARA 290 produced long-lasting, dose-dependent reductions in allodynia coupled to suppression of the spinal microglial neuroinflammatory response.","tier":"preclinical"},{"id":"c8","text":"ARA 290 inhibits macrophage activation and pro-inflammatory cytokine release (IL-6, IL-12, TNF-alpha) and protects cells from cytokine-induced apoptosis.","tier":"preclinical"}]},{"slug":"herniated-disc","title":"Herniated disc: 70% resorb without surgery and 95% recover at one year","claims":[{"id":"c1","text":"A herniated disc is not a broken part. Tissue has moved, that is all: the soft centre of the disc has pushed out through a tear in the tough outer ring.","tier":"mechanistic"},{"id":"c300","text":"The tear almost always sits towards the back and a little to one side, where the tough outer ring is thinnest. A nerve root runs right there, which is why the escaped material ends up pressing on it.","tier":"mechanistic"},{"id":"c2","text":"Most herniated discs shrink away on their own. Pooled data put it at roughly two-thirds of the people who were never operated on.","tier":"human"},{"id":"c3","text":"The biggest herniations are the ones that clear best. A piece squeezed right out through a tear, or one that has broken clean away, disappears completely far more often than a small bulge that never breached the outer ring.","tier":"human"},{"id":"c4","text":"The fragment does not simply dry up and vanish. Scavenger cells from your immune system, called macrophages, move in on the escaped material and eat it.","tier":"mechanistic"},{"id":"c301","text":"Those same scavenger cells set off enzymes and new blood vessel growth, and between them the fragment is dissolved and carried away.","tier":"mechanistic"},{"id":"c5","text":"Mature disc tissue has almost no blood supply of its own, which is why it heals so slowly.","tier":"mechanistic"},{"id":"c302","text":"Recovery depends on new blood vessels growing in at the edge of the herniation, pushed along by a signalling protein called VEGF, bringing a blood supply to a place that normally has none.","tier":"mechanistic"}]}],"question_graph":{"slug":"wolverine-stack-ara-290","questions":[],"evidence":[],"edges":[],"counts":{"questions":0,"evidence":0,"edges":0}},"honesty":{"active_claims":24,"retracted_claims":0,"cut_claims":0,"challenges":0,"scrub_events":0,"note":"Retracted/cut claims stay on ledger but are excluded from ask unless ?include_inactive=1"},"counts":{"claims":24,"claims_total":24,"sources":24,"anecdotal":0,"scientific":0,"user_reports":0,"questions":0,"evidence_ingests":0}}